Asymmetric alkylation of aromatic aldehydes with dialkylzinc catalyzed by novel amino derivatives of hydroxytetrahydropyran

Novel, specially prepared, tetrahydropyran-based gamma-amino alcohols (S)-2 -(aminomethyl)3-hydroxy-6-ethoxy(phenoxy)-tetrahydropyrans (I) (amino=n-Bu2 N, piperidinyl, pyrrolidinyl, azetidinyl) were tested as catalysts in the a symmetric addition of Et2Zn and n-Bu2Zn to (hetero)aromatic aldehydes, In m ost cases the phenoxy derivatives of I acted more enantioselectively than t he ethoxy ones, The dibutylamino derivaties showed the least enantioselecti vity; the pyrrolidinyl derivatives were more active as catalysts than piper idinyl and azetidinyl compounds. The highest enantioselectivity was observe d in the addition of Et2Zn to benzaldehyde in the presence of (S)-2-(N-pyrr olidinylmethyl)-3-hydroxy-6-phenoxytetrahydropyran. The corresponding alcoh ol was prepared with 72% ee (R-configuration), The addition of dibutylzinc proceeded slowly and less selectively, The alkylation of (hetero)aromatic a ldehydes with Et2Zn and n-Bu2Zn was also studied in the presence of the kno wn optical inductor (1S,2R)N,N-dibutylnorephedrine. Some chiral aromatic se condary alcohols were synthesized in high chemical yields and up to 93% ee enantioselectivity, Copyright (C) 1999 John Wiley & Sons, Ltd.