The intrinsic diastereoselectivity of the reduction of a series of cyclic ketones by pentacoordinate
silicon hydride ions was investigated in the gas phase with the use of the flowing afterglow−triple quadrupole
technique. The percent axial reduction of 4-tert-butylcyclohexanone (1), 2-methylcyclohexanone (2), 3,3,5-trimethylcyclohexanone (3), norcamphor (4), 2-tert-butyl-1,3-dioxan-5-one (5), and 2-tert-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 diastereoselectivity of compounds 1−4 and 6 matches their condensed-phase behavior; i.e.,
the percent axial reduction is reduced when steric hindrance of the ketones 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 suggests
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 predictions
made by Houk et al. regarding the diastereoselectivity of the reduction 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 undergo equatorial reduction in the gas phase (33 ± 4% axial reduction) contrasts with the almost exclusive
axial reduction reported in solution (93%). This deviation is likely caused by the strong electrostatic repulsion
between the nucleophilic hydride reagent and the ring heteroatoms in 5. Compound 6 exhibits an even stronger
preference for equatorial reduction (16 ± 4% axial reduction), in agreement with experimental results obtained
by others in the condensed phase. Earlier calculations predict an even stronger preference for equatorial reduction.
These results are readily rationalized in terms of competition among steric, torsional, and electrostatic effects.
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