J Am Chem Soc. 2021 May 12; 143(18): 6817–6822.

Published online 2021 Apr 28. doi: 10.1021/jacs.1c03257

PMCID: PMC8154516

PMID: 33908753

Azine Activation via Silylium Catalysis

Carla Obradors and Benjamin List*

Nitrogen-based heterocycles constitute cardinal pharmacophores in a myriad of biologically active products spanning from synthetic drugs to agrochemicals.1 Still, retrosynthetic analysis of representative targets relies largely on engineered ring condensations and manipulation of prefunctionalized building blocks.2 An array of alternative methods toward late-stage diversification of complex N-heterocycles has consequently arisen,3 capitalizing on Minisci-type reactions, transition-metal-mediated C–H activation processes, or photoredox transformations.4 While significant progress has been achieved, limited selectivity, harsh conditions, or a restricted scope is rather common and preactivation of the substrate remains the prevailing approach to date (Figure ​Figure11A).5 Thus, complementing N-acylation and alkylation approaches,6 perhaps the most prominent strategy involves the formation of an N-oxide motif to enable a nucleophilic addition to the aromatic ring.7 Despite its vast utility, this classical route requires prior preparation—if not isolation—of sensitive intermediates, followed by appendage of the desired scaffold. A tedious step to remove the activating group is also frequently necessary, leading to stoichiometric waste generation. In addition, the required reagents often limit the functional group tolerance of the overall transformation. Therefore, the design of novel methodologies allowing for milder conditions and direct disconnections is a recurrent challenge for chemical synthesis. The preparation of phosphonium salts reported by McNally et al. and a novel bifunctional reagent described by Fier stand out as the latest annexes to the toolkit.8,9 Furthermore, the Buchwald group recently reported an asymmetric copper-catalyzed addition of styrenes to pyridines, in which turnover is achieved upon reaction of the organometallic species with an external reductant.10

Olsen

You may used the old method starting with sugar and phenylenediamine

Good luck