Domino Sequence Research Articles

Tertiary Amines as Synthetic Equivalents of Vinyl Cations: Zinc Bromide Promoted Coupling of Propargylamines with α‐Isocyanoacetamides To Give 2,4,5‐Trisubstituted Oxazoles Initiated by an Internal Redox Process

Crabée interrupted: Propargylamines 1 react with α-isocyanoacetamides 2 in the presence of zinc bromide to afford vinyl oxazoles 3. The transformation, wherein the propargylamine acts as a vinyl cation synthetic equivalent, involves a domino sequence incorporating a 1,5-hydride shift, intermolecular trapping/cyclization, and a 1,6-elimination (see scheme).

A facile regio- and stereoselective synthesis of trans-ethyl 5-aroyl-4-aryl-2-[(arylsulfonyl)methyl]-4,5-dihydrofuran-3-carboxylates

A library of novel trans -ethyl 5-aroyl-4-aryl-2-((arylsulfonyl)methyl)-4,5-dihydrofuran-3- carboxylates were synthesized regio- and stereoselectively in good yields by a three-component domino reaction of ethyl-3-oxo-4-(arylsulfonyl)butanoates, aromatic aldehydes and N- phenacylpyridinium bromide in presence of triethylamine in acetonitrile under heating. This transformation generates C-O, C-C and C=C bonds and presumably proceeds via an �,�- unsaturated ketosulfonyl ester generation/Michael addition/intramolecular cyclisation domino sequence.

ChemInform Abstract: Design and Synthesis of 2‐Acylbenzothiazoles via in situ Cross‐Trapping Strategy from Benzothiazoles with Aryl Ketones.

An I2/KOH synergistically promoted direct ring-opening aroylation of benzothiazoles with aryl ketones has been discovered. Aryl ketones were seen to act as carbonyl sources to construct 2-acylbenzothiazoles. This reaction could provide an example for the convergent integration of self-labor domino sequences based on an in situ cross-trapping strategy.

Synthesis of an Octa‐tert‐butylphthalocyanine: A Low‐Aggregating and Photochemically Stable Photosensitizer

AbstractThe synthesis of a new octa‐tert‐butylphthalocyanine is described. First, the 4,5‐di‐tert‐butylphthalonitrile building block was synthesized in a six‐step approach, in which the last step is a three reaction domino sequence. Then, this phthalonitrile was cyclotetramerized to furnish a new phthalocyanine dye, which presented no aggregation in solution and good photophysical properties.

Palladium-Catalyzed Arylic/Allylic Aminations: Permutable Domino Sequences for the Synthesis of Dihydroquinolines from Morita–Baylis–Hillman Adducts

An efficient palladium-catalyzed synthesis of 1,2-dihydroquinolines has been developed via the reaction between anilines and Morita-Baylis-Hillman adducts derived from o-bromobenzaldehyde. This new Pd(0)-catalyzed pseudo-domino type I sequence involves a Buchwald-Hartwig arylic amination and an allylic amination. When starting from an o-bromo allylic alcohol, the chronology is arylic amination/allylic arylation. However, the sequence reverses when the reaction is performed on the corresponding o-bromo allylic acetate.

Aldol Reactions in Multicomponent Reaction Based Domino Pathways: A Multipurpose Enabling Tool in Heterocyclic Chemistry

The aldol reaction has been evaluated in combination with the Ugi multicomponent reaction to assemble richly decorated mono- and polycyclic systems via expeditious cascade pathways. A small collection of pyrrolinones was generated thereof, and the scarcely accessible pyridoquinoxalinedione scaffold was also prepared by designing an additional nucleophilic substitution step in this domino sequence requiring minimal operational effort.

Facile three-component domino reactions for the synthesis of 2-arylimidazo[1,2-a]pyridines and 2-arylimidazo[2,1-a]isoquinolines

Abstract The three-component domino reactions of pyridine/isoquinoline, phenacyl bromide, and substituted (E)-N-hydroxyarylimidoyl chloride in the presence of triethylamine afforded a series of 2-arylimidazo[1,2-a]pyridines and 2-arylimidazo[2,1-a]isoquinolines. This one pot three-component transformation presumably proceeds via ylide generation/annulation/fragmentation/dehydration domino sequence of reactions.

ChemInform Abstract: One‐Pot Formation of Chiral Polysubstituted 3,4‐Dihydropyrans via a Novel Organocatalytic Domino Sequence Involving Alkynal Self‐Condensation.

AbstractThe presented new organocatalytic hydration/aldol/oxa‐Diels—Alder domino reaction leads to chiral polyfunctionalized dihydropyrans under mild conditions.

Method for Estimating the Domino Effect in Quantitative Assessment

Accidents caused by the domino effect are the most destructive accidents in the chemical process industry. These chains of accidents may lead to catastrophic consequences and may affect not only the industrial sites, but also people, environment and economy. However, quantitative risk assessments do not usually take the domino effect into account in a detailed, systematic way, mostly because of its complexity and the difficulties involved in its incorporation. A method for quantitative assessment of domino effects is presented. The consequence and probability of a certain accident can be estimated. The domino sequences from the initial accident to the last accident can be obtained. The method has been implemented in a case study. The results show that it can indeed be used to estimate the impact of the domino effect in quantitative assessment.

Facile domino reactions for the stereoselective assembly of highly functionalized bis-(trans-2,3-dihydrofuranyl) sulfides

A facile stereoselective synthesis of a series of nineteen novel bis-(trans-2,3-dihydrofuranyl) sulfides from the reaction of (Z,Z)-2,2′-thiobis(1,3-diarylprop-2-en-1-ones) with substituted phenacyl bromides and pyridine in the presence of K2CO3 in acetonitrile via domino reactions is described. This transformation presumably occurs via pyridinium salt formation/ylide generation/Michael addition/intramolecular annulation domino sequence, involving the formation of two C–C and two C–O bonds and four stereocentres in a single step with complete stereoselectivity affording only one diastereomer.

