Preparation of N-(alk-1-enyl) nucleobase compounds by Horner and Horner–Wadsworth–Emmons reactions

A series of new N9-(alk-1-enyl)adenines and N1-(alk-1-enyl)thymines has been prepared by Horner reactions of the new phosphine oxides N9-(diphenylphosphorylmethyl)adenine and N1-(diphenylphosphorylmethyl)thymine derivatives 13a–c, or Horner–Wadsworth–Emmons reactions of the corresponding new phosphonates 14a–b, with benzaldehyde and various ketones. Yields were highest for the Horner reactions (10–79%), and were limited by steric hindrance, enolization of the ketones, and decomposition of some of the N1-(alk-1-enyl)thymines in the presence of excess base (NaH). Butanal gave mixtures of products under Horner conditions, probably because aldol reactions intervened.