New synthesis of 3,5-disubstituted-5H-thiazolo[3,2-a]pyrimidine via ring annulation of 3,4-dihydropyrimidin-2(1H)-thione using alkynyl(aryl)iodonium salts

A transition metal-free protocol for the synthesis of biologically active thiazolo[3,2-a]pyrimidine derivatives has been achieved by the cyclocondensation of 3,4-dihydropyrimidin-2(1H)-thiones with alkynyl(aryl)iodonium tosylates. This reaction demonstrates another useful application of alkynyl(aryl)iodonium tosylates as synthon of alkynyl cation.     

Synthesis, characterization, luminescence and nonlinear optical (NLO) properties of truxene-containing platinum(II) alkynyl complexes

A series of luminescent trinuclear platinum(II) alkynyl complexes containing dihydro-5H-diindeno[1,2-a;1′,2′-c]fluorene (truxene) as the core and aryl alkynyl ligands with different electronic properties at the periphery has been successfully synthesized and characterized. The electronic absorption, emission, nanosecond transient absorption and electrochemical properties of these complexes have been reported. These complexes showed long-lived emissions in degassed benzene solution at room temperature, and their emissions have been assigned to originate from triplet states of intraligand (IL) character with some mixing of metal-to-ligand charge-transfer (MLCT) character. The luminescent platinum(II) alkynyl complexes are found to show two-photon absorption (2PA) and two-photon induced luminescence (TPIL) properties, and their two-photon absorption cross-sections have been determined to be 6-51 GM upon excitation at 720 nm.     

Synthesis of cyclic allyl vinyl ethers using Pt(II)-catalyzed isomerization of oxo-alkynes

Several alkynyl epoxides and one alkynyl allyl alcohol were isomerized to cyclic allyl vinyl ethers (3,4-dihydro-2H-1,4-oxazines) using PtCl₂ as the catalyst. Three of these allyl vinyl ethers were converted to 2-hydroxymorpholine derivatives by hydrolysis and two were converted to piperidine derivatives by thermal Claisen rearrangement.     

Iridium-catalyzed [2+2+2] cycloaddition of α,ω-diynes with alkynyl ketones and alkynyl esters

We found that the combination of [Ir(cod)Cl]₂ and rac-BINAP served as an efficient catalyst for the [2+2+2] cycloaddition of 2,7-nonadiyne derivatives and related compounds with alkynyl ketones and alkynyl esters. The corresponding products were obtained in high yields under mild reaction conditions.     

Hg(OTf)2-Catalyzed cyclization of alkynyl tert-butylcarbonate leading to cyclic enol carbonate

Mercuric triflate was shown to be a powerful catalyst for the cyclization of alkynyl tert-butylcarbonates giving rise to cyclic enol carbonates under mild conditions. Internal alkynyl carbonate affords endo cyclization product selectively, while terminal alkynyl carbonate provides only exo cyclization product.     

π-π Chelation controlled chemoselective conjugate addition of lithium dimethylcuprate

The conjugate addition of Me₂CuLi to ethyl cinnamate derivatives bearing an alkynyl group at the ortho-position, took place preferentially in the presence of the corresponding α,β-unsaturated esters bearing an alkynyl group at the distal position or having no alkynyl groups. The observed chemoselectivity is most probably a reflection of the π-π chelation between π-electrons of the olefinic moiety of the enoates and those of the C-C triple bond located at the proximal position.     

Synthèse régiosélective par voie organométallique de pyridines, 4-picolines et 3,5-lutidines substituées en 2 par un groupe insaturé et/ou fonctionnel

A regioselective one-pot synthesis of 2-substituted pyridine derivatives from N-alkoxycarboxylpyridinium salts and α-unsaturated organozinc compounds is described. Similarly, functional alkynyl organomagnesium compounds lead to 2-alkynyl-ω-functional pyridines, from which (E)-2-alkenyl or 2-alkyl-ω-functio pyridines can be obtained by partial or complete reduction.     

Allenylzincs and tert-butylsulfinylimines: a fruitful marriage for synthesis

The stereoselective synthesis of alkynyl 1,2-amino alcohols by the addition of 3-chloro- and 3-methoxymethoxy- allenylzincs to chiral tert-butylsulfinylimines is described. The methodology is applicable to the preparation of alkynyl 2-amino-1,3-diols (O,N,O stereotriads) using α-alkoxy tert-butylsulfinylimines as chiral starting materials. The scope and limitations of the methodology along with recent applications to the efficient asymmetric syntheses of natural and/or bioactive alkaloids and polyhydroxylated alkaloids are presented.     

