Double Nucleophilic Addition Research Articles

Preparation of Hetero‐π‐Conjugated Compounds by Double Nucleophilic Addition to Haloalkynes and C−H Cyclization

AbstractWhen a mixture containing 1‐halo‐1‐alkyne, a dinucleophilic agent, and a base (Cs2CO3 or K3PO4) was heated in DMF, regio‐ and stereo‐selective nucleophilic addition of the dinucleophilic agent to the acetylenes occurred. This reaction yielded (Z,Z)‐bis(haloalkene), which subsequently underwent Pd‐catalyzed cyclization through C−H bond activation, resulting in the formation of two‐oxygen‐ or ‐nitrogen‐containing hetero‐π‐conjugated compounds. N‐(5‐Hydroxynaphthalen‐1‐yl)methanesulfonamide was treated with 2‐phenyl‐1‐chloroethyne followed by 1‐chloro‐1‐hexadecyne. After these reactions, Pd‐catalyzed double C−H cyclization was employed to produce 1H‐2‐phenyl‐7‐tetradecylbenzofuro[7,6‐g]indole. Notably, this compound transformed into a fan‐shaped structure at 86 °C and transitioned into a smectic A phase characterized by a layered structure.

Synthesis of dispiro-orthoester via an acetal oxo-carbenium ion.

The first dispiro orthoester via a spiroacetal oxo-carbenium ion is presented. Oxidative dearomatization of phloretic esters results in a bifunctional electrophilic spiroacetal oxo-carbenium ion, which undergoes a double nucleophilic addition by diol delivering a range of unusual dispiro-orthoesters with an excellent diversity.

Organocatalytic Tandem Synthesis of Chiral Hexacyclic Bisindoles from Propargylic 3-Methyleneindoles with 2-Indolylmethanols.

A novel chiral phosphoric acid-catalyzed tandem regioselective 1,6-addition/double intramolecular nucleophilic addition annulation of the propargylic 3-methyleneindoles in situ generated from α-indolyl propargylic alcohols with 2-indolylmethanols has been developed. The methodology afforded the new chiral trifluoromethyl pentalenobisindoles bearing an all-carbon quaternary stereogenic center in generally good yields with excellent enantioselectivities.

Convenient synthesis of N-sulfonyl α-hydroxyamides via DMSO oxidation of N-alk-1-ynylsulfonamides

ABSTRACT N-Arenesulfonyl α-hydroxyamides are conveniently synthesized from N-arylethynylsulfonamides (ynamides) via oxidation with dimethyl sulfoxide (DMSO) in the presence of equivalent of trifluoromethanesulfonic acid (TfOH) followed by treatment with water. In this reaction, ynamides are activated by protonation with TfOH and then undergo double DMSO nucleophilic addition and subsequent hydrolysis. Investigations on the substrate scope indicate N-arenesulfonyl and arylethynyl substituted ynamides proceed the oxidation well. Compared to the previous methods, the current method realizes the direct conversion from N-arylethynylsulfonamides to N-arenesulfonyl α-hydroxyamides with mild DMSO as a nucleophilic oxidant in the presence of strong acid trifluoromethanesulfonic acid.

Modular Synthetic Approach to Silicon-Rhodamine Homologues and Analogues via Bis-aryllanthanum Reagents.

A modular synthetic approach toward diverse analogues of the far-red fluorophore silicon-rhodamine (SiR), based on a regioselective double nucleophilic addition of aryllanthanum reagents to esters, anhydrides, and lactones, is proposed. The reaction has improved functional group tolerance and represents a unified strategy toward cell-permeant, spontaneously blinking, and photoactivatable SiR fluorescent labels. In tandem with Pd-catalyzed hydroxy- or aminocarbonylation, it serves a streamlined synthetic pathway to a series of validated live-cell-compatible fluorescent dyes.

Synthesis of substituted 1,2-dihydroisoquinolines via Ni(ii) and Cu(i)/Ag(i) catalyzed double nucleophilic addition of arylamines to ortho-alkynyl donor-acceptor cyclopropanes (o-ADACs).

A concise approach for the synthesis of substituted 1,2-dihydroisoquinolines via double nucleophilic addition of primary arylamines to ortho-alkynyl donor-acceptor cyclopropanes (o-ADACs) in the presence of a catalytic Ni(ClO4)2·6H2O and CuI/AgOTf system has been developed. Further applying this protocol, some of the derived malonates were converted into the corresponding monoesters under Krapcho decarboxylation reaction conditions. Thereafter, these esters were transformed into the respective acids and alcohols. In addition, multifunctionalized 4-(2,2,2-trifluoroacetyl) 1,2-dihydroisoquinolines were also obtained with excess TFAA.

