Electrophile-Induced Ring Expansions of β-Lactams toward γ-Lactams

Abstract

[reaction: see text] An efficient and straightforward route toward 3,4-cis-4-isopropenylazetidin-2-ones was developed from 4-(1-chloroalkyl)azetidin-2-ones. Starting from the latter beta-lactams, a new synthesis of pyrrolidin-2-ones was achieved. When 4-isopropenylazetidin-2-ones were treated with bromine in dichloromethane, diastereoselective electrophile-induced ring expansions toward 5-bromopyrrolidin-2-ones were performed. Further oxidation of 3-benzyloxypyrrolidin-2-ones with bromine toward 3-bromopyrrolidin-2-ones was also established. When 4-isopropenyl-beta-lactams were added to a mixture of NBS and TMSN(3), 5-azidopyrrolidin-2-ones were obtained in moderate to high yields.

A Novel Method for the Synthesis of Haloisoquinolines Involving an Electrophile-exchange Process

“…Substrates with an electron-withdrawing group also reacted (entries 1, 2, 3, 7, 8 and 9). The standard conditions were also compatible with both aliphatic and vinyl alkynes 1e-g (entries [10][11][12][13][14][15][16][17][18]. Substrate 1g with a cyclohexenyl group, for instance, gave the desired product 4g in 88% yield (entry 16).…”

Stereospecific Preparation of γ‐Lactam Derivatives via Ring Expansion of cis and trans β‐Lactam Derivatives: α‐Substituent Effect of β‐Lactam Derivatives

“…The stereochemistry in γ‐lactam has been a great importance in medicinal and synthetic chemistry due to a wide variety of biological activities . The various substituted γ‐lactam derivatives have been prepared stereospecifically via ring expansion from their corresponding β‐lactam derivatives . However, few examples have been reported about the effects of substituents on the α‐position in β‐lactam derivatives via ring expansion to lead γ‐lactam derivatives stereospecifically.…”

Use of functionalized β-lactams as building blocks in heterocyclic chemistry

“…Alternatively, the ring enlargement of β-lactams into γ-lactams was accomplished starting from 4-(1-methylethenyl)azetidin-2-ones 31 through the creation of an electrophilic center by the addition of a suitable electrophile across the olefin [14]. The required 4-isoprenyl-β-lactams 31 were efficiently synthesized starting from 4-(1-chloroalkyl)azetidin-2-ones 30 through dehydrochlorination in dry DMSO at 160 °C for 4 h [14].…”

“…The required 4-isoprenyl-β-lactams 31 were efficiently synthesized starting from 4-(1-chloroalkyl)azetidin-2-ones 30 through dehydrochlorination in dry DMSO at 160 °C for 4 h [14]. 4-(1-Alkenyl)-β-lactams can also be prepared via Staudinger reaction of ketenes with α,β-unsaturated imines, which are accessible by 1,2-dehydrohalogenation of α-haloimines or by condensation of enals with primary amines [15].…”