Cross hydrozirconation

In terms of scope and chemoselectivity, hydrozirconation takes its place between hydroboration and hydroaiumination. However, the synthetic applications of organozirconocene complexes have been considerably expanded over these last few decades, and it can be expected that they will become more and more attractive in the future. Beside the direct substitution sequences, indirect reaction pathways involving transmetalation or activation by ligand abstraction have been successfully applied in a number of cross-coupling and C-C bond-forming reactions. 

Many examples exist for Pd-catalyzed cross-couplings of alkenylzirconocenes with simple carbocyclic aryl or alkenyl halides, whereas few precedents are seen for the coupling of alkenylzirconocenes with heteroaryl halides. Undheim and coworkers reported a Pd-catalyzed cross-coupling of 2,4-dichloropyrimidine with alkenylzirconocene [50]. Hydrozirconation of hexyne readily took place at room temperature with zirconocene chloride hydride in benzene. The resulting hexenylzirconocene chloride (76) was then coupled with 2,4-dichloropyrimidine at the more electrophilic 4 position, giving rise to 2-chloro-4-[( )-l-hexenyl]pyrimidine (77). 

SCHEME 4. Pd-catalyzed hydrozirconation-cross-coupling tandem reaction... 

SCHEME 50. Synthesis of conjugated oligoenes via an iterative hydrozirconation-cross-coupling tandem process149... 

Cross-coupling ofalkynes. A route to isomerically pure 1,3-dienes involves hydrozirconation of an alkyne followed by conversion to the alkyne complex 3, which couples with a second alkyne to give a metallacyclopentadiene 4. Treatment of 4 with dilute acid provides the diene 5, usually as a single isomer (>97%). Overall yields are in the range 53-80%. 

New reports of organozirconium-organic halide cross-coupling reactions have almost completely stopped. Nevertheless, the palladium-catalyzed cross-coupling of vinyl zir-conocenes (from alkyne hydrozirconation) with vinyl halides has been employed in the synthesis of the lipid isobutylamide natural product anacyclin (equation 98). ... 

Hydroboration of acetylenic selenides with 9-BBN led to the regio- and stereoselective formation of a-selanylalkenyl boranes which were then converted into Z-a, -disubstituted vinyl selenides by cross-coupling reaction with aryl bromides [80] (Scheme 58). With unsubstituted acetylenic selenides, an inversion of regioselectivity during the hydrozirconation was observed [81,82]. 

Subsequent studies have shown that alkenylzirconium derivatives generated in situ by hydrozirconation [46] of alkynes also undergo Pd- or Ni-catalyzed cross-coupling. As observed with alkenylalanes, Ni catalysts are generally satisfactory in the cases of alkenyl-aryl coupling [47] (Scheme 1-12), whereas Pd catalysts are more selective and distinctly superior to Ni catalysts in alkenyl-alkenyl and alkenyl-alkynyl coupling [48] (Scheme 1-13). 

Utilization of stereodefined alkenylalanes or alkenylzirconium reagents in palladium-catalyzed cross-coupling reactions greatly enhances the versatility of Negishi-type coupling reactions. These organometallics are readily available by hydroalumi-nation, carboalumination, and hydrozirconation of alkynes, respectively. 

Like hydroalumination and hydrozirconation, hydroboration of alkynes also provides a convenient and Stereospecific route to alkenyl metal reagents. However, initial attempts to achieve palladium-catalyzed cross-coupling of alkenylboranes with alkenyl halides were unsuccessful, due to the poor carbanionic character of these reagents. Later, Suzuki discovered that the desired transformation could be effected in the presence of an alkoxide or hydroxide base weaker bases, such as sodium acetate or triethylamine, were not generally effective. The reaction is suitable for the preparation of ( , )-, ( ,Z)- and (Z,Z)-dienes. Since reactions of alkenylboronates are higher yielding than those of alkenylboranes, the recent availability of (Z)-l-alkenylboronates " substantially improves the Suzuki method for the preparation of (Z)-alkenes. An extension of the methodology to the synthesis of trisubstituted alkenes has also been reported. " ... 

Cross-coupling of acetylenes with aryl halides E)-alkenylarenes. (E)-Atkenyl-zirconium compounds (1), obtained by hydrozirconation of terminal alkynes, react smoothly with aryl bromides and iodides in the presence of 10 mole % of Nl[P(CeH5)3]4 to form (E)-alkenylarenes (2) in yields generally of 70-95%. ... 

Dienes. The (E)-l-alkcnylzirconium compounds, obtained by hydrozirconation of 1-alkynes (6, 177-178), undergo cross coupling with alkenyl halides to form conjugated dienes (cf. the similar reaction of alkcnylalanes with alkenyl halides, 7, 95-96). In the present synthesis tetrakis(triphenylphosphine)-palladium (6, 571-573) can usually serve as catalyst. Nickel catalysts are less effective than Pd catalysts in this case. ... 

The hydrozirconation of alkynes with Cp2ZrHCl (Schwartz s reagent) provides ready access to vinylzirconium reagents, which have been shown to be suitable partners in palladium-catalyzed cross-couplings ( zirconium-Negishi reaction ) with aryl and vinyl electrophiles [1]. Recently, Fu disclosed the first... 

Highly efficient (up to 80%) and selective syntheses of several conjugated dienes (335-336) and trienes (337-338) via alkyne hydrozirconation and Pd-catalyzed alkenyl-alkenyl cross-coupling using (339) (PEPSI-iPr) as a... 

Although further comparisons of alkenylzirconiums to other alkenylmetals in Pd-catalyzed cross-coupling are desirable, the results discussed above clearly indicate that alkenylzirconiums are among the best alkenylmetals in alkenyl-alkenyl coupling, and the hydrozirconation-cross-coupling tandem process provides a convenient and satisfactory route to conjugated dienes and polyenes. 

Organozirconium compounds also undergo the Pd-catalyzed cross-coupling reaction with acyl halides.h i in the presence of ZnCF, the reaction can be carried out more efficiently. Acykirconium species, which are produced via hydrozirconation of alkynes or alkenes by zirconocene hydrochloride followed by insertion of CO, couple with acyl chlorides to give a-diketones (Scheme 12). 

---