FeCl₃-Catalyzed Allylation Reactions onto 3-Hydroxy-2-oxindoles: Formal Total Syntheses of Bis-cyclotryptamine Alkaloids, (±)-Chimonanthine, and (±)-Folicanthine

Abstract

An FeCl-catalyzed efficient strategy for the allylation reactions of 3-hydroxy-2-oxindoles with allyltrimethylsilane has been developed. The reaction affords a variety of 2-oxindoles having quaternary center at the pseudobenzylic position in an operationally simple and inexpensive procedure. Control experiments using enantioenriched 3-hydroxy-2-oxindole show that the reaction proceeds through in situ generated 2H-indol-2-one (8). The methodology presents an efficient and concise access to the pyrroloindoline alkaloids (±)-deoxyeseroline (1a), (±)-esermethole (1b), (±)-physostigmine (1c), (±)-phenserine (1d), and (±)-physovenine (1e). Eventually, we extrapolated the scope of this methodology to the formal total syntheses of dimeric cyclotyrptamine alkaloids (±)-chimonanthine (3a), (±)-folicanthine (3c), and (±)-calycanthine (4).

Palladium-catalyzed allylation and deacylative allylation of 3-acetyl-2-oxindoles with allylic alcohols

“…Compounds 6aa, 20 6ab, 21 6ac, 22 6ad, 23 and 6ba 24 The first step was carried out following the description of section 4.2. for the synthesis of intermediate 2aa. The second step was run according to section 4.4. and, after purification, product 7 25 was isolated in 72% yield.…”

Deacylative Alkylation vs. Photoredox Catalysis in the Synthesis of 3,3'‐Bioxindoles

“…Electron‐deficient 3‐alkylidene oxindoles have been involved in [2+2] photochemical transformations promoted by an energy transfer mechanism, and as Michael‐type acceptor with Morita–Baylis–Hillman (MBH) systems, with alkoxycarbonylmethyl‐pyridinium bromides, 3‐substituted oxindoles, the Hantzsch ester, nitromethane, and with alkyl phosphites to access finally the desired dimeric unit (Scheme c) . Starting from 3‐(3‐indolyl)oxindoles by functional groups transformation non‐symmetrically substituted 3,3'‐bisoxindoles can be obtained (Scheme d) . The last strategy consists in an intramolecular dehydrogenative coupling (IDC) from the corresponding functionalized N‐ acylanilines or the o‐ iodo/triflate substituted surrogates.…”

“…The main interest of the synthesis of 3,3'‐bioxindoles is focused on the preparation of very sophisticated natural products ( 1–10 , Figure ) as, for example, pyrroloindole alkaloids of the Calycanthaceae family such as (+)‐chimonanthine 1 ,[3b], [3c], [4b], [4c], [5e], [5f], [5g], [5h], [14a], [14c], [14d], [15a] (+)‐chimonanthidine 2 ,[5g] (+)‐calycanthidine 3 , (+)‐folicanthine 4 ,[3a], [3b], [3e], [4b], [5f], [5h], [5i], [14a], [14b], [14d], [14e], [14h], [15a] and (+)‐calycanthine 5 ,[3e], [4b], [5f], [5h], [14d] which exhibit diverse therapeutic properties as analgesics, antibacterials, antifungals and antivirals . (+)‐Perophoramidine 6 [14f] exhibits cytotoxicity toward the HCT 116 human colon carcinoma cell line (IC 50 = 60 µ m ) and induces apoptosis via poly(ADP‐ribose) polymerase (PARP) cleavage. [14f] (–)‐Idiospermuline 7 ,[5b], [5c] a polypyrroloindoline natural alkaloid, exhibits hyperpolarization activity on neurochemical transmission in Sprague‐Dawley rat cortical wedge , .…”

“…(+)‐Perophoramidine 6 [14f] exhibits cytotoxicity toward the HCT 116 human colon carcinoma cell line (IC 50 = 60 µ m ) and induces apoptosis via poly(ADP‐ribose) polymerase (PARP) cleavage. [14f] (–)‐Idiospermuline 7 ,[5b], [5c] a polypyrroloindoline natural alkaloid, exhibits hyperpolarization activity on neurochemical transmission in Sprague‐Dawley rat cortical wedge , . (+)‐Communesin F 8 ,[14f] for example, is a complex polycyclicindole alkaloid with cytotoxicity against P388 lymphocytic leukemia cells (ED 50 A: 3.5 µg/mL, B: 0.45 µg/mL) and potent insecticidal activity toward silk‐worms (LD 50 D: 300 µg/g, E: 80 µg/g) .…”

“…[14f] (–)‐Idiospermuline 7 ,[5b], [5c] a polypyrroloindoline natural alkaloid, exhibits hyperpolarization activity on neurochemical transmission in Sprague‐Dawley rat cortical wedge , . (+)‐Communesin F 8 ,[14f] for example, is a complex polycyclicindole alkaloid with cytotoxicity against P388 lymphocytic leukemia cells (ED 50 A: 3.5 µg/mL, B: 0.45 µg/mL) and potent insecticidal activity toward silk‐worms (LD 50 D: 300 µg/g, E: 80 µg/g) . Tryptophan‐based dimeric diketopiperazine alkaloids (–)‐ditryptophenaline 9 [4b], [5f], [5j], [15a] and (–)‐WIN 64821 10 [4b], [5f], [5j], [15a] were isolated from Aspergillus oryzae and sp .…”