Titanium Complexes as Catalysts for the Intermolecular Hydroamination of Alkynes

Abstract

Several titanium complexes can be used as active catalysts for the intermolecular hydroamination of alkynes. The investigated catalysts include various titanocene complexes as well as titanium compounds bearing amido-and chloro-ligands. The activities of the investigated catalysts are compared in two representative hydroamination/reduction sequences.From a synthetic point of view hydroamination reactions of alkenes and alkynes are among the most desirable transformations in organic chemistry. However, efforts to develop efficient hydroamination protocols have met with only limited success. 1 Initialized by our pioneering report that the well known reagent Cp 2 TiMe 2 can be used as a catalyst for the intermolecular hydroamination of alkynes, 2 it was demonstrated in several publications that the titanium complex-catalyzed intermolecular hydroamination of alkynes is a remarkable new tool in organic synthesis. 3 However, besides Cp 2 TiMe 2 only a few other titanium complexes have been used so far. 3b,f,g,h,i Therefore, we decided to investigate the catalytic properties of other titanium compounds. Furthermore, a comparison of the catalytic activity of a wide variety of titanium catalysts for the intermolecular hydroamination of alkynes has not yet been reported.For the mentioned purpose, we first chose two representative test reaction sequences which both include a titanium complex-catalyzed hydroamination step and a subsequent reduction. While in the first reaction sequence (sequence A) a diarylalkyne (diphenylacetylene 1) is reacted with an alkylamine (t-butylamine 2), a dialkylalkyne (3-hexyne 4) and an arylamine (4-methylaniline 5) are used for the second sequence (sequence B, Scheme).A brief screening for catalytic activity revealed that several titanium (IV) complexes bearing two labile ligands such as methyl or dimethylamido ligands show remarkable activity in hydroamination reactions of alkynes. In order to obtain some quantitative information about the differing catalytic activities of the investigated titanium complexes, we performed both test reaction sequences with all identified catalysts under identical conditions. 4 The hydroamination step was always carried out at 105 °C with 5.0 mol% of the investigated titanium complex in toluene. After a reaction time of 24 h a subsequent reduction performed with zinc-modified NaBH 3 CN 5 in methanol at 25 °C gave access to the secondary amine 3 (sequence A) or 6 (sequence B). 6 Besides Cp 2 TiMe 2 7, 7 we used several other titanocene complexes (8-13), 8 cyclopentadienyl(amido) complexes (14-16), 9 imido complexes (17, 18) 10 and the tetra amido complex Ti(NMe 2 ) 4 19, which has recently been used as hydroamination catalyst by Odom et al. 3h,i The corresponding yields of 3 and 6, which were obtained from both test reaction sequences employing 7-19 as hydroamination catalysts, are summarized in the Table. As can be seen from the Table, all employed titanocene complexes (7-13, entries 1-7) gave good results for sequence A. After 24 h reaction time of the hydroam...

Neutral Group‐IV Metal Catalysts for the Intramolecular Hydroamination of Alkenes

“…(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) Ind 2 TiMe 2 [6] (Ind = indenyl) as a highly efficient catalyst for the intermolecular hydroamination of alkynes, we found that Ind 2 TiMe 2 is also a suitable catalyst for the intramolecular hydroamination of alkenes. [7] However, a detailed comparison between the benchmark catalyst Ti(NMe 2 ) 4 and Ind 2 TiMe 2 regarding their scope and limitations has not been described yet.…”

General Zinc‐Catalyzed Intermolecular Hydroamination of Terminal Alkynes

“…After full conversion, subsequent reduction using zinc-modified NaBH 3 CN in methanol at room temperature gave the secondary amine 3 a. [11] As a result of the highly selective Markovnikov functionalization, the branched isomer is produced with excellent regioselectivity (> 99 %) and yield.…”

Development of the Ti-Catalyzed Intermolecular Hydroamination of Alkynes

“…Initiated by our early studies on Ti-catalyzed intermolecular hydroaminations of alkynes, many other Ti complexes have been identified as active hydoamination catalysts by our group 19 and the groups of Bergman, 20 Odom, 21 Beller, 22 Richeson, 23 Schafer, 24 and Ackermann. 25 However, a discussion of all the different Ti-catalysts identified so far is not the purpose of this article.…”

“…19 While in the first reaction sequence (Scheme 23), a diarylalkyne (diphenylacetylene, 11) was reacted with an alkylamine (tert-butylamine, 19), a dialkylalkyne (3-hexyne, 24) and an arylamine (4-methylaniline, 32) were used for the second sequence (Scheme 24). A comparison of Schemes 23 and 24 indicates that titanocene-derived complexes are highly active catalysts for the reaction between diphenylacetylene (11) and tertbutylamine (19).…”

“…19 While in the first reaction sequence (Scheme 23), a diarylalkyne (diphenylacetylene, 11) was reacted with an alkylamine (tert-butylamine, 19), a dialkylalkyne (3-hexyne, 24) and an arylamine (4-methylaniline, 32) were used for the second sequence (Scheme 24). A comparison of Schemes 23 and 24 indicates that titanocene-derived complexes are highly active catalysts for the reaction between diphenylacetylene (11) and tertbutylamine (19). For this reaction, the imido complex Cp 2 Ti=Nt-Bu(Py) gave the best result (98% isolated yield of 59 after only two hours reaction time of the hydroamination and subsequent reduction), while the chloro-substituted imido complex CpTi=Nt-Bu(Py)Cl and the tetra amide complex Ti(NMe 2 ) 4 21a gave modest to poor results.…”