Visible light mediated synthesis of 6-benzo[]chromenes: transition-metal-free intramolecular direct C-H arylation.

A synthetic approach towards the 6-benzo[]chromene ring under visible light and transition-metal-free conditions has been developed. Benzochromenes are synthesized from the corresponding (2-halobenzyl) phenyl ethers or (2-halophenyl) benzyl ethers using KOBu in dimethyl sulfoxide (DMSO) at room temperature (rt) and blue light-emitting diodes (LEDs) as the light source. This methodology replaces the use of ligands or additives, high temperatures and toxic solvents.

Design, Synthesis, and in vitro Evaluation of Tubulin-Targeting Dibenzothiazines with Antiproliferative Activity as a Novel Heterocycle Building Block.

We prepared a series of free NH and N-substituted dibenzonthiazines with potential anti-tumor activity from N-aryl-benzenesulfonamides. A biological test of synthesized compounds (59 samples) was performed in vitro measuring their antiproliferative activity against a panel of six human solid tumor cell lines and its tubulin inhibitory activity. We identified 6-(phenylsulfonyl)-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide and 6-tosyl-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide as the best compounds with promising values of activity (overall range of 2-5.

Transition-Metal-Free and Visible-Light-Mediated Desulfonylation and Dehalogenation Reactions: Hantzsch Ester Anion as Electron and Hydrogen Atom Donor.

Novel approaches for N- and O-desulfonylation under room temperature (rt) and transition-metal-free conditions have been developed. The first methodology involves the transformation of a variety of -sulfonyl heterocycles and phenyl benzenesulfonates to the corresponding desulfonylated products in good to excellent yields using only KOBu in dimethyl sulfoxide (DMSO) at rt. Alternately, a visible light method has been used for deprotection of -methyl--arylsulfonamides with Hantzsch ester (HE) anion serving as the visible-light-absorbing reagent and electron and hydrogen atom donor to promote the desulfonylation reaction.

Room-Temperature and Transition-Metal-Free Intramolecular α-Arylation of Ketones: A Mild Access to Tetracyclic Indoles and 7-Azaindoles.

A novel approach for the synthesis of tetracyclic indoles and 7-azaindoles is reported. The strategy involves four steps, with a fast rt intramolecular α-arylation of ketones as key step. The reaction was inspected synthetically to achieve the synthesis of 11 novel tetracyclic structures with moderate to very good yields (39-85%).

Photoinduced nucleophilic substitution of iodocubanes with arylthiolate and diphenylphosphanide ions. Experimental and computational approaches.

A new synthetic route to modify the cubane nucleus is reported here. Methyl-4-iodocubane-1-carboxylate (1) and 1,4-diiodocubane (2) were employed as reagents to react with arylthiolate and diphenylphosphanide ions under irradiation in liquid ammonia and dimethylsulphoxide. The reactions proceed to afford thioaryl- and diphenylphosphoryl- cubane derivatives in moderate to good yields.

Initiation in Photoredox C-H Functionalization Reactions. Is Dimsyl Anion a Key Ingredient?

Previous studies have reported the arylation of unactivated arenes with ArX, base (KOBu or NaOBu), and an organic additive at high temperatures. Recently, we showed that this reaction proceeds in the absence of additives at rt but employs UV-vis light. However, details of mechanisms that can use a photoinduced base-promoted homolytic aromatic substitution reaction (photo-BHAS) have remained elusive until now.

Synthesis of Dibenzosultams by "Transition-Metal-Free" Photoinduced Intramolecular Arylation of N-Aryl-2-halobenzenesulfonamides.

A new and general synthetic route to prepare dibenzosultams is here reported. This approach involves the synthesis of N-aryl-2-halobenzenesulfonamides (3), followed by intramolecular C-C photoinduced arylation under soft conditions without the use of "Transition Metal". The photostimulated reactions exhibit very good tolerance to different substituent groups with good to excellent isolated yields (42-98%) of products.

“Transition-metal-free” synthesis of carbazoles by photostimulated reactions of 2′-halo[1,1′-biphenyl]-2-amines.

An efficient and simple protocol for the preparation of a series of 9H-carbazoles by photostimulated SRN1 substitution reactions is presented. Substituted 9H-carbazoles were synthesized in low to excellent yields (up to 96%) through an intramolecular C–N bond formation of 2′-halo[1,1′-biphenyl]-2-amines by the photoinitiated SRN1 mechanism under mild and “transition-metal-free” conditions. The biphenylamines used as substrates were obtained with isolated yields ranging from 21% to 84% by two approaches: (A) the cross-coupling Suzuki–Miyaura reaction and (B) the radical arylation of anilines.

Room-temperature and transition-metal-free Mizoroki-Heck-type reaction. Synthesis of E-stilbenes by photoinduced C-H functionalization.

