8 Aliphatic Compounds Part (ii)Other Aliphatic Compounds By A. R. TATCHELL School of Chemistry Thames Polytechnic Wellington St. London SE18 6PF 1 Alcohols and Ethers The search for chiral stationary phases for the resolution of racemates by h.p.1.c. techniques continues. An ionically-bonded chiral stationary phase prepared by passage of a solution of (R)-N-(33-dinitrobenzoyl)phenylglycine through a pre- packed y-aminopropyl silanized column of silica has been shown successfully to resolve racemates having a wide diversity of functionality.'" A model for chiral recognition by the stationary phase leading both to a prediction of elution order and assignment of absolute configuration of arylalkylcarbinols is proposed.'* Fur- thermore the resolution of various racemic 2,2'-disubstituted-l l'-binaphthyls on a preparative scale," previously possible only by classical means should enable the use of these compounds in other stereochemical studies to be exploited further (see refs.13 15 and 29). Low molecular weight (+)-poly(triphenylmethy1 metha-crylate) coated onto silanized silica gel also successfully resolves a similar range of racemic binaphthyls. Optically pure a-[1-(9-anthryl)-2,2,2-trifluoroethoxy]acetic acid has been synthesized from either enantiomer of 2,2,2-trifluoro-1-(9-anthryl)ethanol and used as a chiral derivatization agent for racemic alcohols amines and thiols (R'R2CHX; X = OH NH2,or SH).2The diastereoisomeric esters amides and thioesters exhibit n.m.r. spectra in which chemical shift differences are noted for diastereotopic nuclei notably R' and R2.The proposed preferred conformation for the derivatives [(l) (1) X = O,NH,S,orNR * (a)W. H. Pirkle J. M. Finn J. L. Schreiner and B. C. Hamper J. Am. Chem. Soc. 1981 103 3964; (b)W. H. Pirkle and J. M. Finn J. Org. Chem. 1981 46 2935; (c) W. H. Pirkle and J. L. Schreiner ibid. 1981 46 4988; (d)S. Honda S. Murata R. Noyori Y. Okamoto I. Okamoto H. Takaya and H. Yuki J. Am. Chem. Soc. 1981,103,6971. W. H. Pirkle and K. A. Simmons J. Org. Chem. 1981 46 3239. 167 168 A. R. Tatchell illustrates one diastereoisomer] upon which the n.m.r. interpretation is based is carefully argued and these conformations appear to be stable highly populated even at room temperature unperturbed by strong interactions of R' and R2with the anthryl system and largely unaffected by changes in solvent polarity.Primary alcohols may be acetylated using ethyl acetate in the presence of commercially available Woelm alumina.3a This simple and convenient met hod is also specific in that application to primary-secondary diols results in the formation of primary monoacetates. The methodology has been successfully extended to primary hydroxyalkylphenols and arylamines (phenols and aliphatic amines are unaff e~ted)~' and to carbohydrate^.^' The cleavage of a-diols with sodium metaperiodate supported on silica gel offers a method of promising ver~atility,~ as does the procedure employing triphenyl- bismuth in catalytic amounts with N-bromosuccinimide in moist acetonitrile in the presence of potassium carbonate.A cautionary note has been published with regard to asymmetric syntheses carried out using phase-transfer techniques wherein P-hydroxyammonium compounds (e.g. ephedrine) are used as chiral quaternary ammonium catalysts.6 A careful survey of a range of such reactions is reported including chiral epoxidation processes where artefact formation from the catalyst can cause spurious results. The formation of (R)-1,2-epoxyoctane from oct-1-ene has been achieved in higher yields than hitherto and with enantiomeric excess of >70% using media inoculated with P.oleovorans. The two-phase technique that was developed involved successive transfer of the organic phase to a fresh batch of inoculated media to overcome the problems of cell and enzyme damage.' The asymmetric epoxidation of prochiral allylic alcohols reported last year using t-butyl hydroperoxide with titanium(1v) isopropoxide in the presence of tartrate esters has been further exploited and procedures have been improved to overcome the previous limitation resulting from more water-soluble products.' Similar epoxi- dation processes with racemic allylic alcohols [e.g.(2) Scheme 11when allowed to proceed to 50% conversion revealed that recovered untreated alcohol had a remarkably high enantiomeric purity (frequently >96Y0).