| Abstract
| - Synthesis of 10,11-dihydro-, 10,11,14,15-tetrahydro-, and 10,11-dihydro-12-oxoleukotriene B4compounds (2, 4, 5) was accomplished stereoselectively by using the nickel-catalyzed couplingreaction illustrated in Scheme . The C(1)−C(7) fragments, TBS ether 10a for 2 and 4 andethyoxyethyl (EE) ether 10b for 5, were prepared in enantiomerically pure forms (>99% ee) by amodified literature procedure (ref a). On the other hand, boronate esters 11a and 11b, whichcorrespond to the C(8)−C(20) parts of 2 and 4, respectively, were synthesized from (R)-epichlorohydrin (18) of 99% ee. Briefly, 18 was converted into acetylenes 24 and 32 through epoxidering-opening with LiC⋮CC5H11/BF3·OEt2 or C7H15MgBr/CuCN. Hydroboration of these acetyleneswith (+)-(Ipc)2BH followed by reaction with MeCHO afforded the corresponding diethyl boronates,which upon ligand exchange with Me2C(CH2OH)2 furnished boronate esters 11a and 11b in 75%and 77% yields, respectively. In a similar manner, racemic boronate ester rac-11a, an intermediatefor synthesis of 5, was prepared from racemic epichlorohydrin. For synthesis of 2, borate 25 wasgenerated from 11a (1.5 equiv) and MeLi (1.6 equiv). Without isolation, 25 was submitted to reactionwith 10a (1 equiv) in the presence of a Ni(0) species at room temperature overnight to afford 26,which upon treatment with TBAF furnished 2 in 64% yield from 10a. Similarly, 11b and 10afurnished 4 in good yield. To synthesize 5, rac-11a and EE ether 10b were joined by the couplingreaction to produce 39, which was transformed into 40 by desilylation with TBAF. After hydrolysisof 40, oxidation with PDC followed by deprotection of the EE group furnished 5 in 36% yield from40. In addition, 2 was converted into amide 3 in 92% yield.
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