Investigations detailed herein, including density functional theory (DFT) calculations, demonstrate that the formation of either alkoxy- or hydroxy-Ti(III) complexes considerably decreases the energy of activation for C-O bond homolysis. As a consequence of this observation, we described two new synthetic applications of Nugent's reagent in organic chemistry. The first of these applications is an one-step methodology for deoxygenation-reduction of alcohols, including benzylic and allylic alcohols and 1,2-dihydroxy compounds. Additionally, we have also proved that Ti(III) is capable of mediating carbonyl coupling-olefination. In this sense, and despite the fact that for over 35 years it has been widely accepted that either Ti(II) or Ti(0) was the active species in the reductive process of the McMurry reaction, the mechanistic evidence presented proves the involvement of Ti(III) pinacolates in the deoxygenation step of the herein described Nugent's reagent-mediated McMurry olefination. This observation sheds some light on probably one of the mechanistically more complex transformations in organic chemistry. Finally, we have also proved that both of these processes can be performed catalytically in Cp(2)TiCl(2) by using trimethylsilyl chloride (TMSCl) as the final oxygen trap.

Titanocene monochloride catalyzes the homocoupling of benzylic halides and benzylic gem-dibromides to give the corresponding bibenzyl and stilbenyl systems. Exposure of benzylic bromides to Ti(III) in the presence of aldehydes gave rise to the Barbier-type products. Examples of the utility of the herein described processes are included.

Two new efficient methods for the regioselective homocoupling of allylic halides using either catalytic TiIII or the combination Mn/ZrIV catalyst have been developed. The regio- and stereoselectivity of the process proved to increase significantly when the Mn/ZrIV catalyst is used as the coupling reagent and when cyclic substituted allylic halides are used as substrates. The use of Lewis acids such as collidine hydrochloride allowed the quantity of catalyst to be lowered up to 0.05 equiv. We have proved the utility of these protocols with the synthesis of different terpenoids such as (+)-beta-onoceradiene (1), (+)-beta-onocerine (2), squalene (5), and advanced key-intermediates in the syntheses of (+)-cymbodiacetal (3) and dimeric ent-kauranoids as xindongnin M (4a).

The first total synthesis of potent anti-inflammatory polypodanes (+)-myrrhanol A (1), (+)-myrrhanone A (2), (+)-myrrhanone B (3), and (+)-myrrhanol B (4) has been achieved. Key steps in our convergent, highly stereocontrolled route are a Ti(III)-mediated radical cyclization of a chiral monoepoxide to furnish a bicyclic synthon that combines stereospecifically with an acyclic vinyl iodide via an intermolecular B-alkyl Suzuki-Miyaura cross-coupling.

. -The Nugent reagent (TiCl(Cp)2), generated in situ, efficiently mediates the deoxygenation-reduction of alcohols and carbonyl coupling-olefination reactions. The reactions proceed by formation of alkoxy-or hydroxy-Ti(III) complexes or Ti(III) pinacolates respectively, which lowers the activation energy for C-O bond homolysis. The reactions can be conducted catalytically in titanium by using TmsCl as the final oxygen trap. -(DIEGUEZ, H. R.; LOPEZ, A.; DOMINGO, V.; ARTEAGA, J. F.; DOBADO, J. A.; HERRADOR, M. M.; QUILEZ DEL MORAL, J. F.; BARRERO*, A. F.; J.

The titanocene-mediated cyclization of suitably functionalized acyclic C10 epoxy-polyprenes leads, with moderate stereoselectivity, to high yields of functionalized terpenic cyclopentanes with three contiguous stereogenic centers. These highly functionalized cyclopentanes are useful intermediates for the synthesis of several natural compounds that

The reaction in the presence of Mn/Zr IV proceeds with better regio-and stereoselectivity than the Ti-catalyzed one. The products can be obtained in high yields and almost complete geometrical purity. -(BARRERO*, A. F.; HERRADOR, M. M.; QUILEZ DEL MORAL, J. F.; ARTEAGA, P.; ARTEAGA, J. F.; DIEGUEZ, H. R.; SANCHEZ, E. M.; J.

Polyphenylalkane derivatives Q 0720Coupling of Benzylic Halides Mediated by Titanocene Chloride: Synthesis of Bibenzyl Derivatives. -In the presence of catalytic amounts of TiCl(Cp) 2 , benzylic halides smoothly undergo homocoupling giving dibenzyls like (II). Starting from benzylic dibromides such as (III), stilbenes are obtained in good yields. TiCl(Cp)2 also promotes heterocoupling of benzylic halides with aldehydes. -(BARRERO*, A. F.; HERRADOR, M. M.; QUILEZ DEL MORAL, J. F.; ARTEAGA, P.; AKSSIRA, M.; EL HANBALI, F.; ARTEAGA, J. F.; DIEGUEZ, H. R.; SANCHEZ, E. M.; J. Org.