Methods for the asymmetric preparation of amines ANDERS JOHANSSON Department of Organic Chemistry, Chalmers University of Technology, S-412 96 Goteborg, Sweden Reviewing the literature published up to January 1995 1 2 2.1 2.2 2.2.1 2.2.2 3 3.1 3.1.1 3.1.2 3.2 4 5 Introduction Reduction of the C=N bond Catalytic processes Non-catalytic processes Reductions with chiral reagents Reductions using internal chiral auxiliaries Alkylations Nucleophilic alkylations Alkylations using internal chiral auxiliaries Alkylations using external chiral auxiliaries Electrophilic alkylations Double bond manipulations References 1 Introduction In light of the development of asymmetric synthesis during the past twenty years, it may seem surprising that the asymmetric preparation of amines is still met with such difficulties and is so unpredictable.However, the problems associated with asymmetric aminations are several. One is the lack of an apparent prochiral functional group as a precursor. Another is the different behaviour of what at first glance seem to be quite similar nitrogen-containing prochiral compounds. Nevertheless, several promising methods have emerged. It is noteworthy that completely different approaches have become useful in the past few years, both when it comes to the choice of prochiral functional group and method to convert it into an amino group. Hence, in this review, I have tried to cover the literature within the field as broadly as possible, but I soon realized that a few limitations were necessary, and so decided to deal only with general methods in which a new chiral centre is created as the amine is produced. The methods covered are divided into three categories: reductions, alkylations, and additions to double bonds.Of these, additions to double bonds is the smallest category as cycloaddition reactions are not included. Furthermore, I have excluded asymmetric syntheses of amino acids, because I considered this a topic of its own. 2 Reduction of the C=N bond 2.1 Catalytic processes So far, all asymmetric catalytic processes for the reduction of C=N double bonds have been based on the use of transition metals. A majority of the reported catalytic systems consist of transition metals with a chiral diphosphine ligand.' A selection of ligands used in these C=N reductions are shown below.Some of the results obtained with these ligands are summarized in Table 1. (+)-DIOP (-)-NORPHOS Et-DUPHOS oh P k P PPh, (-)-BDPP (2s ,4S )-BPPM (+)-BIN AP NBD COD In an early example, the (+)-DIOP ligand together with [RhCl(C2H4)], and Ph2SiH2 was used for hydrosilylations of prochiral imines.2 The silyl amines were not isolated, but hydrolysed in situ to produce amines. In all cases, the yields are excellent. The highest selectivity reported (65% e.e.) is achieved with the imine la when the reaction is performed at around 0 "C. Raising the temperature to 60 "C results in a dramatic decrease in selectivity, as an e.e. of only about 27% is observed. In a later paper, the same catalytic system was used for the asymmetric reduction of enamine~.~ A modification, in which [Rh(COD)Cl], was used instead of [RhCl (C2H4)12, appeared several years later! In this study, five-membered cyclic imines 2 were Johansson: Methods for the asymmetric preparation of amines 393hydrosilylated but, contrary to the paper by Kagan et aZ.,2 the amines could not be isolated after hydrolysis.Instead, the silylamines were treated with trifluoroacetic anhydride to yield the trifluoroacetamide derivatives. The best result (64% e.e.) is obtained with an unsubstituted phenyl group at the 2-position, although bromine in thepara- position does not decrease the selectivity significantly. When the phenyl moiety contains a methoxy group in one or several positions, the optical yield is considerably lower. This observation is ascribed to intra- and inter-molecular coordination of the methoxy substituent to rhodium.Hydrosilylations of oximes with this catalyst system have also been studied, but substantially lower selectivities were observed (1.4-18.7% e.e.).5 I / I t a. Ar = Ph n Nb Ph b. Ar = 2-MeO-Ph c: Ar = 4-MeO-Ph d. Ar = 2-OH-Ph 8, Ar = 3-MeO-Ph 1 2 The (R)-( +)-cycphos ligand has been used together with [Rh(NBD)Cl], and KI for the reduction of aromatic imines la-d.6 Here, the presence of a methoxy substituent in thepara- position increases the e.e. Thus, imine l c can be hydrogenated to give an e.e of 91% and imine l a gives 71% e.e. For the ortho-substituted imine lb, the optical yield is somewhat lower and no asymmetric induction was observed with imine Id. The catalyst is not effective for the asymmetric hydrogenation of aliphatic imines.An interesting observation is that the selectivity is significantly lower without KI. A similar decrease in selectivity has been reported earlier,7 although the effect of halide was less dramatic. In a detailed structural study of ( - )-(S, S)-BDPP, Bakos and co-workers' reported a 73% e.e. in hydrogenations of la. In a later paper,' they examined the effect of sulfonation at the meta-position of one or several phenyl groups in the (-)-BDPP ligand. The sulfonated ligands were not purified, but used as a mixture. The compositions were determined with HPLC. When performing the hydrogenation with [Rh (NBD) Cl], and partly sulfonated (-)-BDPP, they were able to obtain high enantioselectivities of aromatic benzylamines la-c and l e (89-96% e.e.).In a comparative study," several chiral diphosphines were used together with [Ir(COD)Cl], (Scheme 1). The most effective ligands are those capable of forming a flexible six- or seven- membered metallacycle, e.g. BDPP, DIOP and BPPM. With