Ring Expansion versus Cyclization in 4‐Oxoazetidine‐2‐ carbaldehydes Catalyzed by Molecular Iodine: Experimental and Theoretical Study in Concert

Abstract

Molecular iodine (10 mol%) efficiently catalyzes the ring expansion of 4-oxoazetidine-2-carbA C H T U N G T R E N N U N G aldehydes in the presence of tert-butyldimethylsilyl cyanide, or allylic and propargylic trimethylsilanes to afford protected 5-functionalized-3,4-dihydroxypyrrolidin-2-ones with good yield and high diastereoselectivity, through a C3 À C4 bond cleavage of the b-lactam nucleus. Interestingly, in contrast to the iodine-catalyzed reactions of 3-alkoxy-b-lactam aldehydes which lead to the corresponding g-lactam derivatives (rearrangement adducts), the reactions of 3-aryloxy-b-lactam aldehydes under similar conditions gave b-lactam-fused chromanes (cyclization adducts) as the sole products, through exclusive electrophilic aromatic substitution involving the C3 aromatic ring and the carbaldehyde. In order to support the mechanistic proposals, theoretical studies have been performed.

Advances in the chemistry of ?-lactam and its medicinal applications

“…139,140 The syn/anti selectivity depends mostly on the N-substituents and PMP gave the best results, i.e. 100% syn selectivity.…”

“…Other nucleophiles such as allyltrimethylsilanes and propargylsilane can be used in this unique reaction. 139 …”

Catalytic effect of molecular iodine in Diels–Alder reaction: a density functional theory study

“…This level of theory is found to be suitable for obtaining accurate energetic and geometrical results for DA reactions [10]. Recently, Domingo employed a similar level of theory to study ring expansion and cyclization in 4-oxoazetidine-2-carbaldehydes catalyzed by molecular iodine [41]. For all structures, frequency calculations were made to determine the nature of the stationary points.…”

Ring Expansions of β-Lactams and β-(thio)lactones

“…Then, after formation of complex 5, the nucleophilic attack of the oxygen to the Si atom causes the formation of the intermediate 5 0 . Finally, the cyanide carbon causes a nucleophilic attack to the carbenium ionic C4 atom of 5 0 to yield irreversibly the complex 2-I 2 , which gives compounds 2 (Scheme 2) [14].…”

“…Besides, β-lactams bearing aliphatic substituents at nitrogen gave the corresponding expansion products 2 chemoselectively, but with decreased diastereoselectivity. The ring expansion reaction has also been investigated using other silylated nucleophiles, such as allylic and propargylic trimethylsilanes [14].…”