β-Lactam Synthesis via Copper-Catalyzed Directed Aminoalkylation of Unactivated Alkenes with Cyclobutanone O-Benzoyloximes

Abstract

A new protocol for amide-directed Cu-catalyzed aminoalkylation of unactivated alkenes using cyclobutanone oxime esters as alkyl radical donors is developed. Both primary and secondary alkyl groups can be selectively installed at the C4 position of terminal or cis-internal 3-alkenamides in moderate to good yield. This reaction offers a useful method for the diastereoselective synthesis of β-lactams bearing 4-cyanoalkyl β-substituents. The use of a weakly coordinating counteranion as the Cu catalyst is critical for the formation of β-lactam products.

Divergent regioselective Heck-type reaction of unactivated alkenes and N-fluoro-sulfonamides

“…2). Of note, under reaction conditions C excluding the aforementioned promoting factors, the β-lactams 5 would dominate the product distribution through a reductive elimination of the high-valent copper intermediate 79 , a process previously observed independently by Zhao 80,81 , He/Chen/Wang 82,83 , and Quan/Liang/Wang 43 in alkylamination of unactivated alkenes. As demonstrated in Fig.…”

“…Moreover, the present strategy could be further applied to other types of alkyl electrophiles. For example, the reaction of our previously employed cycloketone oxime ester 41,83,86 with alkene 1a under conditions B delivered the desired allylic product 19 in 72% yield as a single regio-and E-stereoisomer, while β-lactam 20 was obtained in 68% yield under conditions C (Fig. 7f).…”

One-Pot Construction of Diverse β-Lactam Scaffolds via the Green Oxidation of Amines and Its Application to the Diastereoselective Synthesis of β-Amino Acids

“…Although various methods have been reported for the construction of β-lactam rings (including transition-metal-catalyzed reactions, carbonylations, and enolate-imine condensations), − Staudinger cycloaddition, which is a formal [2 + 2] cycloaddition of an imine and a ketene, is the most versatile method for fabricating β-lactam rings (eq ). This method requires highly pure imines, which are generally susceptible to hydrolysis.…”

Copper(i)-catalyzed radical carboamination reaction of 8-aminoquinoline-oriented buteneamides with chloroform: synthesis of-β-lactams

“… 22 The reaction mode is efficient and can enrich the preparation method of β-lactam. Subsequently, Chen 23 group used cis -3-hexenamide compounds with 8-amino-5-iodoquinoline as the substrates, 4-benzyl Hantzsch esters as the alkyl radical precursor, and rarely used biaryl diphosphine oxide as a chiral ligand to synthesize a series of chiral β-lactam compounds ( Scheme 1b ). In order to verify the applicability of this method, we tried other free radicals.…”