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

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 S_N2′ 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 S_N2′ 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.