Organocatalytic atroposelective N-alkylation: divergent synthesis of axially chiral sulfonamides and biaryl amino phenols

Abstract

Axial chirality exists ubiquitously in numerous natural products and has been extensively recognized for decades in pharmaceuticals and enantioselective transformations. The development of efficient methodologies to obtain enantiopure structures bearing...

Cobalt-catalyzed enantioselective C–H/N–H annulation of aryl sulfonamides with allenes or alkynes: facile access to C–N axially chiral sultams

“…4–9 While numerous methods have been developed for the synthesis of C–N axially chiral anilides, 10–13 the straightforward construction of C–N axially chiral sulfonamide continues to be underdeveloped despite its promising applications in the treatment of pain. 14 Currently, the known method remains predominantly confined to the atroposelective N–H functionalization of sulfonamides by employing organic or transition-metal catalysts, 15–20 pioneered by Taguchi 21 and Curran, 22 for Pd-catalyzed enantioselective N -allylation. Therefore, given the importance of chiral sulfonamides and their limited synthetic methods, the development of efficient and practical strategies to access enantioenriched C–N axially chiral sulfonamides is highly desirable.…”

Construction of Non-Biaryl Atropisomeric Amide Scaffolds Bearing a C–N Axis via Enantioselective Catalysis

“…Organocatalysis, designed to mimic biomimetic catalysis, is a powerful instrument by which to fulfill fascinating transformations [ 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 ]. To date, nucleophilic catalysis has experienced a range of developments regarding the construction of C–N axially chiral compounds by utilizing chiral amines [ 70 , 71 , 72 , 73 , 74 ] or isothioureas [ 75 , 76 ] as catalysts. The first exquisite amine-catalyzed asymmetric allylic alkylation (AAA) reaction to access C–N axially chiral scaffolds 45 was reported by Li and coworkers, which employed anilides 43 and Morita–Baylis–Hillman carbonates 44 as substrates, with the biscinchona alkaloid Cat-3 as the catalyst ( Scheme 12 ) [ 70 ].…”

“…Very recently, the Xiao and Chen groups reported a practical and concise organocatalytic atroposelective N -alkylation to efficiently approach sulfonamides bearing both an allene [ 79 , 80 , 81 ]. and an allyl entity, with high enantioselectivity ( Scheme 16 ) [ 72 ]. Significantly, this methodology also enabled selective N–H activation in the subsequent transformation toward functionalized sulfonamides and achieved the kinetic resolution of NOBIN analogs to obtain a series of chiral catalyst precursors.…”