~ The success of this kinetic resolution process resides in the reaction-rate difference of the two enantiomeric allylic alcohols being in the region of 100 although relative rate differences of 5-10 can still at a 50% conversion lead to e.e.values of recovered alcohol being in the region of 70-90%. It was also noted that the isolated epoxy alcohol had e.e. >96% arising of course from the faster epoxidation of the (S)-enantiomer in the racemic mixture. (a) G. H. Posner S. S. Okada K. A. Babiak K. Miura and R. K. Rose Synthesis 1981 789; (6) G. H. Posner and M. Oda Tetrahedron Letr. 1981 22 5003; (c) S. S. Rana J. J. Barlow and K. L. Matta ibid. 1981 22 5007. D. N. Gupta P. Hodge and J. E. Davies J. Chem. SOC.,Perkin Trans. 1 1Y81 2Y70. D. H. R. Barton W. B. Motherwell and A. Stobie J. Chem. SOC.,Chem. Commun. 1981,1232. E. V. Dehmlow P. Singh and J. Heider J. Chem. Res. (S),1981,292.M.-J. de Smet B. Witholt and H. Wynberg J. Org. Chem. 1981 46 3128. B. E. Rossiter T. Katsuki and K. B. Sharpless J. Am. Chem. SOC.,1981 103,464. V. S. Martin S. S. Woodard T. Katsuki Y. Yamanda M. Ikeda and K. B. Sharpless J. Am. Chem. SOC.,1981 103,6237. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds 6)- (2) threo-(2:98) erythro-slow (R)-(2)___* ihreo-(62:38) erythro-Scheme 1 2 Aldehydes and Ketones Convenient and efficient procedures have been reported for the synthesis of [l-2Hl]aldehydes10 and of [1-"O]aldehydes or ketones," and for deuterium exchange of acidic hydrogens in ketones in compounds having active methylenic hydrogens and in hydrocarbons.'* The alkylation of aldehydes the reduction of ketones and a-ketoaldehydes and the a-alkylation of acyclic and cyclic ketones under conditions which induce chirality in the products has been the subject of an unusually high number of publications.The most significant examples of the wide range of chiral-inducing catalysts that have been employed have been derived from the compounds (3)-(11). The most satisfying feature about most of the reactions reported is the rationalization of the X 3 \ X NHR (3) (4) Bu-N Me OH (7) lo I. Degani R. Fochi and V. Regondi Tetrahedron Lett. 1981,22 1821. B. T. Golding and A. K. Wong Angew. Chem. Int. Ed. Engl. 1981 20 89. G.W. Kabalka R. M. Pagni P. Bridwell E. Walsh and H. M. Hassaneen J. Org. Chem. 1981,46 1513. 170 A. R. Tatchell Me Z = OCN? H CH SC6H4Me-p I (9) enantiomeric excesses obtained on the basis of alternative diastereoisomeric transi- tion-states.Some selected relevant results are now summarized. For example the binaphthyl (3; X = CH,Br) when treated with N,N-dimethyl-l,2-diaminoethane gave a bridged derivative [3; X,X = CH2.N(CHzCHzNMez)CH2], which on reac- tion first with alkyl lithiums and then with aldehydes gave secondary alcohols having e.e. 22-5590 .13 The lithio-derivative of the diaminoalcohol (5) when present in reactions between alkyl lithiums and aldehydes results in e.e. in the secondary alcohols of 40-95% .14 Modified LAH complexes from the binaphthyl(3; X = OH) were found to reduce a range of alkyl alkynyl ketones in selectivities ranging from 57 to 96Y0.l’ Similar complexes from the diamine (4),14 the 1,2-aminodiols (7),16 and alkoxy-amine-borane complexes from (6),” were found to effect reduction of prochiral alkyl aryl ketones to give e.e.of 86-95% 44-57% and 37-60% respectively. The 1,4-dihydropyridine system contained within the chiral macrocycle (8)in the presence of magnesium perchlorate effected reduction of prochiral ketones and a-ketoesters to the extent of e.e. 10-90% ,I8 and the bis-1,4-dihydropyridine (9) was effective with similar substrates to the extent of e.e. 18-98Y0.’~ The methoxy-derivative of the amino-alcohol (6; R = CH2Ph) gave with a range of aliphatic ketones a chiral imine [e.g. (12) Scheme 21; according to the conditions used after the lithiation reaction either the (2)-or (E)-lithioenamine could be generated in high stereoselectivity.The former was the kinetically controlled and the latter the thermodynamically controlled product and both retained their stereo- integrity for the subsequent alkylation process.2o Highest e.e. (77-94%) was obtained when the (E)-isomer was alkylated. The studies have also been extended to the alkylation of cyclic ketones. l3 J.-P. Mazaleyrat and D. J. Gram J. Am. Chem. Soc. 1981,103,4585. l4 T.Mukaiyama Tetrahedron 1981,37 4111. l5 M.Nishizawa M. Yamada and R. Noyori Tetrahedron Lett. 1981 22 247. l6 J. D.Morrison E. R. Grandbois S. I. Howard and G. R. Weissmann Tetrahedron Lett. 1981,22,2619. l7 A.Hirao S. Itsuno S. Nakahama and N. Yamazaki J. Chem. SOC.,Chem. Commun. 