Schwartz’ reagent, hydrozirconation

Hydrozirconation of alkynes with the Schwartz reagent, Cp2Zr(H)Cl (6), and subsequent methylation is also a general method (Eq. 2.5) [16]. 

As an alternative to hydrozirconation of acetylenic tellurides or selenides, Dabdoub and co-workers have more recently described the first additions of the Schwartz reagent (one equivalent) to acetylenic selenide salts 51 (Scheme 4.30) [52]. Subsequent alkylation at selenium produces 1,1-dimetallo intermediates 52, which are cleanly converted in a one-pot process to stereodefined products 53. It is noteworthy that ketene derivatives 52 are of ( )-geometry, the opposite regiochemistry to that which results from hydrozirconation of acetylenic tellurides (vide supra). This new route also avoids the mixtures of regio-isomers observed when seleno ethers are used as educts. The explanation for the stoichiometric use of Cp2Zr(H)Cl in these reactions, in contrast to the requirement for two equivalents with seleno ethers, may be based on cyclic intermediates 54, in which Li—Cl coordination provides an additional driving force. Curiously, attempted hydrozirconation of the corresponding telluride salt 55 under similar conditions was unsuccessful (Scheme 4.31) (Procedure 12, p. 143). 

Acylzirconocene chloride derivatives are easily accessible in a one-pot procedure through the hydrozirconation of alkene or alkyne derivatives with zirconocene chloride hydride (Schwartz reagent) [Cp2Zr(H)Cl, Cp = cyclopentadienyl] and subsequent insertion of carbon monoxide (CO) into the alkyl— or alkenyl—zirconium bond under atmospheric pressure (Scheme 5.1) [2],... 

The first example of a stable 1,1-bidentate Lewis acid based on boron and zirconium has been reported [35]. The synthesis of 22 is outlined in Scheme 7.12. Treatment of hex-l-yne with HBBr2 Me2S followed by conversion of the dibromoboronic ester to the corresponding alkenyl boronic acid and esterification with propane-1,3-diol provided the alkenyl boronic ester. Hydrozirconation of this compound with 3 equivalents of the Schwartz reagent, Cp2Zr(H)Cl [57], afforded the desired product 22 in 86% yield. 

The above-described procedure is advantageous towards the precedent method since (a) the starting lithium alkynyl selenolate is prepared in situ, avoiding the laborious preparation of the acetylenic selenides and (b) the hydrozirconation step is regio- and stereoselective, in contrast with the previously discussed hydrozirconation of acetylenic selenides resulting in a mixtnre of the regioisomers, and requires only 1 equiv of the Schwartz reagent instead of 2 eqniv of the precedent procednre. 

Acyl tri-isopropylsilanes containing alkene or alkyne functionality undergo smooth hydrozirconation with Schwartz reagent, in contrast to the corresponding aldehydes, which also suffer addition to the carbonyl group (Scheme 118)225. 

Vinyl cuprates.3 An attractive route to vinyl cuprates involves transmetalla-tion of vinylzirconates, available by hydrozirconation of 1-alkynes with the Schwartz reagent in THF at 25°. Transmetallation can be effected with CH3Li (3 equiv.)... 

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). 

Hydrozirconation of alkynes with the Schwartz reagent Cp2Zr(H)Cl yields the chlorovinyl zirconocene 17, which is easily converted to the methyl vinyl zirconocene 18 with either methyllithium in THF or methylmagnesium bromide in CH2C12. Compound 18 loses further methane at room temperature to form a zirconacyclopropene intermediate 19, which couples with a second alkyne and forms the metallacyclopentadiene 20 (Scheme 6) [34]. 

Hydrozirconation. The combination of zirconocene dichloride and t-butylmag-nesium chloride in C,H4-ether effects hydrozirconation of monosubstituted alkenes. The actual reagent may be HZrCp,Cl (Schwartz reagent, 6. 175-177) or t-BuZrCp,Cl. The reaction produces monoalkylzirconium derivatives with the metal attached to the terminal position of the alkene. 

The regiochemistry of the hydrozirconation of acetylenic selenides with the Schwartz reagent [Cp2Zr(H)Cl] is dependent on the nature of the substituents. For simple acetylenic selenides (R = Ar, n-Bu), ( j-j9-zirconated vinyl selenides were formed exclusively. The reaction with electrophilic reagents has allowed the stereoselective synthesis of ( j-2-halovinylaryl selenides [75], (Ej-2-aryl-vinyl aryl selenides [76], ( , j-l-arylselanylbutadienes [77] and ( j-2-butyltel-luranylvinyl selenides [78] (Scheme 55). 

Generation of organozirconium species 18 follows the hydrozirconation of the triple bond using zirconocene hydrochloride (Schwartz reagent) 16. This 16-electron, d° Zr(IV) complex is coordinatively unsaturated, so alkyne 15 coordinates to the electrophilic Zr center followed by insertion of the triple bond into the Zr-H bond. The resulting a-vinyl-Zr(lV)-species 18 is formed with a high cA-selectivity and regioselectivity, such that the bulky zirconocene moiety always adds end-on to the terminal multiple bond. 

Instead of the commercially available CpZrHCl, this reagent can be prepared in situ from Cp2ZrCl2 and lithium triethylborohydride. The reaction mixture hydrozirconates terminal acetylenes without affecting e.g. an ester or trimethylsilyl functionality in the alkyne. An application of the Schwartz reagent in natural product synthesis is the hydrozirconation of the terminal triple bond of Me3SiC=C(CH2)4C=CH. A review on hydrozirconation has been published . ... 

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. 

The trans-vmyi iodide is obtained by hydrozirconation, in which zirconocene dichloride is converted in situ into the analogously reactive i-butylzirconocene chloride. [233] Zirconocene dichloride is readily available, and less expensive than the Schwartz reagent, zirconocene hydridochloride. 

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