Dienyl zirconocene

ChinkovM, Marek I (2005) Stereoselective Synthesis of Dienyl Zirconocene Complexes. 10 133-166... 

Keywords Dienyl zirconocene Zirconacyclopentadiene Allylic activation ... 

The addition of Cp2Zr(H)Cl, known as the Schwartz reagent [30], to different alkenes and alkynes is known to be a facile process [31]. Therefore, the hydrozirconation of a variety of readily available enynes 12 is among the first methods developed for the stereoselective preparation of dienyl zirconium reagents 13. This process is both completely chemo- and regioselective with a syn addition of the zirconium hydride across the alkyne [32] (Scheme 5). From the same intermediate, the Zr atom can be isomerized in its internal position such as in 15 via a zirconacyclopropene intermediate 14. Moreover, the addition of trimethylstannyl chloride to 14 led to the stannylated dienyl zirconocene 16 [33] (Scheme 5). 

The protonolysis of the equally substituted zirconacycle 27 with weak acids such as ethanol leads to the monoprotonated dienyl zirconocene compound 28, which is subsequently converted into substituted diene 29 by a palladium crosscoupling reaction with aryl iodide (Scheme 14) [44]. Selective halogenation of such zirconacycle leads, as well, to the formation of zirconated diene 30 and then to the 1,4-dihalogenodiene 31 (Scheme 15) [45]. 

On the contrary, once unsymmetrical zirconacydopentadiene 20 (Scheme 13) is obtained regiospecifically, the formation of stereodefined metalated dienyl zirconocenes 26 requires a regiospecific reaction of only one carbon-zirconium... 

The stereospecific insertion of 2-monosubstituted alkenyl carbenoids was successfully employed in the preparation of 1-alkyl-1-zircono-dienes. The Z and E carbenoids of 1-chloro-l-lithio-l,3-butadiene (69 and 70, respectively) are generated in situ fromE- andZ-l,4-dichloro-2-butene [53] (Scheme 25). Inversion of configuration at the carbenoid carbon during the 1,2-metalate rearrangement stereospecifically yields terminal dienyl zirconocenes 71 and 72 [54] (Scheme 25). As the carbenoid-derived double bond is formed in 9 1=Z E for 69 and >20 1=E Z isomeric mixtures for 70, the metalated dienes 71 and 72 are expected to be formed with the same isomeric ratio. Carbon-carbon bond formation was achieved by palladium-catalyzed cross-coupling with allyl or vinyl halides to give the functionalized products with >95 5 stereopurity [55-57]. 

The impressive results outlined above are perhaps the most compelling examples of the power of zirconocene compounds in organic synthesis but in a general sense, are also illustrative for the serious limitations of the methodologies for the stereoselective preparation of dienyl zirconocene derivatives. These limitations can be summarized as follows ... 

Coming back to the initial problem, namely the stereoselective preparation of dienyl zirconocene derivatives, it was initially thought to apply the strategy described above to the preparation of dienyl systems (transformation of het-erosubstituted conjugated dienes 90 into dienyl zirconocenes 91, as described in Scheme 32). A few examples will be shown later in the chapter. 

Stereoselective Preparation of Dienyl Zirconocene Derivatives Via a Tandem Allylic C-H Bond Activation-Elimination Sequence... 

The presence of a discrete organometallic species as well as the stereochemistry of the metalated diene were first checked by iodinolysis and bromolysis,but the corresponding iodo- and bromodienes were found to be unstable and rapidly isomerized to a mixture of E and Z isomers. Thus, in order to have a better picture of the stereochemical outcome of the process, the crude reaction mixture was treated with AT-chlorosuccinimide (Scheme 37), and the corresponding chlorodiene 103 was isolated in 60% yield with an isomeric ratio >98 2. As alternative solution, the stereochemistry of the reaction was also determined by addition of allyl chloride, in the presence of a catalytic amount of copper salt, to the dienyl zirconocene derivative [74]. Skipped triene 104 was... 

A great number of dienyl zirconocenes are therefore formed by using this methodology, which presents a large flexibility (see Scheme 37), but limitations still remain for 1,1-disubstituted derivatives (as in 98g) or compounds substituted by an alkyl group in the carbon tether (such as in 98h). 

The unique stereochemistry of the diene results therefore from the elimination step and not from a further isomerization of the dienyl zirconocene with zirconocene derivatives (i.e., Cp2Zr-catalyzed stilbene stereoisomerization) [78]), since the hydrozirconation reaction of several l -ene-3-yne and lZ-ene-3-yne derivatives with Cp2ZrH(Cl) leads only to the (E,E) and (Z, ) isomers, respectively, in good yields (see Scheme 5) [33]. 

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