1981,315.*’ P. Jouin C. B. Troostwijk and R. M. Kellogg J. Am. Chem. SOC.,1981 103,2091. l9 M. Seki N. Baba J. Oda and Y. Inouye J. Am. Chem. Soc. 1981,103,4613. *’ A.I. Meyers D. R. Williams S. White and G. W. Erickson J. Am. Chem. SOC.,1981,103 3081. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds (2) (E) iii \ Jiii 25% /e.e. 94Yoe.e. 0 Reagents i LiNPri THF -20 "C; ii reflux 1 h; iii MeI -78 "C Scheme 2 The conformationally rigid 1,3-0xathiane (10) prepared from (+) -pulegone pro- vides a chiral adjuvant which exerts better stereocontrol than the corresponding derivatives reported in earlier years.21a This new reagent has been used for the synthesis of (R)-2-ethyl-2-hydroxypentanal, which was then converted into (R)-3-methylhexan-3-01 having 93% optical purity.Using the same chiral adjuvant (-)-(R)-mevalolactone of 87% optical purity has been synthesized (Scheme 3).216 Reagents i BuLi MeCHO; ii DMSO (CF,CO),O; iii THF MgCl, CH,:CHMgBr; iv N-chloro- succinirnide AgN03 v LAH; vi TsCI; vii KCN; viii BH,-THF; ix H,O,-NaOH; x NaOHaq H,O+ Scheme 3 Finally the sulphoxide (11) has been used for the asymmetric synthesis of a-methoxyaldehydes (Scheme 4).22 " (a9 E. L. Eliel J. E. Lynch and W. R. Kenan jun. Tetrahedron Lett. 1981 22 2855; (b) E. L. Eliel K.Soai and W. R. Kenan jun. ibid. p. 2859. 22 L. Colombo C. Gennari G. Guanti E. Narisano and C. Scolastico J. Chem. Soc. Perkin Trans. 1 1981 1278. 172 A. R. Tatchell Reagents i BuLi THF -78 "C RCHO; ii Bu4NOH-Me2S0,-H20-CH,C1,; iii R = Ph NaI-I,-PPh,; R = CH,Ph NaI-I,-HMPA; iv I,-NaHC0,-H,O dioxan Scheme 4 3 Carboxylic Acids In connection with biosynthetic studies on the inhibitory action of an active fluorocitric acid (1R,2S)- and (lS,2S)-fluorocitric acids [(15a) and (15b) respec- tively] have been synthesized from methyl 4,6-0-benzylidene-2-deoxy-~-erythro-hexopyranosid-3-ulose (13)via a Reformatsky reaction with ethyl bromofluoroace- tate.23 In this reaction (Scheme 5) equatorial attack on the carbonyl carbon was unequivocally demonstrated to give the intermediates (14a) and (14b).H0,C (154 CO,H (13) (14a) X = CO,Et,Y = H (14b) X = H Y = C0,Et H C02H Reagents i Zn CHFBr.CO,Et; ii H,O'; iii KMnO, -OH; iv H30f Wb) Scheme 5 Oxazoline derivatives continue to be used as intermediates in the synthesis of achiral- and chiral-substituted carboxylic acids.For example a-substituted acrylic acids have been formed from saturated unbranched acids (Scheme 6);24alkylation of 2,4-dimethyl-4-(hydroxymethyl)-2-oxazoline(16),when attached to a cross- linked polystyrene via the hydroxy-function yields 2-alkyl- and 2,2-dialkylalkanoic acids. The use of the chiral oxazoline (17) in the polymer provides a promising reagent for asymmetric alk yla tion. 25 Optically pure a,P-ethylenic sulphoxides (18) have been shown to be useful substrates for the synthesis of either enantiomer of chiral 3-alkylalkanoic acids (e.e. 59-65Y0);~~ the reaction (Scheme 7) proceeds via a-lithiation (which was shown to result in neither racemization at sulphur nor E,Z-equilibration) followed by carboxylation and esterification to yield the optically pure a-(methoxycar-bony1)alkenyl sulphoxides (19).Subsequent reactions with dialkylcopper-lithium 23 S. Brandange 0.Dahlman and L. Morch J. Am. Chem. Soc. 1981,103,4452. 24 S. Serota J. R. Simon E. B. Murray and W. M. Linfield J. Org. Chem. 1981 46,4147. " A. R. Colwell L. R. Duckwall R. Brooks and S. P. McManus J. Org. Chem. 1981,46 3097. 173 Aliphatic Compounds -Part (ii) Other Aliphatic Compounds 0 RCH,CO,H RCH,CONHCMe,CH20H -% RCH2<N]Me2 0 0 It N 1 RCHC0,H RC< Me RyH<N)Me, II CH2 CH HOCH Reagents i H,NC(Me,)CH,OH 150 "C;ii 180 "C; iii HCHO; iv 180 "C; v H30+ Scheme 6 Me phhcH ,OH OyN Et (17) reagents were rationalized on the basis of the approximately planar metal chelate (20) and nucleophilic addition from the side opposite to that of the aryl group.26 The method has also been applied to the synthesis of chiral3-alkylcyclopentanones and to 11-oxoequilenin methyl ether.High e.e. values (79-99%) have been obtained in the Michael addition reaction of Grignard reagents to a$-unsaturated acid amides derived from ~-ephedrine;~' the method offers a useful alternative to the oxazoline routes previously published.28 Ph \ Ph :FC02Me Ph Ph -(-:..]