Divergent titanium-mediated allylations with modulation by nickel or palladium.

Titanocene(III)-mediated radical processes are important tools for the formation of C C bonds under mild conditions, and are compatible with many functional groups. Moreover, titanium(III) complexes can be used substoichiometrically, which has allowed the development of enantioselective versions of these reactions. A serious limitation of these radical processes, however, derives from the fact that titanium(III)-mediated radical generation requires reactive substrates, such as allylic halides, which are often cumbersome in introduction and manipulation. Allylic carbonates and carboxylates, in contrast, are easily prepared and handled but are inert against titanocene(III) complexes. Nevertheless, it is known that nickel and palladium complexes can readily activate allylic carbonates and carboxylates I (Scheme 1) to form h-allylmetal complexes (II). On the basis of these results, we deemed that the combination of palladium or nickel derivatives with titanocene(III) complexes would facilitate the development of novel allylation processes using accessible allyl carbonates or carboxylates. In the case of palladium catalysis, it is known that the Oppolzer-type cyclization of organometallic species (II, M= Pd, Scheme 1) to cyclic derivatives (VI) is relatively slow at room temperature. Thus, reduction of II by a singleelectron-transfer reagent, such as [Cp2TiCl], [6] could lead to the allylic radical III, which might be eventually trapped by a second [Cp2TiCl] species to give an allylic titanium(IV) complex IV. Finally, nucleophilic attack of the organometallic derivative IV on an aldehyde or other electrophilic reagent would provide the corresponding allylation product V. On the other hand, nickel-catalyzed carbocyclizations, via intermediates such as II (M=Ni, Scheme 1) to cyclic derivatives VI, are relatively fast at room temperature. Once formed, VI might be reduced by [Cp2TiCl] to a primary radical VII, which could be trapped by a second [Cp2TiCl] species to give an alkyl titanium(IV) complex VIII. Hydrolysis of the organometallic derivative VIII would yield carbocycles IX. Thus, we anticipated that the use of palladium or nickel catalysts could modulate titanium(III) to drive allylation reactions with allyl carboxylates by two different pathways, either through intermolecular coupling with electrophilic reagents or to give carbocyclic derivatives by an intramolecular allylation. To check our hypothesis, we chose allylic carbonate E-1 as a model allylation reagent. Thus, reaction of decanal with carbonate E-1 and an excess of [Cp2TiCl] (2.0 equiv), [8] in the presence of PdCl2 (20 mol%) and triphenylphosphine, [9] gave the expected coupling product 2 as a single stereoisomer in 76% yield (Scheme 2). In contrast, when carbonate E-1 was treated with an excess of [Cp2TiCl] (2.0 equiv) in the presence of [NiCl2(PPh3)2] (20 mol%), a mixture of carbocycles 3 and 4 (4:1 ratio) was obtained in almost quantitative Scheme 1. Mechanism for palladium-catalyzed, titanocene-mediated allylation of carbonyl compounds and nickel-catalyzed, titanocenemediated carbocylization of allylic carboxylates. [M]= transition metal catalyst; Cp= cyclopentadienyl; E=electrophilic reagent (e.g. aldehyde).R=OEt, Me, or Ph.