A BF₃·Et₂O catalyzed atom-economical approach to highly substituted indole-3-carbinols from nitrosobenzenes and propargylic alcohols

Abstract

The BF·EtO catalyzed reaction of nitrosobenzenes and an excess amount of propargylic alcohols was investigated to synthesize highly-substituted indole-3-carbinols. This reaction involves formal [3 + 2]-cycloaddition and the subsequent 1,3-rearrangement in a tandem manner via 3-alkylidene-3H-indole N-oxides. This methodology involves the sequential addition of propargylic alcohols and inexpensive Lewis acid catalyst, occurs in an open-air environment and is atom economical. The highly-substituted indole-3-carbinols were obtained in short time and the operational simplicity allows for a large scale experiment.

Recent Advances in the Synthesis of Heterocyclics via Cascade Cyclization of Propargylic Alcohols

“…Very interestingly, when changing the mole ratio of propargylic alcohols 1 and nitrosobenzenes 138 from 1 : 1 to 2 : 1, the novel indole‐3‐carbinols 140 were obtained in good to excellent yields under the same reaction conditions (Scheme 55). [74] More importantly, the structure of the product could well be controlled through adding order of different propargylic alcohols.…”

Scope and advances in the catalytic propargylic substitution reaction

“…of propargylic alcohols 39 in the presence of BF 3 $Et 2 O as a catalyst, Scheme 22. 51 The mechanism for the propargylation is highlighted in Scheme 23. The key step is the formation of allene carbocation 39b under the inuence of the Lewis acid catalyst, BF 3 $Et 2 O.…”

Acid‐Promoted Cascade Reaction of 4H‐Chromenes: Access to Hexahydronapthalenes via Decarboxylative Intramolecular Cyclization

“…Interestingly, yields of product 6 increased to 53 % (Table 1, entry 8). However, disappearance of 2 and formation of a product 7 [17] in 15 % yields was observed along with 5 (Scheme 3).…”

“…Initially, 2‐amino‐7,7‐dimethyl‐5‐oxo‐4‐phenyl‐5,6,7,8‐tetrahydro‐4 H ‐chromene‐3‐carbonitrile, [,14a] ( 1 , 1.0 equiv) was reacted with 1,1,3‐triphenylprop‐2‐yn‐1‐ol [17] ( 2 , 1.0 equiv) in presence of Zn(OTf) 2 (0.05 equiv) in 1,2‐dichloroethane at ambient temperature for 8 h as per the reported method [18] anticipating the formation of 3 . However, products 4 , 5 , 6 in the ratio of 46 %, 20 % and 30 % yields were observed (Scheme 2).…”