Michael addition cyclopentanes from

An asymmetric domino Michael addition-alkylation reaction between aldehydes and ( )-5-iodo-l-nitropent-l-ene was developed by Enders et al. by using this catalyst and following an enamine-enamine mechanism. This method provided an access to cyclic y-nitroaldehydes of the cyclopentane type containing an all-carbon-substituted quaternary stereogenic centre. Enantioselectivities of up to 97% ee could be reached, whereas both yields and dia-stereoselectivities remained moderate, as shown in Scheme 1.62. Furthermore, a novel cyclic y-amino acid of potential pharmaceutical relevance could be synthesised from a domino product. 

Shibasaki also disclosed an application that incorporates an asymmetric tandem Michael addition-aldol reaction sequence with this family of bimetallic catalysts [117], as shown for the synthesis of the prostaglandin 11-deoxy-PGF (132, Scheme 12.16) [119]. In this route, the first two stereo-genic centers in the cyclopentane ring are installed in the course of an asymmetric Michael addition of malonate 128, followed by trapping of the resulting enolate 129 with aldehyde 130. The sequence provided the trans-cyclo-pentanone 131 in 92% ee. The stereoinduction at Cy was observed to range from dr 6 1 to dr 17 1, although this was inconsequential, as the secondary alcohol at C7 was later excised. 

The synthesis of this compound represents a notable departure from those discussed above. The presence of the carbonyl group at the 9 position of the cyclopentane ring, which classifies this compound as a PGE, removes one asymmetric center and thus somewhat reduces the stereochemical complexity of the synthesis. More importantly, this introduces the possibility of attaching the lower side chain by means of a 1,4-addition reaction the tram relationship of the two side chains should be favored by thermodynamic considerations. The very unusual functionality of the required Michael acceptor, that of a cyclopent-2-en-4-ol-l-one, leads to a rather lengthy albeit straightforward synthesis for the requisite intermediate. 

As an intramolecular version, the vinylcyclopentane 89 was obtained from methyl 4,5-hexadienylcyanoacetate (88) by C-1 attack in 57 % yield using DPPF in the absence of a base [24]. In the intermolecular reaction of 2,3-butadienyl-malononitrile (90) with the activated alkene 91, at first Michael-type addition of malononitrile to the alkene occurred to give 93, which underwent cyclization to give the cyclopentane 92 via the formation of hydridopalladium 94 [25]. 

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