Direct Chan–Lam Amination and Etherification of Aryl BMIDA Reagents

Abstract

We report a method for the direct Chan-Lam coupling of arylboronic acid N-methyliminodiacetic acid esters (ArBMIDA) with amine and alcohol nucleophiles. A wide range of CÀ N and CÀ O cross-coupled products are obtained in 34-99 % yield (34 examples). This method serves to expand the scope of organoboron components that can be used directly in this oxidative coupling reaction and provides opportunities for streamlining synthesis.

Mechanistic Avenues in the Chan‐Lam‐Based Etherification Reaction: A Computational Exploration

“…[10,11] With these advantages, it became quite easy to witness the superiority of the CL couplings over its contemporary nucleophile-electrophile couplings based on Cu and Pd catalytic systems. [12,13,14,15] For the last few decades, there has been a constant commitment towards the methodological development over an extensive range of C-heteroatom bond formation reactions particularly from the research groups of Collman, [16,17,18] Stahl, [19,20] Watson, [21,22,23] Schaper, [24,25] and others. [26,27,28,29,30] Out of the vast volume of data pertaining to the optimization of reaction protocols, the landmark mechanistic studies based on CL etherification and amination reactions, independently pursued by the groups of Stahl and Watson, are noteworthy to mention in the current context.…”

“…[26,27,28,29,30] Out of the vast volume of data pertaining to the optimization of reaction protocols, the landmark mechanistic studies based on CL etherification and amination reactions, independently pursued by the groups of Stahl and Watson, are noteworthy to mention in the current context. [20][21][22] The most significant seminal studies are conducted by Stahl and co-workers based on CL etherification reaction using boronic esters in methanol solvent (Scheme 2a). In-depth kinetic studies based on spectroscopic and EPR measurements provide valuable insights into the mechanistic features of the etherification process leading to the understanding that transmetalation is rate-determining with the boronic ester coordinated Cu II intermediate as resting state.…”

“…For the last few decades, there has been a constant commitment towards the methodological development over an extensive range of C‐heteroatom bond formation reactions particularly from the research groups of Collman, [16,17,18] Stahl, [19,20] Watson, [21,22,23] Schaper, [24,25] and others [26,27,28,29,30] . Out of the vast volume of data pertaining to the optimization of reaction protocols, the landmark mechanistic studies based on CL etherification and amination reactions, independently pursued by the groups of Stahl and Watson, are noteworthy to mention in the current context [20–22] . The most significant seminal studies are conducted by Stahl and co‐workers based on CL etherification reaction using boronic esters in methanol solvent (Scheme 2a).…”

Synthesis of complex aryl MIDA boronates by Rh-catalyzed [2+2+2] cycloaddition

“…40 The BMIDA product can be manipulated using a variety of standard reactions to provide a range of functionalized arene scaffolds (Scheme 3a). This includes Brown oxidation ( 27), direct Chan-Lam amination (28) and etherification (31), 5,6,41 Suzuki-Miyaura cross-coupling (29), formation of the BF 3 K derivative (30), and direct Hayashi conjugate addition (32). Protected phenethyl alcohol derivative 9 and phenethyl amine derivative 14 could be deprotected and undergo direct intramolecular Chan-Lam etherification and amination to deliver fused heterocycle products (Scheme 3b).…”

“…Protected phenethyl alcohol derivative 9 and phenethyl amine derivative 14 could be deprotected and undergo direct intramolecular Chan-Lam etherification and amination to deliver fused heterocycle products (Scheme 3b). 41 For 14, the expected indoline 34 was isolated in low yield, with the major product the indole 35, arising from the desired Chan-Lam followed by Cu-mediated oxidation. [42][43][44] The utility of other protected alkynyl orgnoborons was evaluated through the use of BDAN alkyne 36 (Scheme 3c), which underwent the cycloaddition using the standard conditions (Table 1), displaying good reactivity.…”