these ligands, both reactivity and enantioselectivity are high. Quite contrary, 1,2-diphosphino compounds, such as NORPHOS, are considerably less efficient. Furthermore, a strong halogen effect is observed, as the halogen-free catalytic system [Ir(COD)2] BF@, S)-DIOP produces the (R)-amine with only 4% e.e. and only 30% conversion. Also, the two methyl substituents 3 (2S, 3S)-DIOP 70% 8.8. (2S, 4S)-BPPM 73% 8.8. (2S14S)-BDPP 84% 8.8. Scheme 1 in the ortho-positions of the phenyl group of 3 are important, presumably by hindering the rotation about the N-aryl bond.Another type of iridium-reagent, the dimeric [Ir(P-P)HI2I2, in which P-P is a diphosphine, has been investigated by Osborn et aZ." The reagent was investigated with (+)-DIOP, (-)-BDPP, (+)-BINAP and (-)-NORPHOS as chiral diphosphine ligands. Osborn's findings indicate dissociation of the dimeric catalyst to the monomer and an equilibrium between free imine and monomer and an imine/monomer complex. Moreover, by studying the hydrogenation of deuterated imine 3, they concluded that addition occurs almost exclusively (> 95%) to the C-N bond and not to the enamine tautomer. Of the substrates studied, the highest selectivity is observed in hydrogenation of 4 with (-)-BDPP as the ligand (80% e.e.). 4 5 Oppolzer and co-workers have reported the reduction of 5 with Ru2C14[(R)-( +)-BINAPI2, which proceeds with exclusive formation of one enantiomer.'* A very efficient rhodium-based catalyst has been reported by Burkl3>l4, who used a cationic rhodium complex together with the chiral 1,2-bis(phospholano)-benzene, Et-DuPHOS (Scheme 2).The hydrogenations are performed on N-benzoylhydrazones to yield hydrazines in 72-97% e.e. After the hydrogenation, the N-N bond is readily cleaved with Sm12 to produce amines in high yields without loss of optical purity. An interesting observation is that no hydrogenation takes place without the carbonyl functionality of the hydrazones present. This observation is ascribed to chelation of the N-benzoylhydrazone functionality to the cationic rhodium centre.Furthermore, the hydrogenations are highly chemoselective. For example, little or no reduction is observed for alkenes, alkynes, ketones, aldehydes, esters, nitriles, carbon- halogen bonds, nitro groups, or even imines in competition experiments. This is attributed to the aforementioned substrate chelation of the N-benzoyl hydrazone and the fact that N-benzoylhydrazine inhibits the reduction of aldehydes, alkenes and alkynes among others. 394 Contemporary Organic SynthesisR' = Ph, R2= Me R' = pMew6H4, R2= Me R' = pEtO&C&, R2 = Me R' = pNO2C6H4, R2 = Me R' = pBCsH4, R2 = Me R' = 2-Naphthyl, R2 = Me R' = Cy, R2= Me 95% 8.8. 88% 8.8. 96% e.8. 97% 8.8. 96% 8.8. 95% 8.8. 73% e.8. Scheme 2 Another excellent asymmetric hydrogenation catalyst based on titanium has been developed by Buchwald and co-worker~.~~-~~ The active catalyst is the titanium(n1)hydride 7, which is formed in situ by treating the chiral air stable ansa-titanocene 6'* with Bu"Li and phenylsilane (Scheme 3).The catalyst works extraordinarily well for the reduction of cyclic imines (97-98% e.e.). Though still respectable in several cases, the selectivity is generally lower (53-85% e.e.) when the substrate is an acyclic imine. The observed e.e.s correlate roughly with the antilsyn ratios of the investigated imines. For this observation the authors suggest that both the anti and syn isomers are reactive, giving rise to opposite enantiomers of the product amines." The catalyst has also been used for asymmetric hydrogenations of enamines.*' (i) Bu"Li - (ii) PhSiHI 7 -H Scheme 3 The last two mentioned methods are the subject of an excellent review by Bolm.21 2.2 Non-catalytic processes 2.2.1 Reductions with chiral reagents There are examples of asymmetric reductions of imines and oxime ethers using aluminium h ~ d r i d e s .~ ~ , ~ ~ However, the asymmetric induction is at best fair and, hence, these reagents have given way to boron-based reagents, in some cases combined with Lewis acids, such as ZrC14 or ZnC12/ AlC13. Hitherto, no reports have appeared in which boron reagents are used in a catalytic fashion, as is the case with carbonyl reduction^.^^ Chiral sodium triacyloxyborohydrides such as 8 and 9 can be prepared from NaBH4 and N-carboxyl derivatives of optically active a-amino acids. These reducing agents have proven useful for reductions of certain cyclic imines. Iwakuma et aZ.25,26 have described asymmetric reductions of imines 10a-d. In their study, several acyloxyborohydrides were investigated of which 8 in CH2C12 produces the highest optical yield (Scheme 4).In another in~estigation,~~ the amine 11, a precursor to the antibacterial agent (S)-( -)-ofloxacin,28 has been prepared in 95% e.e. from the corresponding imine using 9 as the reducing agent. Me0 Me0 W N LMeow~t-Me0 R 1084 R 70436% 8.8. 4 R = Me; b. R m ) ; ' 0 c, .Do"" OMe ; d, R w M e OMe 8 R=Bn 9 R=B& Scheme 4 11 A comparative study of several reducing agents efficient in asymmetric ketone reduction has been undertaken by Cho and C h ~ n . ~ ~ The asymmetric reducing characteristics of Itsuno's reagent 12,30 Corey's reagent 13,31 K-glucoride (Brown's reagent) 14,32 Sharpless' reagent 1533 and Mosher's reagent 16,34 were compared with propiophenone N- phenylimine 17 as the substrate (Scheme 5).Under the same conditions as those found most successful for ketone reductions. Itsuno's reagent is the most effective (87% e.e.), whereas 14 and 16 did not reduce the examined imine 17. Further reductions with Itsuno's reagent show that aromatic N-phenyl imines can be reduced with good to high selectivity (71-88% e.e.). Lower optical yields are observed for aromatic N-alkyl imines (ca. 50% e.e.) and for aliphatic N-phenyl imines the selectivity drops significantly. The cyclic imine 10a was inert to the reagent. investigated for several different i m i n e ~ .