10 Synthetic Methods By P. A. CHALONER School of Chemistry and Molecular Sciences University of Sussex Falmer Brighton 8N19QJ 1 Introduction The format of this report remains broadly the same as in previous years with a division of the material considered into two sections. The first details reactions in which new carbon-carbon bonds are formed or broken and new carbon skeleta are constructed. The second section is concerned with functional group transformations. As always such a review must be extremely selective and whilst every effort has been made to include contributions of general interest the author expresses her regret that some valuable material must be excluded. 2 C-C Connection and Disconnection Connection of Separate Fragments.-Endures and their Equivalents.Again this year enolates figure strongly in C-C bond-forming methodology and again stereoselec- tive reactions have proved to be among the most interesting. Reviews of tin(r1) enolates in synthesis,' stereoselective aldol reactions of a-unsubstituted chiral eno- lates,2 and cross-couplings based on acetals3 have been published. The preparation of activated zinc for Reformatsky reagents using trimethylsilyl chloride has been noted! Reaction of the enolates of chiral hydrazones such as (1) with Knoevenagel or Michael acceptors has been achieved in a very stereoselective manner (Scheme l).5 The asymmetric synthesis of alcohols and carboxylic acids may be accomplished by the alkylation of the enolates of piperazine-derived chiral diamides (Scheme 2).6 a-Alkylation of P-aminobutanoates (2) proceeds with good asymmetric induction giving diastereoisomer excesses up to 98% (Scheme 3).7 There has been continued progress and extensive interest in the area of diastereoselective aldol condensations.In the reaction of (3) the nature of the protecting group R was able significantly to change the diastereofacial selectivity ' T. Mukaiyama and N. Iwasawa Nippon Kagaku Kaishi 1987 1099. ' M. Braun Angew. Chem. Int. Ed. Engl. 1987 26 24. T. Mukaiyama and M. Murakami Synthesis 1987 1043. G. Picotin and P. Miginiac J. Org. Chem. 1987 52 4796. D. Enders and B. E. M. Rendenbach Chem. Ber. 1987,120,1223; D. Enders A. S. Demir and B. E. M. Rendenbach Chem. Ber. 1987 120 1731. K. Soai H. Hayashi A.Shinozaki H. Umebayashi and Y. Yamada Bull. Chem. SOC.Jpn. 1987,60,3450. ' D. Seebach and H. Estermann Tetrahedron Left. 1987 28 3103. 241 P. A. Chaloner H JJQOOMe >96% e.e. Reagents i MeCHO 25 "C; ii LDA THF 0 "C; iii Me/\\/COOMe -78 -+ 0 "C; iv O, CH2C12 -78 "C Scheme 1 iv v I R3 H &OH R2 Reagents RZCH2COCI Et,N 0 "C; ii base THF -78 "C; iii R3X; iv Li[HBEt,] THF 30 "C; v HCl H20 Scheme 2 0 PhA NHCOPh 2)yCOOR1goR R2 R2 E (2) 50-98% d.e. Reagents i LDA THF -78 "C; ii E' (alkyl halide or RCHO) -78 -+ 0 "C Scheme 3 of aldol reactions.* Stereoselective aldol reactions were achieved uia titanium eno- lates such as (4)(Scheme 4); the ratio of diastereoisomers in this case ranged from 79:21 to 98:2.The zirconium analogue gave syn-adducts with better than 90% selectivity.' The stereoselective aldol reactions of chiral halogenoethanoate enolates have been studied by Evans' group. The 2-enolate reacts rapidly and with high P. A. McCarthy and M. Kageyama J. Org. Cfiern. 1987 52 4681. P. J. Murphy G. Procter and A. T. Russell Tetrahedron Lett. 1987 28 2037. Synthetic Methods OLi OR ++ OTiCpzCl Nb CNb -C 64-77% (4) 58-96% d.e. Reagents i LDA THF -78 "C; ii Cp2TiC12 -78 +25 "C; iii RCHO -95 +-78 "C; iv [NH,]Cl H@ Scheme 4 i ii iii ____ C1 67% ,. Ph 'Me 95 YO diastereoselective Ph 'Me 1iv v vi NH2 Reagents i Bu2BOTf Et,N Et20 -78 "C; ii MeCHO -78 +0 "C; iii H202 MeOH H20 0 "c; iv ",I-; v LiOH H20; vi Hlr Pd/C CF,COOH Scheme 5 selectivity whereas the E-enolate reacts very slowly and with lower selectivity.The products have been converted into chiral amino acids and monobactams (Scheme 3.'' Condensation of the protected amino acid (5) with aldehydes proceeds in a very stereoselective manner being controlled not only by steric but also by stereoelectronic effects (Scheme 6). Alkylation is similarly selective and after debenzylation the products may readily be hydrolysed to threo-amino alcohols." New catalysts for aldol reactions have emerged this year. Lanthanide salts have been used as Lewis acids in aldol addition cyanohydrin formation and oxirane ring opening (Scheme 7)." Lanthanide-assisted electrochemical aldol condensations were shown to be very selective for aldehydes over ketones; this allowed the cross-aldol condensation of Scheme 8 to proceed in good yield.13 By contrast cerium enolates generated from a-halogenoketones by reaction with cerium(III) halides D.A. Evans E. B. Sjogren A. E. Weber and R. E. Conn Tetrahedron Lett. 1987 28 39. D. Seebach E. Tuaristi D. D. Miller C. Schickli and T. Weber Helv. Chim. Acta 1987 70 237. A. E. Vougioukas and H. B. Kagan Tetrahedron Lett. 1987 28 5513. l3 A. J. Fry M. Susla and M. Weltz 1. Org. Chem. 1987 52 2496. P. A. Chaloner i,i-FHNr; n R2 R' I R' OH Ph Ph X = 0or NMe (5) Reagents i base; ii R'CHO Scheme 6 OSiMe3 . .. OSiMe3 COOMe COOMe 12-5 1 O/o 1146% Reagents i RCHO; ii LnCI or Eu(fod), CH2CI, 25T 1 week Scheme 7 PhCOCH(Br)Me + PhCHO --* PhCOCH(Me)CH(OH)Ph Reagents LaBr, Li[C104] THF 0.2 8 ceramic anode carbon cloth cathode Scheme 8 OSiMe3 4 OH 81-93% 84-93 Oh 96-99% d.e.Reagents TiC14 CH2Cl,; ii [pyH][OOCCl] CH,CI, 25 "C dark; iii (PhCH2),NH CF,COOH 50 "C C6H6 Scheme 9 react successfully with both aldehydes and ketones.14 Rhodium diene biphosphine complexes better known for their activity as hydrogenation catalysts have proved useful in promoting aldol rea$tions between silyl enol ethers and either aldehydes or acetals. 15,16 Aldols have been prepared using butane-l,3-diol acetals as templates by the sequence of Scheme 9.17 Triphenylmethyl perchlorate was used to activate silyl enol ethers towards Michael reactions with CqP-unsaturated orthoesters to give 1,5-dicarbonyl compounds 14 S.Fukuzawa T. Tsuruta T. Fujinami and S. Sakai J. Chem. SOC.,Perkin Trans. I 1987 1473. S. Sato I. Matsuda and Y. Izumi Tetrahedron Lett. 1987 28 6657. 16 M. T. Reetz and A. E. Vougioukas Tetrahedron Lett. 1987 28 793. I. R. Silverman C. Edingon J. D. Elliot and W. S. Johnson J. Org. Chem. 1987 52 180. Synthetic Methods (Scheme 10).I8The stereoselective construction of adjacent tertiary and quaternary carbon atoms has been achieved by Michael addition; the diastereoisomers (6a) and (6b) were obtained in the ratio of 20 1 (Scheme 11). However the selectivity was a little capricious; using the pyrrolidine derivative gave equal amounts of the possible diastereoi~omers.'~ An approach to an enantioselective Michael addition was provided by the reactions of Scheme 12.Condensation of a P-ketoester with a chiral amino acid ester followed by deprotonation provided a potent nucleophile for conjugate addition to an appropriate acceptor; (7) was in general the sole product after hydrolysis and was obtained enantiomerically and diastereomerically pure.*' Hydride abstraction from acetals by triphenylmethyl tetrafluoroborate gives the dioxalynium cation (8). Reaction with a silyl derivative such as (9) allows the Reagents i [Ph,C][ClO,] CH,CI2 -78 "C; ii H20 Scheme 10 (6a) 80'/o (6b) Reagents i LDA THF -78 "C; ii WCOOEt THF -78 "C Scheme 11 i ii 0 R' (7) Reagents i L-ValOCMe,; ii LDA; iii x)=/ -78 "C X Scheme 12 l8 S.Kobayashi and T. Mukaiyama Chem. Lett. 1987 1183. M. Yamaguchi M. Hamada H. Nakashima and T. Minami Tetrahedron Lett. 1987 28 1785. *' K. Tornioka K. Yasuda and K. Koga J. Chem. SOC.,Chem. Commun. 