[2+2] Cycloadditions of Sorbyl Tosylate with Imines/1‐Azadienes: A One‐Pot Domino Approach for α‐Alkylidene‐β‐lactams and Their Computational Studies and Antimicrobial Evaluation

Abstract

The manuscript describes a straightforward and atom-efficient method for the synthesis of α-alkylidene-β-lactams using sorbyl tosylate and imines/1-azadienes at high temperature (80°C). The Density functional theory calculations have shown the prevalence of the first order kinetics in these [2 + 2] cyclo-additions to produce mixture of 3-butadienyl-azetidin-2ones and 3-but-2-enylidene-azetidin-2-ones in good yields. The 3but-2-enylidene-azetidin-2-ones have also shown antimicrobial activity against the E. coli, S. aureus, P. aeruginosa, B. cereus and B. subtilis.

Recent Advances in the Synthesis of Spiro‐β‐Lactams and Spiro‐δ‐Lactams

“…Bhargava et al explored the synthesis of spiro-βlactams through [4 + 2] cycloaddition reactions between α-alkylidene-β-lactams 120 and 4-methyl-[1,2,4]triazole-3,5-dione 121, yielding racemic spiro[ [1,2,4]triazolo[1,2a]pyridazine-5,3'-azetidine]-1,2',3(2H,8H)-triones 122 in good yields (62-75%) (Scheme 36). [52] Recently Luo et al reported a phosphine-mediated reductive cyclopropanation reaction of α-methylene-βlactams 108 a with α-keto esters 123 (Scheme 37). [53] This metal-free protocol provides the efficient syn-thesis of highly functionalized spirocyclopropyl βlactams 124 through a mechanism involving the initial oxophilic addition of the phosphine to α-ketoester to generate Kukhtin-Ramirez intermediates (e. g. oxyphosphonium enolate 125 b), which dipolar structure can behave as a carbene surrogate.…”

“…explored the synthesis of spiro‐β‐lactams through [4+2] cycloaddition reactions between α‐alkylidene‐β‐lactams 120 and 4‐methyl‐[1,2,4]triazole‐3,5‐dione 121 , yielding racemic spiro[[1,2,4]triazolo[1,2‐ a ]pyridazine‐5,3’‐azetidine]‐1,2’,3(2 H ,8 H )‐triones 122 in good yields (62–75%) (Scheme 36). [52] …”

Butadienyl Ketene: An Unexplored Intermediate in Organic Synthesis

“…As a result, a mixture of 3-butadienyl-azetidin-2-ones 12 and 3but-2-azetidin-2-ones 13 was afforded in appreciable yield at elevated temperature. 19 Wang et al designed and synthesized three series of 3dienyl--lactams as inhibitors targeting a binding site of colchicine. 20 The imines 16 were accessed via butadienyl ketene generated in situ by the action of sorbic acid and suitable base in dichloromethane to afford 3-(buta-1,3dien-1-yl)azetidin-2-ones 17 (Table 5).…”

“…As a result, a mixture of 3-butadienyl-azetidin-2-ones 12 and 3-but-2-azetidin-2-ones 13 was afforded in appreciable yield at elevated temperature. 19…”

“…10a-c as major product. This is probably due to the tandem [2+2] cycloaddition of the in situ generated butadienyl ketene with the second imine of the 1,4-diazabuta-1,3 dienes to afford butenylidene-butadienyl-[2,2′-biazetidine]-4,4′-dione 10 as major cycloadducts[19].…”