A convenient synthesis of the β-lactam ring by 3 + 1 cyclization

β‐Lactam Synthesis through Diodomethane Addition to Amide Dianions

“…This selectivity is further confirmed by the known reactivity of amide dianions with Cbased electrophiles. Although this strategy was first described by Hirai et al in 1979, this seminal work was not followed by any other studies on the topic, probably owing to the low reported yields together with the highly restricted range of structures for the starting materials (need for at hiophenyl substituent). Thed ianion reacts with CH 2 I 2 to yield an intermediate iodomethyl Ugi adduct (Figure 2d), which in turn undergoes an internal cyclization reaction to form the final b-lactam ring (Figure 2f).…”

“…[7] We were particularly puzzled by as eminal report by Hirai et al from 1979 that involves using diiodomethane as ad ouble electrophile towards thiophenylamide dianions. [8] At hreesteps mechanism involving an episulfenium ion was proposed (Scheme 1). Although it is an amazingly simple procedure, lowreported yields andnarrowscope have preventedchemists from usingt he method.H erein, we demonstratet hatt he reaction canbetransformed into ageneral andefficient access to b-lactams without requiring any sulfur substituent.…”

“…Although it is an amazingly simple procedure, lowreported yields andnarrowscope have preventedchemists from usingt he method.H erein, we demonstratet hatt he reaction canbetransformed into ageneral andefficient access to b-lactams without requiring any sulfur substituent. [8] Considering these previous elements,w ed ecided to prepare the NH-tert-butyl malonamide 5a as ap latform to test our envisioned b-lactam formation. [9] Beside the work of Hirai et al,t he sole reported addition with amide NH derivatives was performed on derivatives 1 and led only to 2 [10] which probably explains the low yields observed in Hiraiss tudy (Scheme 2).…”

β‐Lactam Synthesis through Diodomethane Addition to Amide Dianions

“…Among these, [3+1] strategies such as CO insertion represent the least explored approaches . We were particularly puzzled by a seminal report by Hirai et al from 1979 that involves using diiodomethane as a double electrophile towards thiophenylamide dianions . A three‐steps mechanism involving an episulfenium ion was proposed (Scheme ).…”

“…Beside the work of Hirai et al, the sole reported addition with amide NH derivatives was performed on derivatives 1 and led only to 2 which probably explains the low yields observed in Hirai's study (Scheme ). Indeed, double intermolecular additions became the main synthetic pathway when trying to perform the reaction in more concentrated medium …”