Carbocydization

Versatile [3 + 2]-cydoaddition pathways to five-membered carbocydes involve the trimethylenemethane (= 2-methylene-propanediyl) synthon (B.M. Trost, 1986). Palladium(0)-induced 1,3-elimination at suitable reagents generates a reactive n -2-methylene-l,3-propa-nediyl complex which reacts highly diastereoselectively with electron-deficient olefins. The resulting methylenecyclopentanes are easily modified, e. g., by ozonolysis, hydroboration etc., and thus a large variety of interesting cyclopcntane derivatives is accessible. 

Tlie constrLiction of carbocydic cotnpoutidi by ring-annulation procedures frequently plays a prominent role in total syntliesis. Tlie tolerance of various functional groups in tlie zinc reagents employed in copper-catalyzed asymmetric 1,4-additions fornis tlie basis for tliree novd catalytic enantioselective annulation metliods discussed bete. 

Intramolecular Sm(n)-mediated coupling of ketones with distal vinylepoxides results in the corresponding carbocydic derivatives with good to excellent diaster-eoselectivity [125], When the reaction was conducted with enantioenriched substrates the products were obtained with poor ees, indicating low it-facial discrimination in this reaction. 

Scheme 6. Chiral medium-ring carbocydes can be prepared by catalytic RCM in conjunction with the directed uncatalyzed alkylation process...

Diallenes such as 256 can lead to carbocydes by electrocyclic ring closure (Scheme 7.38) [80], Whereas 257 is formed on distillation of 256 at -160 °C, other diallenes cyclize at significantly lower temperatures to produce dimethylenecyclobu-tenes (see Scheme 7.7) [105]. 

On the other hand, the reaction of bisallenes with Bu3SnSnBu3 may generate cis-bisallene Pd(SnBu3)2 (C) and/or a chelated cj-allylpalladium complex D reversibly. The fast carbocydization of these intermediates would give rise to a vinylpalladium complex E, which then yields a ds-compound by reductive elimination and/or a cis-bicyclodiene through (T-bond metathesis as a kinetically controlled product (Scheme 16.66). 

The intermolecular carbocyclization with a strained olefin, such as norbornene 35, has been frequently used for proof-of-prindple in challenging metal-catalyzed transformations. The use of rhodium catalysts fadhtates the intermolecular reaction, albeit in modest yield and with poor regioselectivity (Scheme 11.10). Ethylene 39 can also be utilized to this end, but generally affords the carbocydization products in low yield, as... 

Initial attempts at carbocydization of the enyne 82 with Wilkinson s catalyst under an atmosphere of 1,3-butadiene in refluxing toluene furnished only trace amounts of product, which was attributed to the preference for the enyne to undergo homodimerization in a highly stereoselective manner (Tab. 12.8, entry 1 ds 19 1) [38]. Nonetheless, the coordinatively unsaturated (AgOTf-modified) catalyst furnished the [4-i-2-1-2] product in excellent yield (entry 2). The ability to alter the product distribution in this manner prompted further examination of various other silver salts. 

The understanding of the reactivity made possible the development of the rhodium catalyzed [4-+2+-2] carbocydization reaction as outlined in Tab. 12.9. This study demon strated that nitrogen-, sulfur-, and oxygen-tethered enynes furnish the desired cycload... 

Preparation of Highly Functionalized, Optically Active Pyrrolidines, Piperidines, Carbocydes and Tetrahydrofurans... 

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