Bifunctional Brønsted Base Catalyzed [3 + 3] Annulations of Indolin-2-imines and α,β-Unsaturated Imides: An Enantioselective Approach to α-Carbolinones

Abstract

Asymmetric construction of α-carbolinones with easily available starting materials has recently attracted considerable attention from the synthesis community, and the development of effective catalysis for this target is in great demand. Here, a bifunctional Brønsted base catalyzed asymmetric [3 + 3] cyclization of indolin-2-imines and α,β-unsaturated N-acylated succinimides was developed by using the strategy of noncovalent bonding catalysis. With this organocatalytic protocol, a variety of tetrahydro-α-carbolinones bearing different substituents were synthesized with up to 99% yield and up to 96:4 er.

One‐Pot Regio‐ and Diastereoselective Synthesis of Tetrahydro‐α‐carbolines via Cascade Reactions of Iminoindolines with Morita‐Baylis‐Hillman Bromides of Nitroalkenes

“…IR spectra were recorded on PerkinElmer Spectrum One FT spectrometer. Bruker 400 and 500 MHz spectrometers were used to record NMR spectra ( 1 H, 13 C, APT and COSY) by using TMS as the internal standard. Coupling constants (J) are reported in Hz.…”

“…[2] However, methods for the synthesis of tetrahydrocarbolines, particularly, tetrahydro-α-carbolines are rare. [8][9][10][11][12][13][14][15][16] Substrates for the synthesis of tetrahydro-α-carbolines via various intra-and intermolecular cyclizations include 3-substituted indoles, [8] 2-substituted indoles, [9] tosyliminoindolines [10][11][12][13][14] and others such as nitropyridine [15] and o-iodobenzamide. [16] While tosyliminoindoline and its derivatives have been employed for the synthesis of a wide variety of heterocycles, [17] they react in a [4 + 2] [10][11] or [3 + 3] [12][13][14] fashion in the synthesis of tetrahydro-α-carbolines (Scheme 1a).…”

“…[8][9][10][11][12][13][14][15][16] Substrates for the synthesis of tetrahydro-α-carbolines via various intra-and intermolecular cyclizations include 3-substituted indoles, [8] 2-substituted indoles, [9] tosyliminoindolines [10][11][12][13][14] and others such as nitropyridine [15] and o-iodobenzamide. [16] While tosyliminoindoline and its derivatives have been employed for the synthesis of a wide variety of heterocycles, [17] they react in a [4 + 2] [10][11] or [3 + 3] [12][13][14] fashion in the synthesis of tetrahydro-α-carbolines (Scheme 1a). Although α,β-unsaturated carbonyl compounds participate in the [3 + 3] annulation of tetrahydro-α-carbolines, [12][13][14] nitroalkene derivatives have not been employed in such capacity as 3-carbon components.…”

“…[16] While tosyliminoindoline and its derivatives have been employed for the synthesis of a wide variety of heterocycles, [17] they react in a [4 + 2] [10][11] or [3 + 3] [12][13][14] fashion in the synthesis of tetrahydro-α-carbolines (Scheme 1a). Although α,β-unsaturated carbonyl compounds participate in the [3 + 3] annulation of tetrahydro-α-carbolines, [12][13][14] nitroalkene derivatives have not been employed in such capacity as 3-carbon components.…”

Construction of Indole‐Fused Heterocycles Starting from 2‐Thioxoindolines, Iminoindolines, and Their Derivatives

“…Compared with NÀ H free 1, the N-methyl indolin-2-imine provided poor results with regard to yield and enantioselectivity. [10] In 2018, a novel type of azadiene-building block 13, derived from iminoindoline 1, was successfully utilized in the direct sulfide-catalyzed [4 + 3] annulation with bromide 7 (Scheme 5a). After screening of various reaction conditions, the final optimal condition, thiophane C2 as catalyst in the presence of Cs 2 CO 3 in MeCN at room temperature, was determined.…”