SRN1 Mechanism Research Articles

Bay-Substitution of Perylene Bisimides with Bidentate Nucleophiles: The Case of Aryloxide Anions.

In this study, we delve into the regioselectivity of nucleophilic reactions involving brominated perylene bisimides (PBIs) and various bidentate aryloxide anions, previously associated with an SRN1 mechanism. We present herein a new perspective, suggesting that a single-electron-transfer aromatic nucleophilic substitution (SeT-SNAr) mechanism is a more plausible scenario. Our study reveals the favorable impact of photostimulation on reaction yields, making our method a convenient approach for accessing O-arylated PBIs.

Photoreaction of nitrobenzene derivatives with alkyl thiols giving sulfonamides and derivatives

Here, we serendipitously found that photoirradiation of nitrobenzene derivatives with alkyl thiols produced sulfonamides in low yields without the addition of other reagents. We proposed a new photoreaction mechanism, in which the photo-excited nitrobenzene biradical abstracts a hydrogen atom from H-S, the resultant thiyl radical undergoes the coupling with the nitrogen atom in the nitro group, and the two oxygen atoms in the nitro group are transferred onto the sulfur atom. The photoreaction by-produced p-sulfanyl, aniline, and o-sulfonyl derivatives presumably through SRN1 mechanism from the p-substituted nitrobenzene, photo-desulfonylation, and photo-Fries rearrangement from the sulfonamide, respectively. Discovery of this photoreaction will expand the scope of the chemistry of nitro and thiol compounds, since the sulfonamides are expected to find extensive applications.

Examining Heterodimerization by Aryl C-N Coupling in Dynemicin Biosynthesis.

Distinct among the enediyne antitumor antibiotics, the dynemicin subgroup is comprised of two discrete halves, an enediyne and an anthraquinone, but each is ultimately derived from the same linear β-hydroxyhexaene precursor. The linkage of these two halves by an aryl C-N bond is examined here using a variety of experimental approaches. We demonstrate that this heterodimerization is specific for anthracenyl iodide as the corresponding bromo- and amino-substituted anthracenes do not support dynemicin biosynthesis. Furthermore, biochemical experiments and chemical model reactions support an SRN1 mechanism for the aryl C-N coupling in which electron transfer occurs to the iodoanthracene, followed by loss of an anthracenyl iodide and partition of the resulting aryl radical between C-N coupling and reduction by hydrogen abstraction. An enzyme pull-down experiment aiming to capture the protein(s) involved in the coupling reaction is described in which two proteins, Orf14 and Orf16, encoded by the dynemicin biosynthetic gene cluster, are specifically isolated. Deletion of orf14 from the genome abolished dynemicin production accompanied by a 3-fold increased accumulation of the iodoanthracene coupling partner, indicating the plausible involvement of this protein in the heterodimerization process. On the other hand, the deletion of orf16 only reduced dynemicin production to 55%, implying a noncatalytic, auxiliary role of the protein. Structural comparisons using AlphaFold imply key similarities between Orf14 and X-ray crystal structures of several proteins from enediyne BGCs believed to bind hydrophobic polyene or enediyne motifs suggest Orf14 templates aryl C-N bond formation during the central heterodimerization in dynemicin biosynthesis.

Formation of two isomers in the replacement reactions of bay area dibromine atoms in perylene diimides

Three reaction mechanisms were reported in the replacement reaction of bay area dibromine atoms in perylene diimide derivatives in previous studies. However, the effect of the reaction solvents and intermediate compound (perylene diimide radical anion) on the reaction mechanisms and product structure had not been reported. Here, we report the role of the reaction solvents and the perylene diimide radical anion in replacement reactions of bay area dibromine atoms of perylene diimide. Two isomers in the replacement reactions of bay area dibromine atoms in perylene diimides were found when using proton solvents (such as ethanol), and presenting the about 41% 1-bromo-7- ethoxy substituted perylene diimide derivative changed into 1,6- diethoxy substutent perylene diimide derivative in double substituted reaction. In polar non-proton solvents, inorganic base (K2CO3) can induce dibromo perylene diimide to form its radical anion. Further, the substitution reactions is a SN1 mechanism in proton solvents, and the substitution reactions is belong to a SN2 and SRN1 mechanism in polar non-proton solvents.