We report a conceptually different approach toward E-stilbene syntheses by photoinduced direct C-H arylation of alkenes at rt without the addition of transition metals, with a broad range of aryl halides, including ArI, ArBr, and even ArCl. This is the first time that this reaction has been produced without extra solvent but with 18-crown-6 ether and t-BuOK in only 15 min of reaction.

Room-temperature photoinduced direct C-H-arylation via base-promoted homolytic aromatic substitution.

Conceptually different approach toward biaryl syntheses by photoinduced direct C-H arylation of benzene and thiophene in the presence of t-BuOK is reported. The reaction proceeds through photo- and base-promoted homolytic aromatic substitution. The o-, m- and p- substituted ArI, as well as the electron-donating and electron-withdrawing nature of the substituents were found be good to excellent substrates.

Photochemical and photophysical behavior of indolyl anions in photostimulated intramolecular arylation reactions.

O-Arylation reaction is obtained when N-(2-halophenyl) indolo carboxamides are irradiated in a basic medium. On the basis of photochemical and photophysical experiments, we propose that 2-indolylbenzoxazole is formed by intramolecular electron transfer followed by fast dehalogenation of the halophenyl radical anion pendant moiety, finally a radical-radical collapse renders the observed product.

Synthesis of 6-substituted 2-pyrrolyl and indolyl benzoxazoles by intramolecular O-arylation in photostimulated reactions.

The synthesis of a series of 6-substituted 2-pyrrolyl and 2-indolyl benzoxazoles by photostimulated C-O cyclization of anions from 2-pyrrole carboxamides, 2-indole carboxamides, or 3-indole carboxamides has been found to proceed in good to excellent yields (41-100%) in DMSO and liquid ammonia. The pyrrole and indole carboxamides are obtained in good to very good isolated yields by an amidation reaction of different 2-haloanilines with 2-carboxylic acid of pyrrole and 2- or 3-carboxylic acid of indole. To explain the regiochemical outcome of these reactions (C-O arylation vs C-N or C-C arylation), a theoretical analysis was performed using DFT methods and the B3LYP functional.

Synthesis of benzo-fused heterocycles by intramolecular α-arylation of ketone enolate anions.

A two-step synthesis of six-, seven-, eight-, and nine-member benzo-fused heterocycles in good to excellent yields is reported. The synthetic strategy involves the generation of a new intramolecular α-aryl ketone bond by the photostimulated S(RN)1 reaction of ketone enolate anions linked to a pendant haloarene as the key step. On the other hand, an intramolecular C(Ar)-C(Ar) coupling led to the formation of five- and six-member benzo-fused heterocycles (9H-carbazole and phenanthridine) when an aromatic amide anion is competitively formed.

Synthesis of carbolines by photostimulated cyclization of anilinohalopyridines.

A general synthetic route to prepare all four carboline regioisomers by photostimulated cyclization of anilinohalopyridines is described. The methodology affords various substituted carbolines in good to excellent yields. In the case of α-carbolines, the S(RN)1 methodology complements previously reported palladium-catalyzed cyclization approaches.

Synthesis of pyrrole and indole quinoxalinone and oxazinone derivatives by intramolecular copper-catalyzed reactions.

Intramolecular N-arylation of pyrrole and indole carboxamides and carboxylates linked with a pendant haloarene by Cu-catalyzed reactions to synthesize pyrrole and indole quinoxalinone and oxazinone derivatives is reported. The ring closure reactions were carried out by conventional heating and MW irradiation. The use of conventional heating affords moderate to good yields of the quinoxalinone and oxazinone derivatives (34-72%), while by using MW heating the best results are obtained (41-99%).

Short access to 6-substituted pyrimidine derivatives by the S(RN)1 mechanism. Synthesis of 6-substituted uracils through a one-pot procedure.

The synthesis of 6-substituted 2,4-dimethoxypyrimidines with different nucleophiles was accomplished with good to excellent yields (50-95%) through S(RN)1 reactions, starting from commercially available 6-chloro-2,4-dimethoxypyrimidine (1). Hydrolysis of these derivatives gave access to 6-substituted uracils with good yields and short times by the use of microwave irradiation. The preparation of uracils from 1 without the isolation of 2,4-dimethoxypyrimidine derivatives affords a rapid access to these compounds in good yields and excellent purity by avoiding an unnecessary step of purification.

Electron-transfer-mediated synthesis of phenanthridines by intramolecular arylation of anions from N-(ortho-halobenzyl)arylamines: regiochemical and mechanistic analysis.

The synthesis of a series of substituted phenanthridines by photostimulated C-C cyclization of anions from N-(ortho-halobenzyl)arylamines has been found to proceed in very good to excellent yields (79-95%) in liquid ammonia and in DMSO. The N-(ortho-halobenzyl)arylamines are obtained in good to very good isolated yields (44-85%) by nucleophilic substitution of ortho-halobenzylchlorides with different arylamines. The reaction of the anions of a diverse set of N-(ortho-halobenzyl)arylamines was studied, and the methodology was extended to the synthesis of trispheridine, a natural product, in very good yield.

