Ketones asymmetric reduction with Alpine-borane

Table 26.3 Asymmetric reduction of prochiral ketones with Alpine-Borane at 6.08x 10 Pa [8]...

Consequently, a chiral site reinforces or diminish enantioselectivity as well as influence the rate of asymmetric reduction of a-chiral alkynyl ketones with Alpine-Borane. This type of influence of an asymmetric induction has not been observed in the reduction of p-chiral alkynyl ketones [14,20]. 

The high asymmetric induction achieved with Eapine-Borane for the a,p-acetylenic ketones and a-ketoesters led an examination of the reduction of a series of a,p-acetylenic ketones (Eq. 26.16) and a-ketoesters (Eq. 26.17), and the comparative reduction data of Eapine-Borane with Alpine-Borane are summarized in Tables 26.16 and 26.17. It should be mentioned that Eapine-Borane offers no advantage for the reduction of aromatic a-ketoesters. Thus, Eapine-Borane is an efficient reagent for the chiral reduction of a,(3-acetylenic ketones (Table 26.16) [1] and of alkyl a-ketoesters (Table 26.17) [1], of appreciable steric difference between the two groups on both sides of the carbonyl group. 

Midland, M. M McLoughlin, J. I., Gabriel, J. Asymmetric reductions of prochiral ketones with B-3-pinanyl-9-borabicyclo[3.3.1]nonane (Alpine-Borane) at elevated pressures. J. Org. Chem. 1989, 54,159-165. 

Asymmetric reduction of propargyl ketones with (R) or (S) Alpine borane (B-isopinocamphenyl-9-borabicyclo, [3,3,1] nonane(A))... 

Asymmetric reduction of ketones.2 Both Alpine-Borane and B-chlorodiisopino-campheylborane (Ipc2BCl) have one main defect for asymmetric reduction of prochiral ketones they show little cnantiosclectivity in reduction of dialkyl ketones in which the alkyl groups arc similar in size. This problem is now solved by reductions with Eap2BCl (1). Thus acctylcyclohexanc is reduced by 1 in 97% ce and isopropyl methyl ketone is reduced in 95% ee (65% yield). 

Reduction of acetylenic ketones, RC=CCR. Alpine-Borane can effect this reduction in high cnantioselcctivity, but this borane is very sensitive to steric effects. Thus it fails to reduce a carbonyl group adjacent to a /-butyl group. In contrast, asymmetric reduction of alkyl aryl ketones with I is increased by a hindered alkyl group. The same effect obtains in reduction of actylenic ketones (2). Thus as the steric bulk of R increases, the enantioselcctivity also increases. 

Hydroxy-esters. - Once again, most contributions to this area involve the synthesis of chiral hydroxy-esters. Almost complete enantioselectivity is achieved in the reduction of a-keto-esters to a-hydroxy-esters using Alpine-Borane (B-(3-pinanyl)-9-BBN) derived from either (+)- or (-)-a-pinene when the reactions are carried out at relatively high concentrations (>2M). Many other types of prochiral ketones are also reduced with excellent asymmetric inductions although 3-keto-esters may not be particularly suitable substrates as ethyl acetoacetate is reduced to ethyl 3-hydroxybutanoate with an enantiomeric excess of only... 

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)-... 

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]. 

In summary, this chapter shows that organoboron-based asymmetric reducing agents, such as K Glucoride (1), K Xylide (2), Alpine-borane (3), Dip-Chloride (4) and oxazaborolidine-catalyzed boranes are highly effective for the reduction of a variety of a-functionalized ketones. We have established a convenient and simple procedure for the preparation of terminal 1,2-diols, a-hydroxy acetals and epoxides with very high optical purity via oxazaborolidine-catalyzed borane reduction using /V-phenylamine-borane complexes as the hydride source. 

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