Palladium hydrozirconation

Palladium-catalyzed alkenylation reactions involving pyrimidines can be achieved with hydrozirconated terminal alkynes, although the reaction is carried out in the presence of zinc chloride, so transmetallation to the zinc species is presumed to occur prior to the palladium-mediated coupling <1996ACS914, B-2002MI409>. Selective reaction at the 4-position of both 2,4-dichloropyrimidine and 2,4-dichloroquinazoline can be achieved. 

An intramolecular Heck-carbonylation/cyclization of the vinyl iodide 881 provides the 5,6-dihydropyran-2-one 882 during a total synthesis of manoalide (Equation 354) <1997CC1139>. The reaction of but-3-yn-l-ol with diaryl sulfides and carbon monoxide in the presence of a palladium(O) catalyst leads to a novel thiolactonization and hence arylthiosubstituted 5,6-dihydropyran-2-one 883 (Equation 355). Similar results are obtained with diaryl diselenides (Equation 355) <1997JOC8361>. Hydrozirconation of O-protected homopropargylic alcohols followed by carbonyla-tion and quenching with iodine provides a simple route to 5,6-dihydropyran-2-ones <1998TA949>. 

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). ... 

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. " ... 

Schwartz hydrozirconation works on both alkenes and alkynes even at room temperature. It works significantly better in ether solvents than hydrocarbon solvents. In addition, the reaction intermediate can be transmetallated into other organometallics that can be used in palladium-catalyzed reactions or trapped with electrophiles. Review Schwartz, J. Labinger, J. A. Angew. Chem. Int. Ed. 1976,15, 333-340. 

Stork s strategy towards racemic morphine comprises a Diels-Alder cycloaddition reaction of a benzofuran to establish the B- and C-ring of morphine as the key step [53]. The reaction sequence started with the ketahzation of iodoisovaniUin 97 (Scheme 15). Subsequently, the phenol was reacted with methyl propiolate to afford 98 as precursor for the installation of the benzofuran moiety via a palladium-catalyzed Heck cyclization (99). Next, the key intermediate was prepared for the Diels-Alder reaction. Hydrolysis of the acetal under acidic conditions and Wittig homologation afforded aldehyde 100, which was converted to diene 101 via hydrozirconation of acetylene 105 employing the Schwartz reagent and subsequent reaction with aldehyde 100 followed by sUylation of the secondary alcohol. 

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... 

Zirconium Reagents. Ethenylation can be effected via hydrozirconated terminal alkynes (Scheme 83). The alkenylzirconocene gives the -aUcenyl product. The reaction is carried out in the presence of zinc chloride. Presumably metal metathesis occurs before the palladium-mediated coupling takes place. The coupling is regiospecific with initial... 

In most cases, complexes of primary alkyl ligands are more stable than the isomeric complexes of secondary or tertiary alkyl ligands. For example, Reger has shown that the secondary butyl iron complex in Equation 3.18 isomerizes to the corresponding primary n-butyl complex, and that the isopropyl palladium complex in Equation 3.19 isomerizes to the more stable -propyl isomer. Likewise, secondary zirconocene alkyl complexes isomerize to the linear isomers (Equation 320), as shown many years ago by Schwartz, and Labinger and Bercaw have recently shown that the sec-butyl complex of zirconocene, generated by the hydrozirconation of cis-2-butene, isomerizes in several hours to the corresponding n-butyl complex. ... 

Table 1 Efficient and selective four-carbon homologation of oligoenes via hydrozirconation palladium-catalyzed cross-couphng with ( )-BrCH HC=CSiMe3 ...

Intramolecular reductive coupling of the keto-aldehyde (335), prepared by coupling of the hydrozirconation product of (333) with the palladium complex (334), furnishes the diterpene flexibilene (336), found in soft corals, in a remarkably short and eflScient manner. - ... 

A linear iterative method for the construction of (all- )-oligoenes of the (CH CH)n type via hydrozirconation-palladium-catalyzed cross-coupling has been demonstrated by Negishi and co-worker (Scheme 5-112). ... 

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