~ ~ . ~ ~ The e.e.s obtained range from 12 to 73% and it is notable that the only alkyl ketimine in the study, 19, The chiral dialkoxyborane 18 has been Johansson: Methods for the asymmetric preparation of amines 395Tablo 1 Asymmetric catalytic reductions of imines Catalyst Substrate 8.8. Ref. DIOP/(Rh(COD)CIk DIOP/[ Rh(COD)CIJz (R )-cycphos/ [ Rh( NBD)CIWI ( R )-cycphos/ [ Rh(NBD)Clk/KI (R )-cycphost [Rh(NBD)CIklKI (-)-BD PP/ [Rh(NBD)CI]2 (-)-BDPP+)/ [Rh(COD)Clk (-)-BDPP)I [ Rh(C0D)Clk (-)-BDPP+)/ [R h(COD)C1]2 (-)-BDPP+)/ [Rh(COD)Clk (-)-NORPHOS [I r(C0 D)C Ik (+)-DIOP/ [ Ir(COD),BF4YI- (+)-DIOP/ [Ir(COD)Cl]fl- (2S, 4 s )-BPPM/ [Ir(COD)Clk 65% 64% 31 % 33% 60% 79% 91% 71 % 0% 73% 96% 95% 89% 91% 27% 68% 70% 73% 1 3 3 3 3 5 5 5 5 7 8 8 8 8 9 9 9 9 Catalyst Substrate 8.8.Ref. (-)-BD PP/ [Ir(COD)Cl]d/l- (+)-D IOP/ [Ir(COD)C1]& (+)-DIOP/ [Ir(COD)ClkN (+)-DIOP/ [Ir(COD)Cl]fl/l- (-)-BDPP/ [Ir( p- P)H I212 (-)-BDPP/ [Ir( P- P)H I2k NORPHOW [Ir( P-P)H I2k DIOPI [Ir( P-P)H121, BINAPI [Ir(P-P)H1212 7 7 7 7 7 7 7 7 84% 66% 52% 1 6% WYO 80% 4w0 63% 22% 58% 76% 76% 98% 97% 98% 98% 85% 9 9 9 9 10 10 10 10 10 13,14 13,14 13,14 13,14 13,14 13,14 13,14 13,14c 12 Itsuno’s reagent 13 Corey’s reagent 14 K-glucoride 15 Sharpless’ reagent 16 Mosher’s reagent 12 (87% e.eJ 17 Scheme 5 was reduced to the (S)-amine with 71% e.e. No reaction takes place without the addition of MgBr2-OEt2. Oxime ethers are unreactive to these reaction conditions. A selection of asymmetric reductions of imines with chiral reagents are shown in Table 2.While the (E)- and (2)-isomers of an imine are in equilibrium with each other through inversion of the nitrogen, oxime ethers have distinct syn- and anti- isomers,37 as the energy barrier for inversion of the nitrogen is considerably higher. Although the oxygen of the oxime functionality offers an additional stereochemical control element through coordination to the reagent, one must also take into consideration the issue of performing the reduction on pure syn- or anti-isomer, as a mixture of these might decrease the optical yield substantially. Asymmetric reductions of oxime ethers have been reported by Itsuno and co-worker~.~~ Using Itsuno’s reagent 12, the anti-oxime ether 20a is reduced to 18 19 the corresponding amine with 99% e.e.In addition to Itsuno’s reagent 12, other chiral amino alcohols were used to prepare analogues of 12. All of the amino alcohols examined give a high degree of asymmetric induction. The study also includes the effect of various 0-substituents and suggests that both bulkier groups such as SiMe3, and more electron-withdrawing groups such as COMe, decrease the optical yields considerably. When the reaction is performed on the oxime 20b, no asymmetric induction at all is observed. The same type of chiral ligand has been used for reductions with hydride reagents.397‘@ The cfiiral amino alcohol 21 has been used as a ligand together with NaBH, and ZrC14 or ZnC1JAlCl3 (Scheme 6). The amino alcohol is inert to suspensions of NaBH4 in THF and, furthermore, no reduction of the oxime ethers take place under these conditions. Thus, the reducing species is thought to be a mixture of zirconium aminalkoxy borohydrides.It is also noteworthy that no amine is produced with Lewis acids such as CuCl,, ZnC1, or AlC13 alone, or ZnBr,. a, R=Me b , R = H HO 20 OR^ NaBH4/ Lewis acid 21 1 R2 D R’ Lewis acids: R‘ = Ph, R2 = R3 = Me R’ = Ph, R2 = Et, R3 =PhCH, R’ = Ph, R2= *= Me ZrC14 =I4 ZnC12/AICI3 Scheme 6 21 95% yield, 90% 8.8. 88% yield, 72% 8.8. 75% yield, 95% 8.8. Several other amino alcohols have been examined by Didier et uL41 The substrate studied, the oxime ether 20a, is reduced to the corresponding amine with BH3 and the chiral amino alcohols 22,23 and 24 [(-)-norephedrine1 with 95, 94.5 and 93.2% e.e. OH ?H 22 23 24 respectively. In some cases, the reduction of the oxime ether is not complete and a mixture of oxime ether, amine and hydroxylamine methyl ether is obtained.However, after elimination of the oxime ether, the hydroxylamine can be treated with an excess of BH3 to produce the amine without loss of optical purity. Itsuno and c o - ~ o r k e r s ~ ~ have also reported reductions with the polymer supported chiral alcohol 25 and borane, but here the selectivities are lower (6-67% e.e.). 25 A systematic investigation of reduction of syn- or anti-ketoxime ethers has been undertaken by Sakito, Yoneyoshi, and Suzukam0.4~ They examined the reduction of several oxime ethers with BH3 and Johansson: Methods for the asymmetric preparation of amines 397(-)-norephedrine, 24, and obtained either enantiomer of the amine depending on the syn- or anti-configuration of the oxime ether.The most spectacular example is shown in Scheme 7. Thus, the difference in bulkiness of the two R-groups attached to the prochiral carbon seems to be of little importance and, accordingly, oxime ethers in which this steric difference is small can be reduced with high enantioselectivity, as exemplified by the reduction of the oxime ether of octan-2-one (26; 80% e.e., Scheme 8). For a summary of asymmetric reductions of oxime ethers, see Table 3. BH3 I ( R )-24 anfi-oxime Me’O” - ( R 1-amine 92% 8.8. & synoxi me Scheme 7 26 ( R ) or (S), 80% 8.8. Scheme 8 In a different approach,44 the oximes were first converted into phosphinyl imines (Scheme 9). The introduction of the diphenylphosphinyl group enhances the electrophilicity of the imine carbon, thus making it more susceptible to nucleophilic attack.After the reduction, the phosphinyl moiety is easily removed. The reductions were performed on a number of substrates with Mosher’s reagent 16, (R)- or (S)-bi-2-naphthol/LiH4 (Noyori’s reagent),45 and K-glucoride 14 (Brown’s reagent) as reducing agents. The results are somewhat varying, but in some cases both high yields and high optical purities are obtained. The best results are shown in Scheme 9. 