Single enatiomer free-radical chemistry - Lewis acid-mediated reductions of racemic halides using chiral non-racemic stannanes

Additions of one to two equivalents of Lewis acids that include magnesium salts to free-radical reduction reactions involving ester functionalized radicals and (1<i>R</i>,2<i>S</i>,5<i>R</i>)-menthyldiphenyltin hydride <b>4</b>, bis((1<i>R</i>,2<i>S</i>,5<i>R</i>)-menthyl)phenyltin hydride <b>5</b>, tris((1<i>R</i>,2<i>S</i>,5<i>R</i>)-menthyl)tin hydride <b>6</b>, bis((1<i>R</i>,2<i>S</i>,5<i>R</i>)-menthyl)-[8-(<i>N,N</i>-dimethylamino)naphthyl]tin hydride <b>12</b>, bis((1<i>R</i>,2<i>S</i>,5<i>R</i>)-menthyl)-[1-((<i>S</i>)-<i>N,N</i>-dimethylaminoethyl)phenyl]tin hydride <b>13</b> or 3α-dimethylstannyl-5α-cholestane <b>14</b> result in remarkable enantioselectivities. Examples include (<i>S</i>)-naproxen ethyl ester <b>16</b>, produced in 74% yield and greater than 99% ee at −78°C from the bromide and <b>5</b> in the presence of MgBr₂, and ethyl (<i>R</i>)-<i>N</i>-trifluoroacetyl-_<b>D</b>-phenylglycinate <b>18</b>, obtained in 78% yield and 99% ee under identical conditions. Kinetic and computational studies provide insight into the origins of these observations.<br><br><br>