Cobalt–Phenanthroline Catalysts for the ortho Alkylation of Aromatic Imines under Mild Reaction Conditions

Abstract

Chelation-assisted C À H activation followed by insertion of an unsaturated molecule offers a straightforward, regioselective, and atom-economical method for CÀC bond formation. [1] While rare-transition-metal catalysts (e.g. Ru, Rh, Pd) have played major roles in this and related types of CÀH bond functionalization, the development of cost-effective alternatives has attracted increasing interest.[2] We recently developed cobalt-phosphine and cobalt-carbene catalysts that promote ortho alkenylation and ortho alkylation reactions of aryl pyridine and imine derivatives by insertion of alkynes and styrenes, respectively.[3] These reactions represent the recent emergence of cobalt catalysis for CÀH bond functionalization; [4][5][6] cobalt catalysis is attractive because of the low cost of the catalysts as well as the unique reactivities or selectivities often achieved. [7] We report herein a significant expansion of the scope of this chemistry, achieved with cobalt-phenanthroline (L1 or L2) catalysts, which allow the ortho alkylation of aromatic imines with a variety of olefins under mild reaction conditions (Scheme 1). [8][9][10] From the screen of the cobalt catalysts for the addition of the acetophenone imine 1 a (PMP = p-methoxyphenyl) to vinyltrimethylsilane (2 a, 1.2 equiv), we identified 1,10-phenanthroline (L1) as an inexpensive and effective ligand (Table 1). Thus, the reaction took place smoothly at room temperature (20 8C) in the presence of a cobalt catalyst generated from CoBr 2 (5 mol %), L1 (5 mol %), and tBuCH 2 MgBr (40 mol %) to afford the alkylation product 3 a within 6 hours, in 85 % yield upon isolation (Table 1, entry 1). No dialkylation product was observed. The roomtemperature conditions are in stark contrast to those used for the related reactions of imines under rhodium or ruthenium catalysis, which typically require heating at 130-150 8C. [8,9] Among other phenanthroline-type ligands, bathophenanthroline performed as efficiently as L1 (Table 1, entries 2-4). The use of other Grignard reagents such as MeMgCl and Me 3 SiCH 2 MgCl led to lower yields (Table 1, entries 5 and 6). Little conversion was observed when the amount of tBuCH 2 MgBr was reduced to 20 mol % (Table 1, entry 7). The cobalt-phosphine and cobalt-carbene catalysts developed previously by our group [3] were much less effective (Table 1, entries 8-10).The optimized catalytic system was applicable to a wide variety of aromatic imines (Table 2). Tolerated substituents on the aromatic ring included methoxy (3 b, 3 j), chloro (3 d, 3 f), fluoro (3 i), trifluoromethyl (3 g), and cyano (3 h) groups (Table 2, entries 1, 3, and 5-9), although the product yields in the latter two cases were modest. An imine derived from 4-bromoacetophenone did not participate in the reaction but afforded a product resulting from the cross-coupling at the CÀ Br bond with the Grignard reagent (< 5 %). Imines derived Scheme 1. ortho Alkylation of aromatic imines with a cobalt-phenanthroline catalyst. [a] Reaction was performed on a 0.3 mmol scale at 0.3 m...

Cobalt-catalyzed Branched-selective Addition of Aromatic Ketimines to Styrenes under Room-temperature Conditions

“…Note that the present catalytic system also allowed (linear) for the ortho-alkylation of 1a with vinyltrimethylsilane, norbornene, and n-hexene, albeit in a low yield for the last case (75, 91, and 15% yields, respectively; data not shown). 18 The present hydroarylation reaction is scalable enough to allow for further transformation of the 1,1-diarylethane product (Scheme 2). The reaction of 1a and 2a could be performed on a 10 mmol scale with virtually no decrease in the yield and regioselectivity.…”

Development of Cobalt-Catalyzed C–H Bond Functionalization Reactions

“…35 In addition to the styrene hydroarylation reactions, we have also developed addition reactions of aromatic ketimines to 8 (2014)vinylsilanes and aliphatic olefins using cobaltphenanthroline and cobaltneocuproine catalysts, respectively (Scheme 11). 36 Furthermore, intramolecular hydroarylation has also been achieved with an indole substrate bearing an alkene tether and an aldimine directing group on the 1-and 3-positions, respectively (Scheme 12). 37 Interestingly, a cobaltIPr catalyst regioselectively transforms an N-homoallylindole substrate into a tetrahydropyridoindole derivative, while a cobaltSIMes catalyst exhibits an opposite regioselectivity, thus furnishing a dihydropyrroloindole isomer as the major product.…”

Cobalt-Catalyzed C-C Bond-Forming Reactions via Chelation-Assisted C-H Activation

“…29 Unlike the case of styrene hydroarylation, an experiment using pentadeuterated acetophenone imine and vinylsilane resulted in only a limited degree of H/D scrambling between the ortho positions and the ole nic moiety. Furthermore, the ortho deuterium atom was mainly incorporated into the methylene moiety proximal to the silyl group of the product, suggesting that migratory insertion of vinylsilane into a putative cobalt hydride species occurs predominantly in a linear manner.…”