Alkenylzirconocene chlorides

Organylzirconocene derivatives do not show any useful reactivity toward a,[5-unsaturated carbonyl compounds, but the reaction can be promoted by the addition of CuOTf [14], The initial version was stoichiometric in Cu [14], but a Cu-catalyzed version was subsequently developed [112,113]. Adaptation of the Ni salt + DIBAH catalysts for cross-coupling [10] to conjugate addition led to the Ni-catalyzed conjugate addition of alkenylzirconocene chlorides [16,17] (Scheme 1.25). 

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]. 

Insertions into acyclic alkenylzirconocene chlorides. A convergent route to functio-... 

Carbonyl additions AgAsFe-catalyzed addition of alkenylzirconocene chlorides to aldehydes... 

Rather unexpectedly, the reaction product of alkenylzirconocene chlorides can be alkylated with primary alkyl bromides under the influence of a catalyst-solvent system consisting of 2.5% Pd(acac)2, 2 equiv. LiBr and 1 1 THF-NMP without any phosphine and NMI used above881 (Scheme 77). 

SCHEME 77. Pd-catalyzed alkylation of alkenylzirconocene chlorides with primary alkyl bromides... 

Stereoselective formation of carbocycles has been carried out through [RhCl(cod)]2 (cod = cyclooctadiene) catalyzed reaction of alkenylzirconocene chloride to co-carbonyl carboxymide <07TL6471>. When the camphor sultam auxiliary is incorporated into amide 206, the Rh(I)-catalyzed reaction of alkenylzirconocene chloride 207 forms the cyclization product 211 with high diastereoselectivity. The tt-facial differentiation of the double bond in 206 for the initial attack of vinyl group can be explained by taking into consideration either of the reactive conformers A or B. No matter which reactive conformer is involved, the attack of the vinyl group to the less crowded C p si-face would account for the observed chirality. 

Azines have been benzylated via the corresponding organostannanes [91, 109, 110], and alkylated or arylated via the organocuprate precursors [111-113]. Vinyla-tion of isoquinolines or quinolines with alkenylzirconocene chlorides 116 proceeds in excellent yields. Interestingly, an analogous reaction of a reduced derivative, catalyzed by a copper (1) salt in the presence of a chiral amine ligand, furnishes the corresponding adduct 117 in an enantioselective manner. (Scheme 17) [114]. 

PhI OAc)j with alkenylzirconocene chlorides, and the alkynyl analogs by reaction with alkynylsilanes. The direct reaction with uracil derivatives in TfOH affords 5-substituted products/... 

Conjugated dienes. Alkenyl chlorides and alkenylzirconocene chlorides are coupled with LTMP. 

Acylations. Alkenylzirconocene chlorides that are generated from hydrozirconation of alkynes readily undergo copper-catalyzed acylations. Thus, enones containing tin and selenium substituents are available from alkynylstannanes and alkynylselenides, respectively. Alkenyl alkynyl ketones are obtained when the reaction is carried out under carbon monoxide with alkynyliodonium salts. ... 

Heterofunctionalizations. Practically all the substrates are alkenylzirconocene chlorides. They behave well in halogenation, phosphorylation, sulfenylation, sulfiny-lation, selenenylation" and selenoacylation, as well as tellurylation," which gives rise to the substituted alkenes. 

Homoallylic alcohols and 1,3-dienes. Insertion of carbenoids to the C—Zr bond of alkenylzirconocene chlorides by gem-chloroalkyllithium generates reactive reagents that can be exploited in a carbon chain extension. Thus, consecutive reactions of the zirconocene species with Me SiCHjCljLi and aldehydes lead to homoallylic alcohols. Similar insertion with 1-chloro-l-lithioalkenes gives rise to conjugated dienes. This method is adaptable to the synthesis of more extended conjugated systems. 

Allylic alcohols. When alkenylzirconocene chlorides derived from l-alkynes react with epoxides in the presence of AgC104, isomerization of the epoxides to carbonyl compounds intervenes therefore, allylic alcohols result. However, epoxy carbonyl compounds are attacked at the C=0 group. ... 

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