Synthesis of Novel 4-Halomethyl-1,3-oxaselenolane Substituted Spirocyclic Azetidin-2-ones from cis-3-Allyloxy-3-benzylselenoazetidin-2-ones

Abstract

A mild and efficient synthetic approach for the synthesis of novel 4-halomethyl-1,3-oxaselenolane substituted spirocyclic β-lactams via intraselenyl cyclization of cis-3-allyloxy-3-benzylselenoazetidin-2-one mediated by halogens (I2, Br2) is described. The mechanism involves step-wise electrophilic addition-dealkylation sequence generating spiroseleno-β-lactams stereospecifically. The novel synthesized β-lactams have been characterized by spectroscopic techniques viz. NMR ( 1 H, 13 C, 77 Se), FT-IR and elemental analysis. The cis configuration of the nucleophilic substituent at C-3 was assigned with respect to C4-H. Intraselenyl cyclization is a novel approach in the chemistry of β-lactam research.

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

“…used a similar method for the synthesis of 4‐halomethyl‐1,3‐oxaselenolane substituted spiro‐β‐lactams 135 via intraselenyl cyclization of cis ‐3‐allyloxy‐3‐benzylselenoazetidin‐2‐one 134 mediated by halogens, namely I 2 and Br 2 (Scheme 41). [57] Both halogens gave similar yields (68‐70% yield). The mechanism involves the initial generation of a π‐olefinic complex by coordination of the halogen to the alkene moiety followed by a stepwise nucleophilic addition‐dealkylation sequence to provide spiroseleno‐β‐lactams, in a pathway similar to the one proposed for C3 halospiro‐β‐lactams 127 synthesis (see Scheme 38).…”

An update on the synthesis and reactivity of spiro-fused β-lactams

“…Halocyclization of seleno-or thio-substituted β-lactams containing a carbon-carbon multiple bond concerns one of the pioneering methods for synthesis of halogenated 4-pyrazolyl spirocyclic-β-lactams. [79][80][81] Bhalla has recently reported on the synthesis of halogenated 4-pyrazolyl spirocyclic-β-lactams 107-110 via halogen-mediated intrasulfenyl cyclization of cis-3-propynyloxy-4-pyrazolyl-β-lactams 106 (Scheme 32). The effect of halogenating reagents and selectivity on the formation of the product has been carefully considered.…”