Synthesis of 3-Selena-1-dethiacephems and Selenazepines via Iodocyclization

Abstract

A convenient approach to synthesize novel selenium-beta-lactams, 3-selena-1-dethiacephems and selenazepines, was accomplished via the regioselective iodocyclization reaction. The substituent of allenyl moieties dramatically influenced the regiochemical outcome in the iodocyclization of allene-selenourea derivatives.

Selenium-Containing Bicyclic β-Lactams

“…of iodine resulted in the formation of 3-selena-1-dethiacephems 65a-65e as the major product with traces of the corresponding five-membered product isodethiaselenapenams (Scheme 17). 42 Good yields were obtained in all cases, irrespective of the nature of substituent present on the selenourea group (65a-65e).…”

“…41 The retrosynthetic disconnection approach as shown in Figure 3 suggests that a variety of selenium-containing β-lactams having selenium other than at C4-position can be easily prepared from the allene-or alkyne-selenoureas via an iodocyclization reaction. 42 Further, the key intermediates alkyne-selenoureas 60 (Scheme 15) or allene-selenoureas 64…”

“…42 The nature of the R 2 group on the selenourea had very little effect on the reaction rate or product yields. Aryl-substituted selenoureas (60a-60d) gave slightly higher yield than alkyl-substituted selenoureas (60e-60f).…”

“…Further, the presence of iodine in the 3-selena-1-dethiacepham 61a allowed the further structural elaboration, most notably using palladium-catalyzed coupling reaction (Scheme 18). 42 When compound 61a was exposed to Sonogashira coupling conditions 48 with phenylacetylene, the corresponding coupling product 67 was isolated in excellent yield (Scheme 18). 42 The imine group in the 3-selena-1-dethiacepham 67 is advantageous for further functionalization.…”

Facile Synthesis of Selenium‐Containing Bicyclic β‐Lactams through Enyne Metathesis

“…In this context, however, there are very few reports relating to the synthesis of seleniumcontaining bicyclic β-lactams available in the literature, due to the difficulties involved in their preparation. [3] We have recently reported a 2-(trimethylsilyl)ethyl (TSE) protection approach [4] for the incorporation of selenium into penam and cephem nuclei and an iodocyclization approach [5] for the synthesis of selenium-containing β-lactams with a selenium atom at the 3-or 4-position, with the aim of providing some novel compounds of potential biological significance.…”