The direct addition of ammonia or primary and secondary amines to non-activated alkenes and alkynes is potentially the most efficient approach towards the synthesis of higher substituted nitrogen-containing products. It represents the most atom economic process for the formation of amines, enamines and imines, which are important bulk and fine chemicals or building blocks in organic synthesis. While the hydroamination of alkenes is still limited to more or less activated alkenes, great progress has been achieved in the case of alkynes over the last three years. To illustrate this progress, the review will mostly focus on recent developments in the field of intermolecular hydroamination of alkynes. However, if it is necessary for the discussion, older results and intramolecular reactions, which can be achieved more easily, will be mentioned as well.
Catalytic additions of ammonia or primary and secondary amines to non-activated alkenes and alkynes are called hydroaminations. These reactions of fundamental simplicity represent the most atom efficient processes for the formation of amines, enamines and imines, which are important bulk and fine chemicals or building blocks in organic synthesis. Consequently, the development of corresponding hydroamination reactions has received much attention and great progress has been achieved in the case of catalytic hydroaminations of alkynes over the past four years. To illustrate this progress, this tutorial review will mostly focus on recent developments in the field of intermolecular hydroamination of alkynes that appeared in the literature between the end of 2002 and October 31, 2006.
During the last 50 years, group‐IV metal complexes have been used extensively as catalysts in organic chemistry. However, a new and rapidly growing field for group‐IV metal catalysis evolved in the 1990s when the groups of Bergman, Livinghouse and Doye found that zirconium and titanium complexes catalyze the inter‐ and intramolecular hydroamination of alkynes and allenes. Starting from early results obtained with zirconocene bis(amides), this review deals mostly with hydroamination reactions based on titanium catalysts. In this context, studies directed towards catalyst development are presented as well as applications of corresponding processes for the synthesis of biologically interesting compounds. However, the Microreview covers group‐IV metal complex catalyzed hydroamination reactions of alkynes and allenes that appeared in the literature before July 31, 2002. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Titanaaziridines or η(2)-imine titanium complexes are considered key intermediates of the titanium-catalyzed hydroaminoalkylation of alkenes. Herein, we present an efficient synthetic route to this class of compounds, starting from N-methylanilines and a bis(η(5):η(1)-pentafulvene)titanium complex. Consecutive reactions on the η(2)-methyleneaniline complexes, characterized for the first time, prove a high chemical versatility. In particular, hydroaminoalkylation products were found in reactions of the three-membered titanacycles with alkenes. For the first time, all the intermediates of the hydroaminoalkylation of alkenes were isolated and characterized.
Hydroaminations of alkynes and alkenes [1] have attracted much attention during the past few years. Both transformations allow the synthesis of nitrogen-containing molecules in a single step with 100 % atom efficiency. Besides other metal catalysts, [1] titanium complexes have been used extensively for these reactions. [2][3][4] Recently, we recognized during a study of the Ti-catalyzed intramolecular hydroamination of alkenes that the cyclization of 1-amino-5-hexenes to piperidines (Scheme 1) performed with the catalysts [Ti(NMe 2 ) 4 ] or [Ind 2 TiMe 2 ] (Ind = indenyl) takes place along with the formation of aminocyclopentane side products.[4d] Interestingly, a corresponding catalytic C À H bond activation [5] at the sp 3 center in the a-position to a primary amino group has never been observed before during a Ti-catalyzed hydroamination.[6] However, this reaction would represent a very useful chemical transformation if it can be achieved selectively, because it offers a direct and highly atom-efficient conversion of simple amines to more complex molecules through C À C bond formation.A related example of C À H bond activation [5] at sp 3 centers in the a-position to nitrogen atoms [7, 8] is the [Ta(NMe 2 ) 5 ]-catalyzed intermolecular hydroaminoalkylation of alkenes described by Hartwig and Herzon.[9] Although only secondary N-arylated alkyl amines have been used for this reaction and [Zr(NMe 2 ) 4 ] was found to be catalytically inactive, the analogy to the formation of aminocyclopentane side products during Ti-catalyzed hydroaminations is obvious. For this reason, we became interested in whether Ti complexes such as [Ti(NMe 2 ) 4 ] and [Ind 2 TiMe 2 ] can generally be used as catalysts for selective hydroaminoalkylations of alkenes. To our knowledge and with the exception of the mentioned side reaction, [4d] corresponding Ti-catalyzed reactions have never been reported. [10] One possibility to suppress the intramolecular hydroamination that competes with the desired CÀH activation process is to use a 1-amino-6-heptene as the substrate. In this case, the hydroamination would lead to an unfavorable sevenmembered ring, while the C À H bond activation reaction would give a favored six-membered ring. Correspondingly, it can be expected that the desired aminocyclohexane will be formed selectively. Initial studies carried out with 1-amino-2,2-dimethyl-6-heptene (1, Scheme 2) and 5 mol % [Ti(NMe 2 ) 4 ] or [Ind 2 TiMe 2 ] revealed that the formation of the desired aminocyclohexane 2 is slow at 105 8C (less than 10 % conversion in 24 h, as determined by GC). However, when [Ti(NMe 2 ) 4 ] was used as the catalyst, an increase of the reaction temperature (160 8C) and a longer reaction time (72 h) resulted in the formation of the CÀH activation product 2, which could be isolated after conversion to the corresponding p-toluenesulfonamide derivative 3 (46 % yield). Particularly interesting is the fact that the formation of the hydroamination product, an azepane, has not been observed during the entire study performed w...
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