Organocatalytic asymmetric allylic alkylation of 2-methyl-3-nitroindoles: a route to direct enantioselective functionalization of indole C(sp³)–H bonds

Abstract

A direct catalytic asymmetric functionalization of 2-methyl-3-nitroindoles using organocatalysis has been developed.

Direct C(sp3)–H allylation of 2-alkylpyridines with Morita–Baylis–Hillman carbonates via a tandem nucleophilic substitution/aza-Cope rearrangement

“…In their studies, although pyridine derivatives were also applicable in the reaction, the presence of a strong electron-withdrawing NO 2 group was necessary to promote the reaction but only with low yield (30%) ( Scheme 1c ). Recently, electron-deficient 3,5-dimethyl-4-nitroisoxazole and 2-methyl-3-nitroindoles were also served as vinylogous pronucleophiles to proceed the asymmetric allylic alkylation with MBH carbonates [ 25 – 26 ]. Overall, the reported C(sp 3 )–H allylic substitution reactions were mainly applied on the 2-alkyl-azaarenes containing strong electron-withdrawing groups.…”

“…[20][21][22][23]. The allylic substitution reactions using some weak nucleophiles, such as alkyl aza-arenes, were very limited [24][25][26][27][28][29]. In 2014, Rios and coworkers developed a synergistic catalyzed allylic alkylation between electron-deficient 2-ethyl benzoxazoles and MBH carbonates by the combination of a Lewis base and a metal salt [24].…”

Direct C(sp3)-H allylation of 2-alkylpyridines with Morita-Baylis-Hillman carbonates via a tandem nucleophilic substitution/aza-Cope rearrangement

“…The allylic substitution reactions using some weak nucleophiles, such as alkyl azaarenes, were very limited [22][23][24][25][26]. In 2014, Rios and coworkers developed a synergistic catalyzed allylic alkylation between electron-deficient 2-ethyl benzoxazoles and MBH carbonates by the combination of a Lewis base and a metal salt [22].…”

“…In their studies, although pyridine derivatives were also applicable in the reaction, the presence of a strong electron-withdrawing NO2 group was necessary to promote the reaction but only with low yield (30%) (Scheme 1c). Recently, electron-deficient 3,5dimethyl-4-nitroisoxazole and 2-methyl-3-nitroindoles were also served as vinylogous pronucleophiles to proceed the asymmetric allylic alkylation with MBH carbonates [23,24]. Overall, the reported C(sp 3 )-H allylic substitution reactions were mainly applied on the 2-alkyl azaarenes containing strong electron-withdrawing groups.…”

Pentaenolate activation in the organocatalytic allylic alkylation of indene-2-carbaldehydes

“…Morita–Baylis–Hillman (MBH) carbonates were selected as model electrophiles for the devised reactivity due to the fact that their ability to participate in the asymmetric allylic alkylations is well-recognized. 11 It was anticipated that the application of chiral tertiary amines as nucleophilic catalysts would ensure high stereocontrol of the process.…”