9 0 R’ = Me R2 = cyclohexyl R’ = Me: R2 = naphthyl Brown’s 95% yield 84% 8.8. { reagent 14 82% yield: 77% 8.8. lH+ Scheme 9 398 Contempora y Organic Synthesis 2.2.2 Reductions using internal chiral auxiliaries As a substrate bonded chiral auxiliary in C=N bond reductions, phenylethyl amine (27) is by far the most commonly employed.One reason is that it is easily removed with Pd/C to produce primary amines. Also, both enantiomers of 27 are commercially available. Using borane as the reducing agent, a 20 a-steroid is produced with 84% e.e. by reduction of the corresponding phenylethyl imine.46 Other applications of 27 as a chiral promoter include reductions of fluoroalkylated i m i n e ~ , ~ ~ the use of an NADH model as reducing agent,”’ and NaB& reductions of cyclic iminium ions.49 A number of imines derived from 27 have been studied in reductions with lithium aminoborohydrides. Reduction of the tert- butylmethylimine derivative proceeds with 92% d.e.50 Oxime ethers with chiral promoters derived from P-pinene or a-amino acids have been used in reductions with L i H 4 and BH3-SMe2.’l However, the degree of asymmetric induction is generally quite low.For example, the oxime ether 28 is reduced with 44% e.e. using LiAlH4. 27 28 3 Alkylations 3.1 Nucleophilic alkylations 3.1.1 Alkylations using internal chiral auxiliaries Yamamoto and co-workers have studied the addition of allylic metal compounds to aldimine 29,52,53 derived from l-(R)-phenylethylamine and 2-methylpropanal. With allyl-9-BBN’ the Cram They suggest that the reaction proceeds through transition state 30 (Figure l), in which the steric repulsions between the methyl group (and/or the phenyl group) and the other ligands on the metal are minimized. Further experimental data from Hoffmann and EichlerS3 indicatate that increased size of the ligands (L) leads to higher diastereoselectivity. With allylstannane, the selectivity depends strongly on the Lewis acid, as TiC14 gives a 82 : 18 and BF3 a 67 : 33 ratio in favour of the Cram isomer.All metals investigated give the Cram isomer as the major product. derivative 32, gives exclusively the Cram isomer in a syn :anti ratio of 75 : 25 (Scheme 11). Both enantiomers of the vicinal diamine 33 have been prepared by double addition of allylic Grignard reagents to dialdimines prepared from glyoxal and (R)- or (S)-phenylethylamine followed by removal is obtained in a 92: 8 ratio (Scheme 10). Addition of crotyl-9-BBN to the propanalTable 2 Non-catalytic asymmetric reductions of irnines Reducing agent Substrate e.e.Ref. 8 8 Me0 MomN WMe OMe 70% 9 95% 12 12 12 12 N/ph Ph 87% myo 71% 73% NnPh 46% PhAMe 12 25 25 26 29 29 29 29 29 Reducing agent Substrate e.e. Ref. 12 13 15 18 18 18 18 18 18 18 18 52% 78% 66Yo 73% 56% 65% 18% 65% 71 % 72% 36% 29 29 29 35,36 35,36 35,36 35,s 35,36 Table 3 Non-catalytic asymmetric reductions of oxime ethers ~~~ Reducing agent Substrate 8.8. Ref. 12 12 12 12 12 22INaBHJZrCI4 22/NaBH4/ZrCI4 22/NaBHJZrCI4 22/NaBH4/ZrCI4 22/NaBH4/ZrCI4 99% 81 % 91 % 62% 70% 66% 61% 6910 72% 92% 38 38 38 38 38 39,40 39,40 39,40 39,40 40 Reducing agent Substrate 8.8. Ref. BHB’TH F/ 22 BHs‘TH F/ 23 BHiTHF/ 24 BH3.W F/ 24 BHS.THF/ 24 BH3.M F/ 24 BHB.THF/ 24 BH3’TH F/ 24 BH3.THFI 24 N-OMe Ph A Me N.OBn NMOMe Ph4 95% 94.5% 93.2% 92% 90% 91% 92% 80% 86Yo 41 41 41 43 43 43 43 43 43 Johansson: Methods for the a.ymrnetric preparation of amines 399of the chiral auxiliary with Pd/C.55 The (R,R)- or (S, S)-diamines were produced in 6 : 1 ratios, respectively.It was not determined which enantiomer of phenethylamine gives which diamine, but in both cases only trace amounts of the meso- compound were detected. These findings are in accordance with those cited above. With this substrate, double chelation to the metal is suggested to take place, thus forming a bicyclic transition state (Figure 2). 29 ++J- NHR NHR Cram isomer anti-Cram isomer 92 a Addition of methylcopper and dimethyl cuprate to the aromatic aldimines 34 and 35 follow the same patterd6 (Cram : anti-Cram up to 90 : 10; Scheme 12), whereas the aliphatic aldimine 36 shows reversed selectivity (15 : 85).No reaction was observed with compound 37. Addition of allylic Grignard and copper reagents to 34 and 35 followed no general trend and the diastereoselectivity was found to be moderate.57 H H Starting Material (S,S) Cram : (R,S) anticram 34 90 10 35 73 27 36 15 85 37 ~KI reaction Scheme 10 Scheme 12 .L L 30 31 Figure 1 Interactions b e p e n the metal ligands and the chiral auxiliary 1 32 ++y NHR NHR Scheme 11 Me-,; ,Ph H7 Figure 2 55 Crarn-syn Cram-ant i 75 25 Allylic metal reagents based on Zd9 and Mg/Cd7 have been added with excellent diastereoselectivity to imines derived from (S)- valine (38, Scheme 13). The allylic metal species is suggested to add to a five-membered cyclic chelate between the imino ester and Al or Mg.The chiral auxiliary can be removed electrolytically in high yields. OMe eM*m 0 A 0 38 M = Ti, m = At _ _ R = Ph 95% d.e. M=Cu, m= Mg R=Ph 98% d.e. R = n-pentyl 98% d.e. M=Zn R = Ph 90% d.e. Scheme 13 Additions of aliphatic (Me, Et, Bu) organocerium reagents to allylic and prop-2-ynylic imines prepared from amine 39 and an aldehyde,@' provide secondary amines of high diastereoisomeric purity (86-98% d.e. Scheme 14). The auxiliary 39 can be removed without loss of diastereoisomeric purity, although the yields are not excellent. Turning away from imines, the SAMP-hydrazones 40 are very useful for highly asymmetric additions of organolithium6* and organocerium62 reagents to yield optically active hydrazines (Scheme 15). The hydrazines are prone to air oxidation and, hence, or (S, S)-enantiomer HZN NH2 (9 R1-33 400 Contemporary Organic SynthesisMe R'LUCeCb H2N R' Ph (S,S )-3e R2= Me 89% d.e.