TY - JOUR
T1 - Mechanistic Studies of Bismuth(V)-Mediated Thioglycoside Activation Reveal Differential Reactivity of Anomers
AU - Goswami, Manibarsha
AU - Ashley, Daniel C.
AU - Baik, Mu Hyun
AU - Pohl, Nicola L.B.
N1 - Publisher Copyright:
© 2016 American Chemical Society.
PY - 2016/7/15
Y1 - 2016/7/15
N2 - 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.
AB - 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.
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U2 - 10.1021/acs.joc.6b00860
DO - 10.1021/acs.joc.6b00860
M3 - Article
C2 - 27295299
AN - SCOPUS:84978485743
SN - 0022-3263
VL - 81
SP - 5949
EP - 5962
JO - Journal of Organic Chemistry
JF - Journal of Organic Chemistry
IS - 14
ER -