Synthesis of the cycloheptannelated indole fragment of dragmacidin E

Synthesis of the pivotal cycloheptannelated indole fragment of indole alkaloid dragmacidin E is achieved. The synthesis features a Pd-catalyzed indole synthesis reaction for the preparation of 3,7-disubstituted indole, a regioselective intramolecular Friedel–Crafts reaction for the construction of the 3,4-bridged cycloheptannelated indole skeleton, and a coupling reaction of vinyl triflate with diorganocuprate.     

A Novel Pd‐Catalysed Annulation Reaction for the Syntheses of Pyrroloindoles and Pyrroloquinolines

Pd‐catalysed annulation reactions between indole derivatives and internal alkyne esters leading to various pyrrolo[1,2‐a]indoles and pyrroloquinolines have been developed. The strategy involves an intermolecular addition of the indole nitrogen on to the internal alkyne ester followed by an intramolecular insertion of a vinyl–palladium complex into the carbonyl group. This method offers a facile and practical approach to pyrrolo[1,2‐a]indoles and pyrroloquinolines.     

Efficient and general synthesis of oxazino[4,3-a]indoles by cascade addition-cyclization reactions of (1H-indol-2-yl)methanols and vinyl sulfonium salts

An efficient and general approach to oxazino[4,3-a]indole architectures is described. The addition-cyclization cascade of (1H-indol-2-yl)methanols with vinyl sulfonium salts affords oxazino[4,3-a]indole derivatives in high yields.     

Total Synthesis of (−)‐N‐Methylwelwitindolinone B Isothiocyanate

The asymmetric synthesis of (−)‐N ‐methylwelwitindolinone B isothiocyanate is reported. Critical challenges overcome through these studies include the stereoselective installation of the sterically congested C13 alkyl chloride and control of the wayward reactivity of the indole unit to standard oxidants. A Pt‐catalyzed hydrosilylation helped stymie unwanted rearrangements facilitated by vinyl group participation during the chloride installation step, and a new Fe^II‐catalyzed oxidation accomplished the problematic conversion of indole into 2‐indolinone.     

An improved procedure for the conversion of indolines into indoles

The addition of a sacrificial enamine (such as indole), or of a vinyl ether (like dihydropyran) to an indoline during dehydrogenation by phenylseleninic anhydride dramatically improves the yield of the corresponding indole. This is due to scavenging of Se¹¹ phenylselenenating species.     

Palladium-catalyzed synthesis of N-vinyl pyrroles and indoles

A stereospecific palladium-catalyzed N-vinylation of azaheterocycles with vinyl triflates is described. Cyclic and acyclic vinyl triflates along with nonnucleophilic azaheterocycles were found to be substrates for this palladium-catalyzed synthesis of N-vinyl pyrrole and indole derivatives.     

A concise asymmetric total synthesis of aspidophytine

An expedient asymmetric total synthesis of aspidophytine is reported. A highly convergent strategy involving the sequential annulation of vinyl iodide 5 with indole 6 exploits varying modes of indole reactivity to provide aspidophytine in 23% over six steps from 5.     

Synthetic Modulation of an Unstable Dehydrosecodine-type Intermediate and Its Encapsulation into a Confined Cavity Enable Its X-ray Crystallographic Observation

Numerous indole alkaloids such as the iboga- and aspidosperma-type are believed to be biosynthesized via a common hypothetical intermediate, dehydrosecodine. The highly reactive nature of dehydrosecodine-type compounds has hampered their isolation and structural elucidation. In this study, we achieved the first X-ray structural determination of a dehydrosecodine-type compound by integrating synthetic optimization of the reactivity and stabilizing the fragile molecule by encapsulation into a supramolecular host. Formation of a 1 : 1 complex of the dehydrosecodine-type labile guest bearing both vinyl indole and dihydropyridine units with the host was observed. This integrated approach not only provides insights into the biosynthetic conversions but also allows stabilization and storage of the reactive and otherwise short-lived intermediate within the confined hydrophobic cavity.     

Synthetic studies about strychnopivotine: synthesis of the bridged azatricyclic fragment

Pd(0)-promoted coupling of an amino-tethered vinyl iodide and ketone enolate is the key step to synthesize the CDE ring system of the indole alkaloid strychnopivotine. Attempts to induce the same process in a compound bearing an o-nitrophenyl group as a latent indole moiety failed.     

Addition reaction of various azoles to perfluoromethyl vinyl ether

Chemistry of Heterocyclic Compounds - The addition reaction of perfluoromethyl vinyl ether to various azoles – derivatives of pyrrole, imidazole, pyrazole, indole, benzotriazole, carbazole,...     

Vinylation of Nitro‐Substituted Indoles,Quinolinones, and Anilides with Grignard Reagents

The reaction of vinyl Grignard reagents with o‐methoxynitroarenes containing an electron‐releasing substituent para to the nitro group proceeds through a pathway that is different from the initially expected Bartoli indole synthesis. Thus, instead of giving fused indole derivatives, these reactions provide a very mild and efficient new procedure for the synthesis of synthetically relevant aromatic systems containing an o‐nitrovinyl moiety, such as 5‐nitro‐4‐vinylindoles, 6‐nitro‐7‐vinylindoles, 6‐nitro‐5‐vinyl‐2(1H)quinolinones, and 4‐nitro‐3‐vinylanilines.     