(S,S,S) R' = PhCEC R' = PhCEC R2= Et >98% d.e. (S,S,S ) R' = PhCiC R ~ = BU 92% d.e. (S,S,S) R' = Bu'CEC R2= Me >98% d.e. (S,S,S) R2= Me R ~ = BU 86% d.e. (S,S,S) 97% d.e. (S,S,S) Scheme 14 95 100 9 92 R' =Me p = P i , X = B r 5 R' = Et p=c-hex X=Br 0 (i) R2LVlHF, (ii) H20 8.8. of amine after reduction: R' = P f $=Et,X=Br 8 40 R' = Et I?- = Me, X = I 91 R' = But, R2=cyclohexyl R'= BU', R2= Bu" R1= Pt, R2 = ~ y ~ l ~ h e x y l 90% 93% 90% Scheme 16 (i) R2Li/CeC1JWlF, (ii) ClC02R d.e. of carbamates: (R3 = C02R) 0- OBn OH OBn YH OBn R' = PhCH2CH2, F?- = Me 96% R2MgxcR'yl!J? + RlVN$ 1 1 R Ph bh R' = PhCH2CH2, F?- = Ph 96% 92% H bh R' = (E )-CH3CH =CH, R2 = Me 42 Scheme 15 the yields are generally higher for the organocerium protocol, according to which the initially formed metallohydrazines are quenched with methyl or benzyl chloroformate before work-up to obtain the more stable carbamates.The N-N bond is readily cleaved with Raney-Ni without loss of optical purity. If desired, the auxiliary can be recycled. The chiral 1,3-oxazolidine 41, easily prepared in two steps from commercially available (+)-p~legone,~~ has been used by Pedrosa et aE. to prepare aminoalcohols of high diastereoisomeric purity through nucleophilic ring-opening with Grignard reagents.@ Thus, additions of phenyl and alkyl (Et, Pri, Pr", Me and cyclohexyl) Grignard reagents proceed with high diastereoisomeric discrimination (Scheme 16).When the nucleophile is a bromide-based Grignard reagent, the attack occurs from the nitrogen side of the heterocycle and, surprisingly, when the Grignard reagent is prepared from an alkyl iodide, the nucleophilic attack comes from the opposite side. A non-polar solvent such as hexane gives higher diastereoselectivity than diethyl ether. Removal of the chiral auxiliary is effected in a two-step procedure with high yields (the yield for each step is Additions of Grignard reagents to the nitrone 42 to yield hydroxylamines (Scheme 17) were found to 96-98%). 6 5 R' = 4-MeOPh, R2= Ph, X = Br 2 98 1 R'= Ph, I?-= Pr', X = CI R' = Ph, R2 = Bu', X = CI R' = n-pentyl, I?-= Me. X = Br 10 90 R' = n-pentyl, p = Bu'. X = CI 94 95 99 Scheme 17 I Favoured Disfavoured figure 3 Addition of Grignard reagents tgnitrone 42; chelated transition state model take place with high selectivity in most cases (60-96% d.e.).65 Notable exceptions are allyl- and (o-methoxypheny1)-magnesium bromides, which give high yields but low selectivity (56 and 59% d.e., respectively) and tert-butyl- and isopropyl- magnesium chlorides, where the yields remain low, but the selectivities are respectable (90 and 88% d.e., respectively). The stereochemical outcome was explained by invoking a chelated transition state model (Figure 3) which was supported by NMR investigations.Both steric and stereoelectronic Johansson: Methods for the asymmetric preparation of amines 401considerations predict nucleophilic attack from the same side. The hydroxylamines from the Grignard additions are converted into carbamates, reduced p-methoxyphenyl group can be oxidatively removed to produce a primary ami~~e.~' The N-p- methoxyphenyl imine of cinnamaldehyde shows with lithium in liquid ammonia, cleaved with periodic acid, and hydrolysed with aqueous hydrochloric acid to yield primary amines.derived sulfenimines 43 proceeds with high diastereoselectivity (98% d.e.).66 However, alkyl Grignard reagents show varying degrees of asymmetric induction (20-88% d.e.). Chiral oxime ethers 44, prepared from ephedrine and norephedrine, undergo 1,2-nucleophilic addition reactions with alkyllithium reagents with 64-88% d.e. The diastereoselectivity was found to mirror the synlanti ratio of the starting oxime ethers.67 Addition of ally1 magnesium bromide to camphor- 43 R = benzyl or neopentyl 44a X = NMe2, R = Me, Ps or Ph b X = N 3 .R=Pr' 3.1.2 Alkylations using external chiral auxiliaries Compound 45 has been used as an external chiral auxiliary in alkylations of N-(4-methoxyphenyl) imines with organolithium reagents.68 When organolithium reagents are added to N-p-methoxyphenyl-substituted imines in the presence of a stoichiometric amount of 45, asymmetric addition to the C=N bond is observed. The authors have also shown that it is possible to further enhance the enantioselectivity of the reaction by alkylsubstitution of the ortho-position of the N-p-methoxyphenyl moiety (Scheme The PhCH2 M e 2 4 45 H Y = H Y=Me R'= Ph, R2= Me 75Y0 8.8. 90% 8.8. R' = Ph, R2= BU 71% 8.8. 70% 8.8. R' = Ph, R2 = vinyl 77% 8.8.90% 8.8. R' = PhCH=CH, R2 = Me 40% 8.8. 90% 8.8. R' = 1 -Naph, R2 = Me 70% 8.8. 