7 Aliphatic Compounds Part (ii) Other Aliphatic Compounds By B. V. SMITH Department of Chemistry King's College London Kensington Campus Campden Hill Road London W8 7AH 1 Alcohols and Ethers Several papers have concentrated on protection-deprotection methods for the OH-group. Trimethylsilyl bromide cleaves MOM (methoxymethyl) ethers cleanly and in high yields; bis-i-propylthioboron bromide was effective for MOM and MEM (methoxyethoxymethyl) derivatives. The reaction of Et,AlCN with MOM ethers has been exploited in the synthesis of cyanomethyl ethers a useful synthetic equivalent for RO-C=O.' Selectivity toward fluoride ion has been observed for the t-butyl- dimethylsilyl-group (but not for the tetrahydropyranyl group) ; diethylaluminium chloride will remove the latter but not the former.Ethers derived from t-butyl- methoxyphenylsilyl bromide But(MeO)Si( Ph) Br are even more labile towards fluoride ion which leaves other protecting groups unaff ected. Asymmetric induction from a chiral centre has been exploited in the addition of protected allyloxyboronate (1) to ethyl pyruvate; 14:1 diastereoselection was observed in this novel application (Scheme l).3 Conversion of the halide (or enone) as shown in Scheme 2 takes advantage of the dimethylphenylsilyl group acting as a masked OH-group." C-Trapped azo- compounds are a source of alcohols (and alkanes or alkenes) by reaction of (3) [from (2) and a ketone R3R4CO] with a thi01.~ Free radical-initiated decomposition of esters derived from N-hydroxypyridine-2-thione(4) gave nor-hydroperoxides which could be transformed into alcohols (or carbonyl compounds).6 Stereoselec- tivity in transition-metal-catalysed reduction of allylic (and cyclic) alcohols showed a striking dependence on the catalyst used and the catalyst substrate ratio but was independent of hydrogen pressure (with one e~ception).~ The ring-opening (by AlC1,-NaI- MeCN) of unsymmetrical 5-membered ethers occurred preferentially at the less hindered carbon affording the S-iodoalcohol.8 ' S.Hanessian D. Delorme and Y. Dufresne Tetrahedron Lett. 1984 25 2515; E. J. Corey D. H. Hua and S. P. Seitz ibid. p. 3. Y. Ogawa and M. Shibasaki Tetrahedron Lett. 1984 25 663; Y. Guindon R. Fortin C. Yoakim and J. W. Gillard ibid. p. 4717. R. Metternich and R.W. Hoffman Tetrahedron Lett. 1984 25 4095. I. Fleming R. Henning and H. Plant J. Chem. SOC.,Chem. Commun. 1984 29. J. E. Baldwin J. C. Bottaro J. N. Kolhe and R. M. Adlington J. Chem. SOC.,Chem. Commun. 1984.22. D. H. R. Barton D. Crick and W. B. Motherwell J. Chem. Soc. Chem. Commun.,1984 242. D. A. Evans and M. M.Momssey Tetrahedron Lett. 1984 25 4637. 'M. Noda T. Kajimoto K. Nishide E. Fujita and K. Fuji Tetrahedron Lett. 1984 25 219. 119 120 B-V. Smith f /. a C02Me /=C02Me /.. r-r Ox0 Ox0 90 10 Reagents i .to,$ -6 kbar ii H,/Pt; iii TsOH-MeOH; iv TsOH-Me,CO; v KOH-MeOH; vi 0 CH,N,-Et,O Scheme 1 -+ Ph-MgBr Ph -Ph R2 4 PhdRe:l I1 Ph R' R2 R2 Reagents i HBF,; ii MCPBA-Et,N-Et,O RT Scheme 2 An improved route to dialkylboranes of very high optical purity has been described.The method is conceptually simple ;optically pure isopinocampheylalkyl boranes were prepared from prochiral olefins and IpcBH of 100% e.e. and purified further by crystallization. Reaction with MeCHO gave a boronic ester oxidized in the usual way to alcohol of 100% optical purity (Scheme 3). Chiral transfer from boron to Aliphatic Compounds -Part (ii) Other Aliphatic Compounds almost all other elements of interest will allow a simple synthesis of a large number of chiral compounds essentially optically pure; some examples are shown in the Scheme. This method opens up one of the most far-reaching vistas ever seen in asymmetric synthesis of a considerable range of chiral molecule^.^ Chiral acetals undergo TiC1,-mediated coupling with organometallics to form (5) and (6) which are precursors of chiral alcohols [e.g.(5) 4 (7) formed with high optical purity (Scheme 4)]. Silyl derivative (8a) has been used as a chiral primary alcohol equivalent; ~B(OR)Iiv / 1ii * R RB(OMe) I ,-OH H (S) ‘B+< -RBH2- iBX2 H’ (R* = chiral group) Reagents i MeI THF 0°C; ii H,O, NaOH iii RCHO; iv OH- then re-esterification Scheme 3 RY 0.- i 1ii iii Reagents i ZM TiCI,; ii PCC; iii HO-Scheme 4 H. C. Brown and B. Singaram J. Am. Chem. SOC.,1984 106 1799. 122 B. V. Smith (8a) R = H (8b) R = COEt Me Claisen-Ireland rearrangement of (8b) gave 9a :9b in the ratio 94 6 or 7 :93 according to the method used to generate the enolate." Carbanions a to alkoxy- or amino-silyl groups act as a-hydroxyalkylating agents ie.the synthetic equivalent of an a-hydroxyalkyl anion; chiral silyl compounds e.g. (10) react with an alkyl-lithium to form an adduct converted into a chiral alcohol with modest e.e. (Scheme 5)." This reaction represents a new approach through a chiral silane. Racemic esters can be converted by an esterase-catalysed transesterification in biphasic systems into active esters (and alcohols)." The heterocycle (1 1 a) (2-halogeno-l,3,2-oxaphospholidine 2-sulphide) has been recommended for the rapid measurement of enantiomeric purities of alcohols (and amines) by looking at 31Pn.m.r. shifts of (llc).'The oxide (1 lb) was less ~atisfactory.'~ (-Si( Me)O) i ii \ -Li +(lo)? 111.IV lv OH Br Reagents i Et,O 0 "C; ii MgBr,; iii. ,CuI THF; iv 6M HCI; v 90% H202 KHF, DMF Scheme 5 Me (Ila) 2 = S,Y = C1 (llb) Z= 0,Y= C1 (11~) Z = S,Y = OR 10 S. D. Lindell J. D. Elliott and W. S. Johnson Tetrahedron Lett. 1984 25 3947; R. E. Ireland and M. D. Varney 1. Am. Chem. SOC.,1984 106 3668. K. Tamao R. Kanatani and M. Kumada Tetrahedron Lerr. 1984 25 1905 1909 1913. 12 B. Carnbou and A. M. Klibanov 1. Am. Chem. Soc, 1984 106 2687. l3 C. R. Johnson R. C. Elliott and T. D. Penning J. Am. Chem. SOC.,1984 106 5019. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds Secondary alcohols with bromine and a silver salt formed tetrahydrofurans via 6-hydrogen ab~traction.'~ Tertiary alcohols underwent deoxygenation in a radical- initiated decomposition of a mixed oxalate-N- hydroxypyridine-2-thione ester." Hindered alcohols especially secondary and tertiary types are benzoylated cleanly by PhCOOTf (Tf = trifluoromethane sulphonyl) in CH2C12 or CH2C12-CSH5N at -78 OC.I6 Selectivity in oxidation has been reported for secondary alcohols by suitable protection of any primary alcohol and PCC oxidation/deprotection or by use of MeV'/ H202; K2Fe0,/ PTC is selective for allylic and benzylic alcohols (but not other primary gro~ps).'~ Stereodifferentiation in 1,2-diols has been effected by reaction between a chiral acid chloride (12) and the cyclic derivative (13).Variable d.e. was observed in (14). Extension of this approach to prochiral (2-0-protected) glycerol by using the analogue of (13) and a chiral auxiliary gave only modest optical purity.Kinetic resolution of substituted propan- 1,2-diols with D-camphorquinone gave a mixture of diastereoisomeric acetals (which showed some lability when heated). By this method (*)-3-chloropropan- 1,2-diol afforded four separable products one of which was transformed by base into ( R) -chloromethyloxiran.18 Alkenes via an addition-elimination sequence were elaborated to substituted allylic alcohols; chiral epoxyhalides with CH2=CHMgBr/Cu'I followed by iodide gave chiral allylic alcohol^.'^ Branched or linear homoallylic alcohols can be pre- pared from a trialkylborane and the anion of PhSeCH2CH=CH2. The key to this remarkable observation is that rearrangement of (15) is slow; short reaction-time generates linear product and a longer time gives branched product.20 The [2,3] Wittig sigmatropic rearrangement of chiral allylic ethers proceeds with very high chirality transfer (94-97Oh ) and erythro-selectivity (90-96% ) (see Scheme 6).Since (16) has been transformed into (-)-ephedrine this pathway constitutes a formal (chiral) total synthesis. Similar selectivity was noted for the crotyl propargyl ether (17) ;the 2-ether gave 88 :12 and the E-ether 7 :93 respectively erythro threo-product ratio. The silyl ether (S)-2-( 18) after rearrangement and reduction afforded I4 N. M. Roacher and D. K. Shaffer Tetrahedron 1984,40 2643. Is D. H. R. Barton and D. Crich J.Chem. SOC.,Chem. Commun. 1984 774. 16 L. Brown and M. Koneeda J. Org. Chem. 1984,49 3875. 17 T. Nonako S. Kanemoto K. Oshima and H. Nozaki Bull. Chem. Soc. Jpn. 1984 57 2019 8. M. Trost and Y. Masuyama Tetrahedron Lett. 1984,2S 173; K. S. Kim Y. K. Chang S. K. Bae and C. S. Hahn Synthesis 1984 866. 18 T. Mukaiyama 1. Tomioka and N. Shimizu Chem. Lett. 1984 49; M. K. Ellis B. T. Golding and W. P. Watson J. Chem. SOC.,Chem. Commun. 1984 1600. 19 J. Rodriguez J.-P. Dulcere and M. Bertrand Tetrahedron Lett. 1984 25 527; K. C. Nicolaou M. E. Duggan and T. Ladduwahetty ibid. p. 2069. 20 Y. Yamarnoto Y. Saito and K. Maruyama 1.Org. Chem. 1983.48 5408. 124 B. V. Smith .. ... HO Ph (R = Me) (2S 3s)-( 16) Reagents i BuLi (5eq)-THF -85 "C; ii NaI04 KMn04 Bu'OH; iii CH2N2-Et20 Scheme 6 SePh o\ * R' H (S)-(+) -(19) and further reduction gave the alcohol (3S,4S) -(20) the aggregation pheromone of the bark beetle which was formed in 98% e.e.by this path. Trans- mission of chirality via the transition state (21) is therefore highly efficient.21 Allylic butenols undergo Pd-catalysed phenylation with a concurrent 1,3-hydrogen shift. Acyclic allylic alcohols by addition formed iodo-diols or acetoxy-iodoalcohols with high regio- and stereo-selectivity (Scheme 7) ;the iodohydrin gave selectively epoxide (22).22 Syntheses of allenic alcohols and ethers have been reported.23 A2 + OH OR ii 'Ho 0-.. OH I (22) R = H or Ac Reagents i 12/H20 or MeC0,I; ii NaOH Scheme 7 21 N.Sayo E. Kitahara and T. Nakai Chem. Lett. 1984 259; K. Mikami K.