Ketone with neat Alpine-Borane

Table 26.7 Reduction of prochiral simple ketones with neat Alpine-Borane (from 92% ee (+)-a-pinene) at 25 °C [3, 5]...

In the asymmetric reduction of a-ketoesters, the asymmetric induction depends on the steric inequality of two moieties attached to the carbonyl group [9]. The reduction of hindered a-ketoesters yields the corresponding a-hy-droxyesters with optical purities approaching 100% ee (Eq. 26.28). This contrasts strongly with the 11% ee realized in the reduction of 7 (R= i-Pr) with neat Alpine-Borane [9b]. Alpine-Borane (from (-t)-pinene) yields (S)-alcohols in the reduction of both alkylaromatic ketones and a-ketoesters. On the other hand K-glucoride yields (R)-alcohols with aralkylketones and (S)-alcohols with a-keto esters (Table 26.27) [7]. 

The use of elevated pressures (2,000-6,000 atm.) accelerates asym. reduction of prochiral ketones with B-3-pinanyl-9-borabicyclo[3.3.1]nonane while suppressing competing dehydroboration-reduction which erodes enantioselectivity at atm. pressure. E Neat Alpine-Borane at 0° treated with 3-acetylpyridine via a syringe under Nj, stirred for 20 min at room temp., the mixture [in a capped syringe] placed in a high-pressure cell, pressurized to 6,000 atm. for 1.5 days, and worked up by the standard oxidative procedure - (S)-methyl(3-pyridyl)carbinol. Y 67% (100% e.e. ... 

Excess neat Alpine-Borane is used. Ketones 1-5 are reduced with 2 equiv, and ketones 6-8 are reduced with 1.5 equiv. Only one enantiomer of the ketone is used. 

The reaction is extended [3] to the reduction of a-ketoesters, another class of ketones, possessing powerful electron-withdrawing ester group. The reduction of a-ketoesters with 40% excess of neat Alpine-Borane proceeds rapidly at 25 °C (Eq. 26.4 Table 26.9) [3,4b]. 

To circumvent the problem of competitive dehydroboration with ketones, the Alpine-borane reductions can be conducted in neat (excess) reagent [57] or at high pressure (6000 atm, [58]). Experiments done in neat reagent take several days to go to completion, and afford enantioselectivities of 70-98% [57. At pressures of 6000 atmospheres, the reactions are faster and dehydroboration is completely suppressed. Ketones are reduced with slightly higher enantioselectivities (75-100% es) under these conditions [58]. 

Midland and coworkers [Ic] have reported that reduction of alkynyl ketones affords excellent chemical and optical yields that approached 100% in many cases. In general, under Midland s reaction condition, for example, 4-phenyl-3-butyn-2-one takes 48 h for complete reduction at 25 °C with 100% excess of Alpine-Borane. On the other hand Brown has reported [3] the reduction of ketones in 8-12 h, using a 40% excess of the neat reagent (Scheme 26.2 Table 26.12), and products show a substantially higher optical rotation as compared to reported by Midland [Ic]. 

Using neat (S)-Alpine-Borane the reaction is 67% complete in 92 h, and 22-(S)- is obtained in a 7 1 ratio. It is thus apparent that for (R)-Alpine-Borane the double asymmetric inductions are working together, whereas in (S)-Alpine-Bo-rane they are working in opposite direction. A similar change in selectivities is observed in the asymmetric reduction of these acetylenic ketones using (+)-and (-)-A-methylephedrine/LAH [18]. The faster rate of reduction with (R)-... 

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