78% 8.8. R' = 2-Naph, R2= Me 74"/e.e. - R' = l-Naph, R2= Bu" 68%e.e. - lower enantioselectivity and, interestingly, exchange of the N-substituent to cyclohexyl results in 1,4-addition instead of 1,2-addition. When performing the reaction with catalytic amounts of the auxiliary 45, the asymmetric induction is lower.71 Several other chiral additives have been examined in enantioselective alkylations of N-(trimethylsilyl) benzaldehyde by Itsuno et al. (Scheme 19).72 The chiral dialcohol 46 gives up to 62% e.e. when butyllithium is used in the alkylation of N-(trimethylsilyl) benzaldehyde imine, although it is necessary to use four equivalents of the ligand. Surprisingly, the enantioselectivity is substantially lower in non-coordinating solvents such as hexane and toluene.V &ii Ph hexane 9.1% 8.8. diethylether 62% 8.8. tduene 7.2% 8.8. Fjh 46 Scheme 19 Denmark et al. have investigated the bis- isoxazoline 47 (Scheme 20).73 Without the ligand, little or no reaction takes place between methyllithium and 48 at -78 "C, whereas in the presence of 47 the addition is complete after 1 h. Using stoichiometric amounts of 47, the reaction selectivities are generally good (71-89% e.e.) for additions of methyllithium and vinyllithium to the examined imines. The enolizable imine 49 could be alkylated with a comparable level of enantio- selectivity, using a substoichiometric amount (0.2 eq.) of the bis-oxaline 47. Lesser selectivity is 47 50 N R'Li I 47 1 11 A R-H R' 'R' 48R=Ph 49 R = PhCH&H, 1.0 eq.47 0.2 eq. 47 R'Li = MeLi: 48 75% 8.8. 68% 8.8. RZi = MeLi: 49 91% 8.8. 02% 8.8. R U = CH2=CHLi: 49 89% 8.8. 82% 8.8. Scheme 18 Scheme 20 402 Contemporary Organic Synthesisobserved in additions of butyllithium (57% e.e.) and phenyllithium (30% e.e.), which is speculated to arise from weaker coordination of these lithium reagents to the ligand. With these reagents, the bidentate tertiary amine (-)-sparteine was found to be effective (butyllithium and phenyllithium added with 91 and 82% e.e., respectively). react with imines or silylimines in the presence of aminoalcohol promotors and, therefore, imine analogues have to be used together with these reagents. In one approach the N-(amidobenzyl) benzotriazoles (masked N-acylimines) 51 are used as substrates (Scheme 21).75 In the presence of (1 S, 2R)-( -)-N,N-dibutylnorephedrine (52), diethylzinc can be added with good selectivity (76% e.e.is the highest reported). The yields seem to drop as the selectivity goes up, though. In another approach, the N-diphenylphosphinoylimines 53 serve as electrophiles (Scheme 22).76 Hydrolysis of the initial products affords primary amines. The chiral auxiliary used in this study is the chiral aminoalcohol 54. Using diethylzinc, the alkylation proceeds with good selectivity (75-89% e.e.). Other alkyl groups, such as butyl and methyl, show about the same selectivity, but the yields are lower. When using 54 in catalytic amounts, a considerable drop in Unlike lithium reagents, alkylzinc reagents do not Scheme 21 51 Bu",N OH MeHPh 52 lEtzfi 0 PhA Et R = Me 46% yield, 76% 8.8. R = Pr' 80% yield, 41% 8.8.R = But 96% yield, oo/. 8.8. selectivity could be noted, although the enantiomeric mixture could be refined by crystallization. 3.2 Electrophilic alkylations The SAMP-hydrazones 55 (Scheme 23), previously mentioned in section 3.1.1, have also been used in diastereoselective electrophilic alkylati~ns.~~ When treated with lithium diisopropylamide and quenched with alkyl halides, these compounds provide a convenient route to P-chiral amines. After reduction of the C-N-bond and cleavage of the chiral 1-substituted pyrrolidine moiety with Raney-Ni/H2, the resulting amines are produced in 90-95% e.e. Another paper has dealt with the heterocycle 56 (Scheme 24).78 The carboxylic group in the a-position directs the incoming electrophile to the opposite face of the ring system.Thus, the dianion of 56 yields only one diastereoisomer when treated with methyl iodide or benzyl bromide. In contrast, reaction of dilithiated 56 with benzaldehyde afforded two diastereoisomers in a 1 : 1 mixture. However, this could be overcome by transmetallation of the dianion with MgBr,-etherate prior to addition of benzaldehyde: only one of four possible diastereoisomers was formed. The product LN OH MeHPh I I H30*, then OH- 54 1 ArYNH2 R Ar = Ph. R = Et Ar = 2-Naphthy1, R = Et Ar= Ph, R=Me Ar = Ph. R = Bun Ar = 4-MeC6H4, R = Et 90% e.e. 91% e.e. 85% e.e. (46% yield) 87% e.e. (56% yield) 90% e.e. Scheme 22 (iii) Catechoborane 55 R' = Me, R2 = n-pentyl R' = n-pentyl, R2 = Me R' = Me, R2= benzyl R' = benzyl, R2 = Me R' = Me.R2 = iso-hexyl R' = , R2= Me R' = phenyl, f# = Me R'T H f# A2 8.8. of amine after reduction: Scheme 23 Johansson: Methods for the asymmetric preparation of amines 403= Me1 oniy one diistereoisomer RX = BnBr Scheme 24 can be decarboxylated electrochemically. Meyers and co-workers have published several studies of chiral formamidines as vehicles for the production of optically active secondary a m i n e ~ . ~ ~ The strategy has been applied to the total syntheses of morphine," isoquinoline alkaloids" and ( + )-anisomycin.82 In another example, the same group has applied this strategy to the stereoselective alkylation of the formamidine 57 (Scheme 25).83 The anion of 57 is alkylated with 3-methoxybenzyl chloride and the formamidine part removed by treatment of the alkylation product with a mixture of hydrazine- ethanol-acetic acid.The e.e. of the resulting amine is 98%. The cyclic amine is then elaborated into the historically important alkaloid yohimbone 58. The N-benzyloxazolidinone 59 has also been used for asymmetric alkylations.84 Lithiation of 59 and subsequent treatment with an alkyl halide affords alkylation products with e.e.s between 75% and 99% (Scheme 26). Thereafter, the amine is liberated in three steps. In the same paper, electrophilic alkylations of the aminooxazoline 60 are described, but the diastereoselectivity is lower. The auxiliary has been employed for sequential asymmetric alkylations of i~oindoline.