-I. Azuma and T. Nakai Tetrahedron 1984,40 2303; N. Sayo K.-I. Azuma K. Mikami and T. Nakai Tetrahdronn Lerr. 1984 25 565. 22 W.Smadja G. Ville and G. Cahiez Tetrahedron Lett. 1984 25 1793; A. R. Chamberlin and R. L. Mulholland jun. Tetrahedron Len 1984 25 1793; A. R. Chamberlin and R. L. Mulholland jun. Tetrahedron 1984 40,2297. 23 J. Pornet B. Randrianoelina and L. Miginiac Tetrahedron Lett. 1984 25 651. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds Other methods used for epoxidation include use of (i) NaI04-RuC13( H20),- bipyridyl (ii) a microsomal method (iii) NaOCl- meso-tetra(halogenopheny1)por-phyrinato-manganese complexes (iv) a-azohydroperoxides and (v) a peracid de- signed to exploit cis.- trans- alkene reactivity diff erence~.’~ Asymmetric epoxidation has attracted further interest; a chiral ketone and peroxomonosulphate gave oxidation of simple prochiral olefins with small e.e.(9-13%) by a probable path set out in Scheme 8.” Sharpless-type epoxidation of seven homoallylic alcohols using Ti(OPr’),-(+) or (-)-DET-Bu‘OOH gave 23-55% e.e. and enantioface selection opposite to that observed for allylic alcohols. An unprecendented and unexpected 2 + HSO; - I R’ ,Me 2O+ RZ Scheme 8 Ph Ph Ph Ph Ph Ph R’ = RZ= NHCHzPh Reagents “O+ (R3) HO’ 0 i Ti(OPri)4:Bu‘OOH:(R3) = 2:2 1; ii Ti(OPr’),:Bu‘OOH:(R3) = 2:2:2.4. Scheme 9 reversal of selectivity was observed with PhCH=C(Ph)CH20H when the ratio of titanium isopropoxide tartramide was changed (Scheme 9).Use of TiClz(OPri)z afforded chlorodiols from regiospecific opening of intermediate epoxides ; in this case the products are formed with opposite enantioselectivity to those produced by normal asymmetric ep~xidation.~’ Such reversal adds a useful bonus to this valuable method (Scheme 10). G. Balavoine C. Eskenazi F. Meunier and H. Rivikre ibid. p. 3187; V. Schurig and D. Wistuba Angew. Chem. Znt. Ed. Engl. 1984 23,796; B. de Poorter and B. Meunier Tetrahedron Lett. 1984 25 1895; T. Tezuka and M. Iwaki J. Chem SOC.,Perkin Trans. 1 1984 2507; J. Rebek jun. L. Marshall R. Wolak and J. McManus J. Am Chem. SOC.,1984 106 1170. ’’ R. Curci M. Fiorentino and M.R. Serio J. Chem. SOC.,Chem. Commun. 1984 155; B. E. Rossiter and K. B. Sharpless J. Org. Chem. 1984,49 3707; L. D.-L. Lu R. A. Johnson M. G. Finn and K. B. Sharpless ibid. p. 728. 126 B. V. Smith / \ R R OR' I I ii iv Reagents i Ti(OBu'), DET Bu'OOH; ii TiCl,(Oh'),; iii TiC12(0Pri)2DET Bu'OOH; iv NaOH (R' = Ac DET = (+)-diethy1 tartrate) Scheme 10 Stereoselective ring-closure to form trans-epoxides has been noted for P-hydroxy- sulphonium salts and base and from optically pure P-ethanolamines and dichlorocar- bene.26 By this latter route a-amino-acids can be transformed into synthetically useful epoxides. Deoxygenation of epoxides occurs efficiently with diazomalonic ester-Rh" acetate (with stereospecificity) with metals in aprotic solvents (probably via SET) and uia the use of alkyl manganese( 11) Di-lithium tetrabromonickelate( 11) in THF has been recommended as a source of 'soft' bromide ions; regioselective ring-opening gave bromohydrins in good yield and selectivity.28 Other examples of ring-opening reported include the reaction of epoxides with Me,SiNEt2 cuprates and R,CuC N Synthetically useful reactions of epoxides and transformations of 2,3-epoxyal- cohols have been re~iewed.~' 26 M.Shimagaki Y.Matsuzaki I. Hori T. Nakata and T. Oishi Tetrahedron Lett. 1984 25 4775 4779; L. Castedo J. L. Castro and R. Roguera ibid. p. 1205. 27 M. G. Martin and B. Ganem Tetrahedron Lett. 1984 25 251; K. N. Gurudutt M. A. Pasha B. Ravindranath and P.Srinivas Tetrahedron 1984,40 1629; T.Kauffmann and M. Biding Tetrahedron Lett. 1984 25 293. 28 R. D. Dawe T. F. Molinski and J. V. Turner Tetrahedron Lett. 1984 25 2061. 29 A. Papini A. Ricci M.Taddei G. Seconi and P. Dembech J. Chem. SOC.,Perkin Trans. 1 1984,2261; A. Ghibri A. Alexakis and J. F. Normant Tetrahedron Lett. 1984,25,3075,3079,3083; B. H.Lipshutz R. S. Wilhelm J. A. Kozlowski and D. Parker J. 0%.Chem. 1984,49,3928,3938. 3943. 30 J. G. Smith Synthesis 1984 629; C. H. Behrens and K.B. Sharpless Aldrichirnica Acta 1983 16 67. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds 127 2 Alkyl Halides Chloroalkanes were obtained in excellent yields from an alcohol and N,N-diphenylchlorophenylmethyleneiminium chloride-Et,N ; (-)octan-2-01 gave 2-chloro-octane with inversion.Allylic propargylic (and glycosidic) hydroxy-groups were converted into chlorides via TsCl-DMAP-Et3N ; dienyl and other sensitive halides were obtained by use of ZnC1,-EtO2CN=NCO2Et-Ph3P in THF at ambient temperat~re.~~ Polymer-supported Ph3PBr2 (or Ph3P-polymer-CBr,) gave good yields of RBr.32 Direct a-iodination of an acid RCH2C02H was achieved in good yield by 12-AcOH-Cu" (OAC)~.~~ cis-172-Dichlorides were formed indirectly from 1-chloro-2-phenyl selenides by alkylation and subsequent displacement of selenium by chloride ion.34 Several applications of sonication have appeared. Asymmetric induction 30-60% has been noted for addition of a perfluoroalkyl iodide RFI to a chiral arene- chromium complex bearing an aldehyde function (23) ;subsequent decomplexation of the product gave (24).A remarkable change of pathway was claimed for PhCH2Br- KCN-A1203 in an aromatic solvent when sonication promoted nucleophilic displace- ment instead of Friedel-Crafts substitution observed with stirring alone. Alkyl halides in the presence of zinc under sonication add cleanly to a,p-enones in a conjugate manner. Di-iodomethane-zinc is effective for methylenation under such condition^.^' (OC)&r(Ar)CHO AZH(OH)R (23) (24) The species XCH2Li from Br-Li exchange is a precursor for halogenohydrins epoxides and a-halogenomethyl ketones by reaction at low temperature (-1 15 "C) with a carbonyl compound and appropriate recovery pr~cedure.,~a,o-Dihalogenoalkanes with Bu'Li undergo metal-halogen exchange almost certainly involving an SET pathway.Such a path is also suggested for reduction of an alkyl halide by LiAlH4 or AH,; traces of transition metals are not responsible for the effects observed. Ashby and co-workers have also adduced evidence for an SET mechanism in a Williamson ether synthesis and in the reaction between the lithium enolate of PhCOEt and a primary alkyl iodide.37 Reduction of alkyl chlorides was achieved in good yield and with a simple work up by use of Amberlyst A-26 anion exchange resin (BH form).38 31 T. Fujisawa S. Iida and T. Sato Chem. Lett. 1984 1173; C. K.'Hwang W. S. Li and K. C. Nicolaou Tetrahedron Lett. 1984 25 2295; P.-T. Ho and N. Davies J. 0%.Chem. 1984 49 3027. 32 P. Hodge and E. Khoshdel J.Chem. SOC. Perkin Trans. I 1984 195. 33 C. A. Horinchi and J. Y. Satoh Chem. Lett. 1984 1509. 34 A. M. Morella and A. D. Ward Tetrahedron Lett. 1984 25 1197. 35 A. Solladie-Cavallo D. Farkhani S. Fritz T. Lazrak and J. Suffert Tetrahedron Lett. 1984 25 4117; T. Ando S. Sumi T. Kawate J. Ichihara and T. Hanafusa J. Chem. SOC Chem Commun. 1984 439; C. Petrier J.-L. Luche and C. Dupuy Tetrahedron Lett. 1984 25 3463; J. Yamashita Y. Inoue T. Kondo and H. Hashimoto BulL Chem. SOCJpn. 1984 57 2335. 36 R. Tarkhouni B. Kirschleger M. Rambaud and J. Villibas Tetrahedron Lett. 1984.. 25 835. 37 W. F. Bailey R. P. Gagnier and J. J. Patricia J. Org. Chem 1984,49,2098; E. C. Ashby R. N. DePriest A. B. Goel B. Wenderoth and T. N. Pham ibid. p. 3545; E.C. Ashby D.-H. Bae W.-S. Park R. N. DePriest and W.-Y. Su Tetrahedron Lett. 1984 25 5107; E. C. Ashby and J. N. Argyropoulos ibid. p. 7. 38 J.-V. Weber P. Faller and M. Schneider C. R Hebd. Seances Acad. Sci. Il 1984 299 1259. 128 B. V. Smith A general review of photochemical behaviour of alkyl halides in solution has appeared and the competition between carbene and cationic pathways stressed.39 A route to E-1-bromo and 2-1-iodo-alkenes formed in very high purity relies on the treatment of (25) with Br2-MeOH or 12-NaOH.40 Direct preparation of o-bromoalk-1-enes has been effected by dehydrobromination of an a,o-dihalide with HMFT at 195-220 0C.41Functionalized allylic bromides in the presence of Zn and with sonication add regioselectively to terminal alkynes ;the dienes produced were cyclized to 6-or 7-membered carbo- or hetero-cycles.Regioselective head-to-tail coupling of allylic halides and allylic trialkyl stannanes (under high pressure) gave 1,Sdienes; in the presence of a sterically demanding proton equivalent at the y-carbon regioselective alkylation was possible at one site (see Scheme 11). This R -I Ryx -111 Me$ Me3Si Me,Si Reagents i LiCuBu, Et20 -78-100 "C (quant); ii NaCH(C02Et)2-THF; iii LiCuPh2 Et20 -78-+0"C (R = Bu X = Br) Scheme 11 is a valuable method since it allows functionalization at stereodefined alkenyl silanes to form avariety of other compounds!2 Preferential y-attack was noted for alkylation of the trimethylsilylallyl anion with Schlosser's base (K0Bu'-Bu'Li in he~ane).~~ The synthesis and reactivity of organoaluminiums (derived from unsaturated halides) has been reviewed.Copper( 1)-catalysed reactions of RLi/ RMgX have been summarized.44 39 P. J. Kropp Acc. Chem. Res. 1984 17 131; P.J. Kropp J. A. Sawyer and J. J. Snyder J. Org. Chem. 1984,49 1583. 40 H. C. Brown and V. Somayaji Synthesis 1984,919. 41 G. A. Kraus and K. Landgrebe Synthesis 1984 885. 42 Y. Yamarnoto K. Maruyama and K. Matsumota J. Chem. SOC.,Chem. Commun. 