Synthesis of carbazoles by intramolecular arylation of diarylamide anions.

The synthesis of a series of substituted 9H-carbazoles by the photostimulated S(RN)1 substitution reaction with diarylamines as starting substrate was performed. The diarylamines were obtained by two approaches, the Pd-catalyzed reactions (Buchwald-Hartwig) or Cu-catalyzed reactions of 2-haloanilines with aryl halides, or 2-bromoiodobenzene with anilines, with moderate to very good isolated yields (45-89%). Through an intramolecular C-C bond formation of diarylamines by the S(RN)1 mechanism, carbazoles were achieved.

A novel approach to the synthesis of 6-substituted uracils in three-step, one-pot reactions.

From the commercial 6-chloro-2,4-dimethoxypyrimidine (1) and by a photostimulated reaction with Me(3)Sn(-) ions, 2,4-dimethoxy-6-(trimethylstannyl)pyrimidine (2) was obtained in 95% yield. By the cross-coupling reaction of 2 with 1-iodonaphthalene as electrophile catalyzed by Pd (Stille reaction), 2,4-dimethoxy-6-(naphthalen-1-yl)pyrimidine (9) was obtained in 76% yield. By hydrolysis of 9, 6-(1-naphthyl)uracil was obtained in 98% of isolated yield.

Syntheses of aporphine and homoaporphine alkaloids by intramolecular ortho-arylation of phenols with aryl halides via SRN1 reactions in liquid ammonia.

The photostimulated intramolecular ortho-arylation reactions of bromoarenes linked with pendant phenoxy containing N-substituted tetrahydroisoquinolines in liquid ammonia afforded aporphine (54-82% yield) alkaloid derivatives via SRN1 reactions. This strategy was extended for the first time to the synthesis of a homoaporphine derivative (40% yield). Tetrahydroisoquinoline precursors that contained electron-withdrawing groups on nitrogen (i.

Synthesis of functionalized diaryldimethylstannanes from the Me2Sn2- dianion by SRN1 reactions.

[reaction: see text] The reaction of different ArCl with the Me(2)Sn(2)(-) dianion in liquid ammonia under irradiation afforded Ar(2)SnMe(2) in good yields (68-85%). The results obtained clearly indicate that the reaction proceeded through an S(RN)1 reaction. As a synthetic application of these Ar(2)SnMe(2), the homocoupling is described in the presence of Cu(NO(3))(2).

Sequential reactions of trimethylstannyl anions with vinyl chlorides and dichlorides by the SRN1 mechanism followed by palladium-catalyzed cross-coupling processes.

The reactions of trimethylstannyl ions (Me(3)Sn(-)) with vinyl chlorides in liquid ammonia give good yields of vinylstannanes. Some of them react in the dark, and others need light stimulation to react. The fact that these reactions are inhibited by radical and radical anion traps shows that they occur by the S(RN)1 mechanism.

Fast tin-free hydrodehalogenation and reductive radical cyclization reactions: a new reduction process.

The photostimulated reactions of several aryl and alkyl chlorides and bromides with the monoanion of reduced ethyl benzoate 5H furnish the reduced products in high yields. If the aryl moieties have suitable double bonds, the cyclized reduced products are obtained in high yields. The photostimulated reaction of 1-allyloxy-2-bromobenzene (1a) with 5H affords 3-methyl-2,3-dihydro-benzofuran (2a) in 97% yield.

One-pot palladium-catalyzed cross-coupling reaction of aryl iodides with stannylarsanes and stannylstibanes.

[reaction: see text] The reaction of Ph(3)As and Ph(3)Sb with Na metal in liquid ammonia gives Ph(2)M(-) ions (M = As, Sb) that react with n-Bu(3)SnCl to afford n-Bu(3)Sn-MPh(2) (1). The ammonia was allowed to evaporate, and toluene was added. The Pd-catalyzed cross-coupling reactions of these stannanes with aryl iodides afford functionalized triaryl-arsanes and triaryl-stibanes in high yields in a one-pot procedure (80-99%).

Syntheses of 2-substituted indoles and fused indoles by photostimulated reactions of o-iodoanilines with carbanions by the SRN1 mechanism.

2-Substituted indoles (5a,b and 7) and fused indoles (9a-c, 11a,b, and 12) have been obtained by the S(RN)1 mechanism from photostimulated reactions of o-iodoaniline (1) and 1-halo-2-naphthalen-2-ylamines (3a,b) with enolate ions of acyclic (acetophenone (6), 2- (4a) and 4-acetylpyridine (4b)) and cyclic ketones (1- (8a) and 2-indanone (10a), 1- (8b) and 2-tetralone (10b) and 1-benzosuberone (8c)) in DMSO and liquid ammonia as solvents. The carbanions derived from 4a,b, 8a, and 10b are novel nucleophiles that form new C-C bonds by the S(RN)1 mechanism.