Copper-Catalyzed Electrophilic Amination of Organolithiums Mediated by Recoverable Siloxane Transfer Agents

Abstract

The development and validation of copper-catalyzed, electrophilic amination of aryl and heteroaryl organolithiums with N,N-dialkyl -O-benzoylhydroxylamineshavebeenachievedexploitingrecoverablesiloxanetransferagents. Given the readily availability of organolithium compounds, the mild reaction conditions, the ease of product purification and the ready recovery of the siloxane transfer agents, this transformation comprises a useful tactic to access diverse aryl and heteroaryl amines.

A Catalyst‐Free Amination of Functional Organolithium Reagents by Flow Chemistry

“…[1] With an advancement of transition-metal-catalyzed coupling reactions,t he Ullman-Goldberg amination, [2] Buchwald-Hartwig amination, [3] and Chan-Lam coupling reactions [4] have been developed as highly reliable means of carrying out CÀNb ond formations by an ucleophilic amination. [14] Though the direct amination of organolithiums [15,16] has been studied, it still remains an ongoing challenge.T he direct amination of organolithiums suffers from low yields,formation of by-products,and limited scope because of the instability and low selectivity of organolithiums. [8] Many electrophilic aminating reagents have been developed for the electrophilic amination of organometallic compounds such as organomagnesiums, [9] organozincs, [10] organocoppers, [11] and organoaluminums.…”

“…[12] These compounds,h owever,a re often prepared by the metal exchange from the corresponding organolithiums.T herefore,t he direct use of organolithiums would serve as more efficient method, from the persepctive of atom [13] and step economy. [14] Though the direct amination of organolithiums [15,16] has been studied, it still remains an ongoing challenge.T he direct amination of organolithiums suffers from low yields,formation of by-products,and limited scope because of the instability and low selectivity of organolithiums. [7a,d] Thef ield of flow chemistry,w hich is often based on microfluidics,has been rapidly growing in last two decades.…”

Design, Synthesis, and Application of Polymer-Supported Silicon-Transfer Agents for Cross-Coupling Reactions with Organolithium Reagents

“…25 A preliminary example is showed in Scheme 10 in which PNTA-I 200 was used in the copper-catalyzed, electrophilic amination of PhLi to generate the desired aniline 16 . This protocol featured a chromatography-free purification strategy in which the desired amination product was purified by acid-based extraction and the polymer was recovered via precipitation in MeCN and reused for two additional cycles.…”

Transition‐Metal‐Catalyzed Electrophilic Amination: Application of O‐Benzoylhydroxylamines in the Construction of the C−N Bond

“…In 2013, Smith III and co‐workers transformed aryl‐ and heteroaryl organolithiums into aromatic amines by employing the siloxane transfer agents 45 and O ‐benzoylhydroxylamine 46 (Scheme ) . Under the standard reaction conditions, the siloxane transfer agents could be recovered fully.…”

“…In 2013, Smith III and co-workers transformeda ryl-and heteroaryl organolithiums into aromatic amines by employing the siloxane transfer agents 45 and O-benzoylhydroxylamine 46 (Scheme 14). [20] Under the standard reactionc onditions, the siloxanet ransfer agents could be recovered fully.B oth acyclic and cyclic amines performed successfully to give the corresponding anilines in good to excellent yields. However, electron-withdrawing groups on the aromatic ring or sterically hindered organolithiumscould suppress this transformation.…”