1984,548; P. Knochel and J. F. Normant Tetrahedron Left. 1984 25 1475; J. Kang W. Cho and W. K. Lee J. Org. Chem. 1984,49 1838. 43 K. Koumaglo and T. H. Chan Tetrahedron Lett. 1984 25 717. 44 F. Barbot Bull. SOC.Chim. Fr. 11 1984 83; E. Erdik Tetrahedron 1984.40 641.Aliphatic Compounds -Part (ii) Other Aliphatic Compounds 129 3 Aldehydes and Ketones This section again the largest in this Report attempts to highlight initiation or development of processes of interest and therefore cannot be considered a complete summary of all published work. Grignard reagents react efficiently with lithium or sodium formate in boiling THF forming aldehydes in good yield.45 Oxidation of vinylsilanes to carbonyl compounds can be directed according to conditions (and the structure of the substrate) to form aldehyde or acid ur ketone.46 2-and E-epoxysilanes were transformed into corresponding 2-and E-silylenol ethers of an aldehyde; by this approach an alkyne was converted into a 2,2,2-trialkylated aldehyde in which each alkyl group could be different (see Scheme 12).47Chiral acetals e.g.(26) with h S i Me Ph Reagent i BF3:OEt2-CH2C12,-78 "C Scheme 12 CONMe2 R' XYoNMe2 R CONMe2 trialkylaluminium gave an adduct (27) formed in eve. which gave in turn a chiral &substituted aldehyde.48 Chiral oxathione (28) prepared from (+)-pulegone gave (29) in high e.e. (100% when R = Ph) and (30) gave with MeMgI (31) in which the product ratio was 96:4 in favour of (31a); methylation and cleavage of the thiane gave (S)-(-)-atrolactic acid methyl ether (100% e.e.).49 HO rzeH &0 R I (28) (29) krcoR k&R1 kdoH LNTR (30) (314 (31b) (32) 45 M. Bogavac L. ArsenijeviC S. Pavlov and V. ArsenijeviC. Tetrahedron Lett. 1984 25. 1843.46 K. Tamao M. Kumada and K. Maeda Tetrahedron Lett. 1984,25 321. 47 I. Fleming and T. W. Newton J. Chem SOC.,Perkin Trans. I 1984 119. 48 J. Fujiwara Y. Fukutani M. Hasegawa K. Maruoka and H. Yamamoto J. Am Chem SOC.,1984 106 5004. 49 E. L. Eliel and S. Moms-Natschke J. Am. Chem Soc.. 1984 106 2937; J. E. Lynch and E. L. Eliel ibid. p. 2943. 130 B. V. Smith Acyl chlorides reacted smoothly with Grignard reagents in the presence of Fe"'(a~ac)~,in a convenient ketone synthesis; organomanganese reagents RMnI (from RLi or RMgX + MnI,) reacted analogo~sly.~~ Organolithiums (or Grignard reagents) coupled efficiently with N-acylaziridines ;the intermediate (32) on hydroly-sis gave ketones in yields greater than 70% .'l 1,2-Migration of alkyl groups in chiral P-mesyloxyalcohols effected by Et2AlC1 gave optically pure a-alkylketones ;this method looks promising and capable of elaboration.The stereospecificity was presumed to arise from chelation control in (33).52 As shown in Scheme 13 rearrange- ment of (34) gave (35) cleanly at low temperature. Dilithioacetoacetate gave after alkylation and decarboxylation methyl ketones and is a synthetic equivalent to acetone en01ate.~~ The substituted imidazole (36) (from N-methylimidazole-BuLi- R'RZC=O) acts as a masked carbonyl compound since on quaternization and hydrolysis it regenerated the ketone. This may be a useful way of protecting the carbonyl gro~p.'~ Me BU OH . Bu )-COBu MsO H Bu Me H (90%)(35) Reagent Et2AICI -78 "C 1.5h Scheme 13 I I -Me Me Some other published methods for ketone synthesis include carbonylation of ArCHzX which gave ArCH2COCH2Ar and phase transfer catalysis (with Fe(C0)') or with Ni-CO.Palladium-catalysed oxidation of alkenes to ketones has been re~iewed.'~ Several methods for reduction of carbonyl groups have been reported. Photoreduc- tion of aldehydes and ketones with Bu3SnH led to tributylstannyl ethers of derived alcohols and as minor products the analogous derivatives of pinacol~.~~ Methyl ketones MeCOAr were reduced by monoisopinocampheyl borane in modest e.e. V. Fiandenese G. Marchese V. Martina and L. Ronzini Tetrahedron Lett. 1984,25 4805; G. Friour G. Cahiez and J. F. Normant Synthesis 1984 37. " S. Wattanasin and F.G. Kothawala Tetrahedron Lett. 1984 25 84. 52 G. Tsuchihashi K. Tomooka and K. Suzuki Tetrahedron Lett. 1984,25 1817,4253. 53 R. A. Kjonaas and D. D. Patel Tetrahedron Lett. 1984 25 5467. 54 S. Ohta S. Hayakawa K. Nishimura and M. Okamoto Tetrahedron Lett. 1984,25 3251. 55 G. Tanguy B. Weinberger and H. des Abbayes Tetrahedron Lett. 1984,25 5529; S. Inaba and R. D. Rieke Chem. Lett. 1984 25; J. Tsuji Synthesis 1984 369. 56 M. H. Fisch J. J. Dannenburg M. Pereyre W. G. Anderson J. Rens and W. E. L. Grossmann Tetrahedron 1984 40,293. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds which was dependent on the ketone reagent ratio; a 1 :1 mixture gave best results.’’ High pressure (6000atm) gave enhanced e.e. and faster reaction in reduction of ketones by ‘Alpine borane’ and suppressed an undesirable side-reaction ; thus PhCOMe gave optically pure alcoh01.’~ An interesting switch in enantioselectivity on changing from boron to aluminium was reported for 23-( cis-lO-pinany1)-9-borabicyclo(3,3,l)nonane (37) and its aluminium counterpart.” Such a switch in selectivity is useful and promises further application.LAH which has been modified by reaction with R-(or S)-(38) gave high e.e. in ketone reductions and with (37a) (37b) (38) PhCOCH2Br yielded styrene oxide with 95% e.e.60 An improvement in enantioselec- tivity was observed when ketones with iodo- or phenylsulphonyl-groups were reduced by yeasts; subsequent removal of these groups gave alcohols with very high e.e. and much higher than that observed with unsubstituted starting materials.Such microbial asymmetric catalysis has been reviewed.61 N-Benzoylcysteine was an efficient chiral ligand in the reduction of RCOAr by LiBHq?’ At low temperature (-100 -+ -78 “C) Pr”C0Phgave R-PrCH(0H)Ph (92% e.e.). Two applications of Raney Ni in reduction involve firstly modification by (KR)-tartaric acid-NaBr for reduction of ketones (interestingly traces of carboxylic acids e.g. Bu‘C02H improved the optical yield) and secondly ‘deuteration’ which gave exchanged products.63 Stereoselective reduction of acyclic ketones with introduction of chiral centres has been reviewed.64 The reaction shown in Scheme 14 has been achieved (R = Ph) and was selective (e.g. PhCH=CHCHO gave 83% yield of unsaturated al~ohol).~’ Scheme 14 57 H.C.Brown and A. K. Mandal J. Org. Chem. 1984 49 2558. 58 M. M. Midland and J. I. McLoughlin J. Org. Chem. 1984 49 1316. 59 M. M. Midland and J. I. McLoughlin J. Org. Chem. 1984 49 4101; G. Giacomelli L. Lardicci and F. Palla ibid. p. 310. 60 R. Noyori I. Tomino M. Yamada and M. Nishizawa J. Am. Chem. Soc. 1984 106 6717. 61 K. Nakamura K. Ushio S. Oka and A. Ohno Tetrahedron Lett. 1984 25 3979; C. J. Sih and C.-S. Chen. Angew. Chem. Int. Ed. Engl. 1984 23 570. 62 K. Soai T. Yamanoi and H. Oyamada Chern Lett. 1984 251. 63 T. Osawa and T. Harada Bull Chem. Soc. Jpn. 1984 57 1518; P. M. Pojer Tetrahedron Lett. 1984 25 2507. 64 T. Oishi and T. Nakata Acc. Chem. Res. 1984 17 338. 65 J.D. Wuest and B. Zacharie J. Org. Chem. 1984 49 163 166. 132 B. V. Smith Organocerium compounds (from RLi-CeCl, -78 "C THF) reacted cleanly with enolizable ketones giving tertiary alcohols. The advantage of the method is that it avoids enolate formation (from ketone and RLi or RMgX) and undesired side- reactions. Thus (PhCH2)2C0 gave (PhCH2)2C(OH)Bu (96%) by this route cj 20% obtained uia the Grignard reagent.66 The method may also be applied to synthesis of alkenyl- and alkynyl-derivatives. A striking improvement in stereoselectivity of addition of p-C7H7SOCH2X to RCHO was noted when X = ZnCl rather than with X = Li; desulphurization of the adduct (Raney Ni) gave chiral alcohols with very high e.e.67 A chiral amino- alcohol improved the e.e.during addition of Et,Zn to RCH0.68 The nucleophilic acylation (umpolung) of an aldehyde has been achieved by chiral(39) as the synthetic equivalent of (40);69 high e.e. was achieved. The effect (or absence) of chelation control in nucleophilic addition to chiral a-and P-alkoxyaldehydes has been thoroughly explored and s~rveyed.~' A discrepancy between the work of Heathcock and Reetz's group has been cleared up.7' 0 Several papers have exploited boron reagents in synthesis. H. C. Brown has reported very high (86-99%) e.e. in homoallyl alcohols formed from B-allyldi- isocaranyl borane and RCHO; a corresponding selectivity was found with B-methylallyldi-isopinocampheylborane (e.e. >go% ).72 Chiral a-chloroallylboronate esters or 2-y-alkylthioallylboronates,with RCHO gave a high degree of control in formation of homoallylic alcohols and these methods would allow introduction of other functional groups uia the chlorine or sulphur atoms in the products.73 Enol boronates (from aldehydes or ketones) react readily with aliphatic or aromatic aldehydes or ketones; crossed-aldolization of ketones was achieved in moderate yields.High erythro-threo-diasteroselectionwas achieved by this route. A convenient one-pot method exploited the addition of an allylboronate to an aldehyde; complete regio- and stereo-control was noted in this simple and improved process (Scheme 15). The use of (41) implied a synthetic equivalent for (42) or (43).74 Addition of 2-enolborate (44) to RCHO gave the same product ratio as from the E-isomer a 66 T.Imamoto Y. Sugiura and N. Takiyama Tetrahedron Lett. 1984 25 4233. 67 M. Braun and W. Hild Chem. Ber. 1984 117 413. N. Ogumi and T. Omi Tetrahedron Left. 1984 25 2823. 69 M. Braun and W. Hild Angew. Chem. Inf. Ed. Engl. 1984 23 723. 70 M. T. Reek and K. Kesseler J. Chem. SOC Chem. Commun. 