Oxidative Dimerization of 2-Oxindoles Promoted by KO^tBu-I₂: Total Synthesis of (±)-Folicanthine

Abstract

A 'transition-metal-free' oxidative coupling of 2-oxindoles has been demonstrated in the presence of 1.2 equiv each of potassium tert-butoxide and iodine. The method yields a diverse range of structurally different homo- and heterodimerized 2-oxindoles bearing vicinal all-carbon quaternary centers of great synthetic importance. A radical-driven pathway has been tentatively proposed.

Palladium-catalysed intramolecular carbenoid insertion of α-diazo-α-(methoxycarbonyl)acetanilides for oxindole synthesis

“…Pleasingly, we found that when using dichloroethane as the solvent, oxindole 4a was directly obtained (66% yield) from a sequential carbenoid insertion/alkylation process (entry 4). The formation of 4a not only facilitated the isolation of the cyclization product, but also avoided the generation of minor amounts of bisoxindole by-products, 17 which were also observed when using solvents other than DCE. The use of other palladium precatalysts such as Pd(OAc) 2 and Pd(PPh 3 ) 4 resulted in slower reaction rates (entries 5 and 6).…”

Efficient Alkynylation of 2‐Oxindoles with Alkynyl Dibenzothiophenium Triflates: Total Synthesis of (±)‐Deoxyeseroline

“…Then we shifted to inorganic bases at different temperatures. After exhaustive optimization we found that oxidative ethynylation of 2-oxindole methyl-3-carboxylate 4 a could easily be realized via enolalte (5)(6) in the presence of 1.2 equivalent of Cs 2 CO 3 in (CH 2 Cl) 2 solvent (entry 9) at 55°C to afford compound 7 a in 82% (Table 1).…”

“…[5a-f] Furthermore, the dimeric cyclotryptamine alkaloids sharing vicinal all-carbon quaternary stereocentres, with labile C3aÀ C3a'σ-bonds (1 g-j, Figure 1), remain another fascinating target to address especially due to their unique structural arrays and remarkable biological activities. [6,7] In this regard, we thought homo (1 g,1 i) and hetero (1 h,1 j) dimeric 2-oxindole ( Figure 1), would provide an excellent platform to access these alkaloids. The synthetic challenge aggravates even more in molecules where heterodimeric C3aÀ C3a' connectivity is present.…”

Synthesis of 2-oxindoles via 'transition-metal-free' intramolecular dehydrogenative coupling (IDC) of sp2 C–H and sp3 C–H bonds

“…However, if a tertiary radical is responsible for the oxidative process, then one would realize the formation of dimeric 2-oxindoles sharing vicinal all-carbon quaternary centers from dimeric β- N -arylamidoesters 18a and b ( Scheme 4 ). The reason behind our interest towards this direction was due to the prevalence of various dimeric cyclotryptamine alkaloids containing 3a,3a'-bis-pyrrolo[2,3- b ]indole subunits (core structure of alkaloids 22a and b , see, Scheme 5 ) [ 74 – 77 ], sharing a vicinal all-carbon quaternary stereogenic centers with extreme steric congestion at the C3a–C3a' σ-bond as well as the attendant lability of this linkage. Under the optimized conditions, one-pot dimerization of β- N -arylamido ester 3a and b and 9a took place in the presence of 1.2 equivalents of KO t -Bu and I 2 followed by a double IDC on treatment with 1.2 equivalents of KO t -Bu and I 2 affording the dimeric 2-oxindoles (±)- 19a–c in poor to moderate yields (26–45% yield and 2:1 dr) along with 15–18% isolation of dimeric β- N -arylamidoesters (±)- 18a–c ( Scheme 5 ).…”