[3+2] Cycloaddition of metal-containing azomethine ylides for highly efficient synthesis of mitosene skeleton

Efficient synthesis of tricyclic indole derivatives bearing a substituent at the 3-position of the indole nucleus was achieved by the [3+2] cycloaddition reaction of transition metal-containing azomethine ylides derived from N-(o-alkynylphenyl)imines with vinyl ethers. Third-row transition metal complexes, especially PtCl₂, turned out to be highly efficient for the reaction of internal alkynes and imidate substrates with wide generality. Moreover, as strong support for the reaction mechanism, the intermediate Pt-carbene complex was found to undergo intramolecular C-H bond insertion reaction to give tetracyclic indoline derivatives when benzyl vinyl ether was employed as a dipolarophile. This protocol provided a facile synthesis of highly functionalized tricyclic indole derivatives found as the basic skeleton of the mitosene family, such as mitomycin C.     

Formal homo-Nazarov and other cyclization reactions of activated cyclopropanes

The Nazarov cyclization of divinyl ketones gives access to cyclopentenones. Replacing one of the vinyl groups by a cyclopropane leads to a formal homo‐Nazarov process for the synthesis of cyclohexenones. In contrast to the Nazarov reaction, the cyclization of vinyl‐cyclopropyl ketones is a stepwise process, often requiring harsh conditions. Herein, we describe two different approaches for further polarization of the three‐membered ring of vinyl‐cyclopropyl ketones to allow the formal homo‐Nazarov reaction under mild catalytic conditions. In the first approach, the introduction of an ester group α to the carbonyl on the cyclopropane gave a more than tenfold increase in reaction rate, allowing us to extend the scope of the reaction to non‐electron‐rich aryl donor substituents in the β position to the carbonyl on the cyclopropane. In this case, a proof of principle for asymmetric induction could be achieved using chiral Lewis acid catalysts. In the second approach, heteroatoms, especially nitrogen, were introduced β to the carbonyl on the cyclopropane. In this case, the reaction was especially successful when the vinyl group was replaced by an indole heterocycle. With a free indole, the formal homo‐Nazarov cyclization on the C3 position of indole was observed using a copper catalyst. In contrast, a new cyclization reaction on the N1 position was observed with Brønsted acid catalysts. Both reactions were applied to the synthesis of natural alkaloids. Preliminary investigations on the rationalization of the observed regioselectivity are also reported.     

A three-component domino reaction of 2-tetralone, hydroxylamine and acetylene: a one-pot, highly regioselective synthesis of 4,5-dihydrobenz[e]indoles

2-Tetralone, hydroxylamine and acetylene react in the system MOH/DMSO to give 4,5-dihydrobenz[e]indole and its N-vinyl derivatives in up to 41% and 75% (in the case of excess acetylene) yields, respectively. The amount of the alternative regioisomer, N-vinyl-4,9-dihydrobenz[f]indole, does not exceed 2% (GLC-MS), while the corresponding regioisomer of 4,5-dihydrobenz[e]indole is not detectable.     

Synthetic studies on dragmacidin D: synthesis of the left-hand fragment

We report a synthesis of a left-hand fragment of bis(indole)-class marine alkaloid, dragmacidin D. The synthesis features Suzuki-Miyaura reaction for the coupling of imidazolyl boronic acid and (4-indolyl)vinyl bromide.     

Radical dearomatising spirocyclisations onto the C-2 position of benzofuran and indole

Spirolactams were obtained via an intramolecular radical ipso-type spirocyclisation in benzofuran and indole systems. Alkyl, vinyl and aryl radicals, tethered at the C-2 position of the heterocycle underwent radical cyclisation to produce novel tricyclic partially dearomatised heterocycles in moderate yields. Fragmentation of the furan ring was observed subsequent to spirocyclisation of a vinyl radical onto a benzofuran.     

Stereoselective Synthesis of cis-2 and trans-2-(Indol-3-yl) Cyclopropyl Amines,Carboxylic Acids,and Esters

We report a general route for the synthesis of E and Z isomers of indol-3-yl cyclopropyl amines, carboylic acids, and esters. These cyclopropane containing molecules are of interest as conformationally constrained analogues of tryptamine and indole propionic acid, biologically active indoles. The route involves reaction of vinyl indole with ethyl diazoacetate, chromatographic separation of the E and Z stereoisomers of the resulting cyclopropane esters, hydrolysis to form the E and Z cyclopropane acids, and formation of amines by the Curtius reaction.     

Sequential ring-closing metathesis–vinyl halide Heck cyclization reactions: access to the tetracyclic ring system of ervitsine

A chemoselective indole-templated ring-closing metathesis is used to assemble the cyclohepta[b]indole substructure of the indole alkaloid ervitsine. A subsequent intramolecular Heck coupling of the resulting alkene functionality with an amino-tethered vinyl halide accomplishes the closure of the unique 2-azabicyclo[4.3.1]decane framework of the alkaloid with concomitant incorporation of the exocyclic E-ethylidene substituent.     

Development and application of a direct vinyl lithiation of cis-stilbene and a directed vinyl lithiation of an unsymmetrical cis-stilbene

[reaction: see text] The vinyl deprotonation of cis-stilbene can be readily achieved using s-BuLi in THF at -25 degrees C. The generated 1-lithio-1,2-diphenylethene undergoes an in situ Z-to-E isomerization, and subsequent reaction with electrophiles results in an efficient stereoselective synthesis of trisubstituted alkenes. A directed vinyl lithiation of the unsymmetrical cis-stilbene 2-styryl-phenyl-carbamic acid tert-butyl ester can be achieved regioselectively, thereby expanding this methodology for further synthetic applications in indole chemistry.     

Toward the enantioselective total synthesis of lyngbyatoxin A: on the stereocontrolled introduction of the quaternary stereogenic centre

This paper deals with an approach to the enantioselective total synthesis of Lyngbyatoxin A, with focus on the stereocontrolled introduction of the quaternary stereogenic centre. The key step in the synthesis involves an enantiospecific Lewis-acid mediated rearrangement of chiral vinyl epoxides carrying a 7-substituted indole moiety.