High S(N)2' selectivity in the allylic substitution of cyclohexylidene ethyl picolinates with copper reagents prepared from RMgBr and CuBr.Me(2)S was realized by addition of ZnX(2) (X = I, Br, Cl). Furthermore, ZnX(2) accelerated the reaction with the bulky iPr reagent.

Allylic substitution with sp(2)-carbon reagents (aryl and alkenyl anions) was realized by using allylic picolinates and copper reagents derived from RMgBr and CuBr x Me(2)S to afford anti S(N)2' products regio- and stereoselectively. Steric and electronic factors in the reagents and the size of the methylene substituents around the allylic moiety marginally affected the selectivity. The reaction system was compatible with alkyl reagents as well. Furthermore, the substitution was applied to construction of a quaternary center and synthesis of (-)-sesquichamaenol. Electron-withdrawing nature of the pyridyl group and chelation of the C(=O)-C(5)H(4)N to MgBr(2) generated in situ were found to be responsible for the high efficiency of the substitution.

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The picolinoxy group was found to be an extremely powerful leaving group for allylic substitution with aryl nucleophiles derived from ArMgBr and CuBr*Me2S. The substitution proceeds with anti SN2' pathway and with high chirality transfer. The electron-withdrawing effect of the pyridyl group and chelation to MgBr2 are likely the origin of success. Results suggesting these effects were obtained.

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[triple bond]C)2CuLi.LiBr at 0degreesC. 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.