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)

A completely new application of dimethyltitanocene as catalyst for the intermolecular hydroamination of alkynes is presented. With this inexpensive and readily available catalyst, alkynes can be easily converted into imines, amines, and ketones (see reaction scheme).

Irradiation of reaction mixtures containing an alkyne, an amine, and a catalytic amount of Cp 2 TiMe 2 in toluene with microwaves at a frequency of 2.45 GHz and a power output of 180−300 W results in fast reactions to give the corresponding hydroamination products. The initially formed imines can easily be reduced to secondary amines by use of H 2 /Pd, LiAlH 4 , or NaCNBH 3 /p-TsOH. The microwave-assisted hydroamination reactions go to completion within one tenth (or less) of the time required for reactions run conventionally in [a]

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).

Initiated by improved screening methods, a steadily increasing demand for highly flexible synthetic procedures has evolved during the last couple of years. The major purpose of these synthetic methods is the fast generation of various derivatives of a certain class of substances. In the past, we have repeatedly shown that the titanium-catalyzed hydroamination of alkynes [1] is a versatile tool for the highly flexible synthesis of biologically interesting compounds. [2] Expanding these studies, we now present a highly flexible and catalytic one-pot procedure for the synthesis of indoles [3] employing ortho-chloro-substituted 1-phenyl-2-alkyl alkynes or phenyl-(aminoalkyl)alkynes as starting materials.The general principle of the one-pot procedure is shown in Scheme 1. The major expectation is that under basic conditions, the imines, which are regioselectively formed during the hydroamination in the presence of the Ti catalyst [Cp 2 TiMe 2 ] (Cp = C 5 H 5 ) [4] , will be in equilibrium with the corresponding enamines. In addition, an ortho-chloro-substituent in the benzene ring, should offer the possibility to convert the enamines into indoles by a Pd-catalyzed Narylation/cyclization (Buchwald-Hartwig reaction). [5] Since the enamines are removed from the equilibrium during this cyclization step it should be possible to convert the imines completely into indoles. However, to our knowledge, corresponding N-arylations of N-substituted imines under basic conditions in the presence of Pd-catalysts have not been reported. [6] To investigate the scope of the suggested synthetic strategy, which includes two CÀN bond-forming steps, we synthesized a number of ortho-chloro-substituted 1-phenyl-2-alkyl alkynes (1-10, Table 1) by Sonogashira couplings [7] starting from simple 1-chloro-2-iodobenzenes and terminal alkynes. [2c] The alkynes 1-10, which could be isolated in high yields, were then used for the one-pot procedure. For this purpose, the alkynes were first hydroaminated with an arbitrary primary amine in the presence of 5 mol % [Cp 2 TiMe 2 ]. Subsequently, 5 mol % [Pd 2 (dba) 3 ] (dba = dibenzylideneacetone, 10 mol % 1,3-bis(2,4,6-trimethylphenyl)imidazolium chloride, and KOtBu were added directly to the reaction mixture. After heating the resulting mixture to 110 8C, most of the 1,2-, 1,2,5-, and 1,2,6-substituted indoles 11-20 could be isolated in good yields [Eq. (1), Table 1]. However, the reaction of 4 and tert-butylamine gave the corresponding indole 14 in only 39 % yield. This modest result is because the regioselectivity of the [Cp 2 TiMe 2 ]-catalyzed hydroamination of 1-phenyl-2-alkenyl alkynes is worse than that of 1-phenyl-2-alkyl alkynes. [2b] Scheme 1. Outline of a flexible and catalytic one-pot procedure for the synthesis of indoles.