1987 1345. 246 P. A. Chaloner preparation of ketoesters and diketones (Scheme 13).21 Reaction of a ketone enol with the related cation derived from a dithioacetal (lo) led to the formation of an a-oxoketene dithioacetal (Scheme 14).22 Methallyl magnesium chloride has been used as a synthon for the enolate of propanone. The process (Scheme 15) corresponds to an aldol type reaction and should be used in cases in which traditional methods 0-0 n + 40SiMe2CMe3 n __* 0 /O OMe PhCH2CH2-C-CH2COOMe 7 Ph (9) 80% (8) Reagents CH2C12 -45 "C 2.5h Scheme 13 S + asp"U:l - (10) 48-99Oh Reagents CH2C12 25 "C 1.5-24 h Scheme 14 .....II 111 %+ LMgCl * * 100% 1iv ' 74% Reagents i THF 0 +20 "C; ii O, CH2Clz -70 "C; iii DMSO 20 "C; iv HOOCCOOH H20 A Scheme 15 The silyl enol ethers of arylmethyl ketones were oxidatively coupled to the corre- sponding butanediones in modest yields using iodosobenzene/boron trifluor- ide etherate. The key step appears to be attack of the silyl enol ether on ArCOCH21Ph(OBF2).24 a-Methylenated ketones (1l) may be obtained from silyl enol ethers by reaction with bromomethylmethyl ether (Scheme 16); the reaction was used to prepare an intermediate for the synthesis of ~arkomycin.'~ " Y.Hayashi K. Wariishi and T. Mukaiyama Chem. Lett. 1987 1243. 22 J. Nakayama Y. Sugie and M. Hoshino Chem. Lett. 1987 939. 23 W. H. Bunnelle M. A. Rafferty and S. L. Hodges J. Org. Chem. 1987 52 1603. 24 R.Moriarty 0. Prakash and M. P. Duncan J. Chem. SOC.,Perkin Trans. 1 1987 559. 25 M. Hayashi and T. Mukaiyama Chem. Lert. 1987 1283. Synthetic Methods Reagents i MeOCH2Br SnBr, CH2CI2 25 "C 1.540 h; ii DBU CH2C12 25 "C 2 h Scheme 16 Allyl Alkynyl and Alkenyl Anions and their Equivalents. Reviews of the uses of allyltin compounds in organic synthesis and of routes to acyclic stereocontrol via allylic organometallic compounds have been A regiocontrolled syn- thesis of allyl stannanes has been described (Scheme 17). Although several steps are required both stereoisomers could be obtained with good selectivity.28 Allyllead compounds have been generated in situ using catalytic lead(I1) bromide and stoicheiometric aluminium; these were used for the allylation of imine~.~' A similar process was reported using bismuth( 111) chloride; conversion of aldehydes into homoallyl alcohols could then be accomplished in excellent yield in aqueous solvents.30 Selective allylation of ketones in aqueous media was also achieved by reaction of tin or zinc metal with an allyl halide3' (Scheme 18).SnMe3 . .. I I1 - iii - ,COOH I A.R2 OHIiv SnMe3 SnMe3 R' R' L,2 ti4-8m0 1 vi ii 4 1-78 Yo Reagents i Me,SnLi THF -78 "C; ii R'CHO; iii Me,CuLi; iv Me2NCH(OMe), CH2C12 25 "C; v MeOH H,O 25 "C; vi LDA THF -78 "C Scheme 17 26 Y.Yamamoto Aldrichimica Acra 1987 20 45. 27 Y. Yamamoto Acc. Chem. Res. 1987 20 243. I. Fleming and M. Rowley J. Chem. Soc. Perkin Trans. I 1987 2259. 29 H. Tanaka S. Yamashita Y. Ikemoto and S. Torii Chem. Lett. 1987 673. 'O M. Wada H. Ohki and K. Akiba J. Chem. SOC. Chem. Commun. 1987 708. 31 C. Einhorn and J. L. Luche J. Organomet. Chem. 1987,322 177. P. A. Chaloner R' OH 0 R3?X iorii R2+ R' R4 R3 R4 30-90% Reagents i Zn [NHJCI THF H20 25 "C 10-60 min; ii Sn ultrasound THF H,O 15-18 "C 30-60 min Scheme 18 Addition of crotyldiisopinocampheylboranes to aldehydes has again been achieved with good diastereofacial selectivity (Scheme 19).32 The stereoselectivity of the addition of crotylboronates (12a) and (12b) to oximes was shown to depend mainly on the geometry of the boronate and not significantly on that of the oxime (Scheme 20).33 OH OH Reagents -78 "C,<3 h N2 96 4 Scheme 19 NHOH From (12a) 95 5 64% From (12b) 12 98 38% Reagents i B") 9 kbar 46°C; ii /-?iB:O] 9 kbar 45 "C -\ 0 0 (12b) Scheme 20 Allyltin reagents have again figured prominently this year.The stereoselective synthesis of Z-homoallyl alcohols (13) from a-methylcrotylstannanes was accom- pli~hed,~~ whilst in addition to a,P-epoxyaldehydes the products of non-chelation controlled addition (14) were principally obtained.35 Enantioselective allylation has been achieved using a new chiral allylating agent formed from tin(r1) triflate a chiral diamine and an allylaluminium (Scheme 21).36 There have been further reports of the conjugate addition of ally1 silanes to enones catalysed by triphenylmethyl perchlorate; the intermediate silyl enol ether may readily be intercepted by an electrophile (Scheme 22).37 32 H.C. Brown K. S. Bhat and R. S. Randad J. Org. Chem. 1987 52 319 3701. 33 R. W. Hoffmann and A. Endesfelder Liebigs Ann. Chem. 1987 215. 34 C. Hull S. V. Mortlock and E. J. Thomas Tetrahedron Lett. 1987 28 5343. 35 G. P. Howe S. Wang and G. Procter Tetrahedron Lett. 1987 28 2629. 36 N. Minowa and T. Mukaiyama Bull. Chem. SOC.Jpn. 1987 60,3697. 37 M. Hayashi and T. Mukaiyama Chem. Letr. 1987 289. Synthetic Methods RCHO i ii iii R up to 84% e.e. Reagents i Sn(OTf),; ii N I Me ...; 111 AIBu'~ CH2CI2. -78 "C Scheme 21 Reagents i Me3SiCH2CH=CH2 [Ph3C][C104]; ii PhCHO Scheme 22 H-C C-0Et 70% ClCH,CH(OEt) LiCEC-OEt 111 IV RR'C (0H ) -CGC-0Et 7 1-9 5'/o Reagents i LDA THF 0 "C; ii NaCI H,O -78 "C fast addition; iii RCOR'; iv [NH4]CI Scheme 23 New and appreciably improved syntheses of ethoxyethyne and ethoxyethynyl alcohols have been reported (Scheme 23).38Useful ally1 silanes and trimethylsilyl ketones have been prepared via alkynyl boron compounds (Scheme 24).39Interest in the coupling of alkynyl anions with vinyl halides in the presence of palladium(0) complexes has continued (e.g. Scheme 25); (15) was used in a synthesis of the sex pheromone of the processionary moth.40 Selective monosubstitution of 1,l-dichloroethene by either a l-alkyne or a vinylalane was also shown to be catalysed by [Pd( PPh3)J .41 38 S.Raucher and B. L. Bray 1. Org. Chem. 1987 52 2332. 39 K. K. Wang K. E. Yang and S. Dhumrongvaraporn Tetrahedron Lett. 1987 28 1003 1007. 40 J. K. Stille and J. H. Simpson J. Am. Chem. SOC.,1987 109 2138. 41 V. Ratovelomanana A. Harnrnond and G. Linstrurnelle Tetrahedron Lett. 1987,,28 1649. P. A. Chaloner i ii RIB R1 R' -R'-C=C-Li RK!3iMe3 R/-LCSiMe3 \SiMe3 Reagents i R,B THF 0 "C 30 min; ii F,CSO,CH,SiMe, 25 "C; iii MeCOOH H,O; iv H20 NaOH Scheme 24 SiMe3 X // Me3Sn-CEC-SiMe3 + Bu-Bu-~ (15) Reagents [Pd(PPh,),] THF 50 "C or [Pd( MeCN),CI,] Scheme 25 Further reactions of vinylcuprates (readily prepared by alkyne carbocupration) have been described.Coupling with alkynyliodonium tosylates gave enynes with excellent stereoselectivity (Scheme 26).42Reaction with chiral acetals such as (16) proceeded with relatively low diastereoselectivity; the product on hydrolysis was a y,S-unsaturated aldehyde (Scheme 27) which was used in the synthesis of a precursor of the California Red Scale pheromone.43 R-CGC-iPh + )-7 R2 -Rk --0Ts R' CU R' =-R Reagents Et20 -78 -* 25 "C Scheme 26 CuLi 24% d.e (16) )=)-CHO Reagents i CuI.BF,.Et,O; ii H,O+ Scheme 27 42 P. J. Stang and T. Kitamura J. Am. Chem. SOC., 1987 109 7561. 