A Highly Reactive Titanium Precatalyst for Intramolecular Hydroamination Reactions

Abstract

Tetrakisamido titanium complexes are significantly more active than Cp 2 TiMe 2 (1) in the intramolecular hydroamination of aminoalkynes and aminoallenes. In the latter case, the regioselectivity of the transformation depends on the nature of the precatalyst, yielding the most selective and reactive catalysis with the bis(sulfonamido) complex 11.The direct addition of an N-H bond across a carbon-carbon multiple bond, the hydroamination reaction, is the most atom economical way to synthesize substituted amines. 1 Although appreciable progress has been made, 2 a general procedure for this transformation remains elusive.In the early 1990s, we reported the catalytic activity of zirconocene amido complexes in the hydroamination of alkynes. 3 Doye subsequently disclosed the intermolecular hydroamination of alkynes using Cp 2 TiMe 2 4 (1) as the precatalyst. 5 Detailed mechanistic investigations of this reaction in our group revealed that the catalytically active species is generated via a Cp/amide ligand exchange. This conversion of the titanocene species (Cp 2 TiL 2 ) into a monocyclopentadienyl titanium amido complex (CpTi(N-RH)L n ) 6 led to the development of a titanium complex with enhanced catalytic activity in the hydroamination of alkynes and allenes. 7 Therefore, we became interested in studying the catalytic reactivity of noncyclopentadienyl-supported titanium precursors. The recent report by Odom and coworkers 8 that Ti(NMe 2 ) 4 (2) catalyzes the hydroamination of alkynes prompted us to disclose our preliminary results concerning the development of a highly active precatalyst for intramolecular hydroaminations of alkynes and allenes.To compare the reactivity of the bis(cyclopentadienyl)-based precursor Cp 2 TiMe 2 (1) with the tetrakisamide pre-catalyst Ti(NMe 2 ) 4 (2), we initially investigated the intramolecular hydroamination of alkynes (Scheme 1). 6,9 The reactions were performed in d 6 -benzene and monitored by 1 H NMR spectroscopy and GC/MS. In the presence of 5 mol % of 1 the formation of the expected cyclization product 4 was not observed after 12 h at 75 °C. To achieve a Supporting Information Available: Experimental procedures and characterization data for new compounds. This material is available free of charge via the Internet at http://pubs.acs.org. conversion of the terminal alkyne 3, a higher temperature (135 °C) was necessary. The conversion of the internal alkyne 5 was easier and a selective formation of 6 was achieved at 75 °C, while no catalytic activity was observed at room temperature. The commercially available tetrakisamide-based precursor 2 (5 mol %) was much more effective, providing both products quantitatively at room temperature (41 h and 30 min for 4 and 6, respectively). NIH Public AccessHaving illustrated the increased reactivity of tetrakisamido titanium precatalyst 2, we wished to optimize the efficiency of this precursor. Because the hydroamination of alkynes is easily effected by tetrakisamido titanium complexes, these substrates are of limited value for probing ...

Homogeneous Catalytic Hydroamination of Alkynes and Allenes with Ammonia

“…Probably because of steric factors, a different regioselectivity was observed, and only the monohydroamination product 11 c was formed. [24] The results outlined herein demonstrate that (CAAC)-gold(I) cations readily catalyze the addition of NH 3 to nonactivated alkynes and allenes. This reaction leads to reactive nitrogen-containing compounds, such as imines, enamines, and allyl amines, and is therefore an ideal initial step for the preparation of simple bulk chemicals, as well as rather complex molecules, as illustrated by the preparation of heterocycles 4-6.…”

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

“…(7) This leads to the formation of enamines, imines, and amines, which are important building blocks in pharmaceuticals, detergents, and dyes. [63] Furthermore, as many procedures for the synthesis of amines are multi-step and inefficient, [64] catalytic hydroamination has the potential to greatly improve existing methodology. There are no side products in this reaction, thus hydroamination can be used in a tandem reaction sequence, utilizing the imine as an in situ intermediate.…”

“…[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]…”

Asymmetric hydroamination of aminoallenes catalyzed by titanium and tantalum complexes of chiral sulfonamide alcohol ligands

“…There are regiochemical considerations; the corresponding addition to the external double bond yields achiral tetrahydropyridine products (3). The intramolecular hydroamination/cyclization of aminoallenes by silver, mercury, palladium [14e17], titanium [18,19], and lanthanides [13,20,21] is well known. As the cyclization of these aminoallene (and related aminoalkene) substrates results in the formation of a chiral nitrogen heterocycle, there has been much effort to develop the asymmetric reaction.…”

“…One of the first examples of intramolecular hydroamination of aminoallenes using an early transition metal catalyst was reported by Bergman using a racemic titanium sulfonamide complex derived from trans-1,2-diaminocyclohexane (Scheme 3) [18,19]. The parent complex, Ti(NMe 2 ) 4 , was a competent catalyst for the intramolecular hydroamination/cyclization of 4,5-dieneylamine (1c) to give the cyclized product (3c) with only 41% conversion in 26 h at 25 C. The bis-N-Me complex 4a gave only 18% conversion in 24 h at 25 C. However, the corresponding bis-N-tosyl complex 4b gave 100% conversion in 5 h at 25 C. The improved conversion to product was attributed to the electron withdrawing properties of the sulfonamide ligand and not the chelating nature of the ligand due to the similarity between Ti(NMe 2 ) 4 and catalyst 4a.…”