Enantioselective [3+2] annulation of isatin-derived MBH-carbonates and 3-nitroindoles enabled by a bifunctional DMAP-thiourea

Abstract

Highly enantioselective [3+2] annulation of isatin-derived MBH-carbonates and 3-nitroindoles was achieved by a chiral DMAP-thiourea bifunctional catalyst.

Progresses in organocatalytic asymmetric dearomatization reactions of indole derivatives

“…83 In 2020, to solve the issue of controlling the enantioselectivity of the reaction, Tian, Lin, Ge, Gao and coworkers utilized a chiral DMAP-thiourea C42 as a bifunctional catalyst to enable a highly enantioselective CADA [3 + 2] annulation of 3-nitroindoles 176 with MBH carbonates 186, which synthesized a series of cyclopentaindoline-based spirooxindoles 187 in high yields and excellent stereoselectivities (Scheme 44b). 84 Furthermore, preliminary biological evaluation discovered that product 187b displayed promising inhibition activity against pancreatic lipase. Scheme 42 Organo-CADA [3 + 2] cycloaddition of 3-nitroindoles with allenoates by Zhang's group.…”

“…Scheme 44 Organo-CADA [3 + 2] annulation of 3-nitroindoles with MBH carbonates. 83,84 Scheme 45 Organo-CADA spirocyclization of C3-functionalized indoles via cascade catalysis by You and coworkers. 85 Finally, an intramolecular dearomative cyclization occurred, which realized the spirocyclization and afforded products 195.…”

Reactivity of 3-nitroindoles with electron-rich species

“…recently showed that a related enantioselective (3+2) annulation reaction could be performed on electrophilic 3-nitroindoles 1, in the presence of a bifunctional DMAPthiourea organocatalyst 56. 37 Spirooxindoles 57, bearing a cyclopentannulated indoline and three consecutive stereocenters, were thus obtained in high yields and enantioselectivities (Scheme 22). Scheme 22: (3+2) annulation between 3-nitroindoles 1 and isatin-derived MBH carbonate 55 in the presence of the bifunctional organocatalyst 56.…”

“…Scheme 21: (3+2) Formal cycloadditions in the presence of -functionalized allenoates 53.Starting from a different substrate that is an isatin-derived Morita-Baylis-Hillman (MBH) carbonate 55, Gao, Ge, Tian and coll. recently showed that a related enantioselective (3+2) annulation reaction could be performed on electrophilic 3-nitroindoles 1, in the presence of a bifunctional DMAPthiourea organocatalyst 56 37. Spirooxindoles 57, bearing a cyclopentannulated indoline and three consecutive stereocenters, were thus obtained in high yields and enantioselectivities (Scheme 22).…”

Metal-Free C–C/C–N/C–C Bond Formation Cascade for the Synthesis of (Trifluoromethyl)sulfonylated Cyclopenta[b]indolines

“… 2 Synthetic efforts involving these polycyclic systems focus on the development of the dearomatization of indoles 3 either by the electrophilic activation of indole substrates bearing nucleophilic sites ( Scheme 1 a) 4 or by dearomative cycloadditions ( Scheme 1 b). 5 The de novo synthesis of polycyclic indolines, chemical transformations of sophisticated aniline-derived substrates, despite being interesting, required expensive transition metal catalysts. 6 Consequently, we were interested in the development of a novel cascade reaction to produce the polycyclic indolines from easily available aniline-derived substrate A with Tf 2 C=CH 2 (Tf = SO 2 CF 3 ), which exhibits outstanding high electrophilicity ( Scheme 1 c).…”