A Triply Convergent Total Synthesis of L-(-)-Prostaglandin E2

Article abstract of DOI:10.1021/jo00161a010

This paper details a versatile and efficient total synthesis of l-(-)-PGE₂ (3).The key step is a triply convergent conjugate-addition/alkylation reaction involving the 1,4-addition of chiral vinyllithium reagent 7b to chiral vinyl sulfone D-47 to afford sulfone-stabilized anion <57>, which is subsequently alkylated to produce the basic prostaglandin E₂ skeleton 70.The synthesis of chiral vinyl sulfone D-47 involves a five step sequence with an enantioconvergent resolution process as one step and produces vinyl sulfone D-47 from readily available sulfide alcohol DL-11 in an overall yield of 36percent.The preparation of D-47 features two steps that utilize stereospecific S_N2'reactions.The synthesis of l-(-)-PGE₂ (3) involves a seven-step sequence from vinyl sulfone D-47 using mild conditions with an overall yield of 40percent and features an efficient peracetic acid oxidation of secondary amino acid 120 to oximino acid 121, which is, in turn, desulfonylated by 1,4-elimination of phenylsulfinic acid to generate a vinyl nitroso species that undergoes stereospecific 1,4-reduction by sodium borohydride to yield oxime 131.The hydrolysis of oxime 131 to l-(-)-PGE₂ (3) using boron trifluoride and paraformaldehyde is the first reported high-yield method (84percent).This gives an overall yield for the synthesis of l-(-)-PGE₂ (3) from racemic sulfide alcohol DL-11 of 14.5percent, including the resolution process.