Heutling Andreas, Pohlki Frauke, Doye Sven
Organisch-Chemisches Institut, Universität Heidelberg, Im Neuenheimer Feld 270, 69120 Heidelberg, Germany.
Chemistry. 2004 Jun 21;10(12):3059-71. doi: 10.1002/chem.200305771.
[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.
[茚基(2)钛甲基(2)]（茚基=茚基）是一种用于炔烃分子间氢胺化反应的高活性通用催化剂。它催化伯芳基、叔烷基、仲烷基和正烷基胺与内炔和端炔的反应。对于不对称取代的1-苯基-2-烷基炔烃，反应具有适度至优异的区域选择性，其中反马氏规则区域异构体的形成更受青睐。虽然端芳基炔烃氢胺化反应的主要产物总是反马氏规则异构体，但烷基炔烃与芳基胺反应时优选生成马氏规则产物。为了使空间位阻较小的正烷基胺和苄胺与炔烃加成反应达到合理的速率，必须将这些胺缓慢加入反应混合物中。这种行为可以通过以下事实来解释：基于初步动力学研究提出的催化循环包括反应速率随所用胺浓度降低而增加的可能性。此外，在[茚基(2)钛甲基(2)]作为催化剂存在下，1-苯基丙炔与4-甲基苯胺的氢胺化反应中未观察到催化活性亚胺络合物的二聚化。一般来说，[茚基(2)钛甲基(2)]催化的炔烃氢胺化反应与随后的还原反应相结合，能够以良好至优异的产率生成仲胺。特别令人印象深刻的是，[茚基(2)钛甲基(2)]首次使正烷基胺和苄胺与1-苯基丙炔的反应能够以高度区域选择性的方式进行。