A New Henry/Michael/Retro‐Henry/Henry Domino Sequence Promoted by Bifunctional Organocatalysts

AbstractA highly stereoselective route to densely functionalized cyclohexanes is described, via a Cinchona‐based bifunctional organocatalyzed Henry/Michael/retro‐Henry/Henry domino reaction. The peculiar stereoconvergent mechanism allows the creation of up to four contiguous stereocenters in a highly stereodefined manner starting from both achiral aldehydes and racemic nitro alcohols. The simple and efficient protocol can be exploited to synthesize a wide range of substrates and also useful bioactive molecules.

A Four‐Component Reaction Involving In Situ Generated Organometallic Reagents: Straightforward Access to β‐Amino Esters

Four in one: A straightforward synthesis of β(2,3)-amino esters is described through a new zinc-mediated, cobalt-catalyzed four-component reaction between organic bromides, alkyl acrylates, amines, and aldehydes (see scheme). Synthesis involves a Mannich-related conjugate addition/aza-aldol domino sequence, allowing the formation of three single bonds in one step. A reaction mechanism, emphasizing the crucial role of zinc salts, is described.

Design and Synthesis of 2-Acylbenzothiazoles via In Situ Cross-Trapping Strategy from Benzothiazoles with Aryl Ketones

An I2/KOH synergistically promoted direct ring-opening aroylation of benzothiazoles with aryl ketones has been discovered. Aryl ketones were seen to act as carbonyl sources to construct 2-acylbenzothiazoles. This reaction could provide an example for the convergent integration of self-labor domino sequences based on an in situ cross-trapping strategy.

ChemInform Abstract: Concise Synthesis of Acetal‐Protected syn 1,3‐Diols by a Tandem Hemiacetal Formation/Tsuji—Trost Reaction.

AbstractA novel domino sequence for synthesis of the title compounds is developed.

Microwave-assisted three-component domino reaction: Synthesis of indolodiazepinotriazoles.

A microwave-assisted three-component protocol involving N-1 alkylation of 2-alkynylindoles with epichlorohydrin, ring opening of the epoxide with sodium azide, and an intramolecular Huisgen azide–internal alkyne 1,3-dipolar cycloaddition domino sequence has been described. The efficacy of the methodology has been demonstrated by treating various 2-alkynylindoles (aromatic/aliphatic) with epichlorohydrin and sodium azide furnishing annulated tetracyclic indolodiazepinotriazoles in satisfactory yields.

Diastereoselective Synthesis of 1,3-syn-Oxazines via a Tandem Hemiaminalization and Tsuji-Trost Reaction

A novel domino sequence for the rapid assembly of 1,3-syn-substituted oxazines is reported. Mechanistically, the one-pot procedure is based on a three-step sequential process involving a hemiaminalization and Tsuji–Trost reaction. The process generates up to two new stereogenic centers in a concise and convergent fashion from simple and readily available starting materials.

Expedient Synthesis of Chiral Oxazolidinone Scaffolds via Rhodium-Catalyzed Asymmetric Ring-Opening with Sodium Cyanate

A method for synthesizing chiral oxazolidinone scaffolds from readily available oxabicyclic alkenes is described. The reaction utilizes a domino sequence of Rh(I)-catalyzed asymmetric ring-opening (ARO) with sodium cyanate as a novel nucleophile followed by intramolecular cyclization to generate oxazolidinone products in excellent enantioselectivities (trans stereochemistry).

ChemInform Abstract: Dual Reactivity of O‐α‐Allenyl Esters under Palladium(0) Catalysis: From Carbopalladation/Allylic Alkylation Domino Sequence to Decarboxylative Allenylation.

Abstract In a mechanistically-oriented study, O-α-allenyl esters have been evaluated as potential substrates for Pd-catalyzed carbopalladation/allylic alkylation domino sequences and decarboxylative allenylation reactions. The domino sequence turned out to be feasible only with electron-deficient aryl iodides, thereby showing a narrower potential than that previously observed with the malonamide-based series. The decarboxylative allenylation of O-α-allenyl esters was also tested and turned out to be practicable with β-ketoester-based substrates and using specific basic conditions. Plausible reaction mechanisms are proposed to account for the observed reactivities.

Pd(II)-catalyzed intramolecular aminopalladation/direct C–H arylation under aerobic conditions: synthesis of pyrrolo[1,2-a]indoles

Heating a DMA/pivalic acid (v/v=4/1) solution of diversely substituted 6-(phenylamino)hex-2-ynoates in the presence of a catalytic amount of Pd(OAc)2 under oxygen atmosphere afforded pyrrolo[1,2-a]indoles in moderate to good yields. A domino sequence involving intramolecular aminopalladation followed by C–H activation and reductive elimination was proposed to account for the observed bis-cyclization.

Organocatalyzed straightforward synthesis of highly fluorescent 3,5-disubstituted 2,6-dicyanoanilines via domino annulation of α-enolicdithioesters with malononitrile

Piperidine mediated a robust, efficient, and selective one-pot synthesis of previously inaccessible and highly fluorescent 3,5-disubstituted 2,6-dicyanoanilines. This was achieved via the domino carboannulation of α-enolicdithioesters with malononitrile by dehydrative CO/CS bond functionalization. It is presumed that the domino sequence includes base promoted nucleophilic addition, Knoevenagel condensation and ANRORC (addition of nucleophile/ring opening/ring closure) steps. The screening for optical properties identified a strong blue emission with high fluorescence quantum yields.