Stereoselective construction of functionalized (Z)-fluoroalkenes directed to depsipeptide isosteres

Synthetic Methods for Fluorinated Olefins

“…The intermediates A are postulated, smoothly and regioselectively reacting with reactive alkyl halides to give the desired α-alkylated products 66 in an excellent Z-selective manner (Figure 3). [82] Figure 3. Cu-induced reductive defluorination/alkylation.…”

“…In the presence of CuI·2 LiCl, the reaction between the (E)-4,4-difluoro-5-hydroxyalk-2-en-1-ol 77 and Me 3 Al proceeded smoothly to give the defluorinative alkylation product 78 in completely 2,5-syn-selective and Z-selective manner. [92] With (Z)-77, the reaction proceeded in a manner favoring the 2,5-anti product, although the reactivity of the Z isomer relative to the E isomer was clearly low. A free hydroxy functionality at C5 is crucial for the reaction, because the absence of this OH group, protection as its ether derivative, or the presence of an amino group in place of the OH group all resulted in no reaction under the similar conditions, with recovery of the starting material.…”

Imine Additions of Internal Alkynes for the Synthesis of Trisubstituted (E)‐Alkene and Cyclopropane Peptide Isosteres

“…[28,29] The microwave-accelerated Stille coupling [30] of stannyl intermediate 6a proved to be a versatile method for installment of substituents on the alkene sp 2 -carbon (Table 1). Under monomode microwave irradiation conditions, the reaction time was shortened from 24 h to less than 1 h and the scope was extended to sterically hindered substrates like 2,6-dimethyliodobenzene.…”

An efficient synthetic method for Z-fluoroalkene dipeptide isosteres: Application to the synthesis of the dipeptide isostere of Sta-Ala

“…We have been also working in this field for a recent couple of years. A highly Z and 2,5-syn selective allylic alkylation reaction of 5-hydroxy-4,4-difluoroallylic alcohol derivatives with a combination of trialkylaluminum and copper salt is one of our notable achievements [18,19]. We have also communicated that using g,g-difluoroa,b-enoate derivatives 1 as the substrates, a-alkylated (Z)-gfluoro-b,g-enoate derivatives 2 can be prepared through lithiocuprate (Me 2 CuLi) mediated reductive defluorination followed by regioselective a-alkylation of the enolate intermediate 5 with alkyl halide (Scheme 1) [20].…”

“…A highly Z and 2,5-syn selective allylic alkylation reaction of 5-hydroxy-4,4-difluoroallylic alcohol derivatives with a combination of trialkylaluminum and copper salt is one of our notable achievements [18,19]. We have also communicated that using g,g-difluoroa,b-enoate derivatives 1 as the substrates, a-alkylated (Z)-gfluoro-b,g-enoate derivatives 2 can be prepared through lithiocuprate (Me 2 CuLi) mediated reductive defluorination followed by regioselective a-alkylation of the enolate intermediate 5 with alkyl halide (Scheme 1) [20]. When g,gdifluoro-a,b-enoate having a hydroxyl group at d-position (1, Y = OH) was treated with trialkylaluminum in the presence of Cu(I) salt, a direct alkyl-transfer reaction from trialkylaluminum proceeded to give the a-alkylated SN2 0 product (2, Y = OH) (Scheme 1).…”