The Oxidation of Pyrrole

Abstract

The dearomatization of heterocycles has been a powerful means for producing functional molecules in synthesis. In the case of pyrroles, reductive methods (such as the Birch reduction) have been most widely exploited, while oxidative methods are generally dismissed as too difficult or unpredictable to be useful. However, since the early twentieth century considerable research has been carried out on the controlled oxidation of pyrroles to give highly functionalized products, using a variety of oxidants. This review presents a summary of all work up until the present day in the area of pyrrole oxidation, looking at the use of peroxide, singlet oxygen, hypervalent iodine reagents, a range or organic and inorganic oxidants, and electrochemical approaches. It also offers some perspective on the potential future role of pyrrole oxidation in synthesis.

Isolation of 5‐Hydroxy‐γ‐lactams from a Classical 2‐Aminopyrrole Synthesis

“…Hydroxylactam 3 is apparently formed by air oxidation of intermediate lactam 2, which, in turn, is most likely formed by cyclization of the amino group of the αaminoketone onto the ester of methyl cyanoacetate (instead of cyclization onto the cyano group to give aminopyrrole 1). Although we have not observed lactam 2 by any means, such by TLC, its formation is mechanistically sound and the air oxidation of such an intermediate to give 3 is consistent with the oxidation of other pyrrole type compounds at the 5-position to give 5hydroxy-γ-lactams [15], with oxidation to similar hydroxylated pyrroles by air also known [16,17].…”

In situ Generation of Hypervalent Iodine Reagents for the Electrophilic Chlorination of Arenes

“…those that are sufficiently π‐rich to undergo the chlorination, but not so reactive as to undergo the electrophilic iodination to form a diaryliodonium salt. Regarding the nitrogen‐based heterocycles, the reaction was violent and not controlled with pyrrole, 1‐methyl‐1‐ H ‐pyrrole and indole, which were oxidized in the presence of PIFA, and in some cases polymerized . On the contrary, 2‐methylthiophene gave product 2g in 35 % yield.…”

Oxidation of pyrrole by dehaloperoxidase-hemoglobin: chemoenzymatic synthesis of pyrrolin-2-ones

“…Accordingly, extensive research has been devoted to the synthesis and/or functionalization of pyrrole and its derivatives, with an emphasis on traditional organic methods. 14–17 …”