-R2 so \ i-iii \ %[ R2 Met:,'. R' R' C0,Me -0 1v,vi R' Me0 (18) (19) Reagents LiNPri2(2equiv.) THF -78°C; ii CO, -78°C; lii MeI HMPA; iv RZCuLi -15°C; v AI/Hg EtOH-H20; vi NaOHaq Scheme 7 The synthesis of a range of macrocycles incorporating only one chiral unit namely a 2,2'-disubstituted-l,l'-binaphthylsystem has been described and their effective- ness as chiral recognition hosts towards the perchlorate salts of amino-acids and 26 G.H. Posner J. P. Mallamo and K. Miura J.Am. Chem. SOC., 1981 103,2886. 2' '* T. Mukaiyama and N. Iwasawa Chem. Lett. 1981 22 913. A. I. Meyers R. K. Smith and C. E. Whitten J. Org. Chem. 1979 44 2250. 174 A. R.Tatchell their methyl esters e~amined.~' The publication provides a valuable summary of the current state of the art in this sphere and shows that the highest chiral recognition is attained between the macrocycle (21) and the perchlorate salt of phenylglycine.The more stable diastereoisomer is that wherein host/guest is (S)/(S),i.e. (22). a-Amino-acids have been used to form diaza-18-crown-6 derivatives (23) which show chiral recognition towards racemic primary alkylammonium thi~cyanates.~' /O R R" ,-R3 (23) R' = H CHMe2 or CHzPh R2= HorPh R3= Me or CH2Ph The amino-acid constituent of the antitumour antibiotic bleomycin (2S,3S,4R)- 4-amino-3-hydroxy-2-methylpentanoicacid has been synthesized from L-rham- nose;31 (+)-avenic acid A and (-)-2'-deoxymugineic noted in last year's report as iron chelators excreted from the roots of various cereals have been synthesized using pathways that establish the configurations at the chiral 4 Lactones and Macrolides The antitumour properties of various plant lignans has prompted interest in a novel lignan recently isolated from the urine of certain mammals.Two syntheses of this lignan (24) and its corresponding diol have been reported this year. One route33 involves a two-stage Stobbe reaction between diethyl succinate and 3-benzyloxy- benzaldehyde to yield bis-(3'-benzyloxybenzylidene)sucFinic acid which was then converted into (24) by standard procedures. The other involved a Michael 29 D. S. Lingenfelter R. C. Helgeson and D. J. Cram J. Org. Chem. 1981 46 393. 30 D. J. Chadwick I. A. Cliffe I. 0. Sutherland and R. F. Newton J. Chem. Soc. Chem. Commun. 1981,992. 31 T. Ohgi and S.M. Hecht J. Org. Chem. 1981,46,1232. 32 Y.Ohfune and K. Nomoto Chem. Len. 1981,827; S. Fushiya Y.Sato S. Nakatsuyama N.Kanuma and S. Nozoe ibid. 1981,909;Y.Ohfune M. Tomita and K. Nomoto J. Am. Chem. Soc. 1981 103 2409. 33 G. Cooley R. D. Farrant D. N. Kirk and S. Wynn Tetrahedron Lett. 1981 22 349. 34 A. Pelter P. Satyanarayana and R. S. Ward Tetrahedron Lett. 1981 22 1549. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds 175 addition of the anion derived from 3-methoxyphenyldiphenylthiomethane to butenolide (27;R' = R2 = R3 = H) and the intermediate trapped with a sub- stituted benzyl bromide; subsequently the thioacetal group was removed reduc- tively. There has been interest in more general synthetic pathways to P-hydroxy-a- methylene- y-butyrolactones (25)and to a-alkylidene-P-hydroxy- y-butyrolactones (26)because of their physiological activity.The compound (25)(R' = R2 = H) occurs in tuliposide B which has been isolated from tulip bulbs and its prepar- ati01-1~~~ from a-methylene phosphonate (28)356was achieved using the sequence (24) Ar = rn-HOC6HdCH2 (25) (26) (27) generalized in Scheme 8. Here the conversion of (28)into (30)proceeds through the betaine (29)(Homer-Emmons reaction type) and the rearrangement (31)to (32)is the sulphoxide-sulphenate conversion of Mislow and Evans. The P-acetoxy derivative (33) was readily converted with base into (25). PhS ~~O(OEt)2 PhSycozR _* CR'R, R 1R c'A I I OAc -OAc (30) Tco2R 1v _iv F'hiyco2R HRZ PhSO CR'R' 0 CR~R~ AcO R1 I I OAc OAc (33) (32) (31) Reagents i PhSNa; ii R'R'C(0Ac)CHO; iii m-CPBA; iv P(OMe),; v p-TsOH Scheme 8 The series of Lauraceae lactones (26)possess all possible combinations of stereoisomerism at the a-alkylidene residue; they may also have at the y-position either a methylene group or a single methyl group which may be cis or trans related to the P-hydro~y-group.~~ Generalized methods for the formation of some of these lactones are shown in Scheme 9.35 (a)J.-P. Corbet and C. Benezra J. Org. Chem. 1981 46 1141; (b) C. H.Heathcock and W. A. Kleschick ibid. 1978,43 1256. 36 S. W. Rollinson R. A. Amos and J. A. Katzenellenbogen J. Am. Chem. Suc. 1981 103,4114. 176 A. R. Tatchell 1- R3CH2CH2C02Me Li ii . ... 