Pii: S0040-4020(99)01088-1

ÐTitanocene(III) chloride and zirconcene(III) chloride are effective and mild reagents for radical generation in organic synthesis. In carbohydrate chemistry, these species are useful for the conversion of glycosyl halides to glycals, and for the stereospeci®c preparation of C-glycosides. In all cases, the 1-glycosyl radical is an active intermediate, generated by reaction of carbohydrate substrates with the organometallic. q 2000 Elsevier Science Ltd. All rights reserved. Overview of Organic Synthesis with Titanium(III) Reagents Titanium(III) compounds, which are metal centered radicals, are a group of mild reagents with diverse applications in organic synthesis. Titanocene(III) species derived from Cp2Ti BH4 have been used to reduce both aryl and alkyl halides, as well as ketones, aldehydes, and aromatic azo compounds. A titanocene(III) hydride is the active reductant; titanocene(III) hydrides are also proposed for the hydrosilylation of lactones, esters, and ketones. Titanocene(III) chloride ([Cp2TiCl]2, 1) is an effective reducing agent for a variety of compounds, including epoxides. It also reacts with activated halides, such as dibromides; reduction occurs by heteroatom abstraction, which likely generates a Cp2Ti IV species and a carbon radical. The apparent requirement for alkyl halide activation, and the broad range of functional groups 1 tolerates (alcohols; amines; amides; ketones; acids; esters; and aromatic halides) suggest it to be a selective reducing agent. Furthermore, 1 is neither acidic nor basic, and it operates under mild conditions; 1 seems to be ideal, therefore, as a reagent for use with sensitive, variously functionalized substrates, such as carbohydrates. Synthesis of Titanocene Chloride (1) Titanocene chloride (1) is easily prepared by reduction of titanocene dichloride (Cp2TiCl2, 2) with either Zn 22 or Al metal; the alkali metals tend to over reduce the Ti(IV) to Ti(II) or Ti(0) species. Likewise, the initial product of zinc reduction is a bimetallic Zn±Ti complex, which must be decomposed with diethyl ether, to give 1 but only in moderate yield. An improved preparation involves reduction of 2 by Al metal. Simply stirring a solution of red complex 2 with Al foil or wire for 16 h gives green 1; the color change is a helpful indicator of the reaction's progress. The dimer is isolated in very good yield by ®ltration of the reaction mixture, followed by concentration of the ®ltrate. It is also possible to generate the reagent in situ by reducing Cp2TiCl2 with alkyl magnesium halides, 8 zinc, or SmI2. 24 Ligand substitution can also be used to prepare 1, for example by reaction of TiCl3 with thallium(I) cyclopentadienide. Mechanism of Ti(III) Reductions of Substrates Compound 1 has been shown to be a dimer by single-crystal X-ray diffraction where the two d Ti atoms are bridged by chloride ligands. While the Ti centers are formally 17e species, they are coordinatively saturated in the dimer. In order for 1 to react with halides and epoxides via an inner sphere mechanism, it is necessary to have an available coordination site on the metal. Coordinating solvents such as THF readily dissociate the dimer into the reactive monomeric complex. Weakly coordinating solvents, such as diethyl ether and benzene, do not effectively break the dimer, and 1 is less reactive as a reductant in these solvents. The dimer can also be broken through the use of strongly coordinating ligands or solvents, such as amines, pyridines and phosphines, or acetonitrile. But, whereas such ligands (or solvents) completely dissociate 1 into monomeric adducts, they effectively prevent any inner sphere processes, as they do not readily dissociate from the Ti(III) center to provide a site for substrate coordination. Titanocene(III) chloride reacts with epoxides by abstractive ring-opening to generate an organic radical; trapping of Ti(III) generated radicals by a second equivalent of Ti(III) Tetrahedron 56 (2000) 2103±2112 Pergamon TETRAHEDRON 0040±4020/00/$ see front matter q 2000 Elsevier Science Ltd. All rights reserved. PII: S0040-4020(99)01088-1