1.3- Dienes hydrozirconation

The alkenylzirconium 685, prepared by hydrozirconation of a terminal alkyne with hydrozirconocene chloride, reacts with alkenyl halide to afford the conjugated diene 686(545]. The Zr reagent can be used even in the presence of the carbonyl group in 687, which is sensitive to Al and Mg reagents. 

Hydrozirconation of the sterically less hindered double bond in conjugated dienes is generally observed [103]. However, the presence, as the minor regioisomer, of the allyhc product has been reported [5, 86]. Depending on the reaction conditions and the reagents used in the subsequent transformation, the allylic isomer did not form (Scheme 8-12) [2]. 

AUylzirconium complexes are conveniently obtained by the regio- and stereoselective hydrozirconation of allene [127-133] and can be, for example, used subsequently for the MAO-catalyzed allylzirconation of alkynes to prepare enyne derivatives [132]. Alternatively, the preparation of (E)-l,3-dienes from aldehydes and the appropriate allylstannane zirconocene derivative (R = SnBu,) is accomplished (Scheme 8-17) [131], Note that addition of [Cp2Zr(H)Cl[n (1) on the aUenyl reagent with the... 

The only other alkenyl carbenoid with a proton trans to the halide that can readily be generated by deprotonation is the parent 1-lithio-l-chloroethene 57 [43] (Scheme 3.13). Insertion into organozirconocenes arising from hydrozirconation of alkenes and alkynes, followed by protonation, affords terminal alkenes and ( )-dienes 59, respectively [38]. The latter provides a useful complement to the synthesis of 54 in Scheme 3.12 since the stereocontrol is >99%. 

Acetylenic ethers 7 can be hydrozirconated, and subsequent iododezirconation leads to (fc)-iodo enol ethers 8 (Scheme 4.4) [18], These species undergo efficient Sonogashira couplings to give (E)-enynes, which are ultimately converted to stereodefined dienol ethers. These dienes have proven useful in studies of diastereoselective cycloaddition reactions with singlet oxygen, where R in 8 is a nonracemic auxiliary (e. g., menthyl) (Procedure 3, p. 140). 

Hydrozirconation of 1-alkynyl pinacolboronates with Cp2Zr(H)Cl provides gem-boriozirco-nocenes 45. Treatment of 45 with CuBr gives the homocoupled (1 fc, 3fc)-2,3-dibora-l,3-dienes 46 in good yield (Scheme 7.15) [92]. The zirconocene-induced coupling was studied using a series of 1-alkynyl pinacolboronates 47. In this case, two regioisomers 48 and 49 were detected (Scheme 7.15). 

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%. 

When the above-mentioned process is applied to 1-lithio-l-chloroethene 66 [52] and vinyl zirconocene 67, arising from hydrozirconation of terminal alkynes, a stereospecific formation of 2-zirconated dienes 68 is obtained, affording terminal dienes after protonation [53] (Scheme 24). 

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]. 

Allylic zirconocenes, generated by hydrozirconation (see Hydrozirconation) of allenic systems, react with terminal alkynes when activated with MAO to regioselectively afford 1,4-dienes. The same MAO catalyzed process, applied to haloalkynes, leads to excellent yields of the 1,4-enyne (100) (Scheme 23). ... 

Alkynes are universally hydrozirconated as well the only failure in the literature is that of a perfluori-nated compound, C7Fi5(2sCH. Alkynes appear to be more reactive than alkenes, both by qualitative comparison and from the results on enynes (Table 6 also see Section 3.9.3.3.1), Furthermore, hydrozirconation of alkynes can compete with reduction of unsaturated functional groups such as nitriles and esters (Table 5), which is generally not true for alkenes. Dienes can be cleanly monohydrozirconated if one of the double bonds is terminal other cases are considered in Section 3.9.3.3.I. 

Similarly, with 1,3-dienes there is some tendency towards Markovnikov addition, yielding an allylic product, although again there are conflicting results. Buchwald et al. conclude that hydrozirconation of 1,3-pentadiene proceeds as in equation (31), whereas Schwartz finds only terminal isomer (27), but... 

Halogenative cleavage likewise appears completely general for both alkyl- and alkenyl-zirconium complexes (Scheme 10), and proceeds with complete retention of configuration at carbon. For the hydrozirconation products of 3-methyl-1,3-dienes, such as (40), cyclization competes (equation 43). Analogs without the 3-methyl subsitutent, or with more remote double bonds, give only the uncyclized products in good yields. " ... 

The modified Negishi protocoi was used in J.S. Panek s total synthesis of (-)-motuporin to couple the left-hand subunit organozinc compound with the right-hand subunit ( )-vinyl iodide. The left-hand subunit was prepared by the Schwartz hydrozirconation of a disubstituted alkyne to give an ( )-trisubstituted zirconate, which was subsequently transmetalated with anhydrous ZnCl2. The resulting vinylzinc species was immediately treated with one equivalent of the ( )-vinyl iodide in the presence of 5 mol% Pd(PPhs)4 to afford the ( , )-diene coupled product with complete stereoselectivity. 

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. " ... 

Substituted 1,4-dienes are obtained by reductive coupling of allenes and 1-alkynes via hydrozirconation of the allenes. Greatly enhanced regioselectivity is attained by using methoxyaluminoxane as catalyst. 

Formation of methylcyclopropane complexes and reactions of these metal alkyls competes with direct conversion of the homoallylmetal complex. Thus 1,2-hydrozirconation of 1,3-dienes with Schwartz s reagent [bis(cyclopentadienyl)zirconium chloride hydride] leads to homoallyl-zirconium complexes 1 which upon treatment with V-bromosuccinimide give the corresponding l-bromobut-3-enes 2 and the isomeric (bromomethyl)cyclopropanes 3 via intramolecular ring closure. ... 

Continuing studies of the hydrozirconation system Cp2Zr(Cl)H illustrate its versatility. For example, chloro-olefins such as 4-chlorocyclohexane react to give moderate yields of bicyclo[3,l,0]hexane. Ring formation is believed to occur via Zr—X y-elimination. y5-Unsaturated aldehydes and halides have been obtained from CO insertion into the Zr—C bonds of intermediates obtained from 1,3-dienes and Cp2Zr(Cl)H.3 ... 

The relative reactivity is measured qualitatively. At RT the rate of hydrozirconation of various alkenes is 1-octene > cis-4-octene > trans-4-octene > methylenecyclo-hexane > cyclopentene > cyclohexene > 3-methyl-2-butene. In competitive studies, a terminal alkene reacts 70 times faster that a disubstituted alkene. These relative rates are attributed to steric effects. Double bonds y to zirconium are less reactive than dienes since ( -Cp)2Zr(CH2CH2CH=CH2)Cl can be isolated from the reaction of ((j -Cp)2ZrHCl and butadiene . 

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