The mechanism of titanocene-mediated epoxide opening was studied by a combination of voltammetric, kinetic, computational, and synthetic methods. With the aid of electrochemical investigations the nature of a number of Ti(III) complexes in solution was established. In particular, the distribution of monomeric and dimeric Ti(III) species was found to be strongly affected by the exact steric conditions. The overall rate constants of the reductive epoxide opening were determined for the first time. These data were employed as the basis for computational studies of the structure and energies of the epoxide-titanocene complexes, the transition states of epoxide opening, and the beta-titanoxy radicals formed. The results obtained provide a structural basis for the understanding of the factors determining the regioselectivity of ring opening and match the experimentally determined values. By employing substituted titanocenes even more selective epoxide openings could be realized. Moreover, by properly adjusting the steric demands of the catalysts and the substrates the first examples of reversible epoxide openings were designed.

Branching out with hydrogen: Hydrogenation of symmetric or mixed carboxylic anhydrides in the presence of styrenes or activated olefins generates intermolecular hydroacylation products. The use of cationic rhodium catalysts ligated by triphenylarsine (Ph3As) results in the formation of branched coupling products as single regioisomers in high yields (see scheme; cod=cycloocta‐1,5‐diene, ArF=3,5‐(CF3)2C6H3).

Titanocene-mediated [1] and -catalyzed epoxide ring opening [2] continues to be a highly pertinent synthetic transformation in organic chemistry. However, despite its preparative usefulness nothing is known about its mechanism. Herein, we present a study to elucidate this mechanism by a combination of electrochemical, kinetic, computational, and synthetic methods.The determination of catalyst composition and the kinetics of the ring opening are the essential experimental basis for any mechanistic discussion. Thus, Zn-reduced THF solutions of [Cp 2 TiCl 2 ] (1; Cp = cyclopentadiene), 2, and 3 [3] were first analyzed by cyclic voltammetry, a technique uniquely suited for the investigation of redox-active species.[4]The solution derived from 1 consists of two species, [Cp 2 TiCl] (1 b) and the dimer [Cp 2 TiCl] 2 (1 a), which are in rapid equilibrium (K = 3000 m À1 ).[5] Herein, we demonstrate

Novel hydrogen atom donors for the reductive titanocene-catalyzed epoxide opening are presented. While the potentially attractive cyclopentadienes gave only moderate yields of the desired alcohols, substituted, nontoxic, and commercially available 1,4-cyclohexadienes, e.g. g-terpinene, in combination with more elaborate catalysts gave better or similar results than the much more expensive and carcinogenic 1,4-cyclohexadiene. In the practically important reactions of Sharpless epoxides and their derivatives excellent levels of regioselectivity for the epoxide opening could be obtained. The toxic and unpleasant to handle tert-butyl thiol could be replaced while increasing the yields of the desired products.

Exposure of aromatic, heteroaromatic, and aliphatic N-arylsulfonyl aldimines 1a−12a in toluene solution at 60 °C to 2-butyne and hydrogen at ambient pressure in the presence of a cationic iridium(I) catalyst modified by BIPHEP enables formation of reductive coupling products, allylic amines 1b−12b, in good isolated yields as single geometrical isomers (>95:5, E:Z). The nonsymmetric alkynes 4-methyl-2-pentyne couple to imines 6a, 12a, and 13a under standard conditions with complete levels of regioselection. Hydrogenative coupling of 2-hexyne to imines 6a, 12a, and 13a delivers allylic amines 15b, 16b, and 18b in 10:1 regioisomeric ratios in each case. As revealed by 2H NMR analysis, reductive coupling of 2-butyne to imine 2a under an atmosphere of elemental deuterium provides deuterio-2b, which incorporates deuterium at the vinylic position (83% 2H) and at the allylic methyl groups (5% 2H). An equal distribution of deuterium at the allylic methyl groups suggests H−D exchange at the propargylic positions of 2-butyne in advance of C−C coupling.