Copper‐Catalyzed Alkylarylation of Unactivated Alkenes: Synthesis of 3‐Alkyl Indolines from N‐Allyl Anilines and Alkanes

Abstract

Ar are example of C(sp 3 )ÀHf unctionalization of simple alkanes with unactivated alkenes is presented.I n the presence of ac opper salt and di-tert-butyl peroxide (DTBP), N-allyl anilinesu nderwent exo-selective alkylation/ cyclization cascade with unactivated alkenic bonds as radical acceptors and simple alkanes as radicalp recursors, providing ad irect access to 3-alkyl indolines.T he present protocol features simple operation, broad substrate scope and great exo selectivity.Alkanesa re principalc onstituents of fossil fuels such as petroleum, natural gas and coal, [1] and are primary products of petroleumr efining. [2] Hence, efficient conversion of such bulk chemicals into value-added compounds is ac riticalt ask for future sustainable chemistry. [3] CÀHf unctionalization is considered an ideal process in terms of step-anda tom-economy, and in this regard, directf unctionalization of inert alkanic CÀH bonds remains as ignificant challenge due to their intrinsic low acidity and high bond-dissociation energy. [4] Nonetheless,s ignificant progress has been made recently towards C(sp 3 )ÀH functionalization of simple alkanes with arenes, [5] heteroarenes, [6] CO, [7] carbenes, [8] alkynes, [9] isonitriles, [10] heteroatoms, [11] activateda liphatic carbons, [12] or activated olefins, [13][14][15] etc. [16] In sharp contrast, coupling/addition of simple alkanes across unactivated alkenes is rarely reported( Scheme 1a), [17] probably because of polarity mismatching. [18,19] Unactivated alkyl radicals are weakly nucleophilic, and they tend to reactw ith electrondeficients pecies. [5][6][7][8][9][10][11][12][13][14] 16] Dehydrogenativec oupling of simple alkanes with nucleophiless uch as unactivated alkenes is far more difficult. Aryl [17a] /alkynyl migration [17b] or ac yclization process [17c] could facilitate such ap olarity-mismatched reaction, and an elegant anti-Markovnikov hydroalkylation of unactivat-Scheme1.Literature examplesa nd this work.[a] Prof.Supporting information and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

Copper-promoted difunctionalization of unactivated alkenes with silanes

“…On the basis of previous reports 9 b,i , m ,16–25 and above experimental results, a possible mechanism was proposed and is depicted in Scheme 3. In the beginning, the thermal decomposition of DTBP leads to the formation of the t -butoxyl radical which can generate methyl radicals by a β-cleavage pathway.…”

“…For example, acetonitrile (CH 3 CN), azodiisobutyrodinitrile (AIBN), cyclohexane, benzaldehyde, tetrahydrofuran (THF), toluene, acetone, perfluorobutyl iodide ( n -C 4 F 9 I), dimethyl phosphite (HPO(OMe) 2 ) and trifluoromethylating agents have been used as the radical precursor to construct indoline structures in recent years. 16–25 Although remarkable efforts have been made in this field, the silylarylation of unactivated alkenes for the synthesis of 3-silyl indolines has not been studied. As part of our continuous studies on C–H functionalization 26 and organosilicon chemistry, 27 herein, we report the silylation of unactivated alkenes with silanes through a free-radical cascade process to construct 3-silyl indoline compounds (Scheme 1d).…”

C-centered radical-initiated cyclization by directed C(sp3)–H oxidative functionalization

“…It was revealed that even the readily oxidized formyl group was well tolerated and this strategy was also suitable for thioether. In the same year, Liang's group 42 reported another example of C(sp 3 )–H oxidative functionalization of cyclohexane. 3-Alkyl indolines could be obtained using N -allyl anilines and cyclohexane in the presence of di-tert -butyl peroxide (DTBP) and copper salt, providing a novel approach to 3-alkyl-2-unsubstituted indolines from acyclic materials.…”

Advances in C(sp3)–H Bond Functionalization via Radical Processes

“…In 2019, Liang and co-workers reported an exo-selective alkylation/cyclization cascade in the presence of CuI (Scheme 21). 30 N-Allylanilines with unactivated alkenic bonds were used as radical acceptors and simple alkanes as radical precursors enabling direct access to 2-unsubstituted 3-alkylindolines. This protocol is simple operation and has broad substrate scope and great exo-selectivity.…”