43 P. Mangeney A. Alexakis and J. F. Normant Tetrahedron Left. 1987 28 2363. Synthetic Methods 25 1 Stannylation of trimethylsilyldiynes (17) gave initially distannylalkeneynes (Scheme 28); these undergo a variety of metallation and substitution reactions to give enynes dienes and alkenes.44 Deprotonation of styryl sulphone yields a lithiated alkene (18) (Scheme 29); this may be regarded as a synthon for an acyl anion?5 ........R)J R-C=C-C=C-SiMe3 11 111 II IV A RHSnMe3 +, (17) Me3Sn B' SiMe, '$, SiMe3 86% Reagents i Me,SnCu.SMe, LiBr THF -50 +0 "C; ii MeLi; iii Mel; iv BuI Scheme 28 . Ph Ph+ -2 qLi -phvo SOzPh SO2Ph S02Ph PhSOz (18) Reagents i BuLi THF -78 "C 30 min; ii MeI; iii 3-CIC6H4C03H CCI, A 48 h Scheme 29 Other Anions and their Equiualents. The use of higher order mixed organocuprates in organic synthesis has been reviewed.46 The reduction of magnesium chloride by lithium metal at 0°C to give very activated magnesium has been described?' The use of ultrasound in accelerating the formation of alkyllithiums under rather mild conditions has found applications in the reaction of Scheme 30 as well as in aldol and alkylation rea~tions.~~,~~ .HO R ArCH2C1 + Ar'COR -CAr A ArCH=CHAr' Ar' 100% E Z = 70:30-98:2 Reagents i Li sand 2% Na Et,O 0 "C ultrasound; ii 4-MeC6H4S03H Scheme 30 Many workers continue to report examples of the addition of organometallic reagents to carbonyl compounds. A particular favourite this year has been the enantioselective addition of diethylzinc to aldehydes in the presence of chiral catalysts generally amino alcohols including ephedrine derivatives and (19).50,51 44 G.Zweifel and W. Leong J. Am. Chem. Soc. 1987 109 6409. 45 M. Yamamoto K. Suzuki S. Taneka and K. Yamada Bull. Gem. SOC.Jpn. 1987 60,1523. 46 B. H. Lipshutz Synthesis 1987 325. 47 T. P. Burns and R. D. Rieke 1. Org. Chem. 1987 52 3674. 48 1. C. Burkow L. K. Sydnes and D. C. N. Ubeda Acta Chem. Scand. Ser. B 1987,418 235. 49 J. Einhorn and J. L. Luche J. Org. Chem. 1987 52 4124. 50 P. A. Chaloner and S. A. R. Perera Tetrahedron Letr. 1987 28 3013. '' K. Soai S. Yokoyama K. Ebihara and T. Hayasaka J. Chem. SOC.,Chem. Cornmun. 1987 1690. P. A. Chaloner In the asymmetric addition of Grignard reagents to benzaldehyde in the presence of chiral diamines such as (20) the addition of aryloxyaluminium dihalides enhances the optical yield; the function of the aluminium is thought to be to coordinate the oxygen of the aldehyde.52 The chiral amide (21) effected enantioselective deproto- nation of (22) with about 70% optical efficiency (Scheme 31).The products of the reaction with ethanal were used in a synthesis of (+)-~itrinin.’~ I I OMe OMe li + “‘O@JO OMe 0 OMe 0 70% e.e. 74% e.e. 3 1 Reagent i MeCHO Scheme 31 Two new reactions involving lanthanide organometallics have proved interesting. Alkyl and aryl lanthanum triflates may be generated in situ from La(OTf) and RLi; they react readily with tertiary amides to give excellent yields of ketones.54 Addition of organocerium compounds to SAMP hydrazones (23) proceeds with good diastereoselectivity (Scheme 32) leading to a general synthesis of chiral arnine~.~~ Tetraalkyllead compounds are proving to be a new class of stable storeable and selective alkylating agents.Coupling with chiral aldehydes in the presence of titanium( IV) chloride gives good diastereoselectivity (Scheme 33),56whilst coupling with acyl halides in the presence of a palladium(0) complex gave ketones.57 52 K. Tomioka M. Nakajima and K. Koga Tetrahedron Lett. 1987 28 1291; Chem. Lett. 1987 65. 53 A. C. Regan and J. Staunton J. Chem. Soc. Chem. Commun. 1987 520. 54 S. Collins and Y. Hong Tetrahedron Lett. 1987 28 4391. 55 S. E. Denmark T. Weber and D. W. Piotrowski J. Am. Chem. SOC.,1987 109 2224. 56 Y.Yamamoto and J. Yamada J. Am. Chem. Soc. 1987 109 4395. 57 J. Yamada and Y. Yamamoto J. Chem. SOC.,Chem. Commun. 1987 1302. Synthetic Methods 93% d.e. (23) Reagents i BuLi CeCI, THF -78 "C; ii CICOOMe 20 "C Scheme 32 Phx CHO -Ph %Et P h L Et OH OH 93?'a 7% Reagents Et,Pb TiCI4 -78 4 -60 "C Scheme 33 Zinc homoenolate esters may be generated by reaction of zinc(rr) chloride with (24). The intermediate (25) is a three carbon nucleophile with general synthetic utility.'& Direct geminal dimethylation of aryl aldehydes may be accomplished using Me2TiC12. The addition of two different alkyl groups by the sequence of Sch6me 34 should prove val~able.'~ XZn noR Reagents i BuLi; ii Me,TiC12 Scheme 34 Two new and rather general syntheses of amines have been described.In the first organolithiums are reacted with benzylmethylene hydroxylamine which acts as a synthon for +CH2NH+.60 Primary amines were synthesized by the reaction of Grignard reagents with a bis(trimethylsily1)aminomethylating agent (Scheme 35).61 58 E. Nakamura S. Aoki K. Sekiya H. Oshino and I. Kuwajima J. Am. Chem. SOC.,1987 109 8056. 59 M. T. Reetz and S.-H. Kyung Chem. Ber. 1987 120 123. 6o A. Basha and D. W. Brooks J. Chem. SOC.,Chem. Commun. 1987 305. 6L H. J. Bestmann G. Wolfel and K. Mederer Synthesis 1987 848. P. A. Chaloner . .. ... CH,=NOCH,Ph -R'CH2NR2R3 MeOCH,N(SiMe,) -% RCH,N(SiMe,) 2RCH,NH,+CI-Reagents i R'Li Et20 -40 "C; ii R'Li Et20 -40 +0 "C; iii R3X THF 25 "C; iv RMgX Et,O 0 440 "C; v HCI H20 Scheme 35 Methyleneation and Alkylideneation.Two new metals have been added to the armoury of those involved in methyleneation of carbonyl compounds. The use of the uranium derivative (26) was extremely effective even for readily enolizeable ketones giving readily isomerized alkenes.62 Methyleneation of enolizeable carbonyl compounds was also catalysed by ceriurn(Ir1) chloride in a modification of the Peterson reaction (Scheme 36).63 R R . R OH ii iii or iv '>-R''O R1cSiMe3 R' 6 1-98 Yo Reagents i Me3SiCH2Li CeCl, THF -78 "C; ii HF MeCN HzO;iii HF MeCN py H,O; iv KH THF Scheme 36 The Wittig and Wittig-Horner reactions have also seen considerable activity this year. In particular workers have been seeking methods to carry out the reaction under milder conditions or to force unwilling reactions (Scheme 37); techniques used include high pressures,64 gas-liquid phase-transfer catalysis,65 and the use of ultrasound-activated barium hydroxide as the base.66 Ph3P= CHCOOEt -&cooEt + A 96Yo PhCH(R')CHO + (EtO),P(0)CH,COR2 -% PhCH(R')CH=CHCOR' Reagents i 9 kbar xylene 50 "C 30 h; ii K2C03 MeOH polyethylene glycol carbowax 6000 130 "C 5 torr 1.5 h; iii Ba(OH)2 ultrasound dioxan Scheme 37 62 A.Dormond A. El Bouadili and C. Moise J. Org. Chem. 1987 52 688. 63 C. R. Johnson and B. D. Tait J. Org. Chem. 1987 52 281. 64 N. S. Isaacs and G. N. El-Din Tetrahedron Lett. 1987 28 2191. 65 E. Angeletti P. Tundo and P. Venturello J. Chem.SOC.,Perkin Trans. I 1987 713. 66 J. V. Sinisterra A. Fuentes and J. M. Marinas J. Org. Chem. 1987 52 3875; C. Alvarez-Ibarra S. Arias G. Banon M. J. Fernandez M. Rodriguez and V. Sinisterra J. Chem. Soc, Chem. Commun. 1987 1509. Synthetic Methods 255 Stereoselectivity has also been to the fore. The E-selective alkylideneation of aldehydes by RCHI is accomplished via gem-dichromium reagents derived from reduction by chromium( 11) chloride.67 E-Selectivity was also high in reactions of P-diphenylphosphino propanoic acid (Scheme 38) the stereoselection being explained by steric interactions in the betaine.68 Ph2hCH2CH,COOH -RCH=CHR' + Ph2P(0)CH2CH2COO-LR Reagents i base CH,CI,; ii R'CHO Scheme 38 Miscellaneous. Several new pinacol-type reactions of carbonyl compounds have been reported.Titanium on graphite prepared from titanium( 11) chloride and lamellar potassium/graphite proved to be a universal reducing agent for the coupling of carbonyl compounds to give alkenes or diols (Scheme 39).69The complex formed R' R2 I "& 7&96% R2)=o R2 R' \i i R2 R2 or R1-t-+R1 Rg2 R2 R' OH OH 80-95'/! 