Cyclohexanones borane reduction

Reduction of aldehydes and ketones. Earlier work on amine borane reagents was conducted mainly with tertiary amines and led to the conclusion that these borane complexes reduced carbonyl compounds very slowly, at least under neutral conditions, and that the yield of alcohols is low. Actually complexes of borane with primary amines, NHj or (CH3)3CNH2, reduce carbonyl compounds rapidly and with utilization of the three hydride equivalents. BH3 NH3 is less subject to steric effects than traditional complex hydrides. A particular advantage is that NH3 BH3 and (CH3)3CNH2 BH3 reduce aldehyde groups much more rapidly than keto groups, but cyclohexanone can be reduced selectively in the presence of aliphatic and aromatic acyclic ketones. 

The amino groups of ovomucoid, lysozyme, and ovotransferrin were alkylated extensively (40-100%) with various carbonyl reagents in the presence of sodium borohydride. Monosubstitution was observed with acetone, cyclopentanone, cyclohexanone, and benzaldehyde, while 20-50% disubstitution was observed with 1-butanal and nearly 100% disubstitution was observed with formaldehyde. The methylated and isopropylated derivatives of all three proteins were soluble and retained almost full biochemical activities. Recently amine boranes have been shown to be possible alternative reducing agents for reductive alkylation... 

N. G. Gaylord, Reduction with Complex Metal Hydrides. Interscience, New York (1956) H. C. Brown, Boranes in Organic Chemistry, Cornell Univ. Press, Ithaca, NY (1972), pp 209-250 H. 0. House, Modem Synthetic Reactions, Benjamin, New York (1972), p 49 Chem Soc Rev 5 23 (1976) Tetr 35 449 (1979) (stereochemistry and mechanism) Topics Stereochem 11 53 (1979) (stereochemistry) JACS 103 4540 (1981) (stereochemistry of cyclohexanone reductions) J. Seyden Penne, Reductions by the Alumino- and Borohydrides in Organic Synthesis, VCH-Lavoisier (1991), Chpt 2 Comprehensive Organic Synthesis, Eds. B. M. Trost and I. Fleming, Pergamon, Oxford (1991), Vol 8, Parts 1.1 and 1.7 TL 34 5483 (1993) (stereochemistry) ... 

An increase in solvent polarity leads to an increase in the reduction rate and the final product yield. The best results have been obtained with a buffer solution with pH 1 and with acetic acid in these solvents the reduction of cyclohexanone is complete within 30 and 120 minutes, respectively. During this time, as shown by special test, hydrolysis of the borane complex does not occur. The increase in the reactivity of the borane-contain-ing polymer in the acidic medium is attributed to the protonation of both the carbonyl compound and the polymer. The protonation of the carbonyl oxygen increases its reactivity, wheras the protonation of the polymer facilitates swelling of the macromolecule and causes conformation change which increase the accessibility of catalytically active sites. 

An accepted pathway for the reduction of cyclohexanone with borane (B2H6) in oxacyclopentane (THF) is presented in Scheme 9.16. As shown there, it is presumed that, initially, the borane THF complex is converted to a carbonyl group borane complex (i.e., C=0 BH3) and that hydride donation from the complexed borane to the carbon of the carbonyl leads to a monoalkoxyborane. 

Scheme 9.16. An accepted pathway for the reduction of cyclohexanone to cyclohexanol with borane (B2H6).The intermediate tricyclohexylborate is also shown.

Six-membered Rings.—Cyclohexanones. Conversion of an alicyclic ketone into its corresponding methylene derivative is often necessary, but existing methods tend to require vigorous conditions. A mild method has been reported in which the ketone tosylhydrazone is treated with catechol borane in chloroform at 263 K and the reduction product decomposed with sodium acetate. Yields of 40—90% are claimed. 

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