[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.

Cp(2)TiMe(2) has been found to be a competent catalyst for the intermolecular addition of sterically less demanding n-alkyl- and benzylamines to internal alkynes. In the presence of 2.0-6.0 mol % of the catalyst, hydroamination reactions between n-propyl-, n-hexyl-, benzyl-, p-methoxybenzyl- or 2-phenylethylamine and diphenylacetylene, 3-hexyne or 4-octyne go to completion within 24 h or less at 114 degrees C (oil bath temperature). After subsequent reduction of the initially formed imines with zinc-modified sodium cyanoborohydride in MeOH at 25 degrees C, the corresponding secondary amines can be isolated in excellent yields (>78%). Hydroamination/reduction sequences employing the unsymmetrically substituted alkyne 1-phenylpropyne give access to mixtures of regioisomeric secondary amines. The observed regioselectivity is low.

A single precatalyst is used for the sequential combination of the Ti‐catalyzed hydroamination of alkynes with the Ti‐catalyzed hydrosilylation of imines. In this way alkynes and primary amines are converted efficiently into secondary amines in a fully catalytic one‐pot process (see scheme).

For two representative reactions employing enantiomerically pure (S)‐1‐phenylethylamine and (S)‐1‐cyclohexylethylamine it is shown that Ti‐catalyzed hydroamination reactions of alkynes do not generally take place without partial racemization at the chiral center adjacent to the nitrogen atom. However, identified from a selection of nine Ti catalysts, Cp*2TiMe2 and at least two other catalysts can be used for racemization‐free hydroamination reactions of alkynes. Furthermore, the amount of racemization can be reduced significantly by the addition of pyridine to the reaction mixture. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

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...