Base-Promoted Insertion Reactions of Diazocarbonyls to Azlactones

Diazo insertion reactions have been extensively used to build new C-C and C-X bonds. Most of classic methods to perform these reactions are related to strong either Lewis or Bronsted acids. Recent works have demonstrated the power of hydrogen-bonding activators in order to develop metal-free processes to these reactions. Herein, a very interesting methodology which consists in tertiary base-promoted insertion reactions of diazo carbonyls to azlactones is described. Under the optimized reaction conditions, the strategy allows the preparation of a wide range substrate scope concerning both diazo compound and azlactones. Substituents bearing both aromatic and aliphatic were well tolerated and gave the corresponding products in high yields. Moreover, diazo bearing stereogenic centers were successfully adopted. Chiral HPLC analyses revealed no racemization process. Mechanism investigations revealed the protonation step by DIPEA ammonium salt derivative, following by nucleophilic displacement.