64-9 1 '/o R' R2 = Ar H R',R2 = H alkyl Reagents i TiCI, CsK THF A; ii TiC14 C8K THF 0°C Scheme 39 from Cp,TiCl and Bu'MgCl was selective for the pinacolization of aromatic and a,S-unsaturated aldehydes to give mainly threo- products.'' The use of ytterbium metal gave selectively either reduction or coupling according to the mole ratio of the reactants7' Solvent complexes of niobium( 111) chloride were useful in coupling imines with carbonyl compounds with moderate diastereoselectivity (Scheme 40).72 Vicinal diamines could be obtained from nitriles or N-trimethyl~ilylimines.~~ Several one-carbon homologations of carbonyl compounds have been described.Substitution on (27) followed by reduction gave a homologated aldehyde in good to excellent yields (Scheme 41).74A samarium iodide-induced masked formylation of carbonyl compounds (Scheme 42) is thought to proceed via a radical process.75 67 T. Okazoe K. Takai and K. Utimoto J. Am. Chem. SOC. 1987 109 951; K. Takai K. Kataoka T. Okazoe and K. Utimoto Tetrahedron Lett. 1987 28 1443. 68 H. Daniel and M. Le Corre Tetrahedron Lett. 1987 28 1165. 69 A.Furstner and H. Weidmann Synthesis 1987 1071. 70 Y. Handa and J. Inanaga Tetrahedron Lett. 1987 28 5717. 71 Z. Hou K. Takamine Y. Fujiwara and H. Taniguchi Chem. Lett. 1987 2061. 72 E. J. Roskamp and S. F. Pedersen J. Am. Chem. Soc. 1987 109 6551 73 E. J. Roskamp and S. F. Pedersen J. Am. Chem. SOC.,1987 109 3152. 74 M. Ceruti 1. Degani and R. Fochi Synthesis 1987 79. 75 M. Matsukawa J. Inanaga and M. Yamaguchi Tetrahedron Lett. 1987 28 5877. P. A. Chaloner R' R HO threo erythro = 3 1-83 1 Reagents i NbCl, dme THF 1 min; ii R2COR3 30 min Scheme 40 ask CHRlR2 R2 S RZ Reagents i BuLi THF -78 "C; ii H[BF4] Et,O MeCN 25 "C; iii Na[BH4] 0 "C; iv HgO H20 H[BF4] Scheme 41 73-77% Reagents SmI, C,H, HMPT 25 "C 5 min Scheme 42 Cyc1ization.-Free radical cyclizations continue to attract considerable attention and the use of such reactions in synthesis has been reviewed.76 Samarium(I1) iodide has been particularly useful as the initiator of such processes and a new and convenient preparation has been described.77 For example the samarium iodide-mediated cyclization of iodoalkyl ketoesters and ketoamides proceeds with good stereoselec- tivity (Scheme 43);the kinetically favoured ring closure from the more accessible face of the chelated ketyl intermediate is supposed to ~redominate.~~ Asymmetric induction was also noted in intramolecular Reformatsky-type reaction^.^' Eneynes have been a topic of considerable investigation over the last year and several new cyclizations have emerged.In the presence of a nickel/chromium 76 M. Ramaiah Tetrahedron 1987 43 3541. 77 T. Imamoto and M. Ono Chem. Lett. 1987 501. 78 G. A. Molander J. B. Etter and P. W. Zinke J. Am. Chem. SOC.,1987 109,453; G. A. Molander and J. B. Etter Synth. Commun. 1987 17 901; G. A. Molander and C. Kenny Tetrahedron Lett. 1987 28 4367. 79 G. A. Molander and J. B. Etter J. Am. Chem. SOC.,1987 109 6556. Synthetic Methods 0 Srn 3+ I - OH COOEt.-ttPhvia 'R' Y d.e. = >200:1 I Reagents SmI, THF -78 "C Scheme 43 Reagents [ Ni(PPh,),Cl,] CrCl, THF 25 "C Scheme44 catalyst (28) was cyclized to (29) the chromium(I1) salt acting as a one-electron reducing agent (Scheme 44). Five- and six-membered rings could be produced with equal facility.80 Reductive cyclization of 1,6- and 1,7-eneynes occurs in the presence of a palladium(0) catalyst with polymethylhydrosiloxase acting as the reductant (Scheme 45).81 Stereospecific dicobalt octacarbonyl-mediated eneyne cyclization was used in an enantiospecific synthesis of an analogue of 6a-carbocycline (Scheme 46).82 Sequential intramolecular Michael addition followed by alkylation of /3-ketoester ynones resulted in the synthesis of tricyclic compounds shown in Scheme 47.83 Reagents [ Pd(dba),] polymethylhydrosiloxane MeCOOH CaHa 25 "C Scheme 45 %Me3 SiMe3 '.p + HO' H3$-J$o 'H R iR HO Reagent [co,(co)8] Scheme 46 80 B.M.Trost and J. M. Tour J. Am. Chem SOC.,1987 109 5268. 81 B. M.Trost and F. Rise J. Am. Chem. Soc. 1987 109 3161. a2 P. Magnus and D. P. Becker J. Am. Chem. Soc. 1987 109 7495. 83 J.-F. Lavellee and P. Deslongchamps Tetrahedron Left 1987 28 3457. P. A. Chaloner A"'" -& OTS H H 60% 15 Reagents Cs,[CO,] DMF 65 "C Scheme 47 Cycloadditions and Annu1ations.-Reactions Forming Six-membered Rings. The gener- ation and uses in Diels- Alder reactions of orthoquinodimethanes have been reviewed.84 The Diels- Alder reactions of 1,3-dienyl boronates have provided a new route to functionalized carbocycles such as (30) (Scheme 48); stereoselection was m~derate.~' An inverse type of hetero-Diels- Alder reaction has been used in the synthesis of 3-deoxy-2-glyculosonatesand C-aryl glycosides (Scheme 49).86 0 P i_ J3 OOMe 1 1.8 endo exo Reagents i C,H,Me 100 "C,100 h; ii Me,NO Scheme 48 A one-pot four-component annulation of cyclohexanone has been described (Scheme 50).The initial product (31) was readily cleaved using lead(1v) ethanoate as the ~xidant.~' Biomimetic syntheses of polycyclic quinones have been noted; the polyketide intermediate (32) (Scheme 51) closely resembles the intermediates pro- posed in the biosynthetic pathway.88 84 J. L. Charlton and M. M. Alauddin Tetrahedron 1987 43 2873. M. Vaultier F. Trichet B. Carboni R. W. Hoffrnann and I. Denne Tetrahedron Lett. 1987 28 4169. 86 R. R. Schmidt W. Frick B. Haag-Zeino and S. Apparao Tetrahedron Lert. 1987 28 4045. 87 G. H. Posner E. Asirvatharn K. S. Webb and S.-S.Jew Tetrahedron Lett. 1987 28 5071. 88 M. Yamaguchi K. Haseba M. Uchida A. Irie and T. Minami Tetrahedron Lert. 1987 28 2017. Synthetic Methods foBn / foBn RK P h S h OMe A. 0 *COOMe OCOMe R f7-*,0'0 Ph C-aryl glycosides = Me or 3-deoxy-2-heptulosonates OMe COOMe Reagents i MeCOO-Ar 5.2 kbar 60 "C 30 h; ii ==( 5.2 kbar 48 h 60 "C OMe Scheme 49 77% trans cis = 0.7 (31) Reagents i LiSnBu3 THF -78 "C; ii CH,=CHCOEt THF -78 "C; iii MeCHO THF DMF -65 "C; iv Pb(OCOMe), C6H6 A 3.5h Scheme 50 COOMe COOMe i ii iii COOMe COOMe 0 00 COOMe COOMe (32) Reagents i ACOOMe Li+ Na+ THF HMPT 25°C; ii Ca(OCOMe), MeOH 25°C; iii K2[C03] MeOH 25 "C Scheme 51 I? A. Chaloner Chiral non-racemic cyclohexanediols have been prepared by the pathway shown in Scheme 52; the Lewis acidity of the tin is the controlling factor in determining the diastereo~electivity.~~ R,' RZ OH R2 CHO H R R' R2 = H or alkyl 4 1-50 :1 diastereomer ratio Reagents SnF, THF 25 "C Scheme 52 Reactions Forming Fivemembered Rings.Cycloaddition reactions of nitrones have been much in vogue this year and both intra" and intermolecular reactions have proved useful'' (Scheme 53). Nitrile oxides (33) gave similarly successful results in reaction with the acetaldehyde enolate anion produced by treatment of tetrahy- drofuran with butyl lithium and cycloreversion (Scheme 54).92 An enantioselective reaction (Scheme 55) occurred between (34) and Me,C-CrN+-O-; L-Selectride reduction allowed release of the chiral auxi1ia1-y.~~ Oximes are known to react readily with Michael acceptors; in the reaction of (35) (Scheme 56) the process was intramolecular and the product nitrone could be trapped both intra- and inter- molecularly.94 96 4 0 Reagents i MeNHOH.HC1 K,[C03] PhMe A Scheme 53 89 G.A. Molander and D. C. Shubert J. Am. Chem. SOC.,1987 109 576. 90 R. Annunziata M. Cinquini F. Cozzi and L. Raimondi Tetrahedron 1987 43 4051. 91 R. L. Funk and J. U. Dagget Heterocycles 1987 26 2175. 92 L. D. Nunno and A. Scilimati Tetrahedron 1987 43 2181. 93 D. P. Curran B. H. Kim H. P. Pujasena R. J. Loncharich and K. N. Houk J. Org. Chem. 1987,52,2137. 94 P. Armstrong R. Grigg W.J. Warnock and S. Surendrakumar J. Chem. SOC.,Chem. Commun. 