Synthesis of isocoumarins and alpha-pyrones via tandem Stille reaction/heterocyclization

A general route to alpha-pyrones and 3-substituted isocoumarins from (Z)-iodovinylic acids 1a-f or 2-iodobenzoic acids 4a-c is described, including compounds bearing a substituent on the aromatic ring. Treatment of (Z)-beta-iodovinylic acids 1a-f or 2-iodobenzoic acids 4a-c with various allenyltributyltin reagents in the presence of palladium acetate, triphenylphosphine, and tetrabutylammonium bromide in dimethylformamide provided good yields of the corresponding alpha-pyrones 3a-k or 3-substituted isocoumarins 5a-g via tandem Stille reaction and 6-endo-dig oxacyclization.     

Synthesis of isoxazoles via electrophilic cyclization

[reaction: see text] A variety of 3,5-disubstituted 4-halo(seleno)isoxazoles are readily prepared in good to excellent yields under mild reaction conditions by the reaction of 2-alkyn-1-one O-methyl oximes with ICl, I2, Br2, or PhSeBr.     

Synthesis of pyrazoles via electrophilic cyclization

Electrophilic cyclizations of α,β-alkynic hydrazones by molecular iodine were investigated for the synthesis of 4-iodopyrazoles. α,β-Alkynic hydrazones were readily prepared by the reactions of hydrazines with propargyl aldehydes and ketones. When treated with molecular iodine in the presence of sodium bicarbonate, α,β-alkynic hydrazones underwent electrophilic cyclization to afford 4-iodopyrazoles in good to high yields. Iodocyclization was general for a wide range of α,β-alkynic hydrazones and tolerated the presence of aliphatic, aromatic, heteroaromatic, and ferrocenyl moieties with electron-withdrawing and electron-donating substituents.     

Synthesis of polycyclic aromatics and heteroaromatics via electrophilic cyclization

[reaction: see text] A variety of substituted polycyclic aromatics are readily prepared in good to excellent yields under very mild reaction conditions by the reaction of 2-(1-alkynyl)biphenyls with ICl, I(2), NBS, and p-O(2)NC(6)H(4)SCl. This methodology readily accommodates various functional groups and has been successfully extended to systems containing a variety of polycyclic and heterocyclic rings.     

Synthesis of functionalized ellipticinium and ellipticine derivatives via electrophilic cyclization

An efficient methodology for the synthesis of highly functionalized ellipticinium and ellipticine derivatives starting from the corresponding 2-bromocarbazoles via an AgOTf or CuI catalyzed electrophilic cyclization of 2-alkynyl-3-carbazolylaldimines is reported.     

Synthesis of 2(3H)-furanones via electrophilic cyclization

A variety of highly substituted 2(3H)-furanones are readily prepared from 3-alkynoate esters and the corresponding acids via electrophilic cyclization. Successful electrophiles in this process include I2, ICl, and PhSeCl. This highly efficient process proceeds under mild conditions, tolerates various functional groups, and generally provides substituted 2(3H)-furanones in good to excellent yields.     

Synthesis of 2,3-disubstituted benzo[b]selenophenes via electrophilic cyclization

2,3-Disubstituted benzo[b]selenophenes have been prepared by the electrophilic cyclization of various 1-(1-alkynyl)-2-(methylseleno)arenes by Br2, NBS, I2, ICl, PhSeCl, PhSeBr, and Hg(OAc)2. This method tolerates a wide variety of functional groups, including alcohol, ester, nitrile, nitro, and silyl groups, and proceeds under exceptionally mild reaction conditions.     

Synthesis of 3,4-disubstituted 2H-benzopyrans through C-C bond formation via electrophilic cyclization

The electrophilic cyclization of substituted propargylic aryl ethers by I2, ICl, and PhSeBr produces 3,4-disubstituted 2H-benzopyrans in excellent yields. This methodology results in vinylic halides or selenides under mild reaction conditions and tolerates a variety of functional groups, including methoxy, alcohol, aldehyde, and nitro groups.     

Synthesis of benzothiophene derivatives from dilithio reagents, sulfur, and electrophiles via electrophilic cyclization

Benzothiophene derivatives were synthesized in high yields from readily available o-(alkynyllithio)aryllithio compounds, sulfur, and 2 equiv of acid chlorides or other electrophiles. An acid chloride-induced electrophilic cyclization resulted in the formation of the thiophene ring.     

Synthesis of substituted isoquinolines by electrophilic cyclization of iminoalkynes

The tert-butylimines of o-(1-alkynyl)benzaldehydes and analogous pyridinecarbaldehydes have been cyclized under very mild reaction conditions in the presence of I(2), ICl, PhSeCl, PhSCl, and p-O(2)NC(6)H(4)SCl to give the corresponding halogen-, selenium-, and sulfur-containing disubstituted isoquinolines and naphthyridines, respectively. This methodology accommodates a variety of iminoalkynes and affords the anticipated heterocycles in moderate to excellent yields. Monosubstituted isoquinolines and naphthyridines have been synthesized by the metal-catalyzed ring closure of these same iminoalkynes. The silver-catalyzed ring closure is highly effective in cyclizing aryl-, alkenyl-, and alkyl-substituted iminoalkynes at 50 degrees C.     

