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 C1-0 (i.e., C1-O-ext and C1-O-int) on the C1-MeO-substituted glucose (i.e., 1(Me)) and C1-Me2EtSiO-substituted glucose (i.e., 1(Si)) have been investigated. The calculation results show that both mechanisms proceed with the first concerted silyl transfer and the subsequent C1-O-ext or C1-O-int 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 Cl-O-ext reduction is more favorable than C1-O-int reduction for the substrate '&, while the C1-O-int reduction is more favorable for lsi. These results are consistent with the recent experimental outcomes. Analyzing the origin of chemoselectivity for the C1-O-int or Cl Oint cleavage, we found that the more stable precursor of C1-O-ext cleavage and retention of the six-membered-ring structure result in the selective Cl-O-ext reduction of lme. Meanwhile, the higher basicity of the alkyl ether O-int atom (in comparison to the silyl ether 0' atom) and greater steric hindrance in the precursor favor the C1-O-int bond weakening. Therefore, the Cl Oint reduction occurs selectively for 1(Si).