Ketones with Alpine-Borane

Table 2. Acetylenic Secondary Alcohols by Reduction of Ketones with Alpine-Borane...

Table 3. Secondary Alcohols by Reduction of Ketones with Alpine-Borane (Methods A. B) or ( fDiisopino-campheylchloroborane (Method C)...

Similar to the reduction of aldehydes, reduction of ketones with Alpine-Borane also involves two competing reaction pathways, a bimolecular -hydride elimination process (cyclic mechanism) affording optically active product [6], and a dehydroboration-reduction sequence yielding racemic product [2] (Scheme 26.1). 

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 cause for this poor selectivity in the reduction of simple and unreactive ketones with Alpine-Borane is presumed to be the dehydroboration of the reagent in these slow reductions followed by an achiral and very fast reduction of the carbonyl group by 9-BBN produced in the dehydroboration stage. This problem can be overcome by minimizing the unimolecular dissociation of Alpine-Borane by conducting... 

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]. 

Asymmetric reduction of ketones. Both Alpine-Borane and B>chlorodiisopino-campheylborane (IpcaBCl) have one main defect for asymmetric reduction of prochiral ketones they show little enantioselectivity in reduction of dialkyl ketones in which the alkyl groups are similar in size. This problem is now solved by reductions with Eap2BCI (1). Thus acetylcyclohexane is reduced by 1 in 97% ee and isopropyl methyl ketone is reduced in 95% ee (65% yield). 

Reduction with Alpine-Borane, under Pressure Reduction of Prochiral Ketones... 

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. 

Ketone R R Reagent equiv Reaction time Percentage ee (configuration) Percentage ee with Alpine-Borane (configuration)... 

Ketone Reagent equiv Reaction time (h) With Prapine-Borane With Eapine-Borane With Alpine-Borane... 

Methyl alkynic ketones are reduced with slightly lower efficiency and f-butyl alkynic ketones are reduced very slowly. In the latter case, dehydroboration of Alpine-Borane to give 9-BBN competes with the rate of reduction and the liberated 9-BBN reduces the ketone to give products of lower enantiomeric purity. This problem may be overcome by using high pressure or by using 6-10-cij -myrtanyl-9-BBN (eqs 5 and 6). ... 

Enantioselective reduction is not possible for aldehydes, since the products are primary alcohols in which the reduced carbon is not chiral, but deuterated aldehydes RCDO give a chiral product, and these have been reduced enantioselectively with B-(3-pinanyl)-9-borabicyclo[3.3.1]nonane (Alpine-Borane) with almost complete optical purity. Other chiral boranes can be used to reduce aldehydes or ketones. 

Alpine-Borane,prepared by hydroborationofa-pinenewith9-borabicyclo[3.3. Ijnonane (9-BBN), reduces aldehydes, a-keto esters and acetylenic ketones with excellent enantioselectivity. The reduction proceeds via a cyclic process similar to the MPV reaction. 

Saturated ketones are not readily reduced by Alpine-Borane. However, the intramolecular version of this reduction using (Ipc)2BH proceeds with good yield and facial selectivity. ... 

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. 

This complex chiral hydride 12 reduces acetylenic ketones such as 13 with reasonable selectivity.1 The other enantiomer of 14 comes from reduction of 13 with the enantiomeric reagent derived from NOVRAD. Note that the absolute sense of the induction in the reduction of 13 is the same with 12 and with the Alpine borane from (+)-a-pinene, below. 

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

Some methyl acetylenic ketones are reduced with slightly less efficiency, but this can be improved by using NB-Enantrane11 or an analogous Alpine-Borane derivative with a substituent on the... 

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