1984 1079; M. T. Reetz K. Kesseler and A. Jung Tetrahedron Lett. 1984 25 729; M. T. Reetz Angew. Chem. Int. Ed. En& 1984 23 556. 71 H. C. Brown and P. K. Jadhav. J. Org. Chem. 1984,49,4089. 72 H. C. Brown P. K. Jadhav and P. T. Perumal Tetrahedron Lett. 1984 25 5111. 73 R. W. Hoffmann and B. Landmann Angew. Chem. Int. Ed. Engl. 1984 23,437; R. W. Hoffmann and B. Kemper Tetrahedron 1984 40,2219. 74 C. Gennari L. Colombo and G.Poli Tetrahedron Letf. 1984 25 22;3 2283; P. G. M. Wuts P. A. Thompson and G. R. Callen. J. Org. Chem. 1983,48 5398. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds THPO- Li R O V\ RO CO,R (41) (42) (43) Reagents i BCH,Cl ; ii RCHO 0 Scheme 15 surprising result. Kinetic control of product formation was ass~med.~’ Another promising development is the synthesis of chiral boronic and borinic esters uia asymmetric hydroboration-displacement. In the first case 2-butyldi-isopinocam- pheyl borane (from Ipc,BH + but-2-ene) gave with 2 eq MeCHO diethyl 2-butyl- boronate hydrolysed and re-esterified to the (+)-dimethyl analogue; oxidation of this in the usual way gave butan-2-01 of 97% e.e. A chiral borinate (49 with LiCC1,OMe and oxidation gave RCOCH(Me)Et in 70% e.e.76 Chiral or achiral oxazolines e.g.(46) as boronazaenolates reacted with aldehydes to give adducts which on hydrolysis and methylation gave e.g. p-hydroxyester (47) with high threo-preferen~e.~~ The chiral analogue (48) showed a high selectivity but modest e.e. in the formed hydroxye~ter.~~ Enol stannanes of ketones reacted with RCHO at low temperature (with kinetic control) and formed threo-aldols preferentially. Highly diastereoselective cross-ado1 reactions were carried out using tin enolates derived from reaction of stannous 75 R. W. Hoffmann and K. Ditrich Tetrahedron Lett. 1984 25 1781. 76 H. C. Brown P. K. Jadhav and M. C. Desai Tetrahedron 1984,40 1325. 77 A. I. Meyers and Y. Yamamoto Tetrahedron.1984 40,2309. 134 B. V. Smith OMe (47) (48) syn-(49) triflate with carbonyl compounds (93:7 erythro :threo aldol ratio for Et2CO- Pr'CHO). The value of chiral auxiliary in these reactions has been stressed.78 Extension of this approach to the reaction of R'COCH2Br and R2CH0 gave syn- and anti- bromoaldols (49) smoothly converted into oxiranes by KF-18-crown-6. Crotylmetal compounds e.g. (50) with RCHO-BF3 showed high erythro-selectivity which was independent of geometry in the starting material. Under pressure the erythro-threo ratio was lower. The ratio of Cram anti-Cram product was examined and it was concluded that a crown-like transition-state was implicated.79 Keck and co-workers" have studied related processes with chiral a-alkyloxyaldehydes and emphasized the crucial role of the Lewis acid required ; for P-hydroxyaldehydes MgBrz gave a high erythro- threo ratio.Almost three-fold increase in erythro-selec- tivity was achieved by using 2 eq of stannane; interestingly the TiC1,-mediated reaction of crotyltributylstannane and RCHO gave high erythro- or threo-sensitivity according to the order of mixing. The stereochemistry of allylmetal-aldehyde addi- tion was probed via the ring-closure of (51) to (52) and (53); the syn-anti-ratio was 82 18 (TiCl,) but 99 1 with CF3C02H.8' Another variation on this theme was achieved by using stannous azaenoalates derived from chiral 1,3-0xazolidines and aldehydes in the presence of a chiral norephedrine which formed aldols in high e.e.82 CCH0 Q/SnBu3 The significance of chelation control in Lewis acid-mediated aldolization via enol silanes and chiral a-and P-alkoxyaldehydes has been stressed since it represents the only way known at present to achieve such control.With a prochiral enolsilane the selectivity was surprisingly good. This unusual effect has been attributed to syn-complexation of the aldehyde e.g. (54); such an effect in an achiral aldehyde should be expected to lead to selectivity and this was demon~trated.'~ This interesting 78 S. S. Labadie and J. K. Stille Tetrahedron 1984,40 2329; T. Mukaiyama N. Iwasawa R. W. Stevens and T. Haga ibid. p. 1381. 19 Y. Yamamoto H. Yatagai Y. Ishihara N. Maeda and K. Maruyama Tetrahedron 1984,40 2239. G. E. Keck and E.P. Boden Tetrahedron Lett. 1984 25 265 1879; G. E. Keck D. E. Abbott E. P. Boden and E. J. Enholm ibid. p. 3927. 81 S. E. Denmark and E. J. Weber J. Am. Chem Soc,1984 106,7970. 82 K. Narasako T. Miwa H. Hayashi and M. Ohta Chem. Lett. 1984 1399. 83 M. T. Reetz K. Kesseler and H. Jung Tetrahedron 1984.40 4327. 135 Aliphatic Compounds -Part (ii) Other Aliphatic Compounds paper also pointed out that the sense of diastereoselection was independent of geometry in the silane and that for (54) the TiCI,-mediated addition of (55) took place with very high selectivity whereas SnCl or BF3gave stereorandomness. Dubois has discussed the conclusions to be drawn from addition of (56) to R’CHO-TiC1,; the erythro-threo-ratio was determined for R = R’ = But (89:11) and R = Me R’ = But (1 1 :89) and was held to be inconsistent with a cyclic tran~ition-state.~~ Hwos RZ RO H R = PhCH Ph (R = alk Z = OSiMe,) (54) (55) (56) Crotyl metal compounds as enolate equivalents e.g.(57) with RCHO usually give threo-alcohols preferentially; another remarkable reversal occurred with BF3 however to form erythro-alcohols as major products. As an example of the latter process E-(57)(X = Br) and Et,CHCHO gave an erythro threo-ratio of 6:94. Reetz has suggested that (58) satisfactorily accounted for this process; but it should be noted that BF3 did not reverse the threo-diasteroselectivity of MeCH=CHCH2Ti(0P3),.” A new process for chain elongation (by 3 units) has been developed; an aldehyde and a Ti-ate complex (59) [from 1-lithio-(1- a1koxy)allyltrimethyl silane and Ti(OPe),] reacted with high regioselectivity to form dienylethers in high yield.86 The net effect is thus to convert RCHO into RCH2COCH=CH2 and this approach was applied to some natural product syn- theses.Chiral metal complexes e.g. (60) were used as a source of enolate which gave aldolization with high stereoselectivity. As shown in Scheme 16 some choice in selection was achieved by changing conditions although kinetic control was assumed on the basis of time/temperature studies. The aluminium enolate of (60) was used 84 J.-E. Dubois G. Axiotis and E. Bertonnesque Tetrahedron Lett. 1984 25 4655. 85 M. T. Reetz and M. Sauerwald J. Org. Chem 1984,49 2292. 86 A. Murai A. Abiko N.Shimada and T. Masumume Telrahedron Lett. 1984 25 4951. 136 B. V. Smith (60) (XFe = chiral Fe complex) Reagents i LDA; ii MX = BuiAlCI then EtCHO; A:B = 5 1; iii MX = SnCI, then EtCHO; A:B = 1 11.6 Scheme 16 as the key intermediate in preparation of P-hydroxyacids; it is therefore acting as a chiral acetate enolate eq~ivalent.’~ Similar reactions were employed with (61) and C,F,Li; the adduct was transformed into S-(+)-(62) (88% e.e.) and in another path into chiral derivatives of phenylacetic acid.88 A new method for hydroxymethylation which uses PhCH20CH2Cl as a practical equivalent for CH,OH relied on samarium(11) iodide to couple a chloro-ether and a ketone.” Stereoisomerically pure sulphinylmethyldihydroisoxazoleshave allowed a highly stereocontrolled entry into a route leading to chiral p,/?’-dihydroxyketone~.~~ A route to a-ketoesters from aldehydes has been explored.” The keto-enol ratio for aqueous solutions of aliphatic ketones has been remea~ured;’~ for Me,CO the best value of pK was 19.16 * 0.04 and for pK was 8.22 f 0.08.The direct method for resolution of ketones via reaction with the a-lithio- derivative of N,S-dimethyl-S-phenylsulphoximine(63) has been de~eloped.’~ The diastereoisomeric adducts were separated by flash chromatography and separately pyrolysed at 130 “C to regenerate ketone enantiomers. The success of the method depended on lack of racemization during work-up; so in some cases complete resolution was achieved but in others racemization was a severe drawback.The superiority of lithium t-octyl-t-butylamide (over e.g. LDA) in regioselective and stereoselective generation of enolates has been stressed. With Et2C0 the E :2 ratio in the enolate was 98 :2 the highest yet; this ratio was reversed (18 :82) in the presence of HMPA. The hindered base could also be used for near-regiospecific preparations of trimethylsilyl enol esters. Silyl enol ether anions with base rearranged to form a-silylated ketones ;the tri-isopropylsilyl enol ether of e.g. Et2C0 gave with BuLi-Bu‘OK the rearrangement product in 60% yield in 24h. This intramolecular rearrangement occurred preferentially towards a less-hindered ter- minus since Pr’CH,COMe gave Pr‘CH2COCH2Si(Pr’)3 as sole The use of ultrasound-colloidal potassium in toluene has been applied to several processes 87 L.S. Liebeskind and M. E. Walker Tetrahedron Lett. 1984 25 4341 :S. G. Davies 1. M. Dordor and P. Warner J. Chem. Soc. Chem. Commun. 1984 956. 88 A. Solladie-Cavallo and J. Suffert Tetrahedron Lett. 1984,-25 1897. 89 T. Imamoto T. Takeyama and M. Yokoyama Tetrahedron Lett. 1984 25 3225. w R. Annunziata M. Cinquini F. Cozzi and A. Restelli J. Chem. SOC.,Chem. Commun. 1984 1253. 91 D. Home J. Gandino and W. J. Thompson Tetrahedron Lett. 1984 25 3529. 92 J. Toullec Tetrahedron Lett. 1984 25 4401; Y. Chiang A. J. Kresge Y. S. Tang and J. Win J. Am. Chem. SOC.,1984 106 460. 93 C. R. Johnson and J. R. Zeller Tetrahedron 1984,4Q 1225. 94 E. J. Corey and A. W. Gross Tetrahedron Lett. 1984,25,495; E.J. Corey and C. Rucher Tetrahedron Lett. 1984 25 4345. