Copper-Catalyzed Enantioselective Doyle-Kirmse Reaction of Azide-Ynamides via α-Imino Copper Carbenes.

[2,3]-Sigmatropic rearrangement reaction involving sulfonium ylide (Doyle-Kirmse reaction) generated from metal carbenes represents one of the powerful methods for the construction of C(sp3 )-S and C-C bonds. Although significant advances have been achieved, the asymmetric versions via the generation of sulfonium ylides from metal carbenes have been rarely reported to date, and they have so far been limited to diazo compounds as metal carbene precursors. Here, we describe a copper-catalyzed enantioselective Doyle-Kirmse reaction via azide-ynamide cyclization, leading to the practical and divergent assembly of an array of chiral [1,4]thiazino[3,2-b]indoles bearing a quaternary carbon stereocenter in generally moderate to excellent yields and excellent enantioselectivities. Importantly, this protocol represents a unique catalytic asymmetric Doyle-Kirmse reaction via a non-diazo approach and an unprecedented asymmetric [2,3]-sigmatropic rearrangement via α-imino metal carbenes.

Difluoroacetaldehyde N-Triftosylhydrazone (DFHZ-Tfs) as a Bench-Stable Crystalline Diazo Surrogate for Diazoacetaldehyde and Difluorodiazoethane.

Despite the growing importance of volatile functionalized diazoalkanes in organic synthesis, their safe generation and utilization remain a formidable challenge because of their difficult handling along with storage and security issues. In this study, we developed a bench-stable difluoroacetaldehyde N-triftosylhydrazone (DFHZ-Tfs) as an operationally safe diazo surrogate that can release in situ two low-molecular-weight diazoalkanes, diazoacetaldehyde (CHOCHN2 ) or difluorodiazoethane (CF2 HCHN2 ), in a controlled fashion under specific conditions. DFHZ-Tfs has been successfully employed in the Fe-catalyzed cyclopropanation and Doyle-Kirmse reactions, thus highlighting the synthetic utility of DFHZ-Tfs in the efficient construction of molecule frameworks containing CHO or CF2 H groups. Moreover, the reaction mechanism for the generation of CHOCHN2 from CF2 HCHN2 was elucidated by density functional theory (DFT) calculations.

Umpolung Reactivity of Diazo Arylidene Succinimides: Distal C-H Functionalization of α-Thiocarbonyls from the Reactive Carbenoid Center.

Herein, for the first time we have explored the umpolung reactivity of the vinylogous carbon center of diazo arylidene succinimide (DAS) through rhodium catalysis to achieve [2,3]-Stevens rearrangement of α-thioether esters. The protocol has successfully demonstrated the distal C-H bond functionalization of the α-thioether esters. Alongside, the carbenoid reactivity of DAS has also been achieved with Doyle-Kirmse reaction of allyl/propargyl phenyl sulfides. The protocol proved to be practical to synthesize a wide variety of [2,3]-Stevens rearrangement products exclusively and the possible side products emanating from Pummerer rearrangement and [1,2]-Stevens rearrangement were not observed. This catalytic protocol works smoothly in environmentally benign solvent under open air to afford the corresponding desired products with excellent diastereo-, regio- and chemo-selectivities in good to excellent yields. The protocol also proved to be scalable on gram quantity.