Zirconocene carbenoid

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]. 

To complete the range of geometric isomers of terminal and non-terminal dienes and trienes available, systems nominally derived from inaccessible (Z)-alkenylzirconocenes are desirable. Fortunately, insertion of the various carbenoids discussed above into mono- or bis(alkynyl) zirconocenes 64 and 65 affords dienyne products 66 [38], which are readily reduced to the desired ( ,Z,2)-trienes (Scheme 3.15) [45—47]. Insertion of the f5-alkynyl carbenoid 62 allows a convenient access to (Z)-enediynes 67. 

The tandem zirconocene-induced co-cyclization of dienes or enynes/insertion of allyl carbenoid/addition of electrophile is a powerful method for assembling organic structures. Two illustrations of its application are the synthesis of the dollabelane natural product acetoxyodontoschismenol 99 [57,62,63] and the one-pot construction of linear terpenoids 100 (Scheme 3.25) [59,64],... 

Scheme 12.13. Synthesis of acetoxyodontoschismenol using a three-component zirconocene induced co-cyclization/carbenoid insertion/electrophilic trapping, by Whitby and co-workers [38].

The stereospecific insertion of 2-monosubstituted alkenyl carbenoids was successfully employed in the preparation of 1-alkyl-1-zircono-dienes. The Z and E carbenoids of 1-chloro-l-lithio-l,3-butadiene (69 and 70, respectively) are generated in situ fromE- andZ-l,4-dichloro-2-butene [53] (Scheme 25). Inversion of configuration at the carbenoid carbon during the 1,2-metalate rearrangement stereospecifically yields terminal dienyl zirconocenes 71 and 72 [54] (Scheme 25). As the carbenoid-derived double bond is formed in 9 1=Z E for 69 and >20 1=E Z isomeric mixtures for 70, the metalated dienes 71 and 72 are expected to be formed with the same isomeric ratio. Carbon-carbon bond formation was achieved by palladium-catalyzed cross-coupling with allyl or vinyl halides to give the functionalized products with >95 5 stereopurity [55-57]. 

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. 

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. 

Zirconocene(ll) is isolobal with CH2. Based on the analysis of the Dewar-Chatt-Duncanson model (Fig. 1.2), the fiUed bonding orbitals of the carbenoidal zirconocene interact with the empty non-bonding orbitals of alkene or alkyne, while... 

Allenyl carbenoids (3-chloro-l-lithioalk-l-ynes) insert into zirconacy-clopentanes and zirconacyclopentenes to afford cyclic rj -allenyl/prop-2-ynyl zirconocene complexes which give cyclized-alcohol products on addition of aldehydes activated with boron trifluoride-diethyl ether (Eq. 52) [56]. 

In conclusion, five-membered metallacycles of titanocene and zirconocene are convenient starting materials for the construction of five-membered car-bocyclic compounds. The formation of five-membered carbocycles can be accomplished by addition reactions (or insertion reactions) of a variety of electrophiles, such as CO, RCN, RNC, bis(trichloromethyl)carbonate, allenyl carbenoids, halogencarbenoids, aldehyde, acyl chlorides, propynoates, and iodopropenoatesthe to the five-membered metallacycles. 

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