[Ind₂TiMe₂]: A General Catalyst for the Intermolecular Hydroamination of Alkynes

Abstract

[Ind(2)TiMe(2)] (Ind=indenyl) is a highly active and general catalyst for the intermolecular hydroamination of alkynes. It catalyzes the reaction of primary aryl-, tert-alkyl-, sec-alkyl-, and n-alkylamines with internal and terminal alkynes. In the case of unsymmetrically substituted 1-phenyl-2-alkylalkynes, the reactions occur with modest to excellent regioselectivities, whereby formation of the anti-Markovnikov regioisomers is favored. While the major product of hydroamination reactions of terminal arylalkynes is always the anti-Markovnikov isomer, alkylalkynes react with arylamines to preferably give the Markovnikov products. To achieve reasonable rates for the addition of sterically less hindered n-alkyl- and benzylamines to alkynes, these amines must be added slowly to the reaction mixtures. This behavior is explained by the fact that the catalytic cycle proposed on the basis of an initial kinetic investigation includes the possibility that the rate of the reaction increases with decreasing concentration of the employed amine. Furthermore, no dimerization of the catalytically active imido complex is observed in the hydroamination of 1-phenylpropyne with 4-methylaniline in the presence of [Ind(2)TiMe(2)] as catalyst. In general, a combination of [Ind(2)TiMe(2)]-catalyzed hydroamination of alkynes with subsequent reduction leads to the formation of secondary amines with good to excellent yields. Particularly impressive is that [Ind(2)TiMe(2)] makes it possible for the first time to perform the reactions of n-alkyl- and benzylamines with 1-phenylpropyne in a highly regioselective fashion.

Modular N,O‐Chelating Ligands: Group‐4 Amidate Complexes for Catalytic Hydroamination

“…[65][66][67][68] Following an initial report of titanium catalyzed hydroamination by Rothwell and coworkers, [69] research into hydroamination catalysis has also followed the trend of focusing on Cp-based ligand systems and then moving onto non-Cp-based catalysts. A variety of systems have been developed for hydroamination reactions including work from the groups of Bergman, [15,64,[70][71][72][73] Livinghouse, [74,75] Odom, [67,[76][77][78][79][80][81] Beller, [65,[82][83][84][85][86] Doye, [87][88][89][90][91][92][93][94] ourselves, [59,61,62,95,96] and others. [11,[97][98][99][100][101][102][103][104]…”

Zirconium‐Catalyzed Intermolecular Hydroamination of Alkynes with Primary Amines

“…Although better regioselectivities of up to 87:13 were observed with other sulfonamide additives it should be noted that the corresponding Ti-catalyzed processes generally gave much better regioselectivities. [15] Once we had established that hydroamination reactions of 1-phenylpropyne (1) could be achieved with various primary amines using in situ generated mixtures of [Zr-(NMe 2 ) 4 ] and sulfonamides, we examined the reactions of the sterically more demanding alkyne diphenylacetylene (14). In this study we recognized that good results could not be obtained when the hydroamination reactions were performed at 130°C.…”

“…The hydroamination reactions were performed with p-toluidine (2) and 5 mol-% [Zr(NMe 2 ) 4 ] either in the presence or absence of 10 mol-% sulfonamide 5 (Scheme 2). Because terminal alkynes are known to undergo hydroamination reactions under much milder conditions than internal alkynes, [15] the hydroamination step was always performed at 105°C. After a relatively short reaction time of 24 h and subsequent reduction it was possible in all cases to isolate the desired secondary amines in modest yields.…”

“…All products were identified by comparison of their 1 H and 13 C NMR spectroscopic data with those reported in the literature. [15,17] NMR spectra were recorded with Bruker Avance DRX 500 and Bruker Avance III 500 MHz spectrometers. All NMR spectra are reported in δ (ppm) relative to the signal of TMS at δ = 0.00 ppm ( 1 H NMR) and to the central line of the triplet of CDCl 3 at δ = 77.0 ppm ( 13 C NMR).…”

“…Amines 3a and 3b: [15] The general procedure was used to synthesize a mixture of 3a and 3b from 1-phenylpropyne (1; 232 mg, 2.0 mmol) and p-toluidine (2; 235 mg, 2.2 mmol). The hydroamination was performed at 130°C for 96 h with 5 mol-% [Zr(NMe 2 ) 4 ] and 10 mol-% tBuNHpTs (5).…”