1,111,v R3CH2CHC02Me i'iv'v SePh I 1 1 vi-viii Jvi.ix vi,ix R3 0 R3 0 HO Me HO Me HO HO Reagents i LiNPri THF -78 "C; ii PhSeBr THF -78 "C; iii CH,:CHCHO -78 "C; iv HC:CCHO -78 "C; v H,O, H,O 25 "C; vi KOH H,O-MeOH; vii PhSeC1 CH,Cl, 25 "C; viii Bu,SnH PhH A; ix Hg(CF,CO,), CH,Cl, 0 "C Scheme 9 Viable routes to variously substituted butenolides (27) have been reported this year and the essential features of the reaction sequences involved are shown in Scheme Scheme 11,38 Scheme 12,39and Scheme 13.40In Scheme 10 the a-(pheny1thio)ketones are formed either from bis(pheny1thio)acetals or from a-halogenoketones In Scheme 11 the formation of the unsaturated ester of pre- dominantly (2)-configuration requires the use of hindered a-silyl esters.In Scheme 12 the photochemical conversion of furfural into 4-alkoxybutenolide has been previously doc~mented.~~ In Scheme 13 the Grignard reagents from primary alkyl halides yield 4,4-dialkylbutenolides from secondary alkyl halides they yield 4- alkylbutenolides and from primary am-alkyl dihalides they yield the corresponding spiro-4-bicyclobutenolides.COzH / H2C 0 iii R' -3 R' PhS R2 PhS R2 PhS ~2 R3 R2 Reagents i NaH THF 20 "C; ii ICH,CO,Na THF; iii R'MgX (2equiv.); iv NaIO,; v A Scheme 10 37 P. Brownbridge E. Egert P. G. Hunt 0. Kennard and S. Warren J. Chem. SOC.,Perkin Trans. 1 1981,2751. 38 M. Larcheveque Ch. Legueut A. Debal and J. Y. Lallemand Tetrahedron Lett. 1981 22 1595. 39 F. W. Machado-Araujo and J. Gore Tetrahedron Lett. 1981 22 1969. 40 P. Canonne M. Akssira and G. Lemay Tetrahedron Lett.1981 22 2611. 41 M. A. Stevens U.S.P. 2 859 218; Chem. Abstr. 1959 53 10 061. 177 Aliphatic Compounds -Part (ii) Other Aliphatic Compounds Reagents i [Me,SiCHCO,Bu']Li' -78 "C; ii NH,Cl-H,O; iii Si0,-H,S04; iv NaBH Scheme 11 \OR \OH \R Reagents i 02,ROH hv; ii H,O'; iii RLi THF -70 "C Scheme 12 Scheme 13 Carbohydrate derivatives have been further exploited as chiral sources for other natural products. Thus L-glucose is proposed for (SS)-hydroxy-(2S)-methyl-hexanoic acid lactone (the pheromone of the ~arpenter-bee).~~ (+)-Prelog-Djerassi lactone [(+)-(37)] has been prepared from 4,6-O-benzylidene-~-allal,~~ from methyl c~-D-glucopyranoside,~~ Two reports have appeared and from ~-glucal.~' on the formation of (*)-(37)utilizing a cyclic stereoselective hydroboronation process of the 1,5-diene (34)followed by appropriate oxidation procedures [Scheme 14,(34)+ (37)].46An alternative method47 involves the reaction of crotyltrialkyltin with the aldehydic carbonyl group in (38) in the presence of boron trifluoride etherate; the latter reagent chelates the two carbonyl oxygens and induces the crown conformation (39).This conformation ensures that the stereoselective direction of attack of the reagent is in the direction shown to give (40).The most dramatic synthetic achievements of the current year are the asymmetric total synthesis of erythrom~cin~~ and the total synthesis of rifamycin S.49 Both 42 S. Hanessian G. Demailly Y. Chapleur and S. Leger J. Chem. Soc. Chem. Commun.1981,1125. 43 R. E. Ireland and J. P. Daub J. Org. Chem. 1981 46 479. 44 S. Jarosz and B. Fraser-Reid Tetrahedron Lett. 1981 22 2533. 45 M. Isobe Y. Ichikawa and T. Goto Tetrahedron Lett. 1981 22 4287. 46 D. J. Morgan jun. Tetrahedron Lett. 1981,22 3721; W. C. Still and K. R. Shaw ibid. 1981,22,3725. 47 K. Maruyama Y. Ishihara and Y. Yamamoto Tetrahedron $eft. 1981 22 4235. 48 R. B. Woodward E. Logusch K. P. Nambiar K. Sakan and D. E. Ward J. Am. Chem. SOC., 1981 103 3210 3213 3215. Forty-four other authors are cited. 49 N. Nagaoka W. Rutsch G. Schmid H. Iio M. R. Johnson and Y:Kishi J. Am. Chem. Soc. 1980 102 7962; H. Iio H. Nagaoka and Y. Kishi ibid. p. 7965; H. Nagaoka G. Schmid H. Iio and Y. Kishi Tetrahedron Lett. 1981 22 899 2451; H. Nagaoka and Y.Kishi Tetrahedron 1981 37 3873. 178 A. R. Tatchell ROX -+ Meb le (34) R = SiMe2Bu' (35) CHO CO,Me Me uMe Scheme 14 impressive contributions originate from Harvard University and no summary could in any way do justice to the crispness and clarity of the accounts. 5 Lactams An interesting fused p-lactam system (41; R = Et) has been isolated in high yield (80%)from the photolytic reaction of N-ethoxycarbonylmethylene-2-pyridone.50 Modifications of functionality have been effected; for example hydrogenation of the carbon-carbon double bond epoxidation or conversion into the corresponding bromohydrin (42).Photolytic conversion of the isoxazolidine (43),obtainable by a 1,3-dipolar cycloaddition between the nitrone (44)and the nitro-substituted alkene (43 results in the formation of the trans-p-lactam (46).5'In contrast when (43) was heated in methanol it gave the cis-p-lactam (47),which is regarded as the thermodynamically more stable system in this case.When an N-methyl analogue HO (44) 0.. + ,Ph CO,R COiR Bu (41) (42) (43) (45) W. J. Begley G. Lowe A. K. Cheetham and 3. M. Newsam J. Chem. SOC.,Perkin Trans. 