Stereoselective Synthesis of Functionalized Pyrrolidines by the Diverted N−H Insertion Reaction of Metallocarbenes with β‐Aminoketone Derivatives

Abstract

A highly stereoselective route to functionalized pyrrolidines by the metal‐catalyzed diverted N−H insertion of a range of diazocarbonyl compounds with β‐aminoketone derivatives is described. A number of catalysts (rhodium(II) carboxylate dimers, copper(I) triflate, and an iron(III) porphyrin) are shown to promote the process under mild conditions to give a wide range of highly substituted proline derivatives. The reaction starts as a metallocarbene N−H insertion but is diverted by an intermolecular aldol reaction.

Cycloaddition reactions of enoldiazo compounds

“…31–41 Furthermore, several reactive intermediates, such as carbonyl ylides, oxonium ylides, azomethine ylides, and nitrones, can be generated from diazo compounds in the presence of transition metal catalysts and then undergo intermolecular cycloaddition or intramolecular ring closure. 16,32,34,39,42–53 Additionally, the successful combination of metal carbene chemistry and other catalytic strategies ( e.g. , C–H activation, 45,54–62 C–C cleavage, 63–66 and gold catalysis 17,46,67–70 ) is fully illustrated by recent advances in cycloaddition reactions of diazo compounds.…”

Unusual reactions of diazocarbonyl compounds with α,β-unsaturated δ-amino esters: Rh(II)-catalyzed Wolff rearrangement and oxidative cleavage of N–H-insertion products

“…Thus a diastereoselective approach to the synthesis of indolines via intramolecular trapping of ammonium ylides with ketones [11] and double bonds [12] was developed. C. J. Moody and co-workers elaborated an efficient way for the synthesis of pyrrolidines by trapping of ammonium ylides with ketones [13], whereas J. Sun and colleagues showed that similar reactions can be extended to compounds with triple bonds and allene fragments [14].…”

Synthesis of Pyrrolidines and Pyrrolizidines with α‐Pseudoquaternary Centers by Copper‐Catalyzed Condensation of α‐Diazodicarbonyl Compounds and Aryl γ‐Lactams

“…[3,4] Herein, the intermolecular reactivity of N-aryl g-lactams 1 with a-diazodicarbonyl compounds 2 is reported (Scheme 1, bottom). [6] In fact, amide groups are transformed into amines with adjacent acetyl and 2-oxoethanoate chains in one step. [6] In fact, amide groups are transformed into amines with adjacent acetyl and 2-oxoethanoate chains in one step.…”

“…[5] Highly functionalized pyrrolidines 3 with a-pseudoquaternary centers are obtained in good yields (up to 83 %). [6] In fact, amide groups are transformed into amines with adjacent acetyl and 2-oxoethanoate chains in one step. This transformation, which involves acyl (or phosphoryl) group migration, proceeds with very high regioselectivity and is specifically catalyzed by copper salts (10 mol %).…”