~~ 57 (i) Bu'Li.m -MeOBnCI I (ii) N&, WAC I h e several steps1 1 58 (-)-yohimbone Scheme 25 I 59 Ar = Ph RX- Me1 Ar = a-naphthyl RX = Me1 Ar = Ph RX = Bu"Br Ar= Ph RX = BnCl Ar = p -BnOC6H4 RX = BrCH2C02But Ar = Ph RX = EtI Scheme 26 B,ji up Ar "*' 99% d.e. 99% d.e. 99% d.e. 75"/0 d.e. 87% d.e. 93% d.e. 4 Double bond manipulations Diastereoselective 1,4-addition of amines to the furanone 61 has been shown to provide aminolactones (Scheme 27) which can be reduced to 2-amin0-1,4-diols.~~ The addition takes place anti to the menthoxy group and proceeds with high diastereoselectivity (more than 96% in all cases studied). Treatment of the adducts with lithium aluminium hydride affords (R)-2-amino-butane- 1,4-diols in good yields. 61 R' = H, R2= CeH& Scheme 27 Both cyclic and acyclic alkenes have been shown to react with the chiral chloronitroso sugar 62 as shown in Scheme 28.The resulting hydroxylamines can be reduced to allylic a m i n e ~ . ~ ~ The observed enantioselectivity is generally greater than 80%. 62 404 Contemporary Organic SynthesisScheme 30 X = OCOOEt 98 2 RpNH = bemylamine 80% 8.8. ( S ) 95 5 53% 8.8. ( S ) 88 12 X = OCOOEt 63% 8.8. (S) Asymmetric allylic amination has also been performed on substrates of the type 63 (Scheme 29).88 The chiral ferrocenylphosphine 64 is used together with Pd to form a chiral n-ally1 complex of 63, which is converted into an optically active allylic amine by nucleophilic attack by a benzylic amine. When the R-groups of 63 are phenyl, the reaction 63 R = Ph, X = OCOpEt R = Me, X = OP(0)Pb NuH = R = PS, X = OCOOEt NuH = E : Z 9 6 : 4 73% 8.8.23% 8.8. E : Z 100 : 0 97?40 8.8. G P P h 3 64 Scheme 29 X = OAC RdH = benzyhmine RzNH = (BOC)&JH proceeds with high enantioselectivity (85-98% e.e.) producing the (E)-isomer exclusively. With methyl groups, the enantioselectivity is somewhat lower and small amounts of the (2)-isomer can be detected [73% e.e., 4% (2)-isomer]. For other alkyl groups ( P i and P f ), the enantioselectivity is again higher (97 and 82% e.e., respectively) and essentially one geometrical isomer is formed. In a later paper,89 the authors describe the use of the (E)- and (Z)-isomers of 65 for the same operation (Scheme 30). The nucleophilic attack was found to be y-selective, leading to the SN2’ products.However, (2)- or @)-geometry around the double bond of 65 does not unambiguously lead to opposite configurations of the chiral carbon produced. Also, the degree of asymmetric induction varies, but is somewhat higher for the reactions performed on the w-. isomer. Acknowledgement Several people have read and commented on this manuscript. My gratitude goes especially to Dr Thomas Olsson, Magnus Eriksson, Dr Kaye Stern, and Professor Martin Nilsson for their advice and assistance during the preparation of this text. 5 References 1 For chiral auxiliary-based catalytic hydrogenations, see: (a) C.K. Miao, R. Sorcek and P.-J. Jones, Tetrahedron Lett., 1993,34, 2259; (b) R. Sreckumar and C.N. Pillai, Tetrahedron: Asymmetry, 1993,4,2095; (c) M.B. Eleveld, H.Hogeveen and E.P. Schudde, J. OR. Chem., 1986,51,3635; ( d ) A.W. Frahm and G. Knupp, Tetrahedron Lett., 1981, 22, 2633. Lett., 1973, 49, 4865. Chem., 1975,90,353. Wiegrebe,Angew. Chem., Int. Ed. Engl., 1985,24, 995. Organometallics, 1986, 5, 739. and J.P. Kutney, J. Chem. SOC., Chem. Commun., 1988, 1466. 2 N. Langlois, T.P. Dang and B.K. Kagan, Tetrahedron 3 N. Langlois, T.P. Dang and B.K. Kagan, J. Organomet. 4 R. Becker, H. Brunner, S. Mahboobi and W. 5 H. Brunner, R. Becker and S. Gauder, 6 G.-J. Kang, W.R. Cullen, M.D. Fryzuk, B.R. James Johansson: Methods for the asymmetric preparation of amines 4057 S. Vastag, J. Bakos, S. Toros, N.E. Takach, R.B. King, B. Heil and L. Marko, J. Mol. Catal., 1984,22,283. 8 J. Bakos, I. Tbth, B. Heil, G. Szalontai, L.Parkanyi and V. Fiilop, J. Organomet. Chem., 1989,370,263. 9 J. Bakos, A. Orosz, B. Heil, M. Laghmari, P. Lhoste and D. Sinou,J. Chem. SOC., Chem. Commun., 1991, 1684. 10 F. Spindler, P. Pugin and H.-U. Blaser, Angew. Chem., Int. Ed. Engl., 1990, 29, 558. 11 Y. Ng Cheong Chan and J. Osborn, J. Am. Chem. SOC., 1990,112,9400. 12 W. Oppolzer, M. Wills, C. Starkemann and G. Bernardinelli, Tetrahedron Lett., 1990,31, 4117. 13 (a) M.J. Burk, J. Am. Chem. SOC., 1991,113,8518; (b) M.J. Burk and J.E. Feaster, J. Am. Chem. SOC., 1992, 114, 6266; (c) M.J. Burk, J.P. Martinez, J.E. Feaster and N. Cosford, Tetrahedron, 1994,50,4399. hydrogenations of double bonds see M.J. Burk, J.E. Feaster, W.A. Nugent and R.L. Harlow, J. Am. Chem. SOC., 1993, 115, 10125. 15 C.A. Willoughby and S.L.Buchwald, J. Am. Chem. Soc., 1992, 114, 7562. 16 C.A. Willoughby and S.L. Buchwald, J. Org. Chem., 1993,58,7627. 17 In an earlier study, the same chiral moiety was used together with Zr for the enantioselective synthesis of allylic amines: R.B. Grossman, W.M. Davis and S.L. Buchwald, J. Am. Chem. SOC., 1991,113,2321. 18 F.R.W.P. Wild, J. Zsolnai, G. Huttner and H.H. Brintzinger, J. Organomet. Chem., 1982,232, 233. 19 C.A. Willoughby and S.L. Buchwald, J. Am. Chem. SOC., 1994, 116, 8952. 20 N.L. Lee and S.L. Buchwald, J. Am. Chem. SOC., 1994, 116,5985. 21 C. Bolm, Angew. Chem., Int. Ed. Engl., 1993,32, 232. 22 S.R. Landor, 0.0. Sonola and A.R. Tatchell, J. Chem. 23 S.R. Landor, Y.M. Chan, 0.0. Sonola and A.R. 24 See for example L. Delow and M. Srebnik, Chem.25 K. Yamada, M. Takeda and T. Iwakuma, Tetrahedron 26 K. Yamada, M. Takeda and T. Iwakuma, J. Chem. 27 S. Atarashi, H. Tsurumi, T. Fujiwara and I. Hayakawa, 28 K. Sato, Y. Matsura, M. Inoue, T. Une, H. Osada, H. 14 For the use of Et-DUPHOS in asymmetric SOC., Perkin Trans. I , 1978, 605. Tatchell, J. Chem. SOC., Perkin Trans. I , 1984, 493. Rev., 1993, 93, 763, or V. Singh, Synthesis, 1992,605. Lett., 1981, 22, 3869. SOC., Perkin Trans. I , 1983, 265. J. Heterocycl. Chem., 1991, 28, 329. Ogawa and S. Mitsuhashi, Antimicrob. Agents Chemother., 1982, 22, 548. 