Stereoselective Synthesis of β-Lactam-triflones under Catalyst-Free Conditions

Abstract

The first example of the synthesis of β-lactam-triflones is described. Treatment of 2-diazo-1-aryl-2-(trifluoromethylsulfonyl)ethanones 1c-f with imines 2 under catalyst-free heating conditions provides pharmaceutically attractive multisubstituted β-lactam-triflones 3 in good to high yields with regio- and diastereoselectivities. A successive Wolff rearrangement and Staudinger [2 + 2] cycloaddition reaction are key elements for the success of this transformation.

α‐Diazo‐β‐oxosulfones as Partners in the Wolff 1,2,3‐Triazole Synthesis and the Wolff Rearrangement in the Presence of Aromatic Amines

“…This notion is attested to by such examples as glucagon receptor antagonist 10 , cholesterol O ‐acyl transferase inhibitor 11 , antiviral compound 12 as well as compound 13 , an inhibitor of enzymes containing redox‐sensitive cysteines (Figure ). Considering that examples of the Wolff rearrangement of α‐diazo‐β‐oxo sulfones reported in the literature are limited to those of trifluoromethyl sulfones (triflones),, establishing the generality of transformation 1 → 5 appeared a worthy undertaking.…”

“…These compounds, however, are easily accessible from the respective -keto sulfones by diazotransfer reaction [10] and have been reported to undergo such transformations as the thermal Wolff rearrangement with the trapping of the respective ketene intermediate with nitrogen nucleophiles (giving rise to amides 5) [11] and imines (producing -lactams). [12] Puzzled by the lack of reports in the literature on the involvement of α-sulfonyl α-diazocarbonyl compounds 1 (R 1 = SO 2 R) in the Wolff 1,2,3-triazoles synthesis, we decided to investigate this possibility. Filling this methodology void, we reasoned, would provide a streamlined entry in the 1,5-disubstituted 4sulfonyl 1,2,3-triazole core which is featured in a range of biologically active compounds such as bromodomain inhibitor 6, [13] antifungal compound 7, [14] pregnane X receptor antagonist 8 for attenuation of drug metabolism [15] and anti-inflammatory GPR43 receptor agonist 9 [16] (Figure 2).…”

2‐Diazo‐1‐phenyl‐2‐((trifluoromethyl)sulfonyl)ethan‐1‐one: Another Utility for Electrophilic Trifluoromethylthiolation Reactions

“…Even though 1 is a trifluoromethanesulfonyl (SO 2 CF 3 ) compound, it effectively releases electrophilic SCF 3 species via carbene generation. As part of an ongoing research program committed to trifluoromethylthiolation reactions, we were interested in the potential utility of 2‐diazo‐1‐phenyl‐2‐((trifluoromethyl)sulfonyl)ethan‐1‐one ( 2 ), as a shelf‐stable reagent for electrophilic trifluoromethylthiolation reactions.…”

“…Diazo‐triflone 2 was originally developed as an effective SO 2 CF 3 building block for the synthesis of triflones . Under thermal conditions, 2 reacts with imines to provide multiple substituted β‐lactam triflones in essentially quantitative yields via successive carbene‐generation, Wolf rearrangement (ketene), and Staudinger [2+2] cycloaddition (Scheme a) . The similarity of carbene generation from 2 and that from 1 led us to investigate a new utility of 2 for electrophilic trifluoromethylthiolation, via successive carbene‐generation/oxathiirene‐2‐oxide/sulfoxide/thioperoxoate rearrangement (Scheme b) …”

Catalyst-Free Synthesis of Diastereomerically Pure 3-Sulfonyl­azetidin-2-ones via Microwave-Assisted Tandem Wolff Rearrangement–Staudinger Cycloaddition

“…The only example of a similar approach reported in the literature to date is the synthesis of -lactam triflones 4 by Shibata and co-workers (Scheme 1). 13 While investigated for only four diazo triflone precursors 5, this syn-diastereoselective transformation was described as failing for nontrifluoromethyl -diazo--ketosulfones (such as methyl sulfonyl), which was proposed as an evidence for the critical role of the triflyl group in 5 for the success of the reaction. Wondering about the possible reasons for this limitation of the scope, and having a wide range of -diazo--ketosulfones 1 at our disposal, we set off to investigate their ability to produce -lactam sulfones 3 under thermal conditions.…”