Z-fluoroalkene

For the synthesis of the title compound, Oxone or 3-chloroperbenzoic acid2 can be used to oxidize the sulfide to the sulfone. The title compound is a key reagent for the preparation of fluoroalkenes from aromatic11 and aliphatic2 aldehydes. Recently, a stereospecific method to (E)- and (Z)-fluoroalkenes was reported using this reagant.12 13 14... 

The procedure described here provides a stereospecific synthesis of (E)- and (Z)-fluoroalkenes from the corresponding (E)- and (Z)-fluorovinyl sulfones. Fluorovinyl sulfones obtained from ketones are, in most cases, readily separable into (E) and (Z) isomers either by crystallization or by chromatography.4 In the example described, only the (E)-fluorovinyl sulfone 1 is formed (which is converted into the (Z)-fluoroalkene 3 with complete retention of configuration). The reaction sequence has been used for the stereospecific synthesis of fluoroalkene nucleosides5 as well as for... 

Stereoselective construction of (Z)-fluoroalkene depsipeptide (60) through a Cu(l)-mediated allylic substitution reaction... 

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... 

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. 

G. Dutheuil, X. Lei, X. Pannecoucke, J.C. Quirion, A novel diastereoselective synthesis of (Z)-fluoroalkenes via a Nozaki-Hiyama-Kishi-Type reaction, J. Org. Chem. 70 (2005) 1911-1914. 

M. Okada, Y. Nakamura, A. Saito, A. Sato, H. Horikawa, T. Taguchi, Stereoselective construction of functionalized (Z)-fluoroalkenes directed to depsipeptide isosteres. Tetrahedron Lett. 43 (2002) 5845-5847. 

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. 

Olefination of aldehydes with the a-fluoroalkylphosphine oxide (54) provides a highly stereoselective route to the (Z)-fluoroalkenes (55) (Scheme 9).31 A similar reaction with the corresponding phosphonate gave a 1 1 mixture of ( )- and (Z)-alkenes. A new one-pot synthesis of 2-(diphenylphosphinoyl)cycloalkanes (56) by the reaction of cycloalkanone enolates with chlorodiphenylphosphine followed by oxidation has been reported (Scheme 10).32 Attempts to synthesise sarkomycin methyl ester (58) via reaction of the anion of phosphine oxide (57) with formaldehyde were unsuccessful as were similar reactions with other aldehydes, although the corresponding phosphonate anion does undergo olefination reactions. An X-ray structural analysis of (57) is reported. 

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. 

Nakamura, Y., Okada, M., Sato, A., et al. (2005) Stereoselective synthesis of (Z)-fluoroalkenes directed to peptide isosteres Cu(I) mediated reaction of trialkylaluminum with 4,4-difluoro-5-hydroxyallylic alcohol derivatives. Tetrahedron, 43, 5741-5743. 

Electrophilic acetylenes 227 (R = Et02C, CHO or CN R = EtC02, Ph or (EtO)2CH) add the elements of hydrogen fluoride on treatment with caesium fluoride under phase-transfer catalysis to yield mainly (Z)- fluoroalkenes 228 dimethyl acetylenedicarboxylate affords a 85 15 mixture of (Z)- and ( )-adducts under these conditions. No addition occurs in homogeneous solutions ... 

Scheme 5 Reaction mechanism of (Z)-fluoroalkene formatitm by the reduction of 14...

Scheme 6 Peptide isosters having a (Z)-fluoroalkene moiety synthesized by Nagao method...

The reaction of an a-fluorosulfoximine 18 with a nitrone 19 was also reported, and (Z)-fluoroalkene 20 was formed in good yield with high stereoselectivity [46] (Scheme 9). 

When l-phenyl-2,2-difluoro-3-buten-l-ol 27 was subjected to a reaction with a Pd catalyst in the presence of sec-amine, the amine attacked the Jt-allyl intermediate to give aminated (Z)-fluoroalkene 28 stereoselectively [61] (Scheme 11). 

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