Keteniminium‐Driven Umpolung Difunctionalization of Ynamides

Abstract

A three‐component Pd‐catalyzed coupling of ynamides, aryl diazonium salts, and aryl boronic acids for the synthesis of novel triaryl‐substituted enamides is described. This transformation represents the first example of an umpolung regioselective unsymmetrical syn‐1,2‐diarylation/aryl‐olefination of ynamides. The aryl moieties of the diazonium salt (electrophile) and boronic acid (nucleophile) are explicitly incorporated in the electrophilic α‐ and nucleophilic β‐position, respectively, of the ynamide, resulting in a single isomer of the N‐bearing tetrasubstituted olefin. The scope is broad (68 examples), showing excellent functional‐group tolerance. DFT calculations substantiate the rationale of the mechanistic cycle and the regioselectivity. The chemoselectivity and synthetic potential of the enamide products were also studied.

Three Component syn‐1,2‐Arylmethylation of Internal Alkynes**

“…The reaction scalability was verified through the gram scale synthesis of 4 (1.19 g, 90 %) from 1 a (1.0 g, 2.76 mmol), 2 a (2.0 equiv), and 3 a (3.0 equiv) in Pd(TFA) 2 (1.0 mol %; Scheme 5A).We next surveyed the synthetic flexibility of the methylated enamide and methylated allyl acetates. The selectfluor‐assisted oxyfluorination of 4 / 5 provided 68 / 69 in 46/55 % yield, respectively (Scheme 5B) [9b] . The Pd‐catalyzed DDQ promoted methyl oxidation followed by intramolecular arene cyclization of enamides led to β‐amino indenone derivatives 4→70 (41 %), 5→71 (39 %).…”

Regioselective Difunctionalization and Annulation of Ynamide

“…Nonetheless, a recent investigation has demonstrated a promising approach to overcoming this challenge by effecting a keteniminium‐driven umpolung 1,2‐difunctionalization under cationic palladium catalysis (Sahoo, Gandon, and co‐workers in 2020, Scheme 1). [13] The transformation involves the initial electrophilic activation of ynamide 1 a through the use of aryl metal‐complex 2 a . The complex is formed in situ via a barrierless oxidative addition of electrophile Ar 1 N 2 BF 4 ( 2 ) with Pd 0 , resulting in the formation of keteniminium species 4 a at an energy expense of 12.8 kcal mol −1 .…”

(Trifluoromethoxy)Phenylboronic Acids: Structures, Properties, and Antibacterial Activity

“…The syntheses of all isomers of (trifluoromethoxy)phenylboronic acids have been previously reported [ 13 , 14 , 15 ]. The title compounds have been numerously used in synthetic applications, mostly enabling the introduction of the trifluoromethoxyphenyl fragment [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ].…”