When Indoles Meet Allene and its Derivatives

The allene functional group and the indole ring have emerged as recurring building blocks in organic chemistry due to their diverse reactivity and straightforward preparation. In addition, the biological properties and natural occurrence of indole give a remarkable added‐value to newly‐prepared indole‐based structures. In the last decade, the combination of allenes and indoles as co‐reactants has revealed a fruitful reactivity allowing the synthesis of complex structures and the investigation of new mechanistic pathways, such as the challenging asymmetric nucleophilic addition using optically pure allenes as chirality transfer agents, the double nucleophilic addition through metal carbene intermediates, or novel hybrid catalysis in a bimetallic system. Herein we report a critical review into the wide and fascinating ways allenes and indoles can interact, and the structural diversity that can be therefore achieved.

Luminogens for Aggregation-Induced Emission via Titanium-Mediated Double Nucleophilic Addition to 2,5-Dialkynylpyridines: Formation and Transformation of the Emitting Aggregates.

Invited for the cover of this issue are Lutz H. Gade, Claudia Backes, and co-workers at Heidelberg University. The image depicts 2-(1,2,2-triarylvinyl)-pyridines, which are luminogens for aggregation-induced emission which "light up" upon irradiation. Read the full text of the article at 10.1002/chem.201905611.

Front Cover: Luminogens for Aggregation‐Induced Emission via Titanium‐Mediated Double Nucleophilic Addition to 2,5‐Dialkynylpyridines: Formation and Transformation of the Emitting Aggregates (Chem. Eur. J. 19/2020)

Front Cover: Luminogens for Aggregation‐Induced Emission via Titanium‐Mediated Double Nucleophilic Addition to 2,5‐Dialkynylpyridines: Formation and Transformation of the Emitting Aggregates (Chem. Eur. J. 19/2020)

Luminogens for Aggregation-Induced Emission via Titanium-Mediated Double Nucleophilic Addition to 2,5-Dialkynylpyridines: Formation and Transformation of the Emitting Aggregates.

New luminogens for aggregation‐induced emission (AIE), which are characterized by a branched cross‐conjugated 2,6‐bis(1,2,2‐triarylvinyl)pyridine motif, have been synthesized exploiting the one‐pot Ti‐mediated tetraarylation of 2,6‐bis(arylethynyl)pyridines. Thin layer solid‐state emitters were prepared by spin‐coating of the luminogens, while AIE‐colloidal dispersions were investigated in terms of optical density and scattering behaviour. This has given insight into particle size distributions, time evolution of the aggregation and the influence of different functionalization patterns on the luminescence of molecular aggregates. In particular, a combination of extinction spectroscopy and dynamic light scattering is being proposed as a powerful method for investigating the dynamic aggregation process in AIE‐type colloids.

Strategic C-C Bond-Forming Dearomatization of Pyridines and Quinolines.

A one-pot protocol for the dearomative double nucleophilic addition to pyridines and quinolines, providing convenient, regioselective and diastereoselective access to tetrahydropyridines and tetrahydroquinolines under reductant-free conditions is described. This method also offers a new strategy for the general dearomatization of nitrogen heteroaromatics.

Double nucleophilic addition to iminomalonate, leading to the synthesis of quaternary α-amino diesters and desymmetrization of the products.

Alkylation of iminomalonate with Grignard reagents followed by oxidation and allylation gave symmetrical quaternary α-amino diesters in good yields. Subsequent desymmetrization of a diol derivative from these products was conducted via asymmetric carbamylation catalyzed by Cu-Bnbox to give chiral quaternary aminodiol mono-carbamates.

Synthesis of novel antiproliferative hybrid bis-(3-indolyl)methane phosphonate derivatives

An efficient synthetic methodology for the preparation of phosphorus substituted bis-(3-indolyl)methane through a double nucleophilic addition of indole derivatives to an in situ generated α-iminophosphonate is reported. In addition, bis-(3-indolyl)methane substrates showed in vitro cytotoxicity, inhibiting the growth of carcinoma human tumor cell lines A549 (carcinomic human alveolar basal epithelial cell) and SKOV03 (human ovarian carcinoma).

A new synthetic route to 5,6,11,12-tetraarylethynyltetracenes.