1987 1325 1327. Synthetic Methods 26 1 OH 83-100% Reagents i THF 25 "C; ii Na[OMe] MeOH; iii Na[OH] EtOH Scheme 54 Reagents i 25 "C 6 h; ii L-Selectride Scheme 55 Dihydrofurans have been synthesized by reaction of dibromodeoxybenzoin with alkenes in the presence of samarium(11) iodide. The reaction (Scheme 57) is formally a 1,3-dipolar cycloaddition to a ketocarbenoid but the mechanism is not clear since the zinc carbenoid was not a suitable s~bstrate.~' Atom-transfer cycloaddition led to an unusual synthesis of methylenecyclopentanes; the ratio between 5-ex0 and 6-end0 processes ranged from 7 1 to 100 0 (Scheme 58).96 COOMe COOMe + NMe -Hh,oeo NMe H HO (jOH (35) 90% Reagents PhMe 110 "C 3 h Scheme 56 Ph Ph Ph 80O/O Reagents SmI, THF HMPT Scheme 57 95 S.Fukuzawa T. Fujinami and S. Sakai J. Chem. SOC. Chem. Commun. 1987 919. 96 D. P. Curran and M.-H. Chen J. Am. Chem. Soc. 1987 109 6558. P. A. Chaloner R = H or SiMe,; R' = H or alkyl; R2 = carbonyl CN or SOzPh Reagents Bu,SnSnBu, hv C,H6 70-80 "C Scheme 58 <OR' + Me3Si-=-R2 -!+ BrZn ZnBr R'O R'O' " 51-91°/o Reagents i 100 "C 30 h; ii [Pd(PPh3)J 65 "C 24 h Scheme 59 A one-pot synthesis of methylenecyclopentenes has been achieved via an allyl-metallation of 1-silylalkynes by 2-bromozincmethyl-2-propenyl ether followed by palladium-catalysed cyclization (Scheme 59).97Manganese( 111)-promotedannula-tion of enol ethers and esters to fused or spiro cyclopentenones has proved very efficient and a closely related process was used in furannulation (Scheme 60).98 76Yo OMe 92% Reagents i Mn(OCOMe), MeCOOH 23 "C 5 min then 40 "C 30 min; ii NaH PhMe A; iii HCl HzO; iv [Mn,0(OCOMe)7]; v H+ Scheme 60 Other Ring Sizes.The preparation of cyclopropanes by reactions of transition metal carbene complexes with alkenes has been reviewed.99The cyclopropanation of allylic alcohols is promoted by samarium metal or samarium amalgam; the degree of stereocontrol obtained is dependent on the substituents but is generally high."' 97 J. van der Louw J. L. van der Baan F. Bickelhaupt and G. W. Klumpp Tetrahedron Left.,1987,28,2889. 98 E. J. Corey and A. K. Ghosh Tetrahedron Lett.1987,28 175; Chem. Lett. 1987 223. M. Brookhart and W. B. Studabaker Chem Rev. 1987 87 411. 100 G. A. Molander and J. B. Etter J. Org. Chem. 1987 52 3942. Synthetic Methods 263 a$-Unsaturated acetals from dibenzyl threitol(36) undergo diastereoselective cyclo- propanation under Simmons-Smith conditions (Scheme 61)."' Two stereoselective syntheses of p-lactams have been reported by Dutch workers (Scheme 62). In the first an a-iminoester is reacted with diethylzinc to give exclusively the trans-product (37).'02 The reaction of zinc enolates with imines gave (38).'03 Preparative scale syntheses of bicyclobutylidene methylenecyclobutane and cyclo- butanone have been described (Scheme 63); the one-pot procedure compares favour- ably with previously reported rneth~ds."~ P hCH 2 OCH 2 ,C H 2 OCH 2 Ph P hCH 2 OCH 2 ,CH2 OCH2 Ph PhCH20C H 2 ,C H2OC H 2 Ph 7-7 77 77 0 + &>.9 1ii 1 75 % A>. 51% e.e. Reagents CH212 I, Zn/Cu Et,O A; ii HCl H20 MeOH Scheme 61 R'O R iii iv v vi Et2 NCH2COOEt Reagents i Et2Zn; ii -80 -+25 "C;iii LDA C6H6 25 "C; iv ZnC1,; v PhCH=NMe A; vi H,O Scheme 62 101 E. A. Mash and K. A. Nelson Tetrahedron 1987 43 679. 102 M. R. P. van Wet J. T. B. H. Jastrzebski W. J. Kaver K. Goubitz and G. van Koten Red. Trau. Chim. Pu~s-Bus,1987 106 132 103 J. T. B. H. Jastrzebski F. H. van der Steen and G. van Koten Recl. Trau. Chim. Pays-Bas 1987,106,516. L. Fitjer and U. Quabeck Synthesis 1987 299. 264 P.A. Chaloner 67-7 1Yo Reagents i K[OCMe3]; ii 02,50°C; iii (CH20),; iv 0, MeOH CH,CI,; v (NH2)2CS Na[OH] Scheme 63 Several new and high yielding syntheses of medium ring compounds have been reported this year. The [6 + 31 cycloaddition shown in Scheme 64 gave a nine- membered ring presumably via a trimethylenemethane complex.'o5 The [3 + 41 and [3 + 51 annulations of Scheme 65 involve a dianion synthon.lo6 Intramolecular nickel-catalysed cycloadditions of bis-dienes may lead to the formation of eight-membered rings with high yield and excellent diastereoselectivity. The reaction was used in an approach to the taxane ~keleton."~ ( + -m SiMe3 R R 68% Reagents Pd(OCOMe)2 P(OCHMe2)3 PhMe 80-85 "C,3-10 h Scheme64 11 SiMe X2Sn0 + Me3SiX + RQRl SnX, -hR1 Ill 1" n = lor2 Reagents i SnF,; ii RCOCH2(CH2),COR' Scheme65 B.M. Trost and P. R. Seoane J. Am. Chem. SOC.,1987 109 615. 106 G. A. Molander and D. C. Shubert J. Am. Chem. SOC. 1987 109,6877. 107 P. A. Wender and M. L. Snapper Tetrahedron Lett. 1987 28 2221. Synthetic Methods Rearrangements and Fragmentations.-The enantioselective [2,3] Wittig ring con- traction induced by chiral bases was applied in the synthesis of (+)-aristolactone (Scheme 66)."' 82% 65% e.e. Reagents Ph ANAPh THF -20°C I Li Scheme66 Lewis acid-catalysed rearrangement of epoxysilyl ethers such as (39) gave aldols (Scheme 67). The catalytic reaction generally gave superior yields of the aldol to the analogous stoicheiometric version.'o9 The ring expansion of ketones to a-methoxy and a-phenylthioketones was also achieved in the presence of a Lewis acid (Scheme 68).'lo A radical-promoted rearrangement of bromomethyl p-ketoesters was also instrumental in promoting ring expansion generally in good yield (Scheme 69)."' RZ i ii or iii R3 OH 0 R14&3 OSiMe3 12-100% (39) Reagents i Me,SiI; ii Me,SiOTf; iii TiCl Scheme 67 SOzPh 11 _.WSPh a0 + clir H 92% \ iii iv 79'/o Reagents i PhSO,CH(Li)SPh Et,AICl hexane; ii Et,AlCI CH>Cl, -20 "C; iii PhSO,CH( Li)OMe Et,AICl THF -78 "C; iv Et,AlCl CH,Cl, -78 "C Scheme68 108 J. A. Marshall and J. Lebreton Terrahedron Lett. 1987 28 3323. 109 K. Suzuki M. Miyazawa and G. Tsuchihashi Tetrahedron Lett.1987 28 3515. 110 B. M. Trost and G. K. Mikhail J. Am. Chem. SOC.,1987 109 4124. 111 P. Dowd and S.-C. Choi J. Am. Chem. SOC.,1987 109 3493. 266 P. A. Chaloner COOMe 7 1O/O trace Reagents i NaH; ii CH2Br2 A; iii Bu,SnH AIBN C6H, A Scheme 69 Insertion of the metal carbonyl into the three-membered ring of a cyclopropene to give a metallocyclobutene is the first step in the catalytic rearrangement of these compounds to highly substituted naphthols (40) (Scheme 70).' '*An entirely novel synthetic approach to biphenyls has been described (Scheme 71). Two arenes are initially joined by a Wittig reaction to give a stilbene derivative which is then coupled to give a phenanthrene (41) using iodine. The biphenyl is released by ozono~ysis.''~ OH ph'pOMe Ph __* 40 yo aPh Ph Ph OH (40) Reagents [Cr(CO),] Bu,O 3 h A Scheme 70 Reagents (CH,),N, MeCOOH A; ii (EtO),P Na[OMe]; iii hv 1,; iv 03,MeOH; v KI MeCOOH Scheme 71 3 Functional Group Modifications Oxidation.