Pinane-type tridentate reagents for enantioselective reactions: Reduction of ketones and addition of diethylzinc to aldehydes

The reduction of aryl and alkenyl methyl ketones using lithium aluminum hydride modified with (1R,2S,3S,5R)-(+)-10-anilino-3-ethoxy-2-hydroxypinane (10b) afforded chiral secondary alcohols in 83-96% chemical yields and 50-91% ee with dominance of R enantiomers. The reduction of acetophenone in the presence of lithium iodide gave the alcohol product with higher ee. On the other hand, the addition reaction of diethylzinc to benzaldehyde using the pinane-based diols 5-9 as promoters gave 1-phenylpropanol in favor of the S enantiomer up to 88% ee. Using the pinane-based alcohols 10a-e as promoters, the R enantiomer was obtained as the major product. The addition reactions of diethylzinc to various substituted benzaldehydes, employing the diol ligands 5c and 8e, afforded predominantly the corresponding (S)-alcohols. The chiral modifiers 5-10 were prepared from (1R)-(-)-myrtenol and were readily recovered (>90%) after the asymmetric reactions. In this study, LAH reduction and Et2Zn addition are complementary methods for the preparation of optically active secondary alcohols. The ligand 10-butylanilino-2,3-dihydroxypinane 5c promoted the Et2Zn additions effectively, whereas the modifier 10-anilino-3-ethoxy-2-hydroxypinane 10b induced the LAH reductions in a highly enantioselective manner.