Hydrazinediido complexes

Gade and coworkers reported that titanium hydrazinediido complexes act as effective catalysts for hydrohydrazination reactions involving substituted hydrazines and carbodiimides giving rise to aminoguanidines in good yields. On the other hand, Sundermeyer developed titanium phthalocya-nine complexes as catalysts for the synthesis of highly pure carbodiimides from isocyanates under solvent-free reaction conditions. ... 

Hydrazinediido complexes have been identified as active species in the titanium-catalyzed hydrohydrazination [12] and iminohydrazination of alkynes and the subsequent transformation of the hydrazones into indoles or tryptamine derivatives (Scheme 13.5) [13]. The postulated reaction mechanism of the group 4 metal-catalyzed reaction is based on the extensively studied mechanistic scheme for hydroaminations of alkynes, in which imido complexes are the key active species. 

The following sections will focus on two case histories from our own activities in the field that exemplify the key challenges and the way they may be addressed in practice. First, the focus will be on a new class of titanium hydrazinediido halfsandwich complexes, which have displayed remarkable activity in the hydrohy-chazination of terminal alkynes and of carbodiimides. This will be followed by the presentation of a catalytic cascade of N - N and C - H scissions and C - C and C - N coupling steps in the coordination sphere of zirconium, which directly converts alkynes and hydrazines to indoles along a non-Fischer-type reaction pathway. 

A new class of titanium hydrazinediido half-sandwich complexes [Cp Ti(Nxy]N) (=NNR2)(L)] (A) was found to display remarkable activities in catalytic hydro-hydrazinations of alkynes at ambient temperatures (Scheme 13.6). A key feature has been the use of 2-aminopyrrolinato spectator ligands in which the amidinato binding unit is exocyclic with respect to the heterocycle [18]. The possibility of amidinates to convert from to coordination and thus to temporarily liberate a coordination site at the metal may be crucial in the development of active molecular catalysts. 

Our own investigations into the chemistry of the heavier group 4 analogs have primarily focused on the hydrazinediido-zirconium complex [Zr(N2 NpP (NNPh2)(py)l (Figure 13.1) [17]. The latter has displayed similar stoichiometric and catalytic reactivity toward unsaturated substrates as found for titanium. However, its reactivity toward alkynes appears to be characterized by the absence of a hydrohydrazination step in favor of N-N bond cleavage before the formation of a hydrazone and a reaction pathway similar to that depicted in Scheme 13.8 [24]. 

As bis(hydrazido) complexes may be precursors in the generation of hydrazinediido compounds [25], the reaction sequence leading to the indoles was thought to be potentially part of a catalytic cycle for the direct generation of substituted indoles from alkynes and hydrazines. Based on the combined experimental and computational evidence presented in this work, we propose the mechanistic cycle depicted in Scheme 13.11 for the catalytic formation... 

In particular, 1,7-annulated indole derivatives, such as the prototypical Cilansetron A, display high activity as 5-HT3 receptor antagonists and are being clinically tested for the treatment of symptoms in the gastrointestinal system such as the irritable bowel syndrome (IBS) [26]. To extend our previous synthetic strategy based on the reactivity of hydrazinediido zirconium complexes to annulated polycyclic indole derivatives, we aimed to prepare such hydrazides derived from cyclic hydrazines (B). 

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