Ethyl bromide primary steps

Punaglandin 4 (208) is an example of a C-10 chlorinated prostanoid isolated from the Hawaiian octocoral telesto riisei. Its potent antitumor activity has attracted considerable synthetic interest. Characteristic of the a-chain is the same familiar dihydroxy stereochemistry found in (7, 7 )-tartaric acid. Wittig reaction of 167 with the phosphorane of [2-(l,3-dioxan-2-yl)ethyl]triphenylphosphonium bromide (205) followed by catalytic reduction and simultaneous debenzylation affords a primary alcohol, which is converted to aldehyde 206 in two oxidative steps. Aldol coupling of 206 with racemic cyclopentenone 207 (R=MOM) provides a statistical mixture of all four possible diastereomers. After chromatographic purification and protective group transformations, the target molecule 208 is obtained in 30—40% yield. The remaining three aldol products have been similarly converted to the diastereomers of 208 [75] (Scheme 47). 

The third example in Table 6.8 is particularly interesting since the product shown is an intermediate in a general method for the synthesis of various trisubsti-tuted alkenes. Thus, the alkylcopper-magnesium bromide species (the Nonnant reagent) adds to a primary alkyne so that the alkyl and metal addends are Z- (or syn-, or cis- or suprafacial) with the metal at C-1. In a second (and thus separate) step and with stereochemical retention (i), a second alkyl group can be added—as an alkyl iodide, for example, iodoethane (ethyl iodide, CH3CH2I)— which then replaces the metal (ii) a carboxylic add can be formed by treatment of the copper reagent with carbon dioxide (CO2) or (iii) iodine (I2) itself can be used so that a vinyl iodide results (Scheme 6.74). 

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