Metal‐Free Activation of a C(sp)−H Bond of Aryl Acetylenes

Abstract

C(sp)-H Bond activation of acetylene molecule still remains a challenge for synthetic organic chemists. In practice, acetylenes are activated by strong bases and metals. The first example for activating acetylenic protons under base and metal-free conditions is reported here. It involves a general method for synthesizing propargylic derivatives of cotarnine. An array of tetrahydroisoquinolines alkaloids was synthesized by C(sp)-H bond activation of aromatic acetylenes with cotarnine at room temperature. A DFT-based mechanism is proposed for the reaction.

Double C–H bond activation of acetylene by atomic boron in forming aromatic cyclic-HBC2BH in solid neon

“… 34 The present finding reveals the very first example of metal-free double C–H bond activation of acetylene. 38 It provides a possible new reaction route for metal-free C–H bond activation of acetylene in forming new aromatic organo-boron compounds.…”

Metal‐Free Activation of C(sp3)–H Bond, and a Practical and Rapid Synthesis of Privileged 1‐Substituted 1,2,3,4‐Tetrahydroisoquinolines

“…The core unit cotarnine ( 1 ) could be synthesized along with opianic acid in 90 % yield on a gram scale by oxidative degradation of commercially available ( S , R )‐noscapine with 14 % HNO 3 (Scheme ) , …”

“…To our knowledge, there is no report, on the addition of acyl ketone enolates to cotarnine halide salts. However, Yamato and co‐workers[8i] reported a related method based on N,O‐acetal‐derived tetrahydroisoquinolines starting from iminium bromide.…”

“…As part of our goal of research on developing environmentally benign methods for carbon–carbon bond‐formation for use in medicinal chemistry and the development of novel anticancer agents, herein we wish to report an efficient one‐pot synthesis of 1‐substituted 1,2,3,4‐tetrahydroisoquinolines involving cotarnine and a diverse array of ketones in green solvents at room temperature under base‐free conditions to give simplified noscapine analogues in excellent yields. This reaction is scalable to a multi‐gram scale and provides products through a non‐chromatographic method (precipitation in the reaction mixture).…”

Oxygen Bridged Bimetallic CuMoO4Nanocatalyst for Benzylic Alcohol Oxidation; Mechanism and DFT Study

“…[22] Cotarnine derivativeshas very good anti‐tussive and anticancer property. It is noteworthy that the oxidation reaction proceeded smoothly affording corresponding carbonyl products in 83–88% yield without any side product [22c–d] . The starting alcohols were synthesized by reduction of corresponding ketones with 2 eq.…”