Enantioselective synthesis of axially chiral 1-(1-naphthyl)isoquinolines and 2-(1-naphthyl)pyridines through sulfoxide ligand coupling reactions

Racemic 1-(1'-isoquinolinyl)-2-naphthalenemethanol rac-12 was prepared through a ligand coupling reaction of racemic 1-(tert-butylsulfinyl)isoquinotine rac-7 with the 1-naphthyl Grignard reagent 10. Resolution of rac-12 was achieved through chromatographic separation of the Noe-lactol derivatives 14 and 15, providing (R)-(-)-12 of > 99 % ee and (S)-(+)-12 of 90 % ee. The ligand coupling reaction of optically enriched sulfoxide (S)-(-)-7 (62 % ee) with Grignard reagent 10 furnished rac-12, with the absence of stereoinduction resulting from competing rapid racemisation of the sulfoxide 7. Reaction of optically enriched (S)-(-)-7 with 2-methoxy-1-naphthyl magnesium bromide was also accompanied by racemisation of the sulfoxide 7, and furnished optically active (+)-1-(2'methoxy-1'-naphthyl)isoquinoline (+)-3b in low enantiomeric purity (14 % ee). The absolute configuration of (+)-3b was assigned as R using circular dichroism spectroscopy, correcting an earlier assignment based on the Bijvoet method, but in the absence of heavy atoms. Optically active 2-pyridyl sulfoxides were found not to undergo racemisation analogous to the 1-isoquinolinyl sulfoxide 7, with the ligand coupling reactions of (R)-(+)- and (S)-(-)-2-[(4'-methylphenyl)sulfinyl]-3-methylpyridines, (R)-(+)-17 and (S)-(-)-17, with 2-methoxyl 1-naphthyl magnesium bromide providing (-)- and (+)-2-(2'-methoxy-1'-naphthyl)-3-methylpyridines, (-)-18 and (+)-18, in 53 and 60 % ee, respectively. The free energy barriers to internal rotation in 3b and 18 have been determined, and the isoquinoline (R)-(-)-12 examined as a ligand in the enantioselectively catalysed addition of diethylzinc to benzaldehyde; (R)-(-)-12 was also converted to (R)-(-)-N,N-dimethyl-1-(1'-isoquinolinyl)-2-naphthalenemethanamine (R)-(-)-19, and this examined as a ligand in the enantioselective Pd-catalysed allylic substitution of 1,3-diphenylprop-2-enyl acetate with dimethyl malonate. (c) 2005 Elsevier Ltd. All rights reserved.