Zirconocene chloride

A further improvement in the cuprate-based methodology for producing PGs utilizes a one-pot procedure (203). The CO-chain precursor (67) was first functionalized with zirconocene chloride hydride ia THF. The vinyl zirconium iatermediate was transmetalated direcdy by treatment with two equivalents of / -butyUithium or methyUithium at —30 to —70° C. Sequential addition of copper cyanide and methyUithium eUcited the /V situ generation of the higher order cyanocuprate which was then reacted with the protected enone to give the PG. 

Carbon monoxide rapidly inserts into the carbon—zirconium bond of alkyl- and alkenyl-zirconocene chlorides at low temperature with retention of configuration at carbon to give acylzirconocene chlorides 17 (Scheme 3.5). Acylzirconocene chlorides have found utility in synthesis, as described elsewhere in this volume [17]. Lewis acid catalyzed additions to enones, aldehydes, and imines, yielding a-keto allylic alcohols, a-hydroxy ketones, and a-amino ketones, respectively [18], and palladium-catalyzed addition to alkyl/aryl halides and a,[5-ynones [19] are examples. The acyl complex 18 formed by the insertion of carbon monoxide into dialkyl, alkylaryl, or diaryl zirconocenes may rearrange to a r 2-ketone complex 19 either thermally (particularly when R1 = R2 = Ph) or on addition of a Lewis acid [5,20,21]. The rearrangement proceeds through the less stable... 

The synthesis of analogous iminoacyl complexes by isonitrile insertion into linear alkyl-zirconocene chlorides is also known. In an overall regiospecific hydrocyanation of alkenes, iminoacyls 21 derived from tBuNC or Me3SiCN (as the Me3SiNC isomer) may be treated with I2 to rapidly generate an imidoyl iodide and subsequently the nitrile 22 (Scheme 3.6) [22], Less hindered iminoacyl complexes (e. g. R = Bu, Cy) may be hydrolyzed to afford aldehydes 23 [23]. 

In an important communication of 1989, Negishi reported [37] the first insertions of a-and y-haloorganolithium reagents into acyclic zirconocene chlorides. Recently, this work has been extended to a wide variety of carbenoids and organozirconium species, including zirconacycles, to provide a variety of new synthetic methods. These are described below. 

Access to non-terminal ( ,2)-dienes and ( ,Z, )-trienes 61 is provided analogously through deprotonation of ( , )-4-alkyl-l-chloro-l,3-butadienes followed by insertion of the resultant carbenoid 60 into alkyl- and alkenyl-zirconocene chlorides (Scheme 3.14) [38], The corresponding internal (Z,Z)-dienes and (Z,Z, )-trienes are also readily obtained by insertion of (3-alkynyl carbenoids 62 [44] into alkyl- and alkenylzirconocene chlorides, respectively (Scheme 3.14). Reduction of the triple-bond moiety in the products 63 to afford the cis-alkenes is well known [45—47]. 

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],... 

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). 

A sample of Taxol (14.7 g, 17 mmol) was dissolved in pyridine (150 mL) and chlorotriethylsilane (23.03 g, 147 mmol) was added. The reaction was stirred at 25°C under N2. After 20 hours the reaction appeared complete by TLC analysis (7% MeOH/CH2CI2). The mixture was concentrated to remove the pyridine. The residue was dissolved in CH2CI2 and washed with water, 10% CuS04, NaHC03 and brine successively. The organic layer was dried over MgS04, and concentrated to yield 20.89 g of the crude 2,7 -bis(triethylsilyl) Taxol. A portion of crude 2, 7-bis(triethylsilyl) Taxol (14.50 g, 13.4 mmol) was dissolved in dry THF (150 mL). Zirconocene chloride hydride (7.75 g, 30.2 mmol) was added. The reaction was stirred at 25°C under l l2. After 20 hours the reaction appeared complete by TLC analysis. The mixture was poured into... 

Unlike the insertion of 2-monosubstituted alkenyl carbenoids (69, 70, and 73), the reaction of 2,2-disubstituted alkenyl carbenoids with alkenyl zirconocene chlorides afforded the expected products as a mixture of stereoisomers. Thus, when 77, derived from the deprotonation of the stereodefined E-l-chloro-2-methyl-l-octene 76, was reacted with -l-hexenylzirconocene chloride 78 at low temperature, a partial inversion of configuration at the alkenyl carbenoid center occurred before or during the rearrangement to afford the expected metalated diene 79 with an E Z isomeric ratio of 58 42 after hydrolysis (see 80, Scheme 27) [53]. The poor stereocontrol was attributed to the metal-assisted ionization [58-60], which promotes the interconversion of the E- to the Z-alkenyl carbenoids 77. The latter occurs at a rate comparable with that of the insertion into organozirconocene chloride, and hence this is responsible for the loss of stereochemistry. 

Zirconocene hydrochloride aldrich Zirconocene chloride hydride Zirconium, chlorodi-ji-cyclopentadienylhydro- (8) Zirconium, chlorobis(r 5-2,4-cyclopentadien-1-yl)hydro- (9) (37342-97-5)... 

Carbozirconation. The presence of MAO is essential for the reaction of alkynes with the allylic zirconocene chlorides derived fixim allenes. The Lewis acid presumably enhances the carbozirconation of alkynes by promoting formation of cationic Zr species in the same manner as during the polymerization of a-olefins. 

Chloride abstraction of (alkylideneamido)zirconocene chlorides Cp2ZrCl(N=CHR) (R = Me,/>-tolyl), prepared by a hydrozirconation reaction, with lithium butylborate Li+[/z-BuB(C6F5)3] at ambient temperature gives the transient cation [Cp2Zr(N=CHR)]+, which readily dimerizes under the reaction conditions to form the cis/trans-isomers of the dimeric /x-alkylideneamido zirconocene dications 728563 (Scheme 179). Treatment of these dications with acetonitrile leads to the respective mononuclear monocationic adduct complexes. 

The zirconocene bis(arylamido) complex 787 was obtained by the reaction of Cp2ZrCl2 with 2 equiv. of the lithium amide605 (Scheme 195). When the reaction is carried out in a 1 1 ratio, the monoamide zirconocene chloride is generated as the major product. Reaction of in situ-generated Cp 2Zr with 2-(methylmercapto)aniline yields monoamido zirconocene hydride 788, the spectroscopic data of which suggest an interaction between the S atom and the Zr center in this complex. The bis(amido) complex 787 serves as a precursor for the synthesis of amido rhodium and iridium complexes. 

Some examples of the dioxolenium ion alkenylation reaction are shown in Scheme 8.29 [58]. The use of AgC104 on Celite (easier to handle than pure AgC104) and triphenyl phosphite was stated to improve the reproducibility in these reactions. At present, the method is not applicable to alkyl zirconocene chlorides. 

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