Theoretical Study of Ir-Catalyzed Chemoselective C1–O Reduction of Glucose with Silane

Density
functional theory (DFT) calculations have been performed to study
the mechanism of Ir­(III) pincer complex (POCOP)­Ir­(H)­(acetone)+ (POCOP = 2,6-bis­(dibutylphosphinito)­phenyl) catalyzed chemoselective
C1–O hydrosilylative reduction of glucose. The mechanisms for
reduction of the external and internal C1–O (i.e., C1–Oext and C1–Oint) on the C1-MeO-substituted
glucose (i.e., 1Me) and C1–Me2EtSiO-substituted glucose (i.e., 1Si) have been investigated. The calculation results
show that both mechanisms proceed with the first concerted silyl transfer
and the subsequent C1–Oext or C1–Oint bond cleavage and hydride transfer steps. In the hydride transfer
step, the Ir-H moiety acts as the hydride source. The C1–O
cleavage is the rate-determining step of the overall mechanism. The
C1–Oext reduction is more favorable than C1–Oint reduction for the substrate 1Me, while the C1–Oint reduction is more favorable
for 1Si. These results are consistent
with the recent experimental outcomes. Analyzing the origin of chemoselectivity
for the C1–Oext or C1–Oint cleavage,
we found that the more stable precursor of C1–Oext cleavage and retention of the six-membered-ring structure result
in the selective C1–Oext reduction of 1Me. Meanwhile, the higher basicity of the
alkyl ether Oint atom (in comparison to the silyl ether
Oext atom) and greater steric hindrance in the precursor
favor the C1–Oint bond weakening. Therefore, the
C1–Oint reduction occurs selectively for 1Si.