1 1981,2620. A. Padwa K. F. Koehler and A. Rodriguez J. Am. Chem. SOC., 1981,103,4975. Aliphatic Cornpounds -Part (ii) Other Aliphatic Compounds NC NC Bu’ of (43) was used in this reaction series the trans-p-lactam analogue was demon- strated to be the more stable. Other methods for p-lactam synthesis have been described that involve (a) C-2-N bond formation and (b) C-4-N bond formation from appropriate acyclic precursors.The concepts for these cyclizations are not new but the procedures offer useful extensions to existing methods. Thus p-amino-acids may be cyclized by a PTC method using methanesulphonyl chloride in a chloroform-water system and tetrabutylammonium hydrogen sulphate as (R)-and (S)-4-[(methoxycarbonyl)methyl]-2-azetidone[(53) and (52) respectively] have both been synthesized from dimethyl P-aminoglutartrate (48) (Scheme 15).s3 This chemico-enzymic method utilizes the specificity ofpig-liver esterase in the hydrolysis of the unprotected (48) to (50) and protected (49) diester to (51),and cyclization by use of Mukaiyama’s reagent in acetonitrile.iii I_ HO,C C02Me H2x 1i,iv Me02C C02H H (51) (52) Reagents i pig-liver esterase; ii Ph3P-MeCN; iii PhCH20COCl Et,N; iv H2 Pd/C Scheme 15 An interesting method for C-4-N bond formation leading to the synthesis of 3-methylene-azetidin-2-ones (57; Scheme 16)involves the cyclization of substituted acrylamides (56) which are formed by the reaction of secondary a-ketoamide 2,4,6-tri-isopropylbenzenesulphonylhydrazones (54) with excess butyl-lithium and trapping of the intermediate dianion (55) with aldehyde^.^^ ” Y. Watunabe and T. Mukaiyama Chem. Lett. 1981,443. 53 M. Ohno S. Kobayashi T. Iimori Y.-F. Wang andT. Izawa J. Am. Chem. SOC.,1981,103,2405,2406. 54 R. M. Adlington M. J. Betts A. G. M. Barrett P. Quayle and A. Walker J.Chem. SOC.,Chem. Commun. 1981 404; R. M. Adlington and A. G. M. Barrett ibid. p. 65. 180 A. R. Tatchell R’ (57) Reagents i BuLi 3.3equiv. -78°C; 25°C in DME; ii R’CHO -78°C; 25°C; iii H,O; iv BuLi 2 equiv.; v TsCl -78 “C; 25 “C 10 min; vi 25 “C 15 h Scheme 16 6 Amines The method of H. C. Brown for the conversion of trialkylboranes into primary amines has been developed into one of greater convenience by the in situ generation of chloramine from aqueous ammonia and sodium hypochlorite at 0 0C.55(E)-Allylamines have been formed in high stereoselectivity (91-100%) by a chain- elongation process involving an aldehyde vinyltributylphosphonium bromide phthalimide and sodium hydride; the intermediate N-allylphthalimide was decom- posed into the required allylamine with for example hydrazine in high yield.56 In those cases where some (2)-isomer was formed it could be readily removed by recrystallization.Interestingly far lower stereoselectivity was found when vinyltriphenylphosphoniumbromide was used. Two new protecting groups for the primary amino-function have been reported. In one case the reagent is 1,1,4,4-tetramethyl-1,4-dichlorodisilylethylene(58) which is readily available owing to its use as a cross-linking agent in polymer chemistry.” Primary aliphatic and aromatic amines and amino-acid esters give adducts (59) which are however unstable to aqueous acid and alkali although the conversion of the latter into lithio-derivatives and subsequent reaction with elec- trophiles was usefully demonstrated.An acid- and alkali-stable protecting group arises from the reaction of the primary amine (or amino-acid ester) with allyl bromide in the presence of a tertiary amir~e.~* The N,N-diallyl protecting group may be removed with Wilkinson’s catalyst [(Ph,P),RhCl] which effects an allyl- propenyl isomerization and this is followed by an in situ enamine hydrolysis. The usefulness of this protecting group in which the amino-nitrogen exhibits little or no nucleophilic character has been exploited in the synthesis of (+) -anticapsin (60) in about 20% e.e. from L-0-methyltyrosine. ’’ G. W. Kabalka K. A. R. Sastry G. W. McCollurn and H. Yoshioka J. Org. Chem. 1981 46 4296. 