Diarylprolinol Silyl Ether Catalyzed Asymmetric Friedel–Crafts Alkylation of Indoles with α,β‐Unsaturated Aldehydes: Enhanced Enantioselectivity and Mechanistic Investigations

Abstract

A highly enantioselective Friedel-Crafts alkylation of indoles with α,β-unsaturated aldehydes with excellent enantioselectivities (up to Ͼ99 % ee) has been developed, and this improved method offers substantial advantages over traditional approaches, not only by avoiding the use of acids or bases, but also in terms of the higher level of stereoselectivity. In addition, we have demonstrated through a plausible

Highly Active Urea-Functionalized Zr(IV)-UiO-67 Metal–Organic Framework as Hydrogen Bonding Heterogeneous Catalyst for Friedel–Crafts Alkylation

“…The Friedel–Crafts alkylation reaction of indoles with β-nitrostyrene is one of the fundamental organic reactions often catalyzed by the presence of Lewis acids, leading to C–C bond formation. − Among these substrates, nitroalkenes are one of the preferred Michael acceptors widely used in this reaction due to the strong electron-withdrawing nature of nitro group and have been extensively used in organic synthesis . Furthermore, Friedel–Crafts alkylation reactions between arenes and nitroalkenes have been reported with a wide range of homogeneous Lewis acid catalysts. − Although this reaction can afford an asymmetric product, there are limited examples of these types of reactions catalyzed by Lewis acids with high enantiomeric values due to the significant restrictions on the substrates. − …”

Urea-engineering mediated hydrogen-bond donating Friedel–Crafts alkylation of indoles and nitroalkenes in a dual-functionalized microporous metal–organic framework with high recyclability and pore-fitting-induced size-selectivity

“…For example, the Friedel-Crafts alkylation reaction of nitroalkene with indole is one of the fundamental C-C bond forming reactions, catalyzed by the presence of suitable Lewis acids. [1][2][3][4] Among diverse substrates, β-nitrostyrene is considered the most preferred Michael acceptor in this reaction because of the strong electron-withdrawing nature of the nitro group. 5,6 However, the lower nucleophilicity of non-N-substituted indoles compared to their N-alkylated (viz.…”

Enantioselective Organocatalytic Friedel–Crafts Alkylation Reaction of Indoles with 5-Hydroxyfuran-2(5H)-one: Access to Chiral γ-Lactones and γ-Lactams via a Ugi 4-Center 3-Component Reaction

“…Since the first introduction of diphenylprolinol silyl ether in organocatalysis, , its high catalytic efficiency in numerous asymmetric transformations involving iminium or enamine intermediates has elevated it to the class of privileged catalysts. The use of diphenylprolinol silyl ether in the Friedel–Crafts alkylation of indole with α,β-unsaturated aldehydes was recently reported. − The use of 20 mol % catalyst loading and 0.5 equiv of triethylamine allowed addition of indole to α,β-unsaturated aldehydes in good yield (67–95%) and enantioselectivity (92–98% ee) when the reaction was carried out at −20 °C in MTBE for 36 h . When cinamaldehyde derivatives were used as electrophiles, good yield (60–87%) and enantioselectivity (86–93% ee) were also obtained using the same catalyst loading without the use of any additive when carried out in methanol.…”

“…Very recently, higher enantioselectivity was obtained (up to 99% ee) with modified diphenylprolinol silyl ether derivatives. However, only moderate yields (37–65%) were obtained after a prolonged reaction time (45 h) …”