Copper(II) Triflate Catalyzed Regioselective and Enantioselective Propargylation of Isatin Derivatives by Using Allenylboronic Acid Pinacol Ester

Abstract

We report a simple protocol for the synthesis of homopropargyl alcohols with isatin derivatives under milder conditions for the first time. The excellent regioselectivity and yields were observed with copper triflate as a Lewis‐acid catalyst and allenylboronic acid pinacol ester as a nucleophile in aqueous media. A gram‐scale synthesis was done to check the efficiency of the protocol with retention in selectivity. Further one‐step functionalization of these homopropargyl alcohols was established as the synthetic application of these alkynes. The enantioselective synthesis of these chiral propargyl alcohols has also been explored for the first time with an enantiomeric ratio up to 12:88.

Catalytic Enantioselective Allylboration and Related Reactions of Isatins Promoted by Chiral BINOLs: Scope and Mechanistic Studies

“…Eventually, as an obvious extension of asymmetric allylboration of isatins, we studied the reactivity of allenylboronate reagent 28 in our organocatalytic method in view of the importance of homopropargylic alcohols in synthesis (Table ). To the best of our knowledge, only one example of asymmetric propargylation of isatins using allenylboronates has been reported in the literature to date . This metal-mediated method needed copper as a Lewis acid catalyst and chiral ligands to afford the corresponding homopropargylic alcohols with excellent yields but moderate to good enantioselectivity (er up to 88:12).…”

Synthesis and Reactivity of Allenylboron Compounds

“…Motivated by these keto-functionalization strategies, Khan introduced a protocol encompassing both racemic and enantioselective propargylation of isatins, thus obtaining 3-substituted 3-hydroxyindolin-2-ones 49 (Scheme 11e) in good yield. [49] The key step proceeds through the formation of a chiral allenyl copper species, which reacts with the isatin via an S N 2' mechanism. In addition, utilization of trifluoromethyl ketones has been shown by Ding's group to produce a wide range of enantioenriched tertiary α,αdifluoromethyl carbinols 50 promoted by Cat-2 ligated to Cu I (Scheme 11f).…”

“…Under optimized reaction conditions, the silver catalyst was capable of differentiating the two aromatic rings of prochiral benzophenones to produce enantioenriched diaryl carbinols. Motivated by these keto‐functionalization strategies, Khan introduced a protocol encompassing both racemic and enantioselective propargylation of isatins, thus obtaining 3‐substituted 3‐hydroxyindolin‐2‐ones 49 (Scheme 11e) in good yield [49] . The key step proceeds through the formation of a chiral allenyl copper species, which reacts with the isatin via an S N 2′ mechanism.…”

SN2″-Selective and Enantioselective Substitution with Unsaturated Organoboron Compounds and Catalyzed by a Sulfonate-Containing NHC-Cu Complex

“…We envisioned that it might be possible to develop catalytic enantio­selective S N 2″ additions by exploiting a key isomerization (akin to a 3,3′-reductive elimination) that was recently used in designing 1,6-conjugate additions . We imagined a process (Scheme b) through which a dienyl phosphate and commercially available allenyl-B­(pin) 1 (pin = pinacolato) would participate in an S N 2″- and enantio­selective substitution via I , and II (vs allene-containing derivatives by S N 2′ and S N 2 pathways). The propargyl and the 1,3-dienyl groups would render the expected products of considerable utility, especially when containing a stereochemically defined trisubstituted alkene.…”