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

Abstract

A note on versions:The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription. Abstract: A highly stereoselective route to functionalized pyrrolidines from 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 with a metallocarbene N-H insertion but is diverted by an intermolecular aldol reaction.Amongst N-heterocyclic compounds of biological relevance, pyrrolidines are among the most important, and feature in a large number of naturally occurring and unnatural compounds. [1] Examples include the mycotoxin paraherquamide 1, [2] the potent proteasome inhibitor marine product salinosporamide A 2 [3] and the glutamate receptor agonist kainic acid 3 (Figure 1). [4]

Stereoselective synthesis and applications of spirocyclic oxindoles

“…In 2016, Moody at Nottingham University developed a diastereoselective NH insertion of diazooxindole 76 with β-aminoketones to afford spiropyrrolidine 77 (Scheme 53). 250 Very recently, Anbarasan reported Pd-catalysed amination of 3-diazooxindoles with ortho-vinyl anilines. 251 Photoredox.…”

Rapid Assembly of Saturated Nitrogen Heterocycles in One‐Pot: Diazo‐Heterocycle “Stitching” by N–H Insertion and Cyclization

“…[13] In 2015, Sun cyclized homopropargylic amines with Rh and Cu carbenes to form various alkylidine pyrrolidines. [16] We envisaged using diazo compounds as astitch to form 4-,5-, 6-, and 7-membered N-heterocycles,a ll involving the same strategic disconnection. [16] We envisaged using diazo compounds as astitch to form 4-,5-, 6-, and 7-membered N-heterocycles,a ll involving the same strategic disconnection.…”

“…[14,15] Hu and Moody recently independently demonstrated N-H insertion to b-aminoketones followed by intramolecular aldol to access pyrrolidines. [16] We envisaged using diazo compounds as astitch to form 4-,5-, 6-, and 7-membered N-heterocycles,a ll involving the same strategic disconnection.…”