Synthesis of substituted cis‐8,cis‐11,cis‐14‐eicosatrienoic acids, precursors of correspondingly substituted prostaglandins

Abstract

Abstract. The synthesis of the following groups of acids is described: (a) 3-Methyl-c-2,c-S,c-I l,c-l4-, and 3-methyl-t-2,~-8,c-l l,c-14-eicosatetraenoic acid and 3-methyl-c-8,c-1 l,c-14-eicosatrienoic acid, (b) c-8,c-ll,c-14-eicosatrien-5-ynoic acid, (c) ~-2,3-methylene-,t-2,3-rnethylene-,3,3-dimethyl-and 4,4-dimethyl-c-8,c-ll,c-14-eicosatrienoic acid, (d) 18-methyl-, ( S ) -18-methyl-and 19-methyl-c-8,c-ll,c-14-eicosatrienoic acid. They were obtained via coupling of (a) c-7,c-10,c-13-nonadecatrien-2-one with ethoxycarbonylmethylenetriphenylphosphorane and ~-7,~-10,~-13-nonadecatrien-2-yl methane sulfonate with diethyl malonate, (b) l-bromo-c-2,~-5,~-8-tetradecatriene with 5-hexynoic acid, (c) 1-bromo-2,5-undecadiyne with the appropriately substituted 8-nonynoic acids and (d) from the correspondingly substituted 1-bromo pentanes, using standard procedures.

Carbon quaternization of redox active esters and olefins by decarboxylative coupling

“…By contrast, direct C quaternization through radical intermediates sidesteps these inefficient tactics through modular LEGO-like transformations of commercially available building blocks (olefins and acids). For example, the simple alkyne 53 was previously prepared (en route to prostaglandin analog synthesis) in an eight-step route, of which only one step forged a C-C bond and the key quaternary C was purchased in the form of a dimethyl cyclohexanone 52 with a skeleton that was tediously edited (21). By contrast, commercially available olefin 54 was coupled with the RAE derived from the simple commercial alkyne-containing acid (55) under radical quaternization conditions to deliver 53 in only two steps (48% isolated yield).…”

Carbon Quaternization of Redox Active Esters and Olefins via Decarboxylative Coupling

“…For instance, the simple alkyne 53 was previously prepared (en route to prostaglandin analog synthesis) in an eight-step route of which only one step forges a C-C bond and wherein the key quaternary center was purchased in the form of a dimethyl cyclohexanone 52 whose skeleton was tediously edited. 21 In contrast, commercially available olefin 54 can be coupled with the RAE derived from the simple commercial alkyne-containing acid (55) under radical quaternarization conditions to deliver 53 in only 2 steps (48% isolated yield). Ketoaldehyde 56, a useful building block for steroid analog synthesis, was previously accessed relying on classic carbonyl chemistry, C-C homologation, and a variety of undesirable reagents (Br2, Mg, OsO4).…”