Selectivity hydride reductions with chiral

Perlmutter used an oxymercuration/demercuration of a y-hydroxy alkene as the key transformation in an enantioselective synthesis of the C(8 ) epimeric smaller fragment of lb (and many more pamamycin homologs cf. Fig. 1) [36]. Preparation of substrate 164 for the crucial cyclization event commenced with silylation and reduction of hydroxy ester 158 (85-89% ee) [37] to give aldehyde 159, which was converted to alkenal 162 by (Z)-selective olefination with ylide 160 (dr=89 l 1) and another diisobutylaluminum hydride reduction (Scheme 22). An Oppolzer aldol reaction with boron enolate 163 then provided 164 as the major product. Upon successive treatment of 164 with mercury(II) acetate and sodium chloride, organomercurial compound 165 and a second minor diastereomer (dr=6 l) were formed, which could be easily separated. Reductive demercuration, hydrolytic cleavage of the chiral auxiliary, methyl ester formation, and desilylation eventually led to 166, the C(8 ) epimer of the... 

Other selected examples are summarized in Table 2. In addition to aldehydes, both cyclic and acyclic ketones can be reduced equally well. sec-Phenethyl alcohol (11, R = Ph) as hydride source works more effectively than t-PrOH. On the basis of this finding, the asymmetric MPV reduction of unsymmetrical ketones with chiral alcohol in the presence of catalyst 10 was examined [30]. Treatment of 2-chloroacetophenone (12) with optically pure (R)-(+)-sec-phenethyl alcohol (1 equiv.) under the influence of catalytic 10 at 0 °C for 10 h afforded (5)-(+)-2-chloro-l-phenylethanol (13) with moderate asymmetric induction (82 %, 54 % enantiomeric excess, ee Sch. 8). Switch-... 

Several new chiral modifications of lithium aluminium hydride have been reported, including those formed by reaction with chiral secondary benzylamines (14), with diols such as (15) derived from D-mannitol, or with terpenic glycols such as (16). These complexes reduce phenyl alkyl ketones to optically active phenyl carbinols, and enantiomeric excesses of up to 50% have been observed in the case of reagents derived from (14). However, in the diol complexes, believed to have structures of the type shown in (17), lower chiral selectivity is observed, e.g. up to ca. 12% in the case of (15), or up to an optical yield of 30% with an ethanol-modified complex of (16). Better results have been reported with the chiral diamine complex (18), derived originally from L-proline, which reduces acetophenone in 92% optical yield. Asymmetric induction with reagents in this class (i.e. derivatives of lithium aluminium hydride) is usually low in the reduction of aliphatic ketones, but a complex of UAIH4 and the amino-alcohol (19) has been shown to reduce... 

Chiral Induction.—As with many synthetic techniques in organic chemistry, PTC methods have been under investigation to determine whether asymmetric induction (chiral selection) can be achieved. In this case chiral onium salts are necessary, and the systems investigated to date have been quaternary derivatives (23) of A -methyl ephedrine. These salts have been used to catalyse two-phase metal boro-hydride reductions of ketones, and the chiral tetra-alkylammonium borohydride ion pair does accelerate this reaction " in organic solvents. However, either no asymmetric reduction is observed, " or low optical purity of products is achieved (less than 15% enantiomer excess). - A low chiral selectivity is also observed in... 

The auxiliaries R) and (S)-triphenylglycol 172 were also applied to achieve anti-selective propionate aldol additions, as shown by Braun and coworkers. It turned out that, for this purpose, the tertiary hydroxyl group of the propionate (R)-204 had to be protected by silylation. This was easily accomplished by a one-pot procedure that delivered the ester (R)-205. After deprotonation with LICA, the lithium enolate was transmetallated with dichloro(dicyclopentadienyl)zirconium and reacted with aliphatic aldehydes to give predominantly anti-diastereomers 206, the diastereomeric ratio surpassing 95 5. Reduction with lithium aluminum hydride finally led to diols 207 under the release of the chiral auxiliary R)-172. After its removal by chromatography, diastereomerically pure diols 207 were isolated with >95% ee (Scheme 4.45) [107]. For the benzaldehyde adduct 206 (R = Ph), alkaline hydrolysis was also performed and found to lead to epimerization to only a small degree. 

Buchwald reported an important advance in enantioselective C=N reductions with the chiral titanocene catalyst 186 (X,X = l,l -binaphth-2,2 -diolate) [137]. The reduction of cyclic imines with 186 and silanes afforded products with high selectivity however, reductions of acyclic imines were considerably less selective. It was suggested that this arose from the fact that, unlike cyclic imines, acyclic imines are found as mixtures of equilibrating cis and trans isomers. An important breakthrough was achieved with the observation that in situ activation of the difluoride catalyst 187 (X = F) gave a catalytically active titanium hydride species that promotes the hydrosilylation of both cyclic and acyclic amines with excellent enantiomeric excess [138]. Subsequent investigations revealed that the addition of a primary amine had a beneficial effect on the scope of the reaction [138, 139]. A demonstration of the utility of this method was reported by Buchwald in the enantioselective synthesis of the alkaloid frans-solenopsin A (190), a constituent of fire-ant venom (Scheme 11.29) [140]. 

---