Regio- and stereoselective synthesis of isoindolin-1-ones via electrophilic cyclization

[reaction: see text] A variety of substituted isoindolin-1-ones are readily prepared in good to excellent yields under very mild reaction conditions by the reaction of o-(1-alkynyl)benzamides with ICl, I(2), and NBS. In a few cases, substituted isoquinolin-1-ones were obtained as the major product instead. This methodology accommodates various alkynyl amides and functional groups and has been successfully extended to heterocyclic starting materials. This chemistry has been successfully applied to the synthesis of a biologically interesting alkaloid, cepharanone B.     

Highly regio- and stereoselective synthesis of indene derivatives via electrophilic cyclization

[reaction: see text] Indene or naphthalene derivatives are readily prepared in moderate to excellent yields with high regio- and stereoselectivity under very mild reaction conditions by the reaction of acetylenic malonates and ketones with I2, ICl, or NIS. The resulting iodides can be further elaborated using palladium-catalyzed coupling reactions.     

Facile synthesis of diiodinated dihydronaphthalenes and naphthalenes via iodine mediated electrophilic cyclization

A facile, efficient, and general synthetic method for a wide range of 2,3-diiodinated 1,4-dihydrothiophenes and naphthalenes has been developed via the electrophilic iodocyclization of various aryl propargyl alcohols. The resulting product 2p can be used for the synthesis of a rubrene intermediate.     

Synthesis of 2,3-disubstituted benzo[b]thiophenes via palladium-catalyzed coupling and electrophilic cyclization of terminal acetylenes

2,3-Disubstituted benzo[b]thiophenes have been prepared in excellent yields via coupling of terminal acetylenes with commercially available o-iodothioanisole in the presence of a palladium catalyst and subsequent electrophilic cyclization of the resulting o-(1-alkynyl)thioanisole derivatives. I(2), Br(2), NBS, p-O(2)NC(6)H(4)SCl, and PhSeCl have been utilized as electrophiles. Aryl-, vinyl-, and alkyl-substituted terminal acetylenes undergo this coupling and cyclization to produce excellent yields of benzo[b]thiophenes. (Trimethylsilyl)acetylene also undergoes this coupling/cyclization process with I(2), NBS, and the sulfur and selenium electrophiles to afford the corresponding 2-(trimethylsilyl)benzo[b]thiophenes. However, cyclization of the silyl-containing thioanisole using Br(2) affords 2,3-dibromobenzo[b]thiophene.     

Synthesis of Z- and E-polyunsaturated isoprenoids with functional groups initiating electrophilic cyclization

Summary Separate olefination has been carried out for the carbonyl groups of 1,8-diketo-4-methyl-4Z-nonene and 1,12-diketo-4,8-dimethyl-4E, 8E-tridecadiene into 1,5-polyenes which were prepared for electrophilic cyclization.Deceased.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 4, pp. 821–823, April, 1981.     

Synthesis of naphthalenes and 2-naphthols by the electrophilic cyclization of alkynes

[reactions: see text] A wide variety of substituted naphthalenes are readily prepared regioselectively under mild reaction conditions by the 6-endo-dig electrophilic cyclization of appropriate arene-containing propargylic alcohols by ICl, I2, Br2, NBS, and PhSeBr. 3-Iodo-2-naphthols have also been prepared in excellent yields by the cyclization of analogous 1-aryl-3-alkyn-2-ones. This methodology readily accommodates various functional groups and has been successfully extended to the synthesis of substituted carbazoles and dibenzothiophenes.     

Synthesis of substituted 3-iodopyrroles by electrophilic cyclization of propargylic aziridines

The electrophilic cyclization of propargylic aziridines is described. 3-Iodopyrroles having a variety of substituents were conveniently synthesized by the reaction of propargylic aziridines with iodine. The resulting substituted 3-iodopyrrole was further functionalized to the tri-substituted pyrroles with high efficiency.     

Synthesis of difluorinated pyridinecarboxaldehyde via electrophilic fluorination

An efficient synthesis of novel 3,5-difluoropyridine-4-carboxaldehyde using N-fluoro-benzenesulfonimide (NSFi) is described. Difluorination was achieved through the reaction of 3,5-dihalo-1,3-dioxolane pyridine with n-butyllithium followed by N-fluorobenzenesulfonimide at −120 °C in good to high yields. Maintaining the low temperature during the transmetallation was found to be critical for the selective formation of the difluoro-susbstitution over the monofluoro one.     

Synthesis of pyrethroids via epxoyamide cyclization

LDA-induced cyclization of $\text{4}$ yields $\text{5}$, the $\text{trans}$-isomer of which undergoes dehydration using Ph₂S[OC(CF₃)₂Ph]₂ to give the pyrethroid amide $\text{6}$.