1990,3200. 29 B.T. Cho and Y.S. Chun, J. Chem. SOC., Perkin Trans. I , 30 See references 17-19. 31 E.J. Corey, R.K. Bakshi and S. Shibita, J. Am. Chem. SOC., 1987, 109, 5551. 32 H.C. Brown, B.T. Cho and W.S.Park, J. Org. Chem., 1988,53, 1231. 33 J.M. Hawkins and K.B. Sharpless, J. Org. Chem., 1984, 49, 386. 34 S. Yamaguchi and H. Mosher, J. 0%. Chem., 1973,38, 1870. 35 T. Kawate, M. Nakagawa, T. Kakikawa and T. Hino, Tetrahedron: Asymmetry, 1992,3,227. 36 M. Nakagawa, T. Kawate, T. Kakikawa, H. Yamada, T. Matsui and T. Hino, Tetrahedron, 1993,49, 1743. 37 G.J. Karabatsos and N. Hsi, Tetrahedron, 1967,23, 1079. 38 S. Itsuno, M. Nakano, K. Miyazaki, H. Masuda, K. Ito, A. Hirao and S. Nakahama, J. Chem. SOC., Perkin Trans. I , 1985,2039. 39 S. Itsuno, Y. Sakurai, K. Shimzu and K. Ito, J. Chem. SOC., Perkin Trans. I , 1989, 1548. 40 S. Itsuno, Y. Sakurai, K. Shimzu and K. Ito, J. Chem. SOC., Perkin Trans. I , 1990, 1859. 41 E. Didier, B. Loubinow, G.M. Ramos Tombo and G.Rihs, Tetrahedron, 1991,47,4941. 42 S. Itsuno, M. Nakano, K. Ito, A. Hirao, M. Owa, N. Kanda and S. Nakahama, J. Chem. SOC., Perkin Trans. I , 1985,2615. Tetrahedron Lett., 1988, 29, 223. Wambsgans, J. Org. Chem., 1987,52,704. J. Am. Chem. SOC., 1984,106,6709. 29, 2471. 2436. 6005. Lett., 1990,31, 797; (b) R.P. Polniaszek and C.R. Kaufman, J. Am. Chem. SOC., 1989,111,4859; (c) R.P. Polniaszek and J.A. McKee, Tetrahedron Lett., 1987, 28, 4511. 50 J.C. Fuller, C.M. Belisle, C.T. Goralski and B. Singaram, Tetrahedron Lett., 1994,35, 5389. 51 S. Itsuno, K. Tanaka and K. Ito, Chem. Lett., 1986, 1133. 52 Y. Yamamoto, T. Komatsu and K. Maruyama, J. Am. Chem. SOC., 1984, 106, 5031. 53 Y. Yamamoto, S. Ninshii, K. Maruyama, T. Komatsu and W. Ito, J. Am. Chem. SOC., 1986,108,7778.54 (a) D. Cram and F.A. Abd Elhafez, J. Am. Chem. SOC., 1952, 74, 5828; (b) M. Cherest, H. Felkin and N. Prudent, Tetrahedron Lett., 1968,2199. 55 W.L. Neumann, M.M. Rogic and T.J. Dunn, Tetrahedron Lett., 1991,32, 5865. 56 C. Boga, D. Savoia and A. Umani-Ronchi, Tetrahedron: Asymmetry, 1990,1,291. 57 A. Bocoum, C. Boga, D. Savoia and A. Umani-Ronchi, Tetrahedron Lett., 1991,32, 1367. 58 H. Tanaka, K. Inoue, U. Pokorski, M. Taniguchi and S. Torii, Tetrahedron Lett., 1990,31, 3023. 59 A. Bocoum, D. Savoia and A. Umani-Ronchi, J. Chem. SOC., Chem. Commun., 1993, 1542. 60 D. Enders and J. Schankat, Helv. Chim. Acta, 1993, 76, 402. 61 D. Enders, H. Schubert and C. Niibling, Angew. Chem., 1986, 98, 1118 or Angew. Chem., Int. Ed. Engl., 1986, 25, 1109. 62 (a) S.Denmark, T. Weber and D.W. Piotrowski, J. Am. Chem. SOC., 1987,109,2224; (b) D. Enders, J. Schankat and K. Klatt, Synlett, 1994, 795. 63 X.-H. He and E.L. Eliel, Tetrahedron, 1987,21,4979. 64 A. Alnerola, C. AndrCs and R. Pedrosa, Synlett, 1990, 763. 65 Z.-Y. Chang and R.M. Coates, J. 0%. Chem., 1990,55, 3475. 66 T.-K. Yang, R.-Y. Chen, D.-S. Lee, W.-S. Peng, Y.-Z. Jiang, A.-Q. Mi and T.-T. Jong, J, 0%. Chem., 1994, 59, 914. 814. Tetrahedron Lett., 1990,31, 6681. 43 Y. Sakito, Y. Yoneyoshi and G. Suzukamo, 44 R.O. Hutchins, A. Abdel-Magid, Y.P. Stercho and A. 45 R. Noyori, I. Tomino, Y. Tanimoto and M. Nishizawa, 46 G. Demailly and G. Solladie, Tetrahedron Lett., 1975, 47 W.H. Pirkle and J.R. Hauske, J. Org. Chem., 1977,42, 48 J.C.G. van Niel and U.K. Pandit, Tetrahedron, 1985,41, 49 (a) R.P. Polniaszek and L.W. Dillard, Tetrahedron 67 R.K. Dieter and R. Datar, Can. J. Chem., 1993, 71, 68 K. Tomioka, I. Inoue, M. Shindo and K. Koga, 406 Contemporary Organic Synthesis69 I. Inoue, M. Shindo, K. Koga and K. Tomioka, 70 ( a ) F.A. Davis and P.A. Mancinelli, J. 0%. Chem., Tetrahedron: Asymmetry, 1993,4, 1603. 1977,42, 398; ( b ) D.J. Hart, K. Kanai, D.G. Thomas and T.K. Yang, ibid., 1983,48, 289. 71 ( a ) K. Tomioka, I. Inoue, M. Shindo and K. Koga, Tetrahedron Lett., 1991,32, 3095; ( b ) I. Inoue, M. Shindo, K. Koga and K. Tomioka, Tetrahedron, 1994, 50, 4429. Chem. SOC., Perkin Trans. I , 1991, 1341. Am. Chem. SOC., 1994,116,8797. reagents see P. Beak and H. Du, J. Am. Chem. SOC., 1993,115,2516. Asymmetry, 1992,3,437. Chem. Commun., 1992,1097. 368. 1944. 72 S. Itsuno, H. Yanaka, C. Hachisuka and K. Ito, J. 73 S.E. Denmark, N. Nakajima and 0 . J . X . Nicaise, J. 74 For the use of (-))-sparteine and organolithium 75 A.R. Katritzky and P.A. Harris, Tetrahedron: 76 K. Soai, T. Hatanaka and T. Miyazawa, J, Chem. SOC., 77 D. Enders and H. Schubert, Angew. Chem., 1984,96, 78 I. Huber and D. Seebach, Helv. Chim. Acta, 1987, 70, 79 ( a ) A.I. Meyers, Aldrichimica Acta, 1985, 18,59; (b) A.I. Meyers, Lect. Heterocycl. Chem., 1984, 7, 75. 80 A.I. Meyers and T.R. Bailey, J. 0%. Chem., 1986, 51, 872. 81 A.I. Meyers, M. Bos and D. Dickman, Angew. Chem., Int. Ed. Engl., 1984, 23, 458. 82 A.I. Meyers and B. Dupre, Heterocycles, 1987, 25, 113. 83 A.I. Meyers, D.B. Miller and F.H. White, J. Am. Chem. 84 R.E. Gawley, K. Rein and S. Chemburkar, J. 0%. 85 R.E. Gawley, S.R. Chemburkar, A.L. Smith and T.V. 86 B.L. Feringa and B. de Lange, Tetrahedron Lett., 1988, 87 H. Braun, H. Felber, G. Kresse, A. Ritter, F.P. SOC., 1988, 110, 4778. Chem., 1989, 54, 3002. See also Chemtracts, 1989, 2, 46. Ankelkar, J. 0%. Chem., 1988, 53,5381. 29, 1303. Schmidtchen and A. Schenider, Tetrahedron, 1991,47, 3313. Miura and K. Yanagi, J. Am. Chem. SOC., 1989,111, 6301. Tetrahedron Lett., 1990, 31, 1743. 88 T. Hayashi, A. Yamamoto, Y. Ito, E. Nishioka, H. 89 H. Hayashi, K. Kishi, A. Yamamoto and Y. Ito, Johansson: Methods for the asymmetric preparation of amines 407