Enantioselective cis-β-lactam synthesis by intramolecular C–H functionalization from enoldiazoacetamides and derivative donor–acceptor cyclopropenes

Abstract

β-Lactam derivatives are produced through donor–acceptor cyclopropene intermediates in high yield with exclusive cis-diastereoselectivity, and high enantiocontrol.

Cycloaddition reactions of enoldiazo compounds

“…167,168 In these [1+ n ]-cycloaddition processes ( n = 2, 6), catalytically generated metallo-enolcarbenes served as one-carbon synthons (the carbene carbon) to furnish the corresponding cyclopropane, 158–165 cyclopropene, 166 and cycloheptatriene 167,168 derivatives.…”

“…102,122,132,152,167,168 Furthermore, the cyclopropenes, preformed from enoldiazo compounds under catalytic or thermal conditions, have proven to be effective metallo-enolcarbene precursors in several MECC reactions. 102,115,122,124,132,165,167,168 As depicted in Scheme 35, catalyst-controlled divergent outcomes are obtained from cycloaddition reactions of enoldiazoacetate 1a with Isoquinolinium methylide 40a . 132 Coordination of the Lewis basic methylide to the carbene-bound dirhodium catalyst promotes the formation of donor–acceptor cyclopropene from rhodium-enolcarbene.…”

Versatile Donor‐Acceptor Cyclopropenes in Metal Carbene Transformations

“…Donor‐acceptor cyclopropenes, constructed with an electron donating group (e.g., trialkylsilyloxy) at C1 and an electron withdrawing group (e.g., COR) at C2, are drawing increasing interest in organic synthesis owing to their versatile reactivity and convenient accessibility . They have been identified as the first‐formed intermediates in reactions of enoldiazoacetates, and they have been shown to undergo classic metal carbene reactions under very mild conditions . Formed by intramolecular cycloaddition of their precursor vinylcarbene intermediate, these donor‐acceptor cyclopropenes appear to be the carbene resting state for many, if not all, catalytic reactions of enoldiazoacetates and enoldiazoacetamides.…”

“…Recently, our group has discovered and reported that donor‐acceptor cyclopropenes generated from enoldiazo compounds are versatile carbene precursors. The catalytically generated metallo‐enolcarbenes from enoldiazo compounds have been effectively employed for dirhodium(II) catalyzed C−H insertion and cyclopropanation reactions, which are characteristic of metal carbene intermediates. In addition, the electrophilic center of the metallo‐enolcarbene intermediate that is delocalized to the vinylogous carbon makes this vinylcarbenic structure a metallo‐1,3‐dipole equivalent, which allows capture of a dipolar species in a stepwise or concerted process to complete formal [3+3]‐cycloaddition reactions ,.…”

On the Structure of Chiral Dirhodium(II) Carboxylate Catalysts: Stereoselectivity Relevance and Insights

“…In 1993, Hashimoto, Ikegami and co-workers first reported their famous complex, Rh 2 (S-PTTL) 4 [76,77], as a catalyst that manifested (along with its variants) high enantioselectivity levels in wide range of organic transformations [2,54,[78][79][80][81][82][83][84]. For example, in enantioselective [2,3]-sigmatropic rearrangement of the cyclic propargylic oxonium ylide shown in Scheme 5a, Rh 2 (S-PTTL) 4 provided the best enantioselectivity of 79% ee of the corresponding allenic bearing benzofuran-3-one product (Scheme 5a) [85].…”