Ketones Alpine borane

Asymmetric reduction of ketones using Alpine-borane . Alpine-borane = B-isopinocampheyl-9-borabicyclo[3.3.1]nonane. 

Midland and others reported that B-isopinocampheyl-9-borabicyclo[3.3.l]no-nane [Alpine-Borane (7 )-79] is an effective reagent for the highly asymmetric reduction of alkynyl ketones to afford the propargylic alcohol 8030 (Scheme 4.3z). The reagent (R)-19 is prepared from (+)-a-pinene and 9-borabicyclo[3.3.1]no-nane (9-BBN) and often represented as 19banana. The levels of asymmetric... 

Asymmetric Reductions. NB-Enantrane is an analog of B-3-Pinanyl-9-borabicyclo[3.3.1 Jnonane (Alpine-Borane ). Since the absolute configuration of nopol is the opposite of (+)-a-pinene, the reagent provides the opposite mode of asymmetric induction. The reagent provides higher asymmetric induction than Alpine-Borane for cases where the two groups flanking the ketone are relatively small, such as methyl or ethyl alkynyl ketones (eq 2). 

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). ... 

Other Ketones. Ketones such as acetophenone are reduced rather slowly by THF solutions of Alpine-Borane (eq 9). A competing dehydroboration process leads to reduction via 9-BBN (eq 10). 

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. ... 

The first total synthesis of the neuritogenic spongean polyacetylene lembehyne A was accomplished by M. Kobayashi and co-workers. The single stereocenter of the molecule was introduced via the Midland reduction of a propargylic ketone using an Alpine-Borane , which was prepared from (+)-a-pinene and 9-BBN. 

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))... 

Alpine-Borane is an effective, readily available reagent for the reduction of acetylenic ketones. This class of ketones is reduced somewhat slower than aldehydes but the reactions generally proceed at 25 °C. Straight chain alkyl acetylenic ketones are completely reduced after 8 hours at 25 °C using a 0.5 M solution of Alpine-Borane in tetrahydrofuran. More hindered internal acetylenic ketones may require 1 4 days under these conditions, but the process may be accelerated by performing the reaction in the absence of solvent. Acetylenic ketones are reduced faster than other ketones, and can also be reduced in the presence of a methyl ketone24. An example is the selective reduction of 7-nonyne-2,6-dione24. 

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

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... 

Thus, chemoselective reductions of ketones have been achieved in the absence of solvent 5. In general these reactions are performed at room temperature using 40-100% excess Alpine-Borane and typical ketones are reduced in 7-14 days. 

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

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