Synthetic Exploration of α‐Diazo γ‐Butyrolactams

Abstract

DIazo transfer reaction onto γ‐butyrolactams (activated by α‐ethyloxalylation) gave rare α‐diazo γ‐butyrolactams. Decomposition of the latter by Rh2(OAc)4 in the presence of alcohols and water gave products of O–H insertion of the respective metal‐cabene species. Silver triflate (1 mol‐%) was found to convert the γ‐butyrolactams investigated into 1,5‐dihydro‐2H‐pyrrol‐2‐ones which represent versatile building blocks. Particular instability was noted for α‐diazo γ‐butyrolactams bearing alkyl or o‐substituted aryl substituents on the nitrogen atom. These were found to dimerize in solution or upon storage at room temperature to give fully conjugated bis‐hydrazones along with the loss of a nitrogen molecule.

Preparation and in situ use of unstable N-alkyl α-diazo-γ-butyrolactams in RhII-catalyzed X–H insertion reactions

“…Three N-alkyl-α-ethoxalyl-γ-lactams 6a-c, prepared by oxalylation of the respective γ-lactams as decribed previously [1], underwent a rapid diazo transfer reaction via the conventional protocol [4,5] employing 4-nitrobenzenesulfonyl azide and DBU. A quick filtration through a plug of alumina (in lieu of silica gel, which led to decomposition of the diazo compounds 4a-c), and addition of an alcohol, a thiol, or an aromatic amine along with a Rh II catalyst resulted in a rapid insertion reaction and the isolation of the desired α-substituted γ-lactams 7a-o in modest yields (Scheme 1).…”

“…Recently, we described the first synthesis and subsequent transformations of a rare type of cyclic α-diazocarbonyl compounds, namely, α-diazo-γ-butyrolactams [1]. In particular, N-arylα-diazo-γ-butyrolactams 1 were efficiently transformed into pyrrolinones 2 upon the treatment with AgOTf (1 mol %) and into α-alkoxy derivatives 3 via Rh 2 (OAc) 4 -catalyzed O-H insertion reactions with various alcohols.…”

“…The instability of N-alkyl-α-diazo-γ-butyrolactams 4 compared to the N-aryl counterparts 1, was most likely related to the reduced electronwithdrawing character of the lactam carbonyl group in the former compared to the latter. This assumption is further sup-ported by the fact that ortho-substituted N-aryl derivatives 1 (in which the conjugation of the aromatic ring with the lone pair of the lactam nitrogen atom is reduced due to the sterically forced loss of the coplanarity between the aromatic ring and the aminocarbonyl moiety) are as unstable as the N-alkyl derivatives 4 [1].…”

“…Faced with this serious limitation of the reactivity scope, we set off to investigate the possibility of using unstable compounds 4 in situ, promptly after their formation, in various Rh II -catalyzed X-H insertion reactions, particularly the recently described rhodium carbene insertion into O-H [1], N-H [2] and S-H [3] bonds of alcohols, aromatic amines, and thiols, respectively. Herein, we report the results of these studies.…”

N-Acyliminium Ion Chemistry: Improving the Access to Unsaturated γ-Lactams and Their N-α-Methoxylated Derivatives: Application to an Expeditive Synthesis of (±)-Crispine A

“…5 In 2015, Pelkey and co-workers 6 compiled the known syntheses of 3-pyrrolin-2-ones 1. Indeed, compounds 1 or 2 can be synthesized by different methods: oxidation of pyrrole (R = H, Me), 7 cyclization (especially for the synthesis of substituted unsaturated -lactams), 8 elimination, 9 via diazo compounds, 10 condensation with 2,5-dimethoxy-2,5-dihydrofuran (5), 11 and metathesis. 12 The latter two methods are the most popular for the synthesis of unsubstituted compound 1.…”