SELECTIVE REDUCTIONS .52. EFFICIENT ASYMMETRIC REDUCTION OF ALPHA-ACETYLENIC ALPHA'-FLUOROALKYL KETONES WITH EITHER B-CHLORODIISOPINOCAMPHEYLBORANE OR B-ISOPINOCAMPHEYL-9-BORABICYCLO[3.3.1]NONANE IN HIGH ENANTIOMERIC PURITY - THE INFLUENCE OF FLUORO GROUPS IN SUCH REDUCTIONS

A systematic study of the asymmetric reduction of prochiral alpha-acetylenic alpha'-fluoroalkyl ketones with (-)-B-chlorodiisopinocampheylborane [(-)-DIP-Chloride, 1] and (-)-B-isopinocampheyl-9-borabicyclo[3.3.1]nonane (R-Alpine-Borane, 2) reveals that perfluoroalkyl acetylenic ketones can be reduced in very high ee (92-greater than or equal to 99%) with both of these reagents. For example, 1,1,1-trifluoro-4-phenyl-3-butyn-2-one, 1,1,1,2,2-pentafluoro-5-phenyl-1-pentyn-3-one, and 4,4,5,5,6,6,6-heptafluoro-1-phenyl-1-hexyn-3-one are all reduced with 1 in EE at -25 degrees C within 0.25-2 h in 98%, 96%, and 94% ee, respectively. The same ketones ate reduced with 2 under neat condition, within 1-4 h at rt in 98%, 97%, and 96% ee, respectively. Similarly, 1,1,1-trifluoro-3-octyn-2-one, 1,1,1,2,2-pentafluoro-4-nonyn-3-one, and 1,1,1,2,2,3,3-heptafluoro-5-decyn-4-one are reduced with both 1 and 2 in greater than or equal to 97% ee. Difluoromethyl and monofluoromethyl acetylenic ketones are reduced with 2 in relatively high ee (78-88% eel whereas 1 is ineffective for these types of ketones. In all of the above reductions, the fluoroalkyl group acts as the enantiocontrolling group with one exception. A remarkable inversion in selectivity in the reduction of monofluoromethyl acetylenic ketones with 1 is observed as compared to the reduction with 2, indicating that in the transition state the acetylenic moiety acts as the enantiocontrolling group instead of the anticipated monofluoromethyl group. These results highlight the combined effects of both the electronic and steric influences of the fluorine in controlling both the rate and the enantioselectivity in (he asymmetric reduction of prochiral fluorinated acetylenic ketones.