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds e.g. preparation of silyl ethers (and Dieckmann and Wittig reactions). This approach looks useful in a range of carbanion-generating application^.^' Further work has shown that a-alkylation of ketones using activated alkyl halides (or ROAc-Lewis acid) and a ketone was regiospecific for unsymmetrical ketones and avoided polysubstitution. The ZnC1,-promoted addition of (64) to ketones (or enones) allowed entry into a-ketoesters. Tertiary halides also reacted furnishing R3CCOC02Et.96A different approach to alkylation used chiral hydrazones (65) which by metallation reaction with an electrophile and cleavage gave a chiral ketone in good yield and e.e.> 94Y0.~'The reagent Cp2Ti=CH2 methylenates enolizable ketones in a process analogous to the Wittig reaction.98 Other processes repoped and reagents used include a-bromination of ketones (Bu'Br-Me,SO ; via BrSMe2?) generation of enolates from a-halocarbonyls (by Bu3SnAlEt2 or Bu,PbAlEt) cleavage of hydrazones [Fe"'(NO,) on clay] and construction of synthetic equivalents of synthons with three consecutive chiral centres.99 Routes to the thiols (66) and (67) have been developed since they are precursors to a,P-unsaturated aldehydes."' Addition of RLi to a,P-unsaturated acetals and hydrolysis of the formed enol ethers was reported as another entry to enals.'O1 Synthetic methods for enones include the addition of enolates from trimethylsilyl ketones to aldehydes (an efficient process with E-selectivity) alkylation (by Rx) of the carbanion from (68) followed by desulphurization-hydrolysis [it is notable that (69) the precursor of (68) thus acts as a novel homoenolate dianion equivalent] S0,Tol R OMe 95 J.L. Luche C. Petrier and C. Dupuy Tetrahedron Lett. 1984 25 753. 96 M. T. Reetz P. Walz F. Hubner S. H. Huttenhain H. Heimbach and K. Schwellnus Chem Ber. 1984 117 322; M. T. Reetz H. Heimbach and K.Schwellnus Tetrahedron Lett. 1984 25 511. 91 D. Enders H. Eichenauer U. Baus H. Schubert and K. A. M. Kremer. Tetrahedron 1984,40 1345. 98 L. Clawson S. L. Buchwald and R. H. Grubbs Tetrahedron Lett. 1984 25 5733. 99 E. Armani A. Dossema R. Marchelli and G. Casnati Tetrahedron 1984 40,2035; N.Tsuboniwa S. Matsubara Y. Morizawa K. Oshima and H. Nozaki Tetrahedron Lett. 1984,25,2569; R. M. Moriarty and K.-C. Hou ibid. p. 691; P. Laszlo and E. Polla ibid. p. 3309 3313; T. Nakata M. Fukui H. Ohtsuka and T. Oishi Tetrahedron 1984 40,2225. 100 K. Oguro T. Iihama K. Takahashi and H. Iida Tetrahedron Lett. 1984 25 2671; M. Julia and C. Lefebvre ibid. p. 189. 101 C. Mioskowski S. Manna and J. R. Falck Tetrahedron Lett. 1984 25 519. 138 B. V. Smith and palladium-catalysed addition of ArI to a terminal alkyne in the presence of Zn-Cu/CO (other products were also formed).'02 A one-pot process for chiral P-alkoxy-a#-enones used the sodium derivative of an unsymmetrical 1,3-dicarbonyl and chiral alk~xides."~ Identification (and differentiation) of E-and 2-a$-unsaturated ketones (and esters) has been suggested on the basis of differences in 3JC0,Hcoupling constants measured in n.m.r.spectra.'@' Reduction (by L-selectride) of a-methyl-P y-unsaturated ketones showed high threo-selectivity in the formed homoallylic alcohol. The selective reduction of the carbon-carbon double bond in an enone (or a,@-unsaturated nitro-compound) was achieved in excellent yield by using Hantzsch's ester (70) with silica gel in benzene.'" Hindered allylic alcohols and crowded saturated ketones have been obtained from enones in sequences of reduction and addition of organometallics ; addition of (PhMe2Si),CuLi to an a$-unsaturated ketone gave a P-silylated ketone whose enolate showed significant diastereoselection on alkylation.lM In this latter process an open-chain transition state (71) was favoured since the E-enolate from certain substrates cannot form a chelate.Michael addition of P-dicarbonyls to a,p-enones occurred in the presence of CU"(OAC)~. Although yields were variable the use of neutral conditions does have some advantages.'" HH High e.e. (>99%) was noted for the Et,Al-mediated pinacol-type rearrangement of mesyloxylalcohols to substituted p,y-unsaturated ketones. Thus (72) by mesyla- tion and rearrangement gave (73) in a stereospecific process.'o8 Regiospecific formation of y,S-unsaturated ketones was achieved by intramolecular decarboxyla- 102 I. Matsuda H. Okada S. Sat0 and Y. Izumi Tetrahedron Lett. 1984,25,3879; T.Mandai T. Moriyama Y. Nakayama K. Sugino M. Kawada and J. Otera ibid. 1984 25 5913; Y. Tamaru H. Ochiai and Z.-I. Yoshida ibid p. 3861. 103 A. Lubineau and A. Malleron Tetrahedron Lett. 1984 25 1053. 104 B. Gregory W. Hinz R. A. Jones and J. S. Arques J. Chem. Res. (S) 1984 31 1. '05 K. Suzuki E. Katayama and G. Tsuchihashi Tetrahedron Lett. 1984,25,2479; K. Nakamuro M. Fujii A. Ohno and S. Oka ibid. p. 3983. 106 C. Lion J.-E. Dubois and I. Saumtally C. R. Hebd. Seances Acad. Sci. II 1984,298,783; W. Bernhard I. Fleming and D. Waterson J. Chem Soc. Chem. Commun. 1984 28. 107 A. C. Coda G. Desimoni P. Righetti and G. Tacconi Gazz. Chim. Ztaf. 1984 114 417. 108 K. Suzuki E. Katayama and G. Tsuchihashi Tetrahedron Lett. 1984 25 1817.Aliphatic Compounds -Part (ii) Other Aliphatic Compounds tive allylation of ally1 p-ketocarboxylates (or alkenylallyl carbonates) in the presence of Mo- Ni- and Rh-cornple~es.'~~ Stereospecific preparation of E-and 2-enones from y-hydroxyalkylstannanes-Pb(OAc)4reflected the stereochemistry of the starting material e.g. (74) gave only (75)."O Acetylenic ketones have been obtained in an improved method based on acylation of Li( RC_C.BF,) or by phase-transfer-catalysed alkynylation of R'COCH2R2 by BrCH2C_CR3."' The coupling of RCOCl (with Sm"12) formed a-diketones probably via a sequence involving acyl radicals and anions.'12 Acylation of a chiral imide enolate has been developed as a route using chiral P-dicarbonyl synthon equivalents.' l3 A general synthesis of lY4- lY5- and 1,6-diketones is an ingenious exploitation of borane chemistry (see Scheme 17).Il4 Ozonolysis of 1,2-dialkylcyclopentenesaffords a practi-cable specific route to 1,5-diketone~."~ OAc Reagents i CH,=CHR'; ii A(CH,).J\RJ :iii co; iv wc Scheme 17 109 J.Tsuji I. Minami and I. Shimizu Chem. Left. 1984 1721. 110 K. Nakatami and S. Isoe Tetrahedron Lett. 1984 25 5335. Ill H. C. Brown U.S. Racherla and S. M. Singh Tetrahedron Leu. 1984 25 2411; E. V. Vasil'eva E. M. Auvinen and I. A. Favorskaya J. Org. Chem. U.S.S.R 1984 19 1266. 112 J. Souppe J.-L. Namy and H. B. Kagan Tetrahedron Lett. 1984 Z,2869. I I3 D. A. Evans M. D. Ennis T.Le,N. Mandel and G. Mandel 1. Am Chem SOC,1984 106 1154. I14 H.C. Brown U.S. Racherla and S. M.Singh Synthesis 1984,922. I15 K. Abe H.Okumura T. Tsugoshi and N. Nakamura Synthesis 1984,603. 140 B. V. Smith 4 Carboxylic Acids and Esters Anhydrous salts of carboxylic acids were obtained from acyl halides or esters by action of M+O-SSiMe3 in ether or THF.l16 Cu' salts have been employed for decarboxylation or oxidative-decarboxylation of acids yielding hydrocarbons and ketones respe~tively."~ 1,l '-Oxalyl-di-imidazole a new reagent for activating acids reacts to form an acylimidazole which is converted into esters by an alcoho1.118 Zinc salts of acids (or phenols) react with t-alkyl halides in non-polar solvents in the presence of a base forming esters (or ether^)."^ Alkyl halides react with (R0)3B-C0 in the presence of Rh' diene complex and Pdo forming esters in good yield.12' Alkenes when treated with a catalytic amount of Pd(OCOCF,) in the presence of benzoquinone and o-methoxyacetophenone (ligand) gave rise to allylic acetates; the composition of the mixture was variable.The Fe"-S20i-AcOH system gave truns-vicinal diacetates probably uia a free-radical route.121 A range of acids was reduced cleanly to aldehyde by thexylchloroborane-SMe2 reagent usually in yields of 90% (by 2,4-DNP). Other functionalities were unaff ected.'22 Acids with 2eq of amine in PPSE gave imidates presumably uiu the amide. Chiral imidoesters RCH2C(OEt)NR* (* = chiral group) were deprotonated and alkylated in excellent yield and with good/very good asymmetric induction to form a,a-disubstituted carboxylic acids e.g.BuCH( Me)C02Et (optical purity 94% ).123 An asymmetric synthesis of quaternary centres (a,a-disubstituted acids) depended on the chiral bicyclic lactam (76) [from L-valinol and PhCO(CH2)2C02H] ;deproton-ation and sequential alkylation gave after hydrolysis (77) with >95% enantiomeric purity. Control in the alkylation was indicated by obtaining each enantiomer of (77) depending 0.n the order of introduction of the alkyl groups.'24 Alkanoate esters with Et3SiOC103-R3N gave the useful O-silylketen acetals in high yields. Allylic acetates/trifluoroacetatesunderwent CF3C02H-catalysed pheny- lation ;a cationic pathway was s~ggested.'~' 116 E. D. Langanis and B. L. Chenard Tetrahedron Lett. 1984 25 5831. 117 0.Toussaint P.Capdeville and M. Maumy Tetrahedron 1984 40 3229; Tetrahedron Lett. 1984 25 3819. S. Murata Chem. Lett. 1983 1819. B. Ravindranath and P. Srinivas Tetrahedron 1984 40 1623. J. B. Woell and H. Alper Tetrahedron Lett. 1984 25 3791; K. E. Hashem J. B. Woell and H. Alper ibid. p. 4879. 121 J. E. McMurry and P. KoEovskL Tetrahedron Lett. 1984 25 4187; W. E. Fristad and J. R. Peterson Tetrahedron 1984 40 1469. 122 H.C. Brown J. S. Cha B. Nazer and N. M. Yoon J. Am. Chem. Soc. 1984 106 8001. 123 M. Kakimoto S. Ogata A. Mochizuki and Y. Imai Chem Lett. 1984 821; C. Gluchowski T. Tiner-Harding J. K.Smith D. E. Bergbreiter and H.Newcomb J. Org. Chem. 1984 49 2650. 