[1+1+3] Annulation of Diazoenals and Vinyl Azides: Direct Synthesis of Functionalized 1‐Pyrrolines through Olefination

Abstract

A dirhodium carboxylate catalyzed [1+1+3] annulation reaction of diazoenals and vinyl azides that gives synthetically important enal-functionalized 1-pyrroline derivatives was developed. The reaction involves a novel rhodium-catalyzed olefination of diazoenals with vinyl azides via electrophilic enal carbenoids, resulting in a new class of enal acrylates. The annulation reaction was used for the direct synthesis of valuable deuterated 1-pyrrolines. Structural diversification of the enal-functionalized 1-pyrrolines resulted in the biologically important pyrrolidine-fused oxaziridine, amino acid derivatives, and a 6-azabicyclo[3.2.1]octane motif present in polycyclic alkaloids.

Synthesis of spiropyrrolidine oxindoles through Rh(II)-catalyzed olefination/cyclization of diazooxindoles and vinyl azides

“…On the basis of these results [34], a plausible mechanism was proposed, using the reaction of the 3-diazooxindole 1a and vinyl azide 2a as an example (Scheme 5). The Rh(II)-catalyzed denitrogenation of 1a generates the electrophilic rhodium carbenoid A.…”

“…Herein, we report a Rh(II)-catalyzed [3+1+1] annulation of vinyl azides and 3-diazooxindoles, enabling the facile synthesis of spiropyrrolidine oxindoles (Scheme 2d). Coincidentally, while this work was underway, Katukojvala's group [34] reported the synthesis of functionalized 1-pyrrolines via a similar annulation of diazoenals and vinyl azides (Scheme 2c).…”

Enantio‐ and Diastereodivergent Synthesis of Spirocycles through Dual‐Metal‐Catalyzed [3+2] Annulation of 2‐Vinyloxiranes with Nucleophilic Dipoles

“…[22] On the other hand, selective imino oxidation of afforded oxaziridine derivatives 8 in 62 %y ield with 3:1d r (Scheme 3e), which might have potential antimalarial activity. [23] Furthermore,( R,S)-3aa could be converted into the spirocylicthionate lactone 9 in 50 %y ield with 13:1 dr and > 99 % ee using Lawessonsreagent (Scheme 3f). Notably, Nazaspirolactam 10 could be smoothly obtained in 38 %y ield over two steps with retention of diastereoselectivity and enantioselectivity,which is acommon structural core found in natural products and pharmaceuticals (Scheme 3g).…”

Metal-mediated synthesis of pyrrolines

“…Rhodium(I) catalysts with ligands such as (Cy 2 P) 2 NMe and PNP(Cy) are efficient reagents to perform the union of Schelating aldehydes 141 (aldehydes with a methyl sulde group in b position) and allylic amines 142 to deliver linear (Scheme 48). 107 These functionalized 1-pyrrolines can be synthetically modied to provide further structural diversity. The reaction occurs through a rhodium-catalyzed olenation of diazoenals with vinyl azides to produce the enal acrylate and subsequent annulation to access to 1-pyrrolines.…”