Copper-Catalyzed Electrophilic Amination of Organoboron Compounds

Abstract

A new procedure for direct transformation of alkenes to tertiary alkylamines based on hydroboration and copper-catalyzed amination of alkylboranes is described. The new method is presented in a broader context provided by a brief analysis of various approaches to the formation of anti-Markovnikov hydroamination products. A short discussion of the reaction development, scope, and the mechanism are also provided. Finally, the extension of this methodology to the preparation of hindered anilines from aryl boronic esters is presented.The synthesis of alkyl amines is one of the most important and common tasks encountered in the preparation of biologically active molecules. 1 A recent analysis of reactions used in pharmaceutical industry suggests that this task is almost exclusively accomplished by either reductive amination of carbonyl compounds or by substitution of alkyl halides or sulfonates. 2 The synthesis of alkyl amines from most other precursors usually requires functional-group interconversion, followed by amination using one of the two standard methods. As a result, the development of new reactions for direct amination of other functional groups has attracted a lot of attention as a way to facilitate the synthesis of alkyl amines.Alkenes are particularly attractive as synthetic precursors. They are readily available and have orthogonal reactivity to that of polar functional groups found in biologically active molecules. The most direct approach to obtain alkyl amines from alkenes is by addition of an amine across an alkene double bond. 3 This transformation has been the focus of numerous studies ever since initial reports of metalcatalyzed hydroamination under mild conditions appeared more than two decades ago. 4 Today, intramolecular hydroamination can be accomplished with a broad substrate scope and with a number of different catalysts. 5,6 Intermolecular hydroamination is significantly less developed, with most successful examples being focused on the formation of the Markovnikov hydroamination product. 4a,7,8 The formation of the other regioisomer, the antiMarkovnikov product, still represents a major synthetic challenge.For many transition-metal-catalyzed hydroamination reactions, the regiodeterming step is alkene insertion into a metal-amido bond. In a recent computational study of a rhodium-catalyzed propene hydroamination, Hartwig and co-workers found that alkene 1,2-insertion to give the Markovnikov product was both kinetically and thermodynamically preferred over 2, 1-insertion. 9 This finding underlines the difficulties in developing metal-catalyzed anti-Markovnikov hydroamination of alkenes.Despite these challenges, there are several examples of the anti-Markovnikov hydroamination of alkenes. In a seminal contribution, Tobin Marks described the lanthanide-catalyzed intermolecular hydroamination of vinylarenes and vinylsilanes with alkyl amines to give linear (anti-Markovnikov) products (Scheme 1). 10 The origin of regioselectivity is attributed to directing effects of the aryl group during alk...

Copper‐Assisted Amination of Boronic Acids for Synthesis of Bulky Diarylamines: Experimental and DFT Study

“…1 H, 13 C, and 19 FNMR spectralc haracterization of new amines, with complete assignmento fs ignals, was performed in CDCl 3 (see the Supporting Information). For 2,2'-bis(tert-butylphenyl) amine, the assignment of the signals in the 1 HNMR spectra was based on the double-resonance experiment.…”

“…1 H( 400.0 MHz) and 13 CNMR (100.6 MHz) spectra were recorded in CDCl 3 .C hemical shifts were referenced to ar esidual nondeuterated solvent. 19 FNMR chemical shifts were referenced to CFCl 3 .…”

“…It was demonstrated that the presence of even a methyl group in the ortho position to boron had a dramatic influence on the oxidative coupling reaction rate, but a systematic investigation of the influence of a bulky group in the ortho and para positions in the aryl boronic acid or in the N‐containing component (nitroso compound or amine) on the applicability of the methods has not yet been performed. Moreover, it was mentioned in a recent review that the copper‐catalyzed Chan–Lam method was unsuitable for the preparation of hindered anilines …”

“…Moreover,i tw as mentioned in ar ecent review that the copper-catalyzed Chan-Lam methodw as unsuitable for the preparation of hindered anilines. [19] Herein, we aim to report ac omparative investigation of the efficiency of copper-assisted oxidative andr eductive aminations for the synthesis of as eries of bulky diarylaminesw ith ortho-/para-tert-butyl and trifluoromethyls ubstituents on the aromatic rings. To the best of our knowledge, the compounds have not been obtained previously (except symmetrical 4,4'bis(tert-butyl- [20][21][22] ).…”

Copper-Catalyzed Electrophilic Amination of sp2 and sp3 C−H Bonds

“…Electrophilic amination reactions have seen a considerable increase in interest over the past decade as an alternative method for the synthesis of ubiquitous C−N bonds. [35][36][37][38][39][40][41][42][43][44] The key to these amination reactions is the use of [NR 2 ] + synthons as the nitrogen source. Many electrophilic aminations have been achieved using various organometallic reagents, [45][46][47][48][49][50][51][52][53][54][55][56][57][58] while significant advances have also been achieved via C−H functionalization.…”