124 A. I. Meyers M. Hanne and R. Garland J. Am. Chem. Soc. 1984 106 1146.125 C. S. Wilcox and R. E. Babston Tetrahedron Lett. 1984 25 699; Y.Fujiwara H. Kuromaru and H. Taniguchi J. Org. Chem. 1984 49 4309. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds 141 (R)-and (S)-2-acetoxy-1,2,2-triphenylethanol,via deprotonation/aldolization has been converted into chiral P-hydroxyacids; the reagent acts as the synthetic equivalent of a chiral acetate enolate. The lithiated camphor-based oxazoline (78) served as a precursor to chiral a-hydroxyacids and is thus equivalent to a chiral glycolate synthon. a-Hydroxy (and a-mercapto-) acids can be alkylated without racemisation via the method shown in Scheme 18. The 'self-reproduction of chirality' affords a useful entry to this type of system and a chiral auxiliary is not necessary.P-Hydroxyesters (from P-ketoesters and yeast-mediated reduction) were alkylated (2 eq LDA then RX) with high selectivity.'26 R~-CHCO,H I __* XH H x __ H H cis trans + 1 R'R~CCO,H iii "~o~oR *-I XH HX R2 Reagents i Me,CCHO; ii LDA-THF then R2X (or RCHO); iii H+-H~O Scheme 18 Enhancement of selectivity in ketoester reduction has attracted attention. a-Ketoesters gave excellent e.e. (lOOo/~ for PhCOC0,Bu') with Alpine borane or with complexes from Et,Al and Darvon alcohol (2S,3R)-(+)-4-dimethylamino-1,2-diphenyl-3-methylbutan-2-01.In the latter case reduction of menthyl esters was accompanied by a-alkylation. The stereochemistry of the product was dependent on the use of (+)-or (-)-menthol in e~terification.'~' Reduction of P-ketoesters by yeast was improved by a-sulphenylation prior to reduction separation of the erythro-and threo-products and desulphurization; by this route MeCH(OH)CH2C02Et was prepared optically pure.Enhanced e.e. was claimed for reduction of y,y,y-trihalogeno-derivatives. High e.e. (80% +) was noted in the use of a thermophilic bacterium Thermounaerobium brockii to reduce the P-carbonyl function of ketoesters.12* a-Alkylated-P-ketoesters are alkylated cleanly and with good-excellent e.e. by prior conversion into chiral enamines based on S-valine t-butylester followed by the usual deprotonation-alkylation sequence. A solvent dependence in selectivity was noted for the alkylation step.'29 A Wittig sequence was used to prepare y,8-unsaturated-f3-ket0esters.'~~ I26 M.-Braun and R.Devant Tetrahedron Lett. 1984 25 5031; T. R. Kelly and A. Arvanitis ibid. p. 39; D. Seebach R. Naef and G. Caldebari Tetrahedron 1984 40,1313; G. Frater U. Muller and W. Giinther ibid. p. 1269. 127 H. C. Brown G. G. Pai and P. K. Jadhav J. Am Chern. Soc. 1984,106,1531; A. Deberley G. Boireau and D. Abenhaim Tetrahedron Lett. 1984 25 655. 128 T. Fujisawa T. Itoh and T. Sato Tetrahedron Lett. 1984 25 5083; D. Seebach P. Renaud W. B. Schweizer and M. F. Ziiger Helv. Chim Act4 1984.67 1843; D. Seebach M. F. Ziiger F. Giovannini B. Sonnleitner and A. Fiechter Angew. Chem. Int. Ed. Engl. 1984 23 151. 129 K. Tomioka K. Ando Y. Takemasa and K. Koga J. Am. Chem Soc. 1984 106 2718. 130 J. A. M. van den Goorbergh and A.van der Gen 1. R Nerh. Chern. Soc. 1984 103 90. 142 B. V. Smith Nitro-olefins react with dilithiated carboxylic acids (or lithium enolates of esters) at low temperature forming adducts which afford y-keto-acids or esters in a con- venient one-pot process. Silyl nitronates have been used in synthesis of y-ketoesters (and aldehyde^).'^' RgozLi R:B R~ H RZ (79) (80) A novel stereosp cific synthesis of a,P-unsaturated acids has b en developed; a trialkylborane by sequential reaction with a lithiated alkyne and carbon dioxide afforded (79) and .hence the acid (80) as a single isomer.'32 Saturated esters via trimethylsilyl enolates underwent smooth palladium-mediated elimination to their a,@-unsaturated analogues. Stereoselective 2-step preparation of a-alkyl-a,P-unsat-urated esters was achieved using the addition of a-diphenylmethylsilyl enolates to a ketone with high Z-~electivity.'~~ Phase-transfer catalysis of reaction between aryl iodides and unsaturated esters (Heck reaction) has been re~0rted.l~~ Deconjugation of an E-alk-2-enoate (with a bulky alkoxy-group) by potassium disilazide gave 2-alk-3-enoate preferentially.13' A synthesis of allylcarboxylic acid relied on enecar- boxylation using diethyl ketomalonate as the enophilic equivalent of C02. Car- bethoxy-allylation was achieved through a radical pathway.t36 Allylic carbonates with CO and a palladium catalyst gave P,y-unsaturated esters in good ~ie1d.l'~ Addition of BuCu.BF3 to enoates gave predominantly syn-isomers in agreement with prediction of the model adopted by Fleming.'38 Simple ester enolates add to a,P-unsaturated esters with high erythro-selectivity;'39 tellurium tetrachloride addi- tion to allylic esters (and other derivatives) occurs via 1,3-addition and 1,2-migration of an acyloxy group; thus (81) (92% e.e.) gave erythro-(82) which in sequential reaction with Raney nickel and base gave trans- 1,2-dimethyloxiran (goo/ e.e.).131 M. Miyashita R. Yamaguchi and A. Yoshikoshi J. Org. Chem. 1984 49 2857; K. K. Sharma and K. B. G. Torsell Tetrahedron 1984 40,1085. D. Min-zhi T. Yong-ti and K. Wei-hua Tetrahedron Lett. 1984 25 1797. 133 J. Tsuji K. Takahashi I. Minami and I. Shimizu Tetrahedron Lett. 1984,25,4783; G. L. Larson,C. F. de Kaifer R.Seda L. E. Torres and J. R. Ramirez J. Org. Chem. 1984 49 3385. 134 T. Jeffery 1. Chem. SOC.,Chem. Commun. 1984 1287. I35 Y. Ikeda and H. Yamamoto Tetrahedron Lett 25 5181. 136 M. F. Salomon S. N. Pardo and R. G. Salomon J. Am. Chem. Soc. 1984 106 3797; D. H. R. Barton and D. Crick Tetrahedron Lett. 1984 25 2787. 137 J. Tsuji K. Sato and H. Okumoto J. Org. Chem. 1984 49 1341. 138 Y. Yamamoto and K. Maruyama J. Chem. Soc.. Chem. Commun. 1984,904. 139 M. Yamaguchi M. Tsukamoto S. Tankaka and I. Hirao Tetrahedron Lett. 1984,25,5661; L. Engman J. Am. Chem SOC.,1984 106 3977. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds Chiral a,P-unsaturated carboximides have been used in asymmetric Diels-Alder reactions as practical chiral acrylate and crotonate dienophile equivalents.These reactions mediated by Et2AlC1 or Me2AlCl proceeded with high ~electivity.'~' The Ireland-Claisen rearrangement has been studied in detail. Very high chirality transfer was observed for the transformations shown in Scheme 19 and this was i ii 'POMe "OM e og 0 OH \ / A (83) Reagent i LDA-THF or THF-HMPA then R,SiCI; ii Hydrolysis Scheme 19 dictated by two factors. These were the control over enolate geometry and the relative ease of attainment of chair- or boat-like transition states e.g. (83). Chelation control in enolate geometry was important in rearrangement of 0-protonated allylic glycollate esters. The rearrangement of (R)-1 -methyl-E-but-2-enyl hydroxyacetate (84) with ( Me3Si)2NLi occurred with 98% erythro-selectivity and 100% asymmetric transfer giving (85).14* 2-Hex-Cenolide with alkyl cuprates gave 2-alk-4-enoic acids in excellent yield.'42 A facile Pd"-mediated Claisen rearrangement leading to y,S-unsaturated esters has been p~b1ished.l~~ The use of tungsten-[ ( MeCN)3W(C0)3]-catalysed allylic alkyla- tion has been recommended on grounds of selectivity and cheapness (compared to Mo- or Pd-compounds) ;striking results were achieved in the transformation of e.g.(86) into (87) with NaCH(C02Et)2.144 The transformation of RX into 140 D. A. Evans K. T. Chapman and J. Bisaha J. Am. Chem. SOC.,1984 106 4261. 141 M. Nagatsuma F. Shirai N. Sayo and T. Nakai Chem. Left. 1984 1393; S. D. Burke W. Fobare and G.J. Pacofsky 1. Org. Chem. 1983 48 5221; T. Fujisawa K. Tajima and T. Sato Chem. Letf. 1984 1669. 142 T. Fukisawa K. Umezu and M. Kawashima Chem Lett. 1984 1795. 143 M. Ohshima M. Murakami and T. Mukaiyama Chem. Lett. 1984 1535. 144 B. M. Trost and M.-H. Hung. J. Am. Chem. SOC.,1983 105 7757. 144 B. V; Smith X \ S02Me (89) RCH=CH(CH2)n+2C02Hhas used (88) as an ethene di-ide equivalent; deproton- ation and alkylation of (88) followed by base-promoted halogenation gave (89) which with sodium ethoxide gave the product in good ~ie1ds.l~~ Synthesis of terminal allenic acids relied on addition of free radicals to an alkynylstannane.'46 Phenylation of malonic acid derivatives was reported for reaction of aryl-lead triacetate and sodiomalonate esters.14' Microbial hydrolysis (Acinetobac-ter fowji) of diethyl 3-hydroxyglutarate was enantioselective furnishing (S)-ethyl hydrogen 3-hydroxyglutarate and hence in two steps ~-carnitine.'~' 5 Lactones Asymmetric reduction of propargyl ketones (by Alpine borane) furnished the corre- sponding alcohols in high e.e.; from these alcohols routes to a-and &substituted y-lactones were deve10ped.l~~ The ene-reaction of alkenes and diethyl ketomalonate was catalysed by clays; with K10 montmorillonite y-lactones were formed.No reaction was observed in the absence of clay."0 The syn-diastereoselective reactions of the lithiated carbamate (90) gave mainly E-syn-(91) transformed into (92)which offered a selective route to such systems and could be further exploited.'" A stereoselective synthesis of 2,2-dialkylbutyrolactones oia repeated deprotonation- alkylation of (93) is another example of a process leading to an asymmetric quater- nary centre.15* Some other methods for y-lactones include reaction of iodostannyl esters and alkenes in the presence of AIBN the horse liver alcohol dehydrogenase- mediated oxidation of diols (which gave remarkably high e.e.) and selective enzyme- catalysed hydrolysis of cyclic diester~.''