56 A. I. Meyers J. P. Lawson and D. R. Carver J. Org. Chem. 1981,46 3119.’’S. Djuric J. Venit and P. Magnus Tetrahedron Lett. 1981 22 1787. B. C. Laguzza and B. Ganem Tetrahedron €ett. 1981 22 1483. Aliphatic Compounds-Part (ii) Other Aliphatic Compounds Reaction of primary amines with the polycyclic pyrylium triflate (61) gives the corresponding N-alkylacridinium triflate in high yield; pyrolysis at 150"C in the presence of triphenylpyridine affords the terminal alkene.59 7 Other Nitrogen-containing Compounds Carbamates generated from allylic alcohols (62) and the corresponding alkyl or phenyl isocyanates when converted into their dilithiated derivatives undergo reaction with a range of electrophiles (Scheme 17). The overall reaction shows the carbamate to be a readily accessible propanal-d3 equivalent.60 N,N-Dialkylcarba- mates yield a monoanion which reacts with aldehydes and ketones to give S-hydroxyenolcarbamates.of iii,iv ,E~ R' R1 CH,:CHCHOHR~ -@+ 0 NR2 OCONHR~ y- (62) 0 lv ECH ,CH ,COR Reagents i R'NCO; ii BuLi 2.1 equiv. THF TMEDA -78°C; iii EX = RX Me,SiCl (MeS), MeOCO,Me or HNPr;; iv g.1.c or 1.c.; v H,O+ Scheme 17 The use of nitroalkanes as precursors for aldehydes has received impetus from two new approaches to their synthesis. Thus as their nitronate anions nitromethane nitroethane and 2-nitropropane may be C-alkylated with l-alkyl-2,4,6-triphenyl-pyridinium salts generated from primary amines and 2,4,6-triphenylpyrylium tetrafluoroborate.61 In a second route,62 a tertiary nitroalkane (63; Scheme 18) when treated with nitromethane and sodium hydride in DMSO solution and the reaction mixture irradiated gives the primary nitroalkane (64) by an electron -transfer chain-substitution mechanism.Subsequently the nitroalkane may be con- verted into the corresponding aldehyde (65) by an improved oxidative procedure 59 A. R. Katritzky and A. M. El-Mowafy J. Chem. SOC.,Chem. Commun. 1981,96. 6o R. Hanko and D. Hoppe Angew Chem. Znr. Ed. Engl. 1981 20 127; D. Hoppe R. Hanko A. Bronneke and F. Lichtenberg ibid. p. 1024; D. Seebach Angew. Chem. Int. Ed. Engl. 1979 18 239. 61 A. R. Katritzky G. De Ville and R. C. Patel Tetrahedron 1981 37 Supplement No. 9 25. " N. Kornblum and A. S. Erickson J. Org. Chem. 1981,46 1037. 182 A. R. Tatchell R'R2R3CN02 + R'R2R3CCH2N02-+ R'R2R3CCH0 Scheme 18 employing potassium permanganate.62 An alternative reaction for this conversion uses a MooS-pyridine-HMPA reagent.63 8 Sulphur Compounds Photoelectron spectroscopy which was effectively used with /3-dicarbonyl com- pounds to substantiate the existence of two rapidly interconverting enol structures rather than a single electron delocalized form has been applied to p-thioxoketone~.~~ These sulphur compounds may exist as an enethiol-(66)-enol-(67) equilibrium.In agreement with previous results obtained from 'H n.m.r. i.r. and U.V. spectra the photoelectron spectra clearly substantiated the view that thioacetyl- acetone (66; R'=R2 = Me) has comparable amounts of both forms present at equilibrium that 2-acetylcyclohexanethioneexists predominantly as the enethiol (68) and 2-thioacetylcyclohexanone is predominantly the enol (69).The assign- ments of the ionization energies are supported by semiempirical MO calculations. (66) (67) (68) (69) Alkylation of the dianion of secondary thioamides (70) which are generated for example by reaction with 2.2 equivalents of butyl-lithium has been shown to take place at the a-carbon atom rather than at the sulphur which might have been expected on the hard-soft acid-base prin~iple.~' A range of alkyl and aryl halides were used as the electrophilic species. In the case of the monoanions of secondary thioamides (2)-enolate geometry was presumed as subsequent reaction with aldehydes gave pronounced erythro-stereoselection (73; Scheme 19). Here the formation of the preferred enolate was seen to arise from the proton abstraction from the more stable conformer (71)of the thioamide and stereoselection from the more favoured chair transition-state (72).66 Secondary amides do not show such stereoselectivity.A wide range of sulphur-containing macrocycles have been prepared in much higher yields than previous literature reports. The methodology is based upon the ready formation of caesium thiolates from aw-dithiols and caesium carbonate in DMF solution and ring formation by subsequent reaction with aw-dibrornide~.~' M. R. Galobardes and H. W. Pinnick Tetrahedron Lett. 1981 22 5235. 64 F. S. J0rgensen;L. Carlsen and F. Duus,J. Am. Chem. SOC.,1981,103 1350. " Y. Tamaru M. Kagotani Y.Furukawa Y. Amino and Z.Yoshida Tetrahedron Lett. 1981 22 3413. 