-Additions to C=C.There have been further reports of new methodology for the conversion of alkenes into epoxides. Epoxidation of a,@-unsaturated carbonyl compounds by hydrogen peroxide or alkyl hydroperoxides is 112 M. F. Semmelhack S. Ho M. Steigerwald and M. C. Lee J. Am. Chem. SOC.,1987 109 4397. I I3 T. Ho C. Shu M. Yeh and F. Chen Synthesis 1987 795. Synthetic Methods promoted by fluoride ion; the method is also applicable to unsaturated nitriles and nitro compounds.' l4 Sulphamyl oxaziridines (42) have been used in the preparation of a-siloxyepoxides and a-hydroxycarbonyl compounds.Enantioselective versions of the reaction gave rather modest optical yields.' l5 A modified version of the Sharpless reagent has been shown to give excellent enantioselectivities in asymmetric epoxidation with a much reduced reaction time (Scheme 72). The epoxidation of methyl gibberellate fails with the normal Sharpless conditions but succeeded with the modified reagent.' l6 The kinetic resolution pro- cedure effected by Sharpless epoxidation has been used to resolve E-fluoroalkyl ally1 alcohols such as (43)."' i ii iii iv 71% -OH OH 95% e.e. Reagents i [Ti(OCHMe2)4],L-(+)-DET,CaH, SiOz CH2C12 -20 "C 10 min; ii Me3COOH -40 "C 1 h; iii tartaric acid H20 -20 -* 25 'C; iv Na[OH] H,O Et20 0 "C 30 min Scheme 72 Further enantioselective cis-dihydroxylations of alkenes by osmium(vrI1) oxide have been reported.In the presence of the chiral diamine (M),optical yields up to 99% were achieved.lI8 Oxidation of alkenes to 1,2-diethanoates was accomplished using benzenetellurinic anhydride in ethanoic acid."' Other Oxidations. The salts tetrabutylammonium and tetrapropylammonium perruthenate have been prepared and used as new catalysts for alcohol oxidation using NMO as oxidant. Primary alcohols are converted into aldehydes and sec- ondary alcohols into ketones whilst epoxides alkenes indoles and trimethylsilyl- or tetrahydropyranyl-protected alcohols are unaffected.12' The Swern reagent Me,SO/ClCOCOCl oxidizes the trimethylsilyl ethers of primary and secondary alcohols to carbonyl groups.However a useful selectivity difference on steric grounds has emerged in that 1,l -dimethylethyldimethylsilyl ethers are unaff ected.121 Amines have been dehydrogenated to imines under mild conditions by the Swern reagent.'*' This year has been marked by the emergence of a number of practical and high yielding procedures for the oxidation of unfunctionalized benzylic methylene groups. 114 M. Miyashita T. Suzuki and A. Yoshikoshi Chem. Letr. 1987 285. 115 F. A. Davis and A. C. Sheppard J. Org. Chem. 1987 52 954. 116 Z.-M. Wang and W.-S. Zhou Tetrahedron 1987 43 2935. 117 Y. Hanzawa K. Kawagoe M. Ito and Y. Kobayashi Chem. Pharm. Bull 1987 35 1633.118 K. Tomioka M. Nakajima and K. Koga J. Am. Chem. SOC.,1987 109 6213. I19 N. Kambe T. Tsukamoto N. Miyoshi S. Murai and M. Sonoda Chem. Lett. 1987 269. 120 W. P. Griffith S. V. Ley G. P. Whitcombe and A. D. White J. Chem. SOC.,Chem. Commun. 1987 1625. 121 C. M. Alfonso M. T. Barros and C. D. Maycock J. Chem. SOC.,Perkin Trans. 1 1987 1221. 122 D. Keirs and K. Overton J. Chem. SOC.,Chem. Commun. 1987 1660. P. A. Chaloner Reagents have included chromium(v1) oxide/ alkyl hydr~peroxide'~~ and per- manganate under phase-transfer condition^.'^^ Methyl groups were oxidized to methanoyl groups using cerium( IV) methane sulphonate or trifluoromethane sul- phonate'25 or iron(11) chloride and 2-methyl-2-iodopropane in dimethylsul-phoxide/ trifluoroethanoic acid.'26 lodine(II1) reagents have been used (Scheme 73) for the oxidation of silyl enol ethers to a-methoxyketones (45).12'Related species were used in the procedure of Scheme 74 to prepare alkynyl methane sulphonates and 4-methylphenyl sulphonates; these are the first acetylenic esters of any kind to be synthesized.'28 Reagents {PhIO}, BF .Et,O MeOH -70 "C Scheme 73 PhI(OCOMe) + RSO,H.H,O OHII Ph-I-OS0,R ii +-Ph-I-CEC-R' R-CrC-0,SR RS03- Reagents i MeCN 25 "C 30 min; ii R'-CZC-H THF desiccant; iii Cu[OTfl Scheme 74 Oxidation of N-acylpyrrolidines and piperidines with iron(1x) and hydrogen peroxide or an iron oxygen complex has been described in detail and the pro- cedure has been extended to tetrahydroquinolines to allow the synthesis of cyclic hydroxamic acids."' Reduction.-Hydrogenation of Carbon-Carbon Multiple Bonds.The stereoselective hydrogenation of alkenes using cationic rhodium or iridium complexes as catalysts has been reviewed with particular reference to reductions the stereochemistry of which is directed by the presence of a polar functional The enantioselective reduction of substrates other than dehydroamino acids has been a long-standing problem and some progress in this area has been made this year. Unsaturated carboxylic acids such as (46) were reduced in the presence of a ruthenium complex of BINAP (47) with up to 88% optical efficiency (Scheme 75)I3l and 123 J. Muzart Tetrahedron Lett. 1987 28 2131 2133. 124 S. M. Cannon and J.G. Krause Synthesis 1987 915. 125 R. P. Kreh R. M. Spotzitz and J. T. Lundquist Tetrahedron Left. 1987 28 1067. 126 E. Vismara F. Fontana and F. Minisci Gazz. Chim. Ital. 1987 47 135. 127 R. M. Moriarty 0. Prakash M. P. Duncan R. K. Vaid and H. A. Musallam J. Org. Chem. 1987 52 150; R. M. Moriarty M. P. Duncan and 0. Prakash J. Chem. SOC.,ferkin Trans. I 1987 1781. I28 P. J. Stang B. W. Surber Z.-C. Chen K. A. Roberts and A. G. Anderson J. Am. Chem. SOC.,1987 109 228. 119 S. Murata M. Miura and H. Narnura J. Chem. SOC.,Perkin Trans. I 1987 1259; S.-I. Murahashi T. Oda T. Sugahara and Y. Musui J. Chem. SOC.,Chem. Commun. 1987 1471. 130 J. M. Brown Angew. Chem. Int. Ed. Engl. 1987 26 190. 131 H. Kawano Y. Ishii T. Ikariya M. Saburi S.Yoshikawa Y. Uchida and H. Kurnobayashi Tetrahedron Lett. 1987 28 190.5. Synthetic Methods 269 PArz TOoH -YOOH 86-88% e.e. (S) PArz COOH COOH (46) (47) Reagents H, Et3N [(47),Ru2CI4] Scheme 75 Reagents H2 [{(R)-(47)}Ru(OCOMe),] Scheme 76 MeOzClc....e R (49) [(BINAP)Ru(OCOM~)~] was an effective catalyst for reduction of (48) in 99% enantiomer excess (Scheme 76).'32 Diastereoselectivity in the reduction of itaconate esters (49) was excellent in the presence of an achiral rhodium(1) complex and racemic starting material underwent quite effective kinetic resolution in the presence of a chiral cata1y~t.I~~ Hydride reduction of a,/?-unsaturated carbonyl compounds generally occurs at the carbonyl group but again this year a number of contrary examples have been reported.The addition of organolanthanide complexes such as [CpSmC13(THF),] or [CPE~C~~(THF)~] to sodium borohydride gave a particularly selective reagent,'34 and [BH4]- gave efficient reduction of (50) when bound to an ion exchange resin (Scheme 77). In this latter case isolation of the reduced products required only filtration and e~aporati0n.l~~ The conjugate reduction of enones by phenylsilane in the presence of a molybdenum(o) catalyst was also applicable to unsaturated nitriles esters acids and amide~.'~~ 132 H. Takaya T. Ohta N. Sayo H. Kumobayashi S. Akutagawa S. Inoue I. Kasahara and R. Noyori J.Am. Chem. SOC.,1987 109 1596. 133 J. M. Brown and A. P. James J. Chem. SOC.,Chem. Commun.1987 181. 134 S. Komiyama and 0.'isutsumi Bull. Chem. SOC.Jpn. 1987 60,3423. 135 A. Nag A. Sarkar S. K. Sarkar and S. K. Palit Synth. Commun. 1987 17 1007. 136 E. Keinan and D. Perez J. Org. Chem. 1987. 52 2576. P. A. Chaloner 95% I::I -Q54% cis NC COOEt COOEt NCk NC COOEt NC COOEt (50) Reagents [BH4]-/resin seralite SRA-400 EtOH 25 "C Scheme 77 The synthesis and selected reductions of conjugated nitroalkenes has been reviewed.'37 The asymmetric reduction of 2-aryl-1 -nitropropenes has been effected by fermenting baker's yeast (Scheme 78). The optical purity of the product (51) was assessed as between 89 and 98'/0.'~* R RflNo2 R\yrNH2 -R\yrNHMTPA )-?-NO2 H H H (51) Reagents i Baker's yeast; ii Li[AIH4]; iii MTPACI Scheme 78 Hydrogenation of Carbonyl Compounds.In general it has proved easier to reduce aldehydes than ketones but a contrary example has been noted this year. Magnesium metal in methanol reduces 2-hydroxyphenylethanone efficiently in the presence of 2-hydroxyben~aldehyde.'