Tandem Heck–Suzuki–Miyaura reaction: Application to the synthesis of constrained analogues of combretastatin A-4

Synthesis and Structure–Activity Relationships of Constrained Heterocyclic Analogues of Combretastatin A4

“…As we previously reported, under the optimized reaction conditions [Pd(OAc) 2 , PPh 3 , CsF] this tandem reaction occurred with the N-protected propynamide 6 c and the N-free butynamides 6 a and 6 b as starting materials. [21] It should be pointed out that the substitution of the newly formed double bond by a methyl group (R 2 ), in preventing isomerization of the double bond, stabilizes the coupling products and furthermore allowed a domino reaction with secondary amide substrates (X = NH). Thus, the (E)-3-arylmethyleneoxindoles 9 b, 9 c and the (E,E)-3-alkylideneoxindoles 10 a, 10 c were efficiently obtained, in a stereoselective manner, from the 2-iodoanilides 6 a-c and the 3,4,5-trimethoxyphenyl boronic acid 7 or the corresponding styryl derivative 8, respectively.…”

“…The configuration of the newly formed double bond of all the synthesized compounds was unambiguously supported by NOESY experiments. [21,27] …”

“…The filtrate was concentrated under reduced pressure, and the residue was subjected to flash chromatography (cyclohexane/EtOAc 8:2) to give ester 18 as a colorless oil (1.4 g, 70 %); General procedure for the tandem Heck-Suzuki-Miyaura reaction (path A). [21,27] A flask, flame-dried under high vacuum, was charged with the appropriate alkyne (1 equiv), boronic acid (1.1 equiv), CsF (3.3 equiv, flame-dried under high vacuum prior to use) and purged with argon three times. Anhydrous THF (0.03 m) was added, and the resulting mixture was degassed (bubbling argon, 15 min) before Pd(OAc) 2 (5 mol %) and PPh 3 (10 mol %) were added.…”

3‐Alkenyl‐oxindoles: Natural Products, Pharmaceuticals, and Recent Synthetic Advances in Tandem/Telescoped Approaches

“…[60] In 2005, Player and co-workers reported a tandem Heck/ Suzuki-Miyaura coupling process for the synthesis of (E)-3,3-(diaryl)oxindoles 67 (Scheme 11). [61] Using catalytic tetrakis(triphenylphosphane)palladium(0) and copper(I) thiophene-2-carboxylate (CuTC), the tandem sequence pro- Scheme [62] As combrestatin A-4 is known for its ability to selectively target the vascular system of tumours, analogues such as 68 and 69, are currently undergoing biological evaluation. [62] Also in 2005, Takemoto and co-workers reported a palladium-catalysed Heck/Suzuki-Miyaura process and also introduced a carbonylative version, as well as a Heck/Heck sequence for the stereoselective synthesis of a range of 3alkenyl-oxindoles (Scheme 12).…”

“…[61] Using catalytic tetrakis(triphenylphosphane)palladium(0) and copper(I) thiophene-2-carboxylate (CuTC), the tandem sequence pro- Scheme [62] As combrestatin A-4 is known for its ability to selectively target the vascular system of tumours, analogues such as 68 and 69, are currently undergoing biological evaluation. [62] Also in 2005, Takemoto and co-workers reported a palladium-catalysed Heck/Suzuki-Miyaura process and also introduced a carbonylative version, as well as a Heck/Heck sequence for the stereoselective synthesis of a range of 3alkenyl-oxindoles (Scheme 12). [63] Takemoto and co-workers have also utilised N-arylpropionamides 70 in a tandem indium-mediated carbometallation/Pd-catalysed cross-coupling sequence for the stereoselective formation of 3-alkenyl-oxindoles 72 (Scheme 13).…”