~ E-P-t-butylcinnamic acid lactonized to (94) and a bridged carbonium ion was thought the most likely i~~termediate.'~~ D.Scholz Liebig's Ann. Chem. 1984 264. 146 J. E. Baldwin R. M. Adlington and A. Basak J. Chem. SOC.,Chem. Commun. 1984 1284. 147 R. P. Kopinski J.T. Pinhey and B. A. Rowe Aust. J. Chem 1984 37 1245. 148 A. S. Gopalan and C. J. Sih Tetrahedron Lett. 1984 25 5235. 149 M. Midland A. Tramontano A. Kazubski R. S. Graham D. J. S. Tsai and D. B. Cardin Tetrahedron 1984,40 1371. Is' J.-F. Roudier and A. Foucaud Tetrahedron Lett. 1984 25 4375. 151 D. Hoppe and F. Lichtenburg Angew. Chem Znt. Ed. EngL 1984 23. 239. P. J. Curtis and S. G. Davies X Chem SOC.,Chem. Commun. 1984 747. lS3 G.A. Kraus and K. Landgrebe Tetrahedron Lett. 1984,25,3939; G. S. Y. Ng,L.-C. Yuan I. J. Jakovac and J. B. Jones Tetrahedron 1984,40 1235; M. Schneider N. Engel R. Honicke G. Heinemann and H. Gorisch Angew. Chem. Znt. Ed. Engl. 1984 23 67. 154 L. Jalander Tetrahedron Lett. 1984 25 457. 14' Aliphatic Compounds -Part (ii) Other Aliphatic Compounds 145 Me2P Ph Me [(77' -C,HS)Fe(PPh& CO) (=COCH,CH,CH,)]+ 3- 4- and 5-alkynoic acids have been cyclised to enolides by PdC12.(PhCN)2 in THF-Et3N.155 Homoallylic alcohols have been converted into &lactones uia a hydroformylation-oxidation sequence.Chiral &lactones have been obtained by pig-liver esterase-catalysed hydrolysis of diesters of 3-substituted glutaric acids; the chiral monoesters could be transformed into either enantiomer of the 1act0ne.l~~ 6 Amines and Amides Preparative methods reported for primary amines include reduction of nitro- compounds by anhydrous ammonium formate-Pd/ C-MeOH a versatile process in which hydrolysis of an alkyl bis(trimethylsily1)amine is the final step use of (Me3Si),NCH20Me as a synthetic equivalent of +CH2NH2 (hence RX -+ RCH2NH2) and oxidative rearrangement of aliphatic amides uia [I,I-bis(trifluoroacetoxy)iodo]benzene in acid or aqueous-organic solvent^.'^' The Cur- tius decomposition of azides in the presence of Me3SiCH2CH20H gave trimethylsilyl ethyl carbamates which were smoothly cleaved with Bu~N+F- to primary amines ; the reaction was cleaner than usually observed.'58 Unsymmetrical s-amines were obtained from primary amines uia RNHCH2CN as intermediate followed by hydr01ysis.l~~ Activation of a primary amine via PtC12(PPh3)2-SnC12 gave for e.g.Bu"NH2+ Bu;NH a 64% yield; reductive amination of an aldehyde was effected in the presence of borane-pyridine.'60 A route to (bulky) di-t-alkylamines shown in Scheme 20 was very effective; such crowded molecules could only be methylated with Magic Methyl (MeOS0,F) but were inert towards Me1 or K-MeOCH2CH20Me.'61 155 C.Lambert K. Ultimoto and H. Nozaki Tetrahedron Lett. 1984 25 5323. 156 P.G. M. Wuts M. L. Obrzut and P. A. Thompson Tetrahedron Lett. 1984 25. 4051; C. J. Francis and J. B. Jones J. Chem. SOC.,Chem. Commun 1984 579 157 S. Ram and R. E. Ehrenkaufer Tetrahedron Lett. 1984,25,3415; H. J. Bestmann and G. Wolfel Angew. Chem. Int. Ed. Engl. 1984 23 53; T. Morimoto T. Takahashi and M. Sekiya J. Chem SOC,Chem Commun. 1984 794; G. M. Loudon et aL J. Org.Chem. 1984,49 4272 4277. 158 T. L. Capson and C. D. Poulter Tetrahedron Letf. 1984 25 3515. 159 L. E. Overman and R.M. Burk Tetrahedron Lett. 1984 25 1635. 160 Y. Tsuji J. Shida R. Takeuchi and Y. Watanabe Chem. Lett. 1984 889; A. Pelter R. M. Rosser and S. Mills J. Chem. SOC.,Perkin Trans 1 1984 717. 161 E. J. Corey and A. W. Gross Tetrahedron Left 1984 25 491. 146 B. V. Smith ii '\ &NH2 -!+ &NO + N-OBu' -% &NHBu' But/ Reagents i MeC03H-EtOAc; ii 2eq But' ( ButNHNH2-Pb02);iii Scheme 20 Such hindered bases have value in altering direction of enolate alkylation. Stereocontrolled synthesis of 1,2-diaminesY via Diels- Alder adducts derived from a diene and a bis-imide derived from sulphur dioxide makes possible the transforma- tion of dienes of known geometry into diastereoisomeric carbamates. Vicinal diamines have also been obtained from a sequence in which addition ( NBS-NH2CN) to an alkene was followed by ring-closure to an imidazoline hydrolysed to form the product.In this way trans-but-Zene gave (*)-2,3-diaminobutane (61YO,as hydrochloride).'62 A cyclic a-complex has been suggested for such aminations on the basis of low-temperature n.m.r. studies.163 Reduction of oximes to imines was effected by Bu3P-PhSSPh.lW Use of LiAlH4- sugar complexes led to low e.e. in reduction of imines to secondary amine~.'~~ Cram selectivity was high in the reaction between imines and allyl-9-BBN and was rationalized in terms of attainment of the less-hindered transition-state (95). Allenic organometallics and imines showed high threo-selectivity and this affords a method which is complementary to the erythro-selective reaction of allylic systems.166 Oxidative carbonylation of amines (catalysed by Pd) gave carbamates in good or very good ~ie1ds.l~~ Amines are converted into thiols via intermediate (96) ; methyla-tion and hydrazinolysis completed the process.16* Oxidative deamination of primary and secondary amines occurred with (ArS02)202; yields of imines were variable.Phase-transfer catalysis was used to 4 162 H. Natsugari R. R. Whittle and S. M. Weinreb J. Am Chem Soc 1984 106 7867; S.-H. Jung and H. Kohn Tetrahedron Lett. 1984 25 399. 163 B. hermark and K. Zetterberg J. Am Chem Soc 1984 106 5560. 164 D. H. R Barton W. B. Motherwell E. S. Simon and S. Z. Zard J. Chem Soc. Chem Commun. 1984 337. S. R. Landor 0.Sonola and A.-R.Tatchell Bull. Chem. Soc. Jpn. 1984 57 1658. 166 Y. Yamamoto T. Komatsu and K. Maruyama J. Am Chem. Soc 1984 106,5031; Y. Yamamoto W. Ito and K. Maruyama J. Chem. Soc. Chem. Commun,1984 1004. 167 S. Fukuoka M. Chono and M. Kohno J. Chem SOC Chem Commun 1984,399. 168 R. Ueno C. Tanaka and M. Okawara Tetrahedron Lett. 1984 25 2675. 147 Aliphatic Compounds -Part (ii) Other Aliphatic Compounds generate N-nitrosamines from secondary amine~.'~~ Dealkylation of tertiary amines was noted for reaction with a-chloroethyl chlor~formate.'~~ Two reviews of enamine chemistry have appeared.171 Enamine formation is said to be improved by adding the carbonyl component to preformed TiCl,-amine complex.'72 Thermal isomerization of N-carbethoxyaziridines gave primary allylic amines in good yield; allylic phenyselenides were rearranged smoothly and in good yield to N-allylic p-toluenesulphonamides presumably viu a [2,3] sigmatropic shift.'73 High diastereoselectivity was observed in addition to an N-sulphinyl dienophile (97) to E,E-hexa-2,4-diene [15 1 in favour of (98)]; subsequent transformation of (98) by sequential reaction with PhMgBr then (MeO),P-MeOH gave E-threo- hydroxycarbamate (99) as a single isomer.Use of E,Z-hexa-2,4-diene gave a single adduct which in turn gave only E-erythro-hydroxycarbamate. This interesting route thus gives an entry into unsaturated vicinal aminoalcohols with stereo~ontrol.'~~ N-Alkylation of MeCONH in the presence of KF-MeCN or KF-DMF gave modest yields of secondary amide~.'~~ Isocyanates and isothiocyanates with RLi-CO gave after a hydrolytic work up a-0x0-amides or -thi~amides.'~~ Me S/p It N \CO,Bu I Me NHC0,Bu 7 Other Nitrogen Compounds Sonication has been used to speed up hydrolysis of nitriles even under reflux and was shown to be more efficient than mechanical ~tirring.'~~ It has been shown that MeCN and CN-do not form an add~ct.'~~ Palladium-mediated coupling of ArX and CH2(CN) (as the anion) gave excellent ~ie1ds.l'~ Aldehydes reacted with trimethylsilyl cyanide to form a-trimethylsilyloxynitriles useful precursors for a-aminoacids heterocyclic systems etc.18' Chemistry of 3-oxoalkanenitriles has been reviewed.'" a-Tosylisocyanides can be cleaved (Li-liq.NH3) to hydrocarbons.'82 169 R.V. Hoffman and A. Kumar J. Org. Chem. 1984 49 4011 4014; M. Nakajima J. C. Warner and J.-P. Anselme Tetrahedron Lett. 1984 25 2619. I70 R. A. Olofson J. T. Martz J.-P. Senet M. Piteau and T. Malfroot J. Org. Chem 1984 49 2081. V. G. Granik Russ. Chem. Rev. 1984 53 383; P. W. Hickmott Tetrahedron 1984 40 2989. 172 R. Carlson and A. Nilsson Actu Chem. Scand. Ser. B 1984 38 49. 173 A. Laurent P. Mison A. Nafti R. Cheikh and R. Chaabouni J. Chem. Res. (S) 1984 354; J. E. Frankhanser R. M. Peevey and P. B. Hopkins Tetrahedron Lett 1984 25 15. I74 R. S. Garigipati A. J. Freyer R. R. Whittle and S. M. Weinreb J. Am. Chem. Soc. 1984 106 7861. 175 G. 0.Torosyan N. K. Tagmazyan and A. T. Bayaban J. Org. Chem. USSR 1984,20 456.176 D. Seyferth and R. C. Hui Tetrahedron Lett. 1984,25 5251. 177 J. Elguero P. Goya J. Lissavetzky and A. M. Valdeomillos C. R Hebd. Seances Acad. Sci 11 1984 298 877. 178 D. Fgrcasiu G. Marino K. D. Rose G. A. Digenis and M. Jay Tetrahedron 1984,40 1487. 179 M. Uno K. Seto and S. Takahashi J. Chem. Soc. Chem. Commun. 1984 932. 180 K. Mai and G. Patil Tetrahedron Lett. 1984 25 4583. 181 M. H. Elnagdi M.R. H. Elmoghayar and G. E. N. Elgemei Synthesis 1984 1. 182 J. S. Yadav and P. S. Reddy Tetrahedron Lett. 1984 25 4025. 148 B. V. Smith A new route for azides utilised reaction between Pb(OAc),,(N,) (from Pb(OAc),-Me,SiN,) and a borane R,B; unfortunately a mixture of products was formed in this route.ls3 Aldoximes are dehydrated to nitriles by dimethylsuccinimidylsulphonium chloride-Et,N in high yield.The dianions of aldoximes can be alkylated efficiently e.g. MeCH=NOH gave with PhCH,Br Ph(CH,),CH=N-OH (2-isomer 1OOoh).ls4 Spontaneous rearrangement was reported in the attempted preparation of N-methyl pentanehydroxamic acid (from BuC02Me and MeNHOH) in which only BuC0,NHMe was is01ated.l~~ A new route to nitro-compounds relies on ozonolysis of RN=PRi (from RN3 and R4P) since the ozonide is presumed unstable and gives RN02 and RiP0.1s6 The Bu,P-PhSSPh reagent reduced nitro-groups to imines trapped by pyrrole f~rmation.'