Oxidative Dearomatization of 4,5,6,7‐Tetrahydro‐1H‐indoles Obtained by Metal‐ and Solvent‐Free Thermal 5‐endo‐dig Cyclization: The Route to Erythrina and Lycorine Alkaloids

Abstract

A facile one-pot approach based on a thermally induced metal- and solvent-free 5-endo-dig cyclization reaction of the amino propargylic alcohols in combination with Dess-Martin periodinane-promoted oxidative dearomatization of 4,5,6,7-tetrahydroindole intermediates provides an efficient and robust access to 5,6-dihydro-1H-indol-2(4H)ones. Green, relatively mild and operationally simple characteristics of the synthetic sequence are the major advantages, which greatly amplify the developed methodology. The utility of obtained indolones as unified key precursors is demonstrated by the application of these products to the formal total syntheses of a whole pleiad of Erythrina- and Lycorine-type alkaloids, namely (±)-erysotramidine, (±)-erysotrine, (±)-erythravine, (±)-γ-lycorane, and abnormal erythrinanes (±)-coccoline and (±)-coccuvinine.

Ruthenium-catalyzed acceptorless dehydrogenative coupling of amino alcohols and ynones to access 3-acylpyrroles

“…Interestingly, the cyclic b-amino alcohol 1g is also proven to be effective coupling partner, yielding the substituted 4,5,6,7-tetrahydro-1H-indole 3ga in a reasonable yield, the structure motif of which as valuable intermediate has wide application in a variety of total syntheses of alkaloids. 16 A time-concentration curve of model reaction (Fig. S1 in ESI †) and several control experiments were performed to gain insight into the possible mechanism.…”

Catalytic Asymmetric 1,3-Dipolar Cycloaddition/Hydroamination Sequence: Expeditious Access to Enantioenriched Pyrroloisoquinoline Derivatives

“…13 C NMR (75 MHz, CDCl 3 ): δ 176.0, 174. 4,170.1,162.3 (d,J = 248.7 Hz), 141.5 (d, J = 7.7 Hz), 134.0 (d, J = 8.2 Hz), 119.1 (d, J = 3.3 Hz), 114.9 (d, J = 22.0 Hz), 113.2 (d, J = 24.0 Hz), 95.2, 77.7, 77.4, 77.2, 61.6, 61.6, 52.4, 47.7, 47.3, 30.9, 25.1, 22.2, 19.4, 13.7. 19 (1S,3R,3aS,6aR)-Methyl 3-(2-(Hex-1-yn-1-yl)-4,5-dimethoxyphenyl) -5-methyl-4,6-dioxooctahydropyrrolo[3,4-c]pyrrole-1-carboxylate (endo-3i).…”

“…Typical Procedure for the Hydroamination/Reduction Sequence. (6S,8S,8aR,11aS,11bR)- 8,8a,9,10,11,11a,4′:3,4]pyrrolo[2,1-a]isoquinoline-8-carboxylate (7a). A solution of endo-3a (31.8 mg, 0.08 mmol) in dichloromethane (1 mL) was added to a solution of JohnPhosAuMeCN SbF 6 (6.7 mg, 8 × 10 −3 mmol) in dichloromethane (1 mL) under an argon atmosphere at room temperature.…”

“…13 C NMR (75 MHz, CDCl 3 ): δ 175. 7, 174.9, 169.2, 142.4, 134.4, 131.7, 128.8, 128.3, 127.4, 127.3, 126.4, 126.2, 125.6, 68.7, 68.3, 61.0, 51.9, 46.5, 45.5, 38.9, 25.2 (6S,8S,8aR,11aS,11bR)- 8,8a,9,10,11,11a,4′:3,4]pyrrolo[2,1a]isoquinoline-8-carboxylate (7g). Following the typical procedure, the hydroamination/reduction of endo-3g (34.4 mg, 0.09 mmol) afforded, after purification by silica gel flash chromatography (cyclohexane/EtOAc 3:1), 7g (20.7 mg, 60%, brown oil).…”

“…The pyrroloisoquinoline unit is an important motif, present in a family of natural occurring alkaloids with relevant biological activities. For example, Crispine A displays important cytotoxic properties, Harmicine shows strong antileishmania activity, Erysotramidine exhibits hypotensive, sedative, and anticonvulsive properties, and Lamellarins, a family of marine natural products, possess promising antitumor activities (Figure ). Furthermore, some unnatural derivatives containing this heterocyclic system also display potential pharmacological properties …”