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Enynes and diynes react with "ZrCp," (where Cp = 7'-CSHs) generated by treating C12ZrCp, with Mg and HgCl, or 2 equiv of an alkyllithium, such as n-BuLi, or a Grignard reagent, such as EtMgBr, and can produce in excellent yields zirconabicycles represented by 2 (M = Zr) and 8, respectively. Their protonolysis can provide the corresponding exocyclic alkenes and conjugated dienes 9, respectively. Iodinolysis of 2 (M = Zr) can give the corresponding diiodides in high yields, while carbonylation of 2 (M = Zr) can produce bicyclic enones 3 (Y = 0) in moderate to good yields. Although the bicyclization reaction fails with terminal alkyne containing substrates, various types of substituents on the alkyne moiety, such as alkyl, alkenyl, aryl, trialkylsilyl, and trialkylstannyl groups, can be accommodated. Investigation of the n-BuLi-C12ZrCp, reaction has revealed that it gives first (~-B U )~Z~C~, at -78 "C, which then decomposes to give Cp,Zr(CH,=CHEt), identified as its PMe3 complex 11. The PMe3-stabilized complex reacts with diphenylacetylene to produce a crystalline compound which has been identified as a zirconacyclopropene, 36a. This demonstrated, for the first time, the feasibility of converting alkynes into zirconacyclopropenes. The reaction of preformed, three-membered zirconacycles with alkynes gives five-membered zirconacycles. The reaction of diphenylacetylene is ca. 150 times as fast as that of (@stilbene. These results support a mechanism involving formation of a zirconacyclopropene intermediate followed by its intramolecular carbometalation with the alkene moiety of enynes for the Zr-promoted bicyclization of enynes.Direct conversion of enynes into the corresponding metallabicycles followed by their conversion into bicyclic or even monocyclic organic compounds is, in principle, a synthetically attractive methodology2 (eq 1). Consideration of molecular orbital /=-z 3 \= R 1 4 R=C and heteroatom-containing chain. X=H. halogen,etc , Y = O , e t c , Z = H . C , S i , G e , o r Sn ( 1 )interactions suggested to us that it would be desirable to generate a 14-electron species with a t least one filled nonbonding orbital (5) or its equivalent containing a transition metal for facile conversion of 1 into 2 via a concerted process. Interaction of 1 with 5 can, in principle, lead to the formation of 6 or 7 through the use of a pair of orbitals: a filled nonbonding orbital ( H O M O ) and an empty orbital ( L U M O ) . Intramolecular carbometalation involving the second empty orbital should lead to the formation of 2 (eq 2). Indeed, "ZrCp," equivalents, where C p = $-C5H5, generated by two-electron reduction of Cp,Zr(IV) derivatives were (1) Metal-Promoted Cyclization. 19. Part 18: Negishi, E.; Boardman, L. D.; Sawada, H.; Bagheri, V.; Tour, J. M.; Rand, C. L. J. Am. Chem. SOC. 1988, 110, 5383. Some preliminary results of the work have been communicated: (a) Neghish, E.; Holmes, S. J.; Tour, J. M.; Miller, J. A. A cobalt-promoted methodology for converting 1 into 3 was known at the outset of our investigation. (a) Kha...

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The efficacy of all major insecticide classes continues to be eroded by the development of resistance mediated, in part, by selection of alleles encoding insecticide insensitive target proteins. The discovery of new insecticide classes acting at novel protein binding sites is therefore important for the continued protection of the food supply from insect predators, and of human and animal health from insect borne disease. Here we describe a novel class of insecticides (Spiroindolines) encompassing molecules that combine excellent activity against major agricultural pest species with low mammalian toxicity. We confidently assign the vesicular acetylcholine transporter as the molecular target of Spiroindolines through the combination of molecular genetics in model organisms with a pharmacological approach in insect tissues. The vesicular acetylcholine transporter can now be added to the list of validated insecticide targets in the acetylcholine signalling pathway and we anticipate that this will lead to the discovery of novel molecules useful in sustaining agriculture. In addition to their potential as insecticides and nematocides, Spiroindolines represent the only other class of chemical ligands for the vesicular acetylcholine transporter since those based on the discovery of vesamicol over 40 years ago, and as such, have potential to provide more selective tools for PET imaging in the diagnosis of neurodegenerative disease. They also provide novel biochemical tools for studies of the function of this protein family.