Oxidation of Pyrrole-2-carboxylates with o-Chloranil and Its Synthetic Application

Abstract

t-Butyl 3,4-dialkyl-1H-pyrrole-2-carboxylates were oxidized with o-chloranil in the presence of MeOH to afford the corresponding 5-methoxypyrrolin-2-one derivatives. The resulting 5-methoxypyrrolin-2-one was reacted with various nucleophiles under acidic conditions to afford the functionalized pyrrolinone derivatives in good yields. Toward elucidation of the structure and function of the linear tetrapyrrole (bilin) chromophores in phytochromes, we have succeeded in synthesizing phytochromobilin (PΦB), phycocyanobilin (PCB), modified PCBs, biliverdin (BV) and its analogs including sterically locked derivatives in free acid forms by developing efficient methods for the preparation of each pyrrole ring and a new coupling reaction between them. In order to synthesize different types of locked chromophores, it was necessary to prepare various pyrrole and pyrrolinone derivatives bearing a wide variety of functional groups. In our previous syntheses, pyrrole rings with an electron withdrawing group were constructed by a modified Barton reaction starting from aldehydes, 1-nitroalkanes, and isonitrile compounds. The produced tosyland ester-substituted pyrroles were converted into Aor D-ring and Bor C-ring, respectively. It would be ideal for the synthesis of the locked bilin chromophores if the various types of pyrroles and the related pyrrolinones could be available from a common pyrrole by a simple manipulation. Recently we have developed a regioselective oxidation of the α-position of the C-4 substituents on t-butyl pyrrole-2-carboxylates with DDQ and the subsequent substitution reaction via azafulvene intermediates (Scheme 1). Herein we describe an oxidation of t-butyl pyrrole-2-carboxylates with o-chloranil and its application toward the synthesis of various types of functionalized pyrrolinone derivatives. N H CO2 tBu DDQ AcOH N H CO2 tBu R OAc R Nu base N H CO2 tBu Nu