Self anion radical induced breaking carbon–oxygen bond in bay area of perylene diimide, and nucleophilic substitution with SRN1 mechanism

Perylene diimide and its various derivatives tend to form their anion radicals after obtaining one electron, which will alter their chemical properties. Herein, we reported firstly synthesis of the unsymmetrically substituted perylene diimide in bay area using the degradation of the symmetrically substituted perylene diimide. The perylene diimide anion radical that is obtained by thermal electron transfer can induce breaking carbon-oxygen bond at bay area, and to form new perylene diimide derivative by nucleophilic substitution with SRN1 Mechanism. Experimental and theoretical simulation indicated that anion radical can promote the C–O bond breaking in this system.

Catalytic Asymmetric [4+1] Spiroannulation of α-Bromo-β-Naphthols with Azoalkenes by an Electrophilic Dearomatization/S RN 1-Debromination Approach

Catalytic Asymmetric [4+1] Spiroannulation of α-Bromo-β-Naphthols with Azoalkenes by an Electrophilic Dearomatization/S _RN 1-Debromination Approach

Coupling of thiols and aromatic halides promoted by diboron derived super electron donors.

We have proven that pyridine-boryl complexes can be used as superelectron donors to promote the coupling of thiols and aromatic halides through a SRN1 mechanism. The reaction is efficient for a broad substrate scope, tolerating heterocycles including pyridines, enolizable or reducible functional groups. The method has been applied to intermediates in drug synthesis as well as interesting functionalized polythioethers through a controlled and consecutive intramolecular electron transfer process.

A Dearomatization/Debromination Strategy for the [4+1] Spiroannulation of Bromophenols with α,β‐Unsaturated Imines

AbstractA novel [4+1] spiroannulation of o‐ & p‐bromophenols with α,β‐unsaturated imines has been developed for the direct synthesis of a new family of azaspirocyclic molecules. Notably, several other halophenols (X=Cl, I) were also applicable for this transformation. Moreover, a catalytic asymmetric version of the reaction was realized with 1‐bromo‐2‐naphthols by using a chiral ScIII/Py‐Box catalyst. Mechanistic studies revealed that this domino reaction proceeded through electrophile‐triggered dearomatization of phenol derivatives at their halogenated positions and followed by halogen‐displacement with N‐nucleophiles via a radical‐based SRN1 mechanism.

Domino Synthesis of 2-Substituted Benzothiazoles by Base-Promoted Intramolecular C-S Bond Formation.

A new, transition-metal-free, domino synthesis of 2-substituted benzothiazoles has been developed, involving base-promoted one-pot addition of active methylene compounds to o-iodoarylisothioacyanates and subsequent intramolecular C-S bond formation of the resulting thioamidate anion. The reaction proceeds at room temperature within 1-3 h, affording diversely substituted benzothiazoles in high yields. A possible radical intermediate pathway, via an SRN1 mechanism, has been proposed for intramolecular C-S bond formation.

Highly diastereoselective preparation of chiral NHC-boranes stereogenic at the boron atom.

Stereogenic main group elements are clearly generating interest in the enantioselective catalysis field. Surprisingly, while chiral organoboron reagents are very useful in stereoselective transformations, few scaffolds stereogenic at boron and configurationally stable have been reported to date. Herein, we describe an original library of chiral NHC-boranes, stereogenic at the boron atom, that has been prepared in only a few steps and in good yields (up to 93%). Key steps involve a chlorination/arylation sequence in the presence of simple Grignard reagents from bicyclic NHC-boranes. The high and unprecedented diastereoselectivity observed during the second step (up to 99 : 1 dr) has been rationalized through a plausible SRN1 mechanism thanks to EPR observations and DFT calculations.

Manganese‐Catalyzed Cross‐Coupling of Aryl Halides and Grignard Reagents by a Radical Mechanism

The substrate scope and the mechanism have been investigated for the MnCl2‐catalyzed cross‐coupling reaction between aryl halides and Grignard reagents. The transformation proceeds rapidly and in good yield when the aryl halide component is an aryl chloride containing a cyano or an ester group in the para position or a cyano group in the ortho position. A range of other substituents gave no conversion of the aryl halide or led to the formation of side products. A broader scope was observed for the Grignard reagents, where a variety of alkyl‐ and arylmagnesium chlorides participated in the coupling. Two radical‐clock experiments were carried out, and in both cases an intermediate aryl radical was successfully trapped. The cross‐coupling reaction is therefore believed to proceed by an SRN1 mechanism, with a triorganomanganate complex serving as the most likely nucleophile and single‐electron donor. Other mechanistic scenarios were excluded based on the substrate scope of the aryl halide.

