A new approach to synthesize optically active β-amino-α-hydroxyl acid derivatives via chiral Brønsted acid-Rh(2)(OAc)(4) cocatalyzed three-component reactions of diazo acetates with alcohols and imines is reported. A matched reaction system was identified to give the products in moderate diastereoselectivity and good enantioselectivity. Application of this methodology is demonstrated in the efficient synthesis of a taxol side chain and (-)-epi-cytoxazone.