Selective methods for the synthesis of highly-substituted cyclopentadienyl and indenyl ligands.

摘要

Annulation methods involving cyclization of five-membered rings are regioselective approaches to highly substituted indenyl and cyclopentadienyl ligands for use in metallocene catalysts. The object of our research has been to develop two novel ring annulation methodologies: the first method intramolecularly employs a carbonyl addition known as the Nozaki-Hiyama-Kishi or Ni(II)/Cr(II) mediated coupling reaction and the second method employs ring-closing metathesis with Grubbs' and Schrock's catalysts to form the five-membered rings of these desirable ligands.; We applied the Nozaki-Hiyama-Kishi or Ni(II)/Cr(II) mediated coupling reaction in a three step approach to chiral annulated indenes from (1 R)-(+)-camphor, (1R,5S)-(+)-nopinone, and (−)-menthone. This method involved C-alkylation of the lithium enolates of the chiral ketones with 2-bromobenzyl bromide, followed by intramolecular Ni(II)/Cr(II) mediated coupling of the aryl bromide to the ketone, and dehydration of the resultant alcohol to form the chiral annulated indenes.; We executed a proof of concept for the use of ring-closing metathesis with Grubbs' II and Schrock's catalysts for five-membered ring formation in the synthesis of substituted indenes, tetrahydroindenes, and cyclopentadienes. We found that Schrock's catalyst formed the trisubstituted olefin of the five-membered ring of 1H-3-methylindene quantitatively, but did not form the tetrasubstituted olefin of 1H-2,3-dimethylindene. We synthesized tetrahydroindene, 1H-2-phenyl-tetrahydroindene, and the s-trans diene 1-phenylbicyclo[4.3.0]nona-1,5-diene from cyclohexanone in low unoptimized yields through C-alkylation with allylbromide reagents followed by addition of vinyl Grignard reagents to form olefin substituted cyclohexanols, which were ring-closed with Grubbs' II catalyst in benzene at 65–70°C. The yields, 10–20% for ring-closure, were presumably low due to the strain involved in formation of the trans -fused five-membered rings of the [4.3.0] bicyclic skeletons. The ring-closure of 3-ethyl-4-methyl-6-phenylhept-1,6-dien-3-ol to regioselectively form an unannulated trisubstituted cyclopentadiene, 1-ethyl-2-methyl-4-phenylcyclopenta-1,3-diene, with Grubbs' II catalyst was very facile and resulted in an unoptimized yield of 35%.