66 Y. Tamara T. Harada S.Nishi M. Mizutani T. Hioki Z. Yoshida J. Am. Chem. SOC.,1980,102,7806. " J. Buter and R. M. Kellogg J. Org Chem 1981,46 4481. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds Reagents i BuLi THF -78 "C; ii R'CHO; iii H30+ Scheme 19 The high polarizability of the large caesium cation leading to tight ion-pairs in DMF is thought to be responsible for the success of this reaction; smaller cations (K+ Na+ or Li') lead to poorer or negligible yields. 9 Phosphorus Compounds A range of allenic phosphonates [e.g. (74)] having additional carbon-carbon bond unsaturation have been prepared by the route outlined in Scheme 20. The sub- sequent rearrangements on heating were dependent upon the nature of the sub- stituent groups and the length of the saturated carbon-chain.Thus (75) underwent a Cope rearrangement which resulted in the formation of (76) and (77) in a 1:4 ratio; the compound (78) on heating gave first diethyl 3,5-dimethylhexa-1,3,5- trienylphosphonate via a [1,5]-hydride shift which then cyclized to the correspond- ing cyclohexadiene.68 R1= (CH*),CH:CHR'R Reagents i HC i CNa; ii (EtO),PCI NR Scheme 20 /*@PO(OEt), c 3 PO(OEt) (75) (76) (77) (78) 6R D. Cooper and S. Trippett J. Chem. SOC.,Perkin Trans. I 1981 2127. 184 A. R. Tatchell 10 Miscellaneous Two reviews have appeared describing recent developments in the chemistry of carbodi-imide~.~~.~~ Other reviews include the use of halogenated ketenes in the formation of four-membered rings by cycloaddition processes leading to cyclic ketones lactones lactam and squaric acid derivative^,^^ and the preparation structure and synthetic applications of nitroenamine~.~~ The use of a selection of polymers containing functional groups either for effecting a simple chemical trans- formation of a substrate or for providing a protecting group for a substrate while functional group modification processes are carried out at a remote site has been Reviews have also appeared on the use of chiral organoboranes for asymmetric hydroboration of alkenes and for the asymmetric reduction of carbonyl on homogeneous asymmetric hydr~genation,~’ and on the use of sulphoxides as chiral inducing agent^.^^*^' The conformational preferences of macrocyclic ketones and lactones have been assessed and the product ratios arising from for example C-alkylation determined; a consistent argument has been presen- ted wherein the high kinetic diastereoselection is seen to result from control of the asymmetric induction processes by these preferred conformations and the preferred direction of reagent attack.78 Stereoselection in acyclic systems has been the subject of numerous publications including contributions from the work of D.A. Evans,79 C. H. Heathcock,80 R. W. Hoffman,81S. Masamwe,** and Y. Yarnam~to.~~ 69 M. Mikolajczyk and P. Kielbasinski Tetrahedron 1981 37 233. 70 A. Williams and I. T. Ibrahim Chem. Reu. 1981,81,589. 71 W. T. Brady Tetrahedron 1981 37 2949.72 S. Rajappa Tetrahedron 1981 37 1453. 73 J. M. J. Frichet Tetrahedron 1981 37 663. 74 H. C. Brown P. K. Jadhav and A. K. Mandal Tetrahedron 1981 37 3547. 7s V. Ciplar G. Cornisso and V. SunjiC Synthesis 1981 85. 76 G. SolladiC Synthesis 1981,185. 77 S. Colonna R. Annunziata and M. Cinquini Phosphorus Sulfur 1981 10 197. 78 W. C. Still and I. Galynker Tetrahedron 1981 37 3981. 79 D. A. Evans J. Bartroli and T. L. Shih J. Am. Chem. SOC.,1981,103 2127; D. A. Evans and L. R. McGee ibid. p. 2876; D. A. Evans J. V. Nelson E. Vogel and T. R. Taber ibid. p. 3099. C. T. White and C. H. Heathcock J. Org. Chem. 1981,46 191; C. H. Heathcock C. T. White J. J. Morrison and D. VanDerveer ibid. p. 1296; C. H. Heathcock M. C. Pirrung J. Lampe C. T.Buse and S. D. Young ibid. p. 2290; C. H. Heathcock M. C. Pirrung S. H. Montgomery and J. Lampe Tetrahedron 1981 37 4087; C. H. Heathcock J. P. Hagen E. T. Jarvi M. C. Pirrung and S. D. Young J. Am. Chem. SOC.,1981,103,4972. R. W. Hoffman and T. Herold Chem. Ber. 1981 114 375; R. W. Hoffman and H.-J. Zeiss J. Org. Chem. 1981,46,1309;R. W. Hoffman and B. Kemper Tetrahedron Lett. 1981,22,5263. 82 S. Masamune W. Choy F. A. J. Kerdesky and B. Imperiali J. Am. Chem. SOC.,1981 103 1566; I. Masamune M. Hirama S. Mori S. A. Ali and D. S. Garvey ibid. p. 1568; W. Choy P. Ma and S. Masamune Tetrahedron Lett. 1981 22 3555. Y. Yamamoto H. Yatagai and K. Maruyama J. Chem. SOC.,Chem. Commun. 1981 162; J. Am. Chem. SOC.,1981 103 3229; Y. Yamamoto and K. Maruyama Tetrahedron Lett.1981 22,2895.