American Chemical Society
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Formation of Chiral C(sp3)−C(sp) Bond by Allylic Substitution of Secondary Allylic Picolinates and Alkynyl Copper Reagents

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journal contribution
posted on 2009-10-02, 00:00 authored by Yohei Kiyotsuka, Yuichi Kobayashi
To establish allylic substitution of secondary allylic alcohol derivatives with alkynyl copper reagents, allylic esters bearing the (2-pyridine)CO2-, (2-pyrazine)CO2-, (EtO)2PO2-, C6F5CO2-, o-(Ph2P)C6H4CO2-, MeOCO2-, or AcO- group were examined. First, picolinate (R1 = Me, R2 = CH2OPMB) was subjected to reaction with (TMS-CC)2CuLi·LiBr at 0 °C. Although no substitution took place, MgBr2 (3 equiv) was found to promote the reaction to produce the anti SN2′ product in 93% yield with 94% regioselectivity and 99% chirality transfer. In contrast, substitution of the other esters with the copper reagent in the presence of MgBr2 were less reactive ((2-pyrazine)CO2-) or marginally reactive (other cases). Generality of the substitution using picolinates was established with five picolinates (R1 = Me, Ph(CH2)2, PMBO(CH2)3; R2 = Me, CH2OPMB, CH2OTBS, C5H11, c-C6H11) and seven alkynyl copper reagents (R3 = TMS, Ph, p-TBSOC6H4, p- and o-MeOC6H4, p-MeC6H4, p-FC6H4), furnishing anti SN2′ products in 61−93% yields with high regioselectivity (usually >90%) and high chirality transfer (usually >95%). In addition, transformation of the products was briefly studied.