Copper-Catalyzed ipso-Borylation of Fluoroarenes

ipso-Borylation of fluoroarenes has been achieved using an air-stable copper complex as a catalyst. Mechanistic studies suggest that the reaction proceeds via an SRN1 mechanism involving a single-electron-transfer (SET) process and not via the typical SNAr mechanism. This method differs from the previously reported nickel/copper-cocatalyzed system in terms of scope of the substrate and has exhibited good scalability. Double and triple ipso-borylations of several di- and trifluoroarenes have been also achieved efficiently, enhancing the synthetic utility of this method.

One-Pot, Metal-Free Conversion of Anilines to Aryl Bromides and Iodides.

A metal-free synthesis of aryl bromides and iodides from anilines via halogen abstraction from bromotrichloromethane and diiodomethane is described. This one-pot reaction affords aryl halides from the corresponding anilines in moderate to excellent yields without isolation of diazonium salts. The transformation has short reaction times, a simple workup, and insensitivity to moisture and air and avoids excess halogenation. DFT calculations support a SRN1 mechanism. This method represents a convenient alternative to the classic Sandmeyer reaction.

Photochemical Conversion of Phenanthro[9,10-d]imidazoles into π-Expanded Heterocycles.

We discovered that phenanthro[9,10-d]imidazoles bearing a 2-halogenoaryl substituent at position 2 undergo swift photochemically driven direct arylation, leading to barely known phenanthro[9',10':4,5]imidazo[1,2-f]phenanthridines. The reaction is high-yielding, and it does not require any sensitizer or base. The discovered process is tolerant of a variety of substituents present both at positions 1 and 2; i.e., strongly electron-donating and electron-withdrawing substituents are tolerated as well as various heterocyclic units. Steric hindrance does not affect this process. The evidence gathered here indicates that SRN1 mechanism is operating in this case with the formation of radical anion as a critical step, followed by heterolytic cleavage of a carbon-halogen bond. Also TfO groups were shown to undergo cyclization, which allows the use of salicylaldehydes in the construction of heterocyclic systems. Efficiency of this photochemically driven direct arylation has been demonstrated by the synthesis of two systems possessing 13 and 17 conjugated rings, respectively. Phenanthro[9',10':4,5]imidazo[1,2-f]phenanthridines are blue-emitters, and they exhibit strong fluorescence in solution and in the solid state in direct contrast to their precursors.

“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. Some key aspects of the proposed mechanism were evaluated at the B3LYP/6-311+G* level.

ChemInform Abstract: Recent Advances in the Synthesis of Stannanes and the Scope of Their Posterior Chemical Transformations

AbstractReview: [64 refs.

First single electron transfer reaction on propargylic chloride in 5-nitroimidazole series

We report here the first example of an SRN1 reaction on propargylic chloride in heterocyclic series. The reaction of 4-(3-chloroprop-1-ynyl)-1,2-dimethyl-5-nitro-1H-imidazole with nitronate anions led to both the formation of the C-alkylated product through an SRN1 mechanism and the predominant ethylenic compound resulting from nitrous acid elimination on the C-alkylated product. Interestingly, in contrast to our previous works on SRN1 reactivity, no O-alkylated product was observed.

Influence of structural features of tri-functionalized aryl phosphates on the outcome of the SRN1 process with stannyl anions: a DFT study

Under irradiation, 1,3-bis(diethoxyphosphoryloxy)-4-chlorobenzene (2), 1,4-bis(diethoxyphosphoryloxy)-3-chlorobenzene (3) and 1,3-bis(diethoxyphosphoryloxy)-5-chlorobenzene (4) react with trimethyltinsodium (1) in liquid ammonia giving entirely different distribution of stannylated products. These differences are explained through theoretical DFT studies. Experimental evidence for the involvement of an SRN1 mechanism was obtained.

Synthesis of ε-oxo acids by photostimulated reactions of 2-(2-iodophenyl)acetate ion with carbanions by the SRN1 mechanism. Synthesis of novel 3-benzazepin-2-ones

Fil: Guastavino, Javier Fernando. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Investigaciones en Fisico-quimica de Cordoba. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas. Instituto de Investigaciones en Fisico-quimica de Cordoba; Argentina

Two-step synthesis of di- and tristannylarenes from anilines via an SRN1 mechanism

The synthesis in good yields (71-85%) of di- and tristannylated benzenes from commercially available anilines, involving their conversion to the corresponding aryltrimethylammonium salts followed by the reaction with Me3SnNa 1 in liquid ammonia, is described. The results obtained clearly indicate that the stannylation reactions proceed through an SRN1 mechanism.