Fluoroalkene dipeptide isosteres

Otaka et al. reported the synthesis of (Z)-fluoroalkene dipeptide isosteres utilizing an organocopper-mediated reduction (Scheme 23) [69,70]. Reduction of 65 with Me2Cu(CN)Li2 2 LiBr-2 LiCI (4 equiv.) in THF-Et20 at -78°C for 15 min, proceeded unequivocally to yield the desired (Z)-fluoroalkene dipeptide isostere, eoc-Phei/r[(Z)-CF=CH]Gly-OEt (64) in 85% isolated yield. 

A. Otaka, H. Watanabe, A. Yukimasa, S. Oishi, H. Tamamura, N. Fujii, New access to a-substituted (Z)-fluoroalkene dipeptide isosteres utilizing organocopper reagents under reduction-oxidative alkylation (R-OA) conditions. Tetrahedron Lett. 42 (2001) 5443-5446. 

This highly stereoselective reaction would provide an efficient method for the preparation of fluoroalkene dipeptide isosteres 62 and related molecules such as depsipeptide isosteres 61 (see Scheme 10.21) [29,30]. 

Narumi, T., Niida, A., Tomita, K., et al. (2006) A novel one-pot reaction involving organocop-per-mediated reduction/transmetalation/asymmetric alkylation, leading to the diastereoselective synthesis of functionalized (Z)-fluoroalkene dipeptide isosteres. Chem. Commun., 4720-4722. 

Synthesis of funtionalized (Z)-fluoroalkene-type dipeptide isosteres (36) via Sml2-mediated reduction of y,y-difluoro-ot, -enoates 2.3.19. Reductive formation of fluoroolefins and subsequent conversion to diketopiperazine mimics (71). Nonpeptidic amide bond replacement... 

Methyl fluoro(diethoxyphosphono)dithioacetate (34) has been prepared from difluorinated precursors [56], Fluorophosphonothioacetamides (35) derived from this dithioester, have been successfully transformed into highly functionalized fluoroalkenes (36). Judicious selection of the aldehyde coupling partner can lead expeditiously to the preparation of fluoroolefin dipeptide isosteres following elaboration of the carboethoxy group and desulfurization (Scheme 11). 

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