Cyclopentene scaffolds

SCS-MP2 and the new perturbative B2-PLYP density functional methods provide accurate reaction barriers and outperform MP2 and B3-LYP methods when applied to the 1,3-dipolar cycloaddition reactions of ethylene and acetylene.39 Phosphepine has been shown to catalyse the asymmetric 3 + 2-cycloaddition of allenes with a variety of enones (e.g. chalcones) to produce highly functionalized cyclopentenes with good enantiomeric excess.40 The AuPPh3SbF6 complex catalysed the intramolecular 3 + 2- cycloaddition of unactivated arenyne- (or enyne)-yne functionalities under ambient conditions.41 A review of the use of Rh(I)-catalysed 3 + 2-cycloadditions of diaryl-and arylalkyl-cyclopropenones and aryl-, heteroaryl-, and dialkyl-substituted alkynes to synthesise cyclopentadienones for use in the synthesis of natural products, polymers, dendrimers, and antigen-presenting scaffolds has been presented.42... 

Five- and six-membered carbocycles have also been ineorporated as efficient scaffolds. Examples using phenyl (known as terphenyls) (356,357), cyclopentene (356,358-362), cyclo-pentadiene (359), cyclobutenone (363), and naphthyl (356) cores or scaffolds have been described. The cyclopentene series was optimized to a high degree, producing many very potent and selective COX-2 inhibitors with good in vivo activity (e.g., 56, SC-57666). 

The core skeleton of geissoschizine, an important biosynthetic precursor to numerous polycyclic indole scaffolds, was the target of a nickel-catalyzed alkylative coupling strategy. Cyclization precursor 13 was prepared by ozonolysis and double reductive amination of cyclopentene 12 (Scheme 8.13) [35]. Nickeldeprotection/oxidation sequence followed, and chromatography led to complete inversion of the C3 stereocenter. A Fisher indole synthesis followed to afford ( )-deformyl-isogeissoschizine, the core skeleton of geissoschizine. 

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