Chiral Synthesis via Organoboranes. 14. Selective Reductions. 41. Diisopinocampheylchloroborane, an Exceptionally Efficient Chiral Reducing Agent

Article abstract of DOI:10.1021/ja00213a030

Diisopinocampheylchloroborane, readily prepared in both enantiomers in high chemical and optical purities (99percent ee) via hydroboration followed by treatment with dry hydrogen chloride in ethyl ether, reduces prochiral ketones at convenient rates in tetrahydrofuran at -25 deg C.Reduction of simple dialkyl ketones, 2-butanone, 2-octanone, and 3-methyl-2-butanone, yields the corresponding alcohols with 4percent, 7percent, and 32percent optical induction.On the other hand, aralkyl ketones are reduced with very high asymmetric induction.Thus, acetophenone, propiophenone, butyrophenone, and decanophenone are reduced with 98percent, 98percent, and 97percent ee, respectively.Branching of the alkyl chain diminishes the induction.Isobutyrophenone and pivalophenone are reduced in 78percent and 79 ee, respectively.Functional groups in the aromatic ring are not affected by the reagent and do not appear to influence significatly the optical yield realized.Thus, 2',5'-dimethoxypropiophenone is reduced in 96percent ee. 1-Indanone and α-tetralone are reduced in 98percent and 87percent ee, respectively. 2'-Acetonaphthone is reduced in 98percent ee.Heteroaryl alkyl ketones are also reduced with excellent optical induction.Thus, 3-acetylpyridine and 2-acetylthiophene are reduced in 92percent and 91percent ee, respectively.The reagent reduces α-tertiary aliphatic ketones under neat condition at room temperature with very high optical induction. 3,3-Dimethyl-2-butanone, ethyl 2,2-dimethylacetoacetate, 2,2-dimethylcyclopentanone, 2,2-dimethylcyclohexanone, and spiro<4.4>nonan-1-one are reduced to the corresponding alcohols in 95percent, 84percent, 98percent, 91, and 95percent ee, respectively.Some α,β-unsaturated ketones are reduced with lesser optical induction, such as 4-phenyl-3-butyn-2-one and 2-cyclohexenone, which are reduced to the alcohols in 21 and 36percent ee respectively.On the other hand, trans-4-phenyl-3-buten-2-one is reduced to the alcohol.Certain α-keto esters are reduced in 50-70percent ee.The mechanism of the reduction is postulated to be via a six-membered cyclic "boatlike" transition state.X-ray crystal structure data for the reagent are presented.