Functionalized cyclopentenes, stereoselective synthesis

A similar intermolecular cyclization was recently utilized in the synthesis of highly substituted dihydropyrrole derivatives [133 -135]. In a specific example, the addition of pentadienyltosylamide derivatives 177 to propynyl(phenyl)iodo-nium triflate initiates a sequence of transformations that furnishes the complex, highly functionalized cyclopentene-annelated dihydropyrrole products 178 in moderate yields with complete stereoselection (Scheme 66). Under similar reaction conditions, the isomeric isoprene-derived tosylamide 179 reacts with propynyl(phenyl)iodonium triflate to give azabicyclo[3.1.0]hexane 180 as the final product [134]. 

Very likely the ammonium fluorides are the proton sources and therefore the reason for incomplete conversions, since potassium fluoride in acetonitrile gives high yields in a very elegant [3 + 2]-annuIation process 87). It combines a Michael addition to a vinyl phosphonium salt with an intramolecular Wittig reaction and proceeds only in the presence of 18-crown-6 with satisfying yield. This cyclopentene synthesis has been executed in a repetitive manner to prepare linear triquinanes as illustrated in Scheme 6. Unfortunately, the sequence is non-stereoselective with regard to the ethoxycarbonyl functions. 

Further studies on the scope and stereochemical course of the oxyanion-accelerated vinylcyclopropane reairangement were reported in 1981. This paper introduced a general [4+1] annulation strategy for the synthesis of cyclopentene derivatives in which the anion-accelerated VCP rearrangement functions as the key step. In this report, the accelerated version of the vinylcyclopropane rearrangement was also shown to proceed with remarkably high stereoselectivity, in further contrast to the thermal process. 

The cyclopalladation of allylic or homoallylic amines and sulfides proceeds due to the chelating effect of N and S atoms, and has been used for functionalization of alkenes. For example, i-propyl 3-butenyl sulfide is carbopalladated with methyl cy-clopentanecarboxylate and Li2PdCl4. Reduction of the chelated complex with sodium cyanoborohydride affords the alkylated keto ester in 96% yield (eq 24). Functionalization of 3-N,N-dimethylaminocyclopentene for the synthesis of a prostaglandin skeleton has been carried out via a IV-chelated palladium complex as an intermediate. In the first step, malonate was introduced regio- and stereoselectively by carbopalladation (eq 25). Elimination of a /3-hydrogen generated a new cyclopentene, and its oxypalladation with 2-chloroethanol, followed by insertion of 1-octen-3-one and /3-elimination, afforded the final product. 

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