Diastereoselectivity in gas-phase hydride reduction reactions of ketones

The intrinsic diastereoselectivity of the reduction of a series of cyclic k etones by pentacoordinate silicon hydride ions was investigated in the gas phase with the use of the flowing afterglow-triple quadrupole technique. Th e percent axial reduction of 4-tert-butylcyclohexanone (1), 2-methylcyclohe xanone (2), 3,3,5-trimethylcyclohexanone (3), norcamphor (4), 2-tert-butyl- 1,3-dioxan-5-one (5), and 2-terr-butyl-1,3-dithian-5-one (6) was determined by collision-induced dissociation experiments. The results show that axial (exo) reduction dominates for 1, 2, and 4, whereas equatorial reduction is dominant for 3, 5, and 6. The trend observed for the reduction diastereose lectivity of compounds 1-4 and 6 matches their condensed-phase behavior; i. e., the percent axial reduction is reduced when steric hindrance of the ket ones is increased (1, 99 +/- 3%; 2, 68 +/- 5; 3, 9 +/- 3%). The remarkable consistency of the results obtained in the gas phase and in solution sugges ts that environmental effects are either unimportant or cancel out and that the reduction diastereoselectivity is a property that can be attributed to the intrinsic nature of the isolated reactants. Qualitatively, the predict ions made by Houk et al. regarding the diastereoselectivity of the reductio n of 5 and 6 in the gas phase were confirmed, i.e., a preferred equatorial approach of the hydride reducing agent. The preference of compound 5 to und ergo equatorial reduction in the gas phase (33 +/- 4% axial reduction) cont rasts with the almost exclusive axial reduction reported in solution (93%). This deviation is likely caused by the strong electrostatic repulsion betw een the nucleophilic hydride reagent and the ring heteroatoms in 5. Compoun d 6 exhibits an even stronger preference for equatorial reduction (16 +/- 4 % axial reduction), in agreement with experimental results obtained by othe rs in the condensed phase. Earlier calculations predict an even stronger pr eference for equatorial reduction. These results are readily rationalized i n terms of competition among steric, torsional, and electrostatic effects.