A new synthetic route to 5,6,11,12-tetrakis(arylethynyl)tetracenes, π-extended rubrenes, was developed via [4 + 2] cycloadditions of dialkynylisobenzofuran and 1,4-naphthoquinone. Introduction of arylethynyl groups by double nucleophilic additions to tetracenequinone gave sterically congested (arylethynyl)tetracenes after reductive aromatization. The photophysical properties of the newly prepared π-conjugated molecules are also evaluated.

Dual reactivity pattern of Mn(I) carbyne complexes Cp(CO)2Mn+≡C–R (R = Ar, Alk) vs. dppm: Subtle balance between double intramolecular nucleophilic addition and nucleophilic addition followed by migratory CO insertion

The Mn(I) cationic carbyne complexes [Cp(CO)2Mn+≡C–R]BX4 (R = Ph, Tol, Me, Bn; X = F, Cl, Ph) react with bis(diphenylphosphino)methane to afford selectively either cyclic λ5-1,3-diphosphetium semi-ylides [RC–P+Ph2CH2P+Ph2)]BPh4 ([R4]BPh4; R = Ph, Tol), or Mn(I) complexes [Cp(CO)Mn(η3-(P,C,C)-Ph2PCH2P+Ph2C(R)=C=O)]BX4 ([R5]BX4; R = Me, X = Ph; R = Bn, X = F) featuring unprecedented phosphonioketene ligands depending on the nature of the carbyne substituent, aryl or alkyl, respectively. The selective formation of these products is tentatively rationalized through the key formation of a transient cationic Mn(I) phosphoniocarbene complexes [Cp(CO)2Mn=C(R)PPh2+CH2PPh2]BX4 bearing a pendent phosphine moiety. The molecular structures of semi-ylide [Ph4]BPh4 and complex [Bn5]BF4 were elucidated by single-crystal X-ray diffraction.

1,3-Dialkynyl- and 1,3-Dialkenylisobenzofurans: New π-Extended Congeners Prepared by Double Nucleophilic Addition of Alkynyllithiums to o-Phthalaldehyde

Efficient synthetic route to 1,3-dialkynyl- and 1,3-dialkenylisobenzofurans, new π-extended congeners of isobenzofurans, was reported. A three-step protocol including double nucleophilic additions of alkynyllithiums to o-phthalaldehyde and selective oxidation enables us to prepare various functionalized π-extended isobenzofurans. The photophysical properties of these π-extended isobenzofurans are also evaluated.

Copper-Catalyzed anti-Markovnikov Hydroindolation of Terminal Alkynes: Regioselective Synthesis of Bis(indolyl)alkanes.

An efficient copper-catalyzed intermolecular hydroindolation reaction of terminal aryl alkynes to expeditiously synthesize bis(indolyl)alkanes in moderate to high yields is described. The double nucleophilic addition of two molecules of indole to one molecule of alkyne occurs in a tandem manner through an anti-Markovnikov pathway. Various arenes and alkynes allow for this transformation. Preliminary mechanistic study sheds light on the observed regioselectivity involving a Cu-vinylidene complex, and 3-styryl-1H-indole as probable intermediates.

Direct transformation of esters into arenes with 1,5-bifunctional organomagnesium reagents.

A direct transformation of carboxylic acid esters into arenes with 1,5-bifunctional organomagnesium reagents is described. This efficient and practical method enables the one-step defunctionalization of various carboxylic acid esters to prepare benzene, anthracene, tetracene, and pentacene derivatives. A double nucleophilic addition of the 1,5-organodimagnesium reagent to the ester is followed by an immediate 1,4-elimination reaction that leads to the direct [5+1] formation of a new aromatic ring.

ChemInform Abstract: Beyond the Divinyl Ketone: Innovations in the Generation and Nazarov Cyclization of Pentadienyl Cation Intermediates

AbstractReview: 57 refs.

Beyond the Divinyl Ketone: Innovations in the Generation and Nazarov Cyclization of Pentadienyl Cation Intermediates.

The requirement for new strategies for synthesizing five-membered carbocycles has driven an expansion in the study of the Nazarov cyclization. This renewed interest in the reaction has led to the discovery of several interesting new methods for generating the pentadienyl cation intermediate central to the cyclization. Methods reviewed include carbon-heteroatom ionization, functionalization of a double bond, nucleophilic addition, or electrocyclic ring opening. Additional variations employ unconventional substrates to produce novel pentacycles, such as the iso- and imino-Nazarov. Herein, we provide an overview of these unconventional, yet highly useful versions of the Nazarov cyclization.