~~ a-nitro-olefins react with secondary amines and a Pd(0) catalyst to form allylic amines. Allylic nitro compounds undergo regioselective y-attack with LiCuR in an SN2'process.'88 8 Sulphur Compounds Synthetically useful OL -trimethylsilyl vinyl sulphides were formed in high yield by deoxygenation of sulphoxides by LDA-Me3SiC1.1s9 Addition of an allylic sulphide to e.g.methyl propiolate showed dependence on the Lewis acid used; AlCI favoured the E-and ZnCl the Z-add~ct.''~ A molybdenum persulphide complex (NH4)2[(S2)2Mo(S2)2Mo(S2)2]brings about alkylation and coupling; e.g. RBr fur- nished RSR and RSSR. The acid chlorides RSOCl and RSO2C1 also formed disul- phides.'" A range of organosulphur compounds showed copper-induced solvolysis with CU"(OAC)~-ACOH.'~~ 2-1-Phenylpropene added [(ArS),SAr]+SbC& to form thiiranium ion which added chloride ion to form P-chlorosulphidesof Markovnikov orientation.An open ion could not however be e~c1uded.l~~ Asymmetric oxidation of a dialkyl sulphide by Corynebacterium equi IF0 3730 gave sulphoxides in surprisingly high e.e. (80-1000/,). Sulphone formation was observed with long-chain systems but in other cases was absent e.g. MeSC,H,Me gave sulphoxide and recovered starting materials only. The Sharpless reagent cleanly brought about the same oxidation and the optimum mixture was Ti(OPr'), DET :H20:Bu'OOH = 1:2 :1:2. Again no significant sulphone formation was noted.'94 Ring closure of a-sulphinyl carbanions is a convenient route to methylene 183 Y. Masuda M. Hoshi and A. Arase Bull. Chem SOC.Jpn. 1984 57 1026. 184 N. K. A. Dalghrd K. E. Larsen and K. B. G. Torsell Acta Chem. Scand.Ser. B 1984,38 423; R. E. Gawley and T. Nagy Tetrahedron Lett. 1984 25 263. G. I. Nikishin E. I. Troyansky I. V.Svitanko and 0. S. Chishov Tetrahedron Lett. 1984 25 97. E. J. Corey B. Samuelsson and F. P.Luzzio J. Am. Chem. SOC.,1984 106 3682. 187 D. H. R.Barton W.B. Motherwell and S. Z. Zard Tetrahedron Lett. 1984 25 3707. R. Tamura K. Hayashi Y. Kai and D. Oda Tetrahedron Lett. 1984,25,4437; N. Ono I. Hamamoto and A. Koji J. Chem. SOC.,Chem. Commun. 1984 274. 189 R.D. Miller and R.Hossig Tetrahedron Lett. 1984 25 5351. 190 K. Hayakawo Y.Kamikawaji A. Nakita and K. Kanematsu J. Org. Chem. 1984 49 1985. 191 D. N. Harpp and J. G. McDonald Tetrahedron Lett. 1984 25 703. 192 D. Uguen Chem. Lett. 1984,25 541. 193 G. H. Schmid and D. I. Macdonald Tetrahedron Lett.1984 25 157. 194 H. Ohta Y. Okamoto and G. Tsuchihashi Chem. Lett. 1984 205; P. Pitchen and H. B. Kagan Tetrahedron Lett. 1984 25. 1049. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds cyclopentenones.19' The Diels- Alder addition of chiral sulphur-containing dienophiles to cyclopentadiene has been explored as a method for selective prepar- ation of nor-bornenyl dia~tereoisomers.'~~ Reduction of a-arylthio-P-oxosul-phoxides by complex hydride was an efficient route to protected a -hydroxyaldehydes of high optical purity; thus from (loo) (101) was obtained in >99 1 isomer yield.Ig7 Cholesterol with MeSOC1-Et3N gave separable epimeric esters MeS02C27H45 ;reac-tion of each ester with RMgX gave MeSOR in 95-100% optical 0 STol To1 (To1 = C7H7) STol Regiocontrolled polyalkylation of a -trifyl-dimethylsulphoneenabled four alkyl groups to be introduced at the a-sites; elimination of SO2 gave the alkene RR4C=CR2R3.In this ingenious reaction the overall change is equivalent to 2-2-successive regiospecific alkylation of a polyanion C =C ! Unfortunately the final elimination was not stereospecific since the fourth alkylation gave rise to diastereois~mers.'~~ The chiral auxiliary (102) with the magnesium derivative of C7H,S02CH2CH=CH2 formed a complex which with acetone gave high selectivity in formation of (103).200 Allylic sulphonates were rearranged to sulphones by palladium(0)-mediated catalysis.20' The preparation and uses of chiral [l60,170,180] sulphate esters has been described.Organic reactions of carbon disulphide have been reviewed.*02 Me HO TolSO 9 Phosphorus Compounds Asymmetric reduction of (*)-phosphine oxides gave phosphines with low e.e. Efficient chiral synthesis of a range of phosphines and other compounds was 195 M. Pohmakotr and S. Chancharunee Tetrahedron Lett. 1984 25 4141. 196 T. Koizumi I. Hakamada and E. Yoshii Tetrahedron Lett. 1984,25 87; C. Maignan A. Guessos and F. Rouessac ibid. p. 1727. 197 G. Guanti E. Narisamo F. Pero L. Banfi and C. Scolastico J. Chem SOC.,Perkin Trans. 1 1984 189. 198 K. K. Andersen B. Bujnicki J. Drabowin M. Mikolaynyk and J. B. O'Brien J. Org. Chem. 1984 49 4070. 199 J. B. Hendrickson G. J. Boudreaux and P. S. Palumbo Tetrahedron Lett.1984 25 4617. 2oo T. Akiyama M. Shimizu and T. Mukaiyama Chem Lett. 1984 611. 201 K. Hiroi R. Kitayama and S. Sato J. Chem. SOC Chem Commun. 1984 303. 202 G. Lowe and S. J. Salamone J. Chem. SOC.,Chem Commun. 1984,466; M. Yokoyama and T. Imamoto Synrhesis 1984 797. 150 B. V. Smith achieved by reaction of alkylthiophosphonium salts and (Me2N)3P-CH2C12; thus (I?)-(-)-Et(Ph)P(=S)OPr’ by sequential treatment with CF3S03Me and tris-DMAP gave (S)-(-)-Et( Ph)POPr’ converted back into starting material (by reaction with S) with no loss of optical activity.203 The preparation and properties of functionalized tertiary phosphines have been reviewed.204 The merits of carrying out phosphonium salt preparations under pressure have been ill~strated.~~’ The diphosphine BINAP {2,2‘-bis(dipheny1phosphino)-1,l’-binaphthyl}has been prepared and resolved.As a hydrogen-transfer catalyst it was highly efficient and selective; thus 2-a-(benzamid0)cinnamic acid gave with (R) -BINAP N-benzoylphenylalanine (96% 96%e.e.) and with (S)-BINAP (97% 100% e.e. of the isomer). This report represents the first account of synthesis and resolution of an atropoisomeric bis-triaryl diphos- phine.206 Stereospecificity in elimination from the adduct of EtPh,PO-BuLi-PhCHO has been confirmed by X-ray structural analysis of 2( 1RS,2SR)-diphenylphosphinoyl- 1 -phenylpropan-1-01 and exclusive formation of 2-1 -phenylpropene by base. A vari- ation on this theme led to single isomers of homoallylic Deproton-ation/alkylation of Et( Ph)P( =O)CH2C02Men gave alkylation 01 to the carboxyl group; this product with LiC1-H20-Me2S0 gave Et(Ph)P( =O)CH2R in almost complete optical purity.208 Some evidence for reversibility in the Wittig reaction of Ph3PCH(CH2)0Li and hexanal was secured by addition of octanal and observation of crossover.A possible bonus here was predominance of the E-isomer of either product.2w The use of heterogeneous media for the Wittig-Horner reaction has been extended and a mild method recommended for base-sensitive aldehydes or phosphonates in which LiCl and an amine with a pK comparable to that of (EtO),P(=O)CH,CO,Et may be used. With DBU in MeCN-LiCl reaction was swift and for e.g. Bu’CHO gave high yield and E :Z-ratio.210 Exploratory work using a-alkoxyphosphonium bromides (as precursors to enol ethers) a chiral phosphonate as a precursor for chiral enediols and a route to homologation of aldehydes has been published.2” The Petersen reaction (the silicon equivalent of the Wittig reaction) has been reviewed as has a broad scope of phosphorus chemistry (in honour of Arbuzov’s eightieth birthday).212 10 Miscellaneous Two new powerful and versatile oxidants have been introduced.Magnesium and zinc permanganates are safe only when supported on silica gel and used in CH2C12. 203 A. J. Macpherson and D. J. H. Smith J. Chem. Res. (S) 1984,32; J. Omelannuk and M. Mikolajayk Tetrahedron Lett. 1984 25 2493. 2w0. A. Erastov and G. N. Nikonov Russ. Chem. Rev. 1984 53 369. 205 W. G. Dauben J. M. Gerdes and R.A. Bunce J. Org. Chem 1984,49,4293. 206 A Miyashita H. Tayako T. Souchi and R. Noyori Tetrahedron 1984,40 1245. 207 A. D. Buss W. B. Cruse 0.Kennard and S. Warren J. Chem. SOC,Perkin Trans. 1 1984 243; A. D. Buss N. Greeves. D. Levin and S. Warren Tetrahedron Lett. 1984 25 357. 208 K. M. Pietrusiewin M. Zablocka and J. Monkiewin J. Org. Chem 1984,49 1522. 209 A. B. Reitz and B. E. Maryanoff J. Chem Soc. Chem Commun. 1984 1548. 210 J. VilliCras and M. Rambaud Synthesis 1984 406;M. A. Blanchette W. Choy,.J. T. Davis A. P. Essenfeld S. Masumune. W. R. Roush and T. Sakai Tetrahedron Lett. 1984 25 2183. 211 J. B. Ousset C. Mioskowski Y.-L. Yang and J. R. Falck Tetrahedron Lett. 1984 25 5903; T. Hiyama K. Kobayashi and M. Fujita ibid. p. 4959; N.L. J. M. Braekhof and A. van der Gen 1. R Nefh. Chem. SOC..1984. 103 305 312. 212 D. J. Ager Synthesis 1984 384; Arbuzov dedication Russ. Chem. Rev. 1983 52 1012. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds A wide range of compounds is susceptible; clearly the compound needs careful handling since a number of solvents inflamed including AcOH. Bis(2,2'-bipyridyl)copper( 11) permanganate seems safer and versatile in the number of compounds Trost has reviewed selectivity -its pursuit and the role of strain in achieving it.214 Reviews of three carbon homologating agents and synthesis of chiral (non- racemic) compounds have appeared.215 213 S. Wolfe and C. F. Ingold J. Am Chem. SOC.,1983 105 7755; H. Firouzabadi A. R.Sardarian M. Naden and B. Vessal Tetrahedron 1984 40 5001. 214 B. M. Trost Chem. Bn'f. 1984 315; Gazz. Chim. IfaL 1984 114 139. 215 J. C. Stowell Chem. Reu. 1984 84 409; A. I. Meyers (ed.) Tetrahedron 1984,40 1213.