~~ Facile conversions of carboxylic acids into aldehydes have been noted using thexylbromoborane/dimethylsulphide in carbon disul-phide.14' Esters were reduced to aldehydes using lithium aluminium hydride in the presence of diethylamine; the aluminium hydride generated in the initial attack is held in a stable amine/alane c~mplex.'~' Stereoselective reactions have again been widely reported. Synthesis of optically pure amino alcohol derivatives by yeast reduction of (52) has been and the sulphur functionality of (53) did not affect efficiency.In the latter case the product was used in a synthesis of the pine saw-fly pher0m0ne.l~~ A novel reaction using 'non-fermenting' baker's yeast without nutrients and in tap water proved equally successful (Scheme 79).14j 137 G. W. Kabalka and R. S. Varma Org. Prep. Proc. Int. 1987 19 283. 138 H. Ohta K. Ozaki and G. Tsuchihashi Chem. Lett. 1987 191. 139 M. Bordoloi and P. Sarmah Chem. Ind. (London) 1987 459. 140 J. S. Cha J. E. Kim S. Y. Oh J. C. Lee and K. W. Lee Tetrahedron Lett. 1987 28 2389; J. S. Cha J. E. Kim and K. W. Lee J. Org. Chem. 1987 52 5030. 141 J. S. Cha and S. S. Kwon J. Org. Chem. 1987 52 5486. 142 T. Fujisawa H. Hayashi and Y.Kishioka Chem. Lett. 1987 129. 143 T. Itoh T. Sato and T. Fujisawa Nippon Kagaku Kaishi 1987 1414. 144 D. Seebach S. Roggo T. Maetzke H. Braunschweiger J. Cercus and M. Kreiger Helu. Chim. Acta 1987 70 1605. Synthetic Methods 271 0 EtOzC EtozcQU U 86‘/o >99’/0 diastereoselective >99% enantioselective Reagents Baker’s yeast tap water 30 “C 10 h Scheme 79 Chiral additives for or chiral complexes of known reducing agents have continued to be popular and (54) (55) and (56) have shown some excellent selec- tivjty. 145-147 Asymmetric hydrogenation of P-ketoesters in the presence of [(BINAP)Ru(OCOMe)2] gave p-hydroxy esters in 98-100% enantiomer excess.14* ,;-a. K+ N>B’ /BH \ R (541 (55) CHz-S-S-CHl HtC-NH Ph/Li[BH4] I I COOH COOH (56) 145 H.C. Brown B. T. Cho and W. S. Park J. Org. Chem. 1987 52 4020. 146 E. J. Corey R. K. Bakshi S. Shibata C. Chen and V. K. Singh J. Am. Chem. Soc. 1987 109 7925; E. J. Corey R. K. Bakshi and S. Shibata J. Am. Chem. Soc. 1987 109 5551. 147 K. Soai S. Niwa and T. Kobayashi J. Chem. Soc. Chem. Commun. 1987 801. 148 R. Noyori T. Ohkurna M. Kitamura H. Takaya N. Sayo H. Kumobayashi and S. Akutagawa J. Am. Chem. Soc. 1987 109 5856. I? A. Chaloner Other Reductions. The reduction of secondary and tertiary benzylic alcohols to hydrocarbons was accomplished using Me3SiC1/NaI/ MeCN; the method was applied in a short synthesis of (*)-art~rmerone.'~~ A mild and convenient reduction of organic halides occurs using a solution of samarium(11) iodide in THF containing HMPT.Aryl alkyl and steroidal halides were reduced.15' Denitrohydrogenation of nitro compounds is effected by triethylsilane in the presence of a Lewis acid such as S~CI,or AICI~.'~~ Methods for the stereospecific deoxygenation of epoxides to alkenes have been reviewed.15*Samarium(11) iodide may be used either for regioselective reduction of epoxides to alcohols,153or for complete deoxygenation (Scheme 80).'54 Mixed-solvent systems were crucial in the chemo-and regio-selective reductions using borohydride; the reaction tolerated carbamoyl carboxyl nitro cyano and bromo fun~tionalities.'~~ >2OO 1 regioisomeric excess I I Reagents i Sml, HMPT Me2NCH2CHzOH THF 25"C 1 min; ii SmJ,X; iii Me,NCH,CH,OH or glutaric anhydride; iv 2 SmI Scheme 80 Deoxygenation of pyridine N-oxides may be effected using a titanium(0) reagent even in the presence of a halogen s~bstituent.'~~ Both sulphoxides and pyridine N-oxides were reduced using either WCl,/BuLi or [MOO,(S,CNEt,),]/ PPh .1577158 a-Chelation-controlled hydride addition to acyclic alkoxy ketone oximes proceeds with anti-selectivity in a useful preparation of chiral primary amines (Scheme 81).159 .$ ,+ JH iorii + NH2 OMOM OMOM OMOM anri SY n Reagents i AIH, anti syn = 86 14 ii Li[AIH,] anti:svn = 81 19 Scheme 81 149 T. Sakai K. Miyata M. Utaka and A. Takeda Tetrahedron Lett. 1987 28 3817. 150 J. Inanaga M. Jshikawa and M.Yarnaguchi Chem. Lett. 1987 1485. 151 N. Ono T. Hashimoto T. X. Jun and A. Kaji Tetrahedron Lett. 1987 28 2277. 152 H. N. C. Wong C. C. M. Fok and T. Wong Heterocycles 1987 26 1345. 153 K. Otsubo J. Inanaga and M. Yamaguchi Tetrahedron Lett. 1987 28 4437. 154 M. Matsukawa T. Tabuchi J. Inanaga and M. Yarnaguchi Chem. Lett. 1987 2101. 's5 A. Ookawa H. Hiratsuka and K. Soai Bull. Chem. Soc. Jpn. 1987 60,1813. 146 M. Malinowski and L. Kaczmarek Synthesis 1987 1013. 157 T. Wen-Ming L. Ji-Sheng and T. H. Chan Huaxue Xuebao 1987,45 472. 158 X.-Y. Lu X.-C. Tao and J.-H. Sun Youji Huaxue 1987 376 378. I59 H. Iida N. Yamazaki and C. Kibayashi J. Chem. Soc. Chem. Commun. 1987 746. Synthetic Methods Ph (57) Acetophenone oxime 0-alkyl ethers were reduced enantioselectively (4&100% ) by lithium aluminium hydride in the presence of the amino alcohol borane complex (57) as catalyst.16' Non-redox Conversions.-Substitutions af sp3-Hybridized Carbon.The functionaliz- ation of chiral enolates has continued to be an area of much activity and silylation azidination and bromination have all been achieved with good enantioselectivity (Scheme 82).161*162 Phenyldimethylsilyl groups may be converted into hydroxyl groups with good retention of stereochemistry using Br,/ MeC02H/ MeC0,H or Hg(OCOMe),/MeCOOH/MeC03H at 25 0C.163 18-96% d.e. 67-86% 95- 100% 78-95% d.e. 99% e.e. OMe - OMe 0 NHN R' li-siMe2R iv v VI + R2 >96% e.e. R2 R2 Reagents i Bu,BOTf CH2CI2,NBS -78 "C; ii tetramethylguanidinium azide CH2C12 0 "C; iii Li[OH] THF H20; iv LDA Et20 0 "C; v RMe2SiOTf -78 "C 2 h -25 "C 10 h Scheme 82 A number of new routes for the conversion of alcohols into halides have been reported.Halides were prepared using [(Ph2PCX2)2]'64 and fluorides from primary halides using methanesulphonylfluoride caesium fluoride and 18-crown-6.16' A one-pot conversion of alcohols into amines was accomplished by the pathway of Scheme 83.'66 Primary alkyl halides were converted into fluorides using either copper( I) fluoride or tetrabutylammonium difl~oride.'~' 160 S. Hsuno Y. Sakurai K. Ito A. Hirao and S. Nakahama Bull. Chem. SOC.Jpn. 1987,60 395. 161 D. A. Evans J. A. Ellman and R. L. Dorow Tetrahedron Lett. 1987 28 1123; D.A. Evans and T. C. Britton J. Am. Chem. Soc. 1987 109 6881. 162 D. Enders and B. B. Lohray Angew Chem. Int. Ed. EngL 1987 26 351. 163 I. Fleming and P. E. J. Sanderson Tetrahedron Lett. 1987 28 4229. 164 S. P. Schmidt and D. W. Brooks Tetrahedron Lett. 1987 28 767. 165 K. Makino and M. Yoshida J. Fluorine Chem. 1987 35 677. 166 E. Fabiano B. T.Golding and M. M. Sadeghi Synthesis 1987 190. 167 N. Yoneda T. Fukuhara K. Yamagishi and A. Suzuki Chem Lett. 1987 1675. P. A. Chaloner PhCH,OH 2PhCH,N=PPh -!!+ PHCH2NH3+CI-68% Reagents i HN, C6H6 PPh, Me2CH02CN=NC0,CHMe2 THF 50°C; ii H20 50°C Scheme 83 The stereoselective synthesis of methyl- 1,2-thioglycosides (58) was accomplished using MeSSiMe3/BF,. The synthetic utility of the product has been greatly increased by recently developed methods for activation of the anomeric thioalkyl group (e.g.Scheme 84).'68,'69 AcO /OAc AcofioAc AcO OAc OAc BnO& BnO OBn SEt ii BnO Brio? + -0 /OH 87'/o a:p = 3.5:l 00 00 X X Reagents i MeSSiMe3 BF, CH,C12 ; ii Me03SCF3 4 A sieves Et20 Scheme 84 Substitution at sp2-Hybridized Carbon. Various routes to the preparation of aryl-amines have been noted this year. N-Phenylation of amines may be achieved using either Ph3Bi/Cu(OCOMe)2 or PhPb(OCOMe) with either Cu(OCOMe) or CU(OCOCF~)~ .'" Iodination of aromatic compounds by Lewis acid (AlCl or better GaCl,) catalysed transiodination with 2,6-diiodo-4-methylphenolhas been described.17' N-Fluoro(perfluoroalky1)sulphonimides were prepared in high yield from the sulphonimides and elemental fluorine.They were stable for long periods at room temperature in a fluoropolymer plastic container and proved to be excellent 168 P. Bosch F. Cambs E. Chamorro V. Gasel and A. Guerrero Tetrahedron Lett. 1987 28 4733; V. Pozsgay and H. J. Jennings Tetrahedron Lett. 1987 28 1375. 