Cyclization of Chromium Oligoene -yne Carbenes

The [3-i-2]cycloaddition of metal alkenylcarbenes with 1,3-dipoles is generally regioselective but produces diastereomeric mixtures of cycloadducts. 

The regio- and diastereoselective [3-r2]cycloaddition of azomethine ylide 49 generated in situ with (-)-8-phenylmenthol-derived carbene complex 48 has been applied to the total synthesis of phosphodiesterase inhibitor (-r)-rolipram 51 

The substitution pattern in the enolate is crucial for the ring size of the cyclization product. Upon reaction with carbene complex 58 /3-substituted lithium enolates 59a H) lead to densely substituted cyclopentanols 60 suggesting a [2-i-2-i-l]cycloaddition pathway. /3-Unsubstituted lithium enolates 59b (R =H), however, form 1,3,3,5-tetrasubstituted cyclohexane-l,4-diols 61 that indicates a [2-I-2-I-1-I-1] sequence [41]. The branching point in the mechanism seems to be intermediate B formed upon addition of the allyl magnesium bromide to penta-carbonylchromate intermediate A. Intermediate B formed from /3-substituted enolates 59a is supposed to undergo an intramolecular carbometallation reaction to give cyclopentanol derivative 60. In contrast, intermediate B originating from 

Cydopentenone 64 bearing a carbonyl group in the substitutent R may serve for the synthesis of the angularly fused triquinane skeleton 66 based on a double Michael addition to the cyclopentadienone generated via base-promoted elimination of the dialkylamine [45]. Spiro[4.4]nonenone 65 appears as the relevant intermediate from the first Michael addition. Biscyclopentannulated cyclobutane 67 

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