Catalytic Asymmetric Nucleophilic Addition of 3-Vinyl Indoles to Imines

Abstract

The 3-vinyl indole is used as a nucleophile to react with aromatic and aliphatic imines. Chiral 3-substituted indoles bearing multiple functional groups are produced with up to 99% yield, a 98:2 E/Z ratio, and 97% ee. A possible mechanism is proposed to explain the observed stereoselectivities. This strategy provides an efficient way for the preparation of novel chiral 3-substituted indoles.

Selecting Chiral BINOL‐Derived Phosphoric Acid Catalysts: General Model To Identify Steric Features Essential for Enantioselectivity

“…Although, large proximal sterically derived catalysts are predicted not to be selective for reactions involving large displaced nucleophiles, they should proceed with high levels of enantioselectivity with small displaced nucleophiles. Examples of reactions exhibiting this trend are summarized in the Table …”

“…However, whether the reaction benefits from large proximal sterics or small depends on the sterics of the nucleophile. For smaller displaced nucleophiles, large proximal sterics are advantageous, disfavouring Type I E pathways 29, 33, 35, 36, 37, 38, 72, 73, 74, 75, 76, 77, 78. However, if the nucleophile is large, small proximal sterics are essential 32, 34, 39, 79, 80.…”

One‐Pot Synthesis of 3‐(2‐Fluoroalkenyl)indoles

“…Some examples of substituted 3‐vinylindoles have been reported to demonstrate anticancer and antibacterial activities . These molecules have found application as building blocks for the synthesis of a number of significant biologically active compounds: indole alkaloids, carbazole derivatives, β‐carbolines, cyclopentaindoles; chiral 3‐substituted indoles, tryptophan derivatives, bisindolylmethanes, indole‐substituted 1,2,3,4‐tetrahydroquinolines and flavonoids as well as indole‐substituted 1,1‐diarylethanes and 1,1,1‐triarylethanes. In addition the latter have been reported to exhibit impressive cytotoxicity against a number of human cancer cell lines …”

Development of the Vinylogous Pictet–Spengler Cyclization and Total Synthesis of (±)‐Lundurine A

“…As for the mechanism of this novel transformation, we hypothesize that upon treatment with aL ewis acid, ghydroxylactam 5 is converted into reactive N-acyliminium ion 7, [11][12][13] which may furnish the observed product through two paths.N ucleophilic attack of the vinyl group of indole 7 onto the N-acyliminium ion would lead to tetracycle 8, followed by deprotonation to generate tetrahydroazocinoindole 6 (path a). Alternatively,nucleophilic attack of indole 7 at the C3 position would lead to spirocycle 9,w hich could undergo a1 ,4-shift to yield the tetrahydroazocinoindole product (path b).…”