169 H. Lonn J. Carbohydr. Chem. 1987,6 301. I70 D. H. R. Barton N. Yadav-Bhatnagar J.-P. Finet and J. Khamsi Tetrahedron Lett. 1987 28 3111; D. H. R. Barton J.-P. Finet and J. Khamsi Tetrahedron Lett. 1987 28 887. 171 M. Tasturo T. Makashima and S. Hone J. Chem. Rex S 1987 342. Synthetic Methods OMe R (59) The fluorinating agents towards arene~.~~~regioselective demethoxylation of alkyltrimethoxybenzenes such as (59) to (60) was used in a synthesis of 0liveto1.”~ More examples of the enantioselective formation and hydrolysis of acid derivatives catalysed by enzymes have been reported this year.The uses of enzymes as reagents for organic synthesis have been ~eviewed.”~’ Particularly prominent have been reactions (Scheme 85) of meso-compounds such as (61).17’ In a strictly chemical process chiral( *)-carboxylic anhydrides such as (62) underwent kinetic resolution catalysed by diphenylboryl trifluoromethane ~u1phonate.l~~ H 1iii,iv 0 Reagents i Pig liver esterase pH 7 H,O; ii BH,.Me,S THF -10-20 “C 6 h; iii Li[BF,] Et,O A 2 h; iv MeOH A 0.5 h Scheme 85 0 OBPhz LOMe 2az 0 + Ph YOMe (62) Ph 90‘/o 99% d.e.(1 S 2R) Reagents i Ph,BOTf PhMe 0°C; ii CH2N2 Scheme 86 172 S. Singh D. D. DesMarteau S. S.Zuberi M. Witz and H.-N. Huang 1.Am. Chem. SOC.,1987,109,7194. 173 U. Azzana T. Denurra G. Melloni and G. Rassu J. Chem. SOC.,Chem. Commun. 1987 1549. 174 A. Akiyama M. Bednarski M.-J. Kim E. S. Simon H. Waldmann and G. M. Whitesides Chem. Brit. 1987 23 645. 175 G. Sabbioni and J. B. Jones J. Org. Chem. 1987. 52 4565. 176 M. Ohshima and T. Mukaiyama Chem. Left. 1987 377; M. Ohshima N. Mioshi and T. Mukaiyama Chem. Letf. 1987 1233. l? A. Chaloner New processes for the interconversions of carboxyl derivatives continue to be reported. Acids were easily converted into anhydrides amides esters and thioesters using 1,l '-oxalyldiimidazole (63) and 1,l '-oxalyldi( 1,2,4-triazole) (64); 177p178 (65) was also useful as an esterification reagent.'79 Selective deacetylation of anomeric sugar ethanoates was accomplished using tin alkoxides.'80 Guanidine effected instantaneous deacetylation of acetylated carbohy- drates.Using this method phenolic ethanoates are cleaved in the presence of benzylic ethanoates whilst ethanamides benzoates and 2,2-dimethylpropanoates remain unchanged.181 Addition to Carbon- Carbon Multiple Bonds. Supported reagents have been used in a facile and selective two-phase addition to carbon-carbon double bonds (Scheme 87).lg2 Stereospecific iodofluorination of alkenes in the presence of polymer- supported HF was achieved in useful ~ie1ds.l~~ Reagents K[SCNl Na[N,] or K[OCOMe] CaF, SiO or A1203 I, CH,C12 2-72 h Scheme 87 An improved general synthesis of amines from alkenes via organoboranes has been described by Brown (Scheme 88); the major problem is that all the R groups are not used.'84 Boranes may be converted into primary amines using hydrazoic acid; this rather hazardous substance is best generated insitu from sodium azide and hydrochloric acid.lg5 Ph ph>= i ii iii or i iv iii ' WNH2 Reagents i BH, THF 1h; ii H,NCI Na[OH] H,O 25 "C 1 h; iii HCI H20; iv NH20S03H THF A,3h Scheme 88 177 T.Kitagawa H.Kuroda H. Sasaki and K. Kawasaki Chem. Pharm. Bull. 1987 35,4294. 178 T. Kitagawa H. Kuroda and H. Sasaki Chern. Pharrn. Bull. 1987 35 1262. 179 K.Takeda K. Tsuboyama H. Takayangi and H.Ogura Synthesis 1987 560. 180 A. Nudelman J. Jerzig H. E. Gottlieb E. Keinan and J. Sterling Carbohydr. Res. 1987 165 145. 181 N. Kunesch C. Miet and J. Poisson Tetrahedron Lett. 1987 28 3569. 182 T. Ando J. H. Clark D. G. Cork M. Fujita and T. Kimura J. Chem. Soc. Chern. Commun. 1987 1301. A. Gregorcic and M. Zupan Bull. Chem. SOC.Jpn. 1987 60,3083. H. C. Brown K.-W. Kim M. Siebnik and B. Singaram Tetrahedron 1987 43 4071. 185 G. W. Kabalka D. A. Henderson and R. S. Varma Organometallics 1987 6 1369. Synthetic Methods Oxazolidinones were prepared from alkenes in an organotellurium-mediated process (Scheme 89).'86 This process is equivalent to a cis-hydroxyamination and was also observed on the reaction of vinyl epoxides with isocyanates in the presence of palladium(0) catalysts.In this case the mechanism involves a palladium ally1 complex as an ir~termediate.'~~ 0 Ph-II 92% + PhTe02CCF3 -Phh HNKo 0 Reagents BF,.Et20 NH,COOEt CICH,CH,CI A 6-20 h Scheme 89 Miscellaneous. A modified procedure for the preparation of Schwartz's reagent [ HZrCp,Cl] has been described. It does not require expensive reducing agents can be accomplished in 3-4 hours and does not require the use of a glove box.'88 Triorganotin halides were synthesized directly (Scheme 90); the quaternary tin halide and halide ion may be recovered from the by-product and re-u~ed.'~~ 3RX + R',QX + 2Sn -+ R3SnX + R',QSnX Q = N P As or Sb R R' = alkyl Reagents 120-140 "C no solvent Scheme 90 The dioxolanation of a,P-unsaturated aldehydes using (66) and trimethylsilyl trifluoromethylsulphonate has been described.The conditions used are mild and aprotic alkenes do not isomerize and tetrahydropyranyl and vinyl ether moieties survive.'9o Anhydrous iron(II1) chloride on silica is known to be a mild reagent for deacetalization and has been used in a convenient preparation of the useful inter- mediate (67) in 55% yield from the bis-acetal.'" 186 N. X.Hu Y. Aso T. Otsubo and F. Ogura J. Chem. Soc, Chem. Commun. 1987 1447. 187 B. M. Trost and A. R. Sudhaker J. Am. Chem. SOC.,1987 109 3792. 188 S. L. Buchwald S. J. LaMaire R. B. Nielsen B. T. Watson and S. M. King Tetrahedron Lett. 1987 28 3895. 189 F.S. Holland Appl. Organomet. Chem. 1987 1 185. 190 J. R. Hwu L.-C. Leu J. A. Rohl D. A. Anderson and J. M. Wetzel J. Org. Chem. 1987 52 188. 191 A. Fadel R. Yefsah and J. Salaun Synthesis 1987 37. I? A. Chaloner Cleavage of 1,l-dimethylethyldimethylsilyl ethers occurs in the presence of 1,l-dimethylethyl hydroperoxide with dioxo bis(pentanedionato)molybdenum(vr) as the catalyst. The mild conditions avoid the formation of a basic alkoxide ion.19* Tetrahydropyranyl ethers could be selectively cleaved in the presence of 1,l-dimethylethyldimethylsilyl ethers using magnesium bromide in ether. Under these conditions MOM ethers were cleaved slowly but MEM ethers were inert.'93 RNHXNH RN(2)-XNHZ -!!+ RN(2)-XN(Z)BOC 1 liv RNHXNHBOC -RN(Z)XNBOC 2 = PhCH2OCO-BOC = Me3CCO-R = Et X = CH,CH, or R = Me X = 0 Reagents i ZCI pyridine; ii (BOC),O DMAP MeCN 25 "C; iii [HC00][NH4] HCOOMe Pd/C; iv TMG MeOH 25 "C 1.5 h; v Z,O CH2CI2or ZC1 pgridine Scheme 91 The azepine derivative (68) was used for the efficient resolution of ketones the hydrazones being separated chromatographically.'94 Selective protection of primary and secondary amines led to a simple preparation of spermidine derivatives (Scheme 91).195 192 T. Hanamoto T. Hayama T. Katsuki and M. Yamaguchi Tetrahedron Left. 1987 28 6329. I93 S. Kim and J. H. Park Tetrahedron Lett. 1987 28 439. 194 F. Fernandez and C. Perez Heterocycles 1987 26 2411. 195 M. L. S. Almeida L. Grehn and U. Raguarsson J. Chem. SOC. Chem. Commun.1987 1250.