Domino synthesis of 2-arylbenzo[b]furans by copper(II)-catalyzed coupling of o-iodophenols and aryl acetylenes

A wide range of 2-arylbenzo[b]furans are synthesized through domino intermolecular C_(aryl)-C_(alkynyl) bond formation followed by intramolecular C_(alkynyl)-O bond forming cyclization via copper(II)-catalyzed coupling of o-iodophenols and aryl terminal acetylenes. This method requires neither expensive palladium catalyst nor oxophilic phosphine ligands, can tolerate different functional groups. The methodology is successfully utilized in formal synthesis of β-amyloid aggregation inhibitor 5-chloro-3-[4-(3-diethylaminopropoxy)benzoyl]-2-(4-methoxyphenyl) benzofuran.     

Modular synthesis of a block copolymer with a cleavable linkage via “click” chemistry

A diblock copolymer poly(ethylene glycol)-block-polystyrene or PEG-b-PS with an olefinic double bond at the PEG and PS junction has been prepared by modular synthesis via “click” chemistry. This involved the synthesis of PS by atom transfer radical polymerization and the nucleophilic substitution of the terminal bromide group with azide to yield azide-terminated PS. PEG with an alkynyl terminal group was prepared from reacting carboxyl-end-functionalized PEG with 4-hydroxybut-2-enyl prop-2′-ynyl succinate, which contained an alkynyl group as well as an olefin group. The PS and PEG polymers were linked via the 1,3-dipolar cycloaddition of the end azide and alkyne groups. The obtained copolymer was characterized by ¹H NMR spectroscopy and size exclusion chromatography (SEC). SEC analysis indicated that the diblock copolymer produced could be readily cleaved by ozonolysis to regenerate the constituent homopolymers.     

Palladium-catalyzed alkynylselenation of acetylenedicarboxylates leading to enyne selenides and application to synthesis of multisubstituted aryl selenides

Upon treatment of a mixture of alkynyl selenides and acetylenedicarboxylates with Pd(OAc)₂/P(o-tol)₃/K₂CO₃/H₂O-catalytic system, the alkynylselenation of acetylenedicarboxylates takes place to give the corresponding alkynylvinyl selenides. Furthermore, alkynyl selenides undergo the intermolecular [2+2+2] cycloaddition reaction in the presence of PdCl₂(PPh₃)₂ as a catalyst, affording the corresponding multisubstituted aryl selenides selectively.     

Highly stereoselective synthesis of C-(alkynyl)-pseudoglycals from δ-hydroxy-α,β-unsaturated aldehydes

An efficient and novel methodology for the synthesis of C-(alkynyl)-pseudoglycals from δ-hydroxy-α,β-unsaturated aldehydes has been developed.     

Oxidative additions of alkynyl/vinyl iodides to gold and gold-catalyzed vinylation reactions triggered by the MeDalphos ligand

The hemilabile Ad₂P(o-C₆H₄)NMe₂ ligand promotes fast, quantitative and irreversible oxidative addition of alkynyl and vinyl iodides to gold. The reaction is general. It works with a broad range of substrates of various electronic bias and steric demand, and proceeds with complete retention of stereochemistry from Z and E vinyl iodides. Both alkynyl and vinyl iodides react faster than aryl iodides. The elementary step is amenable to catalysis. Oxidative addition of vinyl iodides to gold and π-activation of alkenols (and N-alkenyl amines) at gold have been combined to achieve hetero-vinylation reactions. A number of functionalized heterocycles, i.e. tetrahydrofuranes, tetrahydropyranes, oxepanes and pyrrolidines were obtained thereby (24 examples, 87% average yield). Taking advantage of the chemoselectivity for vinyl iodides over aryl iodides, sequential transformations involving first a hetero-vinylation step and then a C–N coupling, a C–C coupling or an heteroarylation were achieved from a vinyl/aryl bis-iodide substrate.

The hemilabile Ad₂P(o-C₆H₄)NMe₂ ligand promotes fast, quantitative and irreversible oxidative addition of alkynyl and vinyl iodides to gold.     

