Mechanistic Studies of Bismuth(V)-Mediated Thioglycoside Activation Reveal Differential Reactivity of Anomers.
The mechanism of bismuth(V)-mediated thioglycoside activation was examined using reaction kinetics and quantum chemical reaction models. NMR experiments show an unusual nonlinear growth/decay curve for the glycosylation reaction. Further studies suggest an anomeric inversion of the β-glycoside donor to the α-donor during its activation, even in the presence of a neighboring 2-position acetate. Interestingly, in situ anomerization was not observed in the activation of an α-glycoside donor, and this anomer also showed faster reaction times and higher product diastereoselectivites. Density functional theory calculations identify the structure of the promoter triphenyl bismuth ditriflate, [Ph3Bi(OTf)2, 1], in solution and map out the energetics of its interactions with the two thioglycoside anomers. These calculations suggest that 1 must bind the thiopropyl arm to induce triflate loss. The computational analyses also show that, unlike most O-glycosides, the β- and α-donor S-glycosides are similar in energy. One energetically reasonable anomerization pathway of the donors is an SN1-like mechanism promoted by forming a bismuth-sulfonium adduct with the Lewis acidic Bi(V) for the formation of an oxacarbenium intermediate. Finally, the computed energy compensations needed to form these α vs β Bi adducts is a possible explanation for the differential reactivity of these donors.
Department of Chemistry, Iowa State University , Ames, Iowa 50011, United States.
Manibarsha
M
Goswami
Department of Chemistry, Indiana University , Bloomington, Indiana 47405, United States.
Daniel C
DC
Ashley
Department of Chemistry, Indiana University , Bloomington, Indiana 47405, United States.|Center for Catalytic Hydrocarbon Functionalizations, Institute for Basic Science (IBS) , Daejeon 305-701, Korea.|Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST) , Daejeon 305-701, Korea.
Mu-Hyun
MH
Baik
Department of Chemistry, Indiana University , Bloomington, Indiana 47405, United States.|Department of Chemical and Biological Engineering, Iowa State University , Ames, Iowa 50011, United States.
Nicola L B
NL
Pohl