Chiral Nickel(II) Complex Catalyzed Enantioselective Doyle–Kirmse Reaction of α-Diazo Pyrazoleamides

Abstract

Although high enantioselectivity of [2,3]-sigmatropic rearrangement of sulfonium ylides (Doyle-Kirmse reaction) has proven surprisingly elusive using classic chiral Rh(II) and Cu(I) catalysts, in principle it is due to the difficulty in fine discrimination of the heterotopic lone pairs of sulfur and chirality inversion at sulfur of sulfonium ylides. Here, we show that the synergistic merger of new α-diazo pyrazoleamides and a chiral N, N'-dioxide-nickel(II) complex catalyst enables a highly enantioselective Doyle-Kirmse reaction. The pyrazoleamide substituent serves as both an activating and a directing group for the ready formation of a metal-carbene- and Lewis-acid-bonded ylide intermediate in the assistance of a dual-tasking nickel(II) complex. An alternative chiral Lewis-acid-bonded ylide pathway greatly improves the product enantiopurity even for the reaction of a symmetric diallylsulfane. The majority of transformations over a series of aryl- or vinyl-substituted α-diazo pyrazoleamindes and sulfides proceed rapidly (within 5-20 min in most cases) with excellent results (up to 99% yield and 96% ee), providing a breakthrough in enantioselective Doyle-Kirmse reaction.

Bimetallic Rhodium(II)/Indium(III) Relay Catalysis for Tandem Insertion/Asymmetric Claisen Rearrangement

“…reaction proceeded smoothly,a ffording a-vinylated-g-oxo-bamino ester 3aa in 95 %y ield with high diastereoselectivity (95:5 dr) after 2h,r evealing as trong background reaction. To our delight, switching the central metal from Zn(OTf) 2 to In(OTf) 3 led to ad ramatic increase of enantioselectivity (entry 8, 98:2 er vs.1 8:82 er) with almost completely maintained yield and diastereoselectivity (94 %y ield, 95:5 dr). Next, bimetallic relay catalytic system was introduced to validate the efficiencyo ft he proposed approach.…”

“…[1,2] Alternative precursors,such as pyridotriazoles, [3] 1,2,3-triazoles, [4] and 1H-tetrazoles [5] have been developed to overcome some drawbacks of diazo compounds and to richen the diversity of carbene intermediates.Among them, 1,2,3-triazoles,firstly explored as synthetic equivalents of azavinyl carbenes by Gevorgyan, Fokin, and co-workers, [4d] have the capacity of the formation of unique rhodium(II)-bound imino carbene intermediates I with the loss of dinitrogen, enabling numerous useful synthetic transformations. [1,2] Alternative precursors,such as pyridotriazoles, [3] 1,2,3-triazoles, [4] and 1H-tetrazoles [5] have been developed to overcome some drawbacks of diazo compounds and to richen the diversity of carbene intermediates.Among them, 1,2,3-triazoles,firstly explored as synthetic equivalents of azavinyl carbenes by Gevorgyan, Fokin, and co-workers, [4d] have the capacity of the formation of unique rhodium(II)-bound imino carbene intermediates I with the loss of dinitrogen, enabling numerous useful synthetic transformations.…”

“…Metal carbenes intermediates derived from diazo compounds have been extensively studied in organic synthesis over the past several decades. [1,2] Alternative precursors,such as pyridotriazoles, [3] 1,2,3-triazoles, [4] and 1H-tetrazoles [5] have been developed to overcome some drawbacks of diazo compounds and to richen the diversity of carbene intermediates.Among them, 1,2,3-triazoles,firstly explored as synthetic equivalents of azavinyl carbenes by Gevorgyan, Fokin, and co-workers, [4d] have the capacity of the formation of unique rhodium(II)-bound imino carbene intermediates I with the loss of dinitrogen, enabling numerous useful synthetic transformations. [6,7] Fore xample,t he tandem insertion/[3,3]sigmatropic rearrangement of N-sulfonyl-1,2,3-triazoles with allyl alcohol derivatives [6c,d] give access to b-amino and gamino acid derivatives,w hich are highly valuable in many scientific areas.…”

“…Next, bimetallic relay catalytic system was introduced to validate the efficiencyo ft he proposed approach. In the presence of Rh 2 (esp) 2 ,v arious metal salts were screened with N,N'-dioxide L 3 -PiPh as the ligand ( Table S2 in the Supporting Information). To our delight, the complexes of Zn(OTf) 2 or In(OTf) 3 with L 3 -PiPh could promote the reaction, delivering the corresponding product 3aa with 27:73 er and 55:45 er, respectively (entries 2 and 3).…”

“…Other reaction parameters including solvent, concentration, and temperature were also studied, however, no better results were obtained (for details,s ee the Supporting Information). To our delight, switching the central metal from Zn(OTf) 2 to In(OTf) 3 led to ad ramatic increase of enantioselectivity (entry 8, 98:2 er vs.1 8:82 er) with almost completely maintained yield and diastereoselectivity (94 %y ield, 95:5 dr). [13] This tandem reaction performed equally well when the chiral N,N'-dioxide-indium(III) catalyst loading was lowered from 10 mol %to2mol %( entry 9).…”