BINAL

Optically active 1-alkoxyallylstannanes are more readily available by asymmetric reduction of acylstannanes using either ( + )-(/J)-BINAL-Il105 106 or LiAlH4-Darvon alcohol [(2S,3/ )-4-dimethylamino-3-mcthy]-1,2-diphenyl-2-butanol] 06 followed by O-alkylation. The stereoselectivity of the BINAL-H reductions differs from that usually observed, and has been attributed to a tin-oxygen hypervalent interaction107, l08. 

Coleman established the hydroxypropyl stereochemistry via addition of a homochiral a-alkoxyalkyl organometallic species. This reagent was prepared in high enantiomeric excess using a Noroyi BINAL-H reduction of organostannane 33, which was transmetallated with ra-BuLi to achieve the desired organolithium reagent 35 (Scheme 7.5). Both enantiomers of 35 could be obtained via this route. 

An alternative route to nonracemic a-alkoxy stannanes entails the reduction of acyl stannanes with chiral hydrides61 62. Accordingly, conjugated stannyl enones yield (S)-a-alkoxy allylic stannanes by reduction with (J )-(+)-BINAL-H. As expected, (S)-(—)-BINAL-H gives rise to the enantiomeric (7 )-a-alkoxy allylic stannanes (equation 29)61. Upon treatment with Lewis acids, these stannanes undergo a stereospecific anti 1,3-isomerization to the (Z)-y-alkoxy allylic stannanes61. 

TABLE 6-4. Enantioselective Reduction of Aromatic Ketones with BINAL-H (R"0=C2H50) ... 

Scheme 6-26. Some important compounds prepared via BINAL-H reduction.

BINAL-H reagents 45 are not effective in the enantioselective reduction of dialkyl ketones.53 For example, reaction of benzyl methyl ketone with (S)-45 gives (S )-l-phenyl-2-propanol in only 13% ee (71% yield). Reaction of 2-octanone with (R)-45 produces (S )-2-octanol in 24% ee (67% yield).53 This drop of ee values in the reaction may be explained by the lower energy difference between the favored transition state 48 and unfavored transition state 49 caused by the lack of the above-mentioned n-n repulsion between the reductant and the substrate dialkyl ketone. 

Various catalytic or stoichiometric asymmetric syntheses and resolutions offer excellent approaches to the chiral co-side chain. Among these methods, kinetic resolution by Sharpless epoxidation,14 amino alcohol-catalyzed organozinc alkylation of a vinylic aldehyde,15 lithium acetylide addition to an alkanal,16 reduction of the corresponding prochiral ketones,17 and BINAL-H reduction18 are all worth mentioning. 

Methods such as borane reduction and BINAL-H reduction are discussed in Chapter 6, and indeed ketone 89 can be reduced by chiral borane, providing the co-side chain 90 at 65% yield and 97% ee (Scheme 7-26). 

Another method for ketone reduction, BINAL-H asymmetric reduction, can also be used in co-side chain synthesis. An example of applying BINAL-H asymmetric reduction in PG synthesis is illustrated in Scheme 7-27. This has been a general method for generating the alcohol with (15. -configuration. The binaphthol chiral auxiliary can easily be recovered and reused. As shown in Scheme 7-27, when the chiral halo enone 91 is reduced by (S -BINAL-H at — 100°C, product (15S)-92 can be obtained with high enantioselectivity. 

Scheme 7-30 shows how the diketone 94 can be reduced by (S )-BINAL-H to give the desired (3i )-hydroxy-propenone 95 with 65% yield and 94% ee. 

The reduction of dialkylketones and alkylaryl ketones is also conveniently accomplished using chiral oxazaborolidines, a methodology which emerged from relative obscurity in the late 1980s. The type of borane complex (based on (,V)-diphenyl prolinol)[39] responsible for the reductions is depicted below (10). Reduction of acetophenone with this complex gives (/ )-1 -phenylethanol in 90-95% yield (95-99% ee) [40]. Whilst previously used modified hydrides such as BiNAL-H (11), which were used in stoichiometric quantities, are generally unsatisfactory for the reduction of dialkylketones, oxazaborolidines... 

Their main application, however, continues to lie in their reduction with (V)-BINAL-H to give the corresponding carbinol in high enantiomeric excess.161... 

For recent syntheses of chiral allenes via enantioselective hydrogenation using (S)-BINAL-H, see K. M. Brummond,... 

For applications in total synthesis this method was also thought to be applicable to chiral aldehydes, leading to matched and mismatched situations. Therefore, vinylogous ketene acetal 40 was put to reaction with chiral aldehyde 44 and both enantiomers of Carreira s catalyst. Reaction of aldehyde 44 with the (S)-Tol-BINAL-CuF catalyst (matched case) produced only one diastereomeric... 

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