Studies on the Pauson–Khand reaction of alkynyl sulfoxides. Unexpectedly easy racemization of their dicobalt hexacarbonyl complexes

The scope and limitations of the Pauson–Khand reactions of alkynyl sulfoxides with strained alkenes have been studied. (S)-1-Hexynyl p-tolyl sulfoxide and (S)-2-phenylethynyl p-tolyl sulfoxide afforded β-(p-tolylsulfinyl)enones in moderate yields and low diastereoselectivities. The diastereomeric mixtures were easily separated by column chromatography and the sulfinyl group could be cleaved by a sequence involving reduction to sulfide, carbonyl reduction and enol thioether hydrolysis to afford 1,3-rearranged enantiomerically enriched α-butyl and α-phenyl enones. The absolute configuration of the Pauson–Khand adducts was determined by X-ray diffraction. The decreased enantiomeric excess of the final products uncovered an unprecedented low temperature racemization of the hexacarbonyl dicobalt complexes of alkynyl sulfoxides.     

α,β-Unsaturated acyl cyanide synthesis via triethylamine catalyzed redox cyanation

Stereoselective redox cyanation of alkynyl aldehydes was explored, furnishing (E)-α,β-unsaturated acyl cyanides. This reaction was catalyzed by mild TEA base, as a dual role of Lewis base and Brönsted base. TMSCN treated with TEA was an effective reagent for generating umpolung intermediates from alkynyl aldehydes, and this nucleophilic intermediate can be protonated by equimolar amount of EtOH, promoting the efficient conversion into α,β-unsaturated acyl cyanides. The synthesized acyl cyanides were successfully applied as the synthetic precursors in the iron-catalyzed arylation reactions.     

Stereoselective electrochemical carboxylation of α,β-unsaturated sulfones

As an attractive C1 synthon, carbon dioxide (CO₂) has been extensively used in organic synthesis to produce carboxylic acids. In this research, stereoselective electrochemical carboxylation of α,β-unsaturated sulfones has been developed under transition-metal-free conditions. All the cinnamic acids and the derivatives are obtained selectively in the E-configuration. Besides, arylpropiolates also can be produced from alkynyl sulfones.     

Metal-free synthesis of benzimidazo[2,1-a]ellipticines via tandem inter and intramolecular cyclization

Synthesis of the new benzimidazo[2,1-a]ellipticine derivatives via tandem inter and intramolecular, 5-endo,6-endo cyclization of various 9-ethyl-2-(alkynyl)carbazole-3-carbaldehydes with different 1,2-aryldiamines is reported under metal free condition in good yields.     

The Renaissance of an Old Problem: Highly Regioselective Carboxylation of 2‐Alkynyl Bromides with Carbon Dioxide

A steric effect‐controlled, zinc‐mediated carboxylation of different 2‐alkynyl bromides under an atmospheric pressure of CO₂ has been developed by careful tuning of different reaction parameters, including the metal, solvent, temperature, and additive. 2‐Substituted 2,3‐allenoic acids were afforded from primary 2‐alkynyl bromides, whereas the carboxylation of secondary 2‐alkynyl bromides yielded 3‐alkynoic acids in decent yields. A rationale for the observed regioselectivity has been proposed.     

Pyridazine derivatives. Part 33: Sonogashira approaches in the synthesis of 5-substituted-6-phenyl-3(2H)-pyridazinones

Several 6-phenyl-3(2H)-pyridazinones bearing different alkynyl groups at position 5 have been prepared by a palladium-catalysed Sonogashira cross-coupling reaction. An interesting base-promoted electronically permitted isomerization has been observed during the coupling of 1-phenyl-2-propyn-1-ol. This rearrangement afforded the E-chalcone 6 in excellent yield.     

A Review on Generation and Reactivity of the N-Heterocyclic Carbene-Bound Alkynyl Acyl Azolium Intermediates

N-heterocyclic carbene (NHC) has been widely used as an organocatalyst for both umpolung and non-umpolung chemistry. Previous works mainly focus on species including Breslow intermediate, azolium enolate intermediate, homoenolate intermediate, alkenyl acyl azolium intermediate, etc. Notably, the NHC-bound alkynyl acyl azolium has emerged as an effective intermediate to access functionalized cyclic molecular skeleton until very recently. In this review, we summarized the generation and reactivity of the NHC-bound alkynyl acyl azolium intermediates, which covers the efforts and advances in the synthesis of achiral and axially chiral cyclic scaffolds via the NHC-bound alkynyl acyl azolium intermediates. In particular, the mechanism related to this intermediate is discussed in detail.