Phenyl acetylene cycloaddition

The ring fused pyrroles 480 have been prepared by in situ trapping of the meso-ionic l,3-oxazol-5-ones (479) with alkynes. This 1,3-dipolar cycloaddition was found to be regiospecific when phenyl acetylene was used as 1,3-dipolarophile, the only products being 480, R = H or MeO, R = Ph, R2 =... 

Addition to acetylenes proceeds exclusively by [2 + 4] cycloaddition. Thus phenyl-acetylene gives (5) exclusively. 

Generality of this mechanochemical protocol was demonstrated in one-pot, two-step synthesis of triazole (Scheme 3.102). The first synthetic step, 1,3-dipolar cycloaddition ( click reaction ) of 4-iodobenzyl azide with phenyl acetylene employing copper powder (1 equiv.) was complete in lOmin and follows the synthetic procedure described in chapter Cycloaddition Reactions [67], Ullmann Af-arylation of tiiazole 371 with ethylenediamine in optimized reaction conditions provided the corresponding W-arylated triazole 372 in 56% yield, albeit reaction required 2h of ball milling to complete. 

The same research group has also demonstrated a catalytic enantioselective tandem carbonyl yhde formation-cycloaddition of the a-diazo-j8-ketoester 91 using 0.5 mol% of Rh2(R-DDBNP)4 95, as catalyst to afford the cycloadduct 93 in good yields (Scheme 28) with up to 90% ee [ 109]. A detailed study on enantioselective reaction using a series of dirhodium tetrakiscar-boxylate and tetrakisbinaphtholphosphate catalysts under different solvent conditions has been described [56]. These studies indicate that dirhodium tetrakisbinaphtholphosphate catalysts are superior to the more commonly used carboxylates and carboxamidates in asymmetric transformations. Typically, the reaction [58] of the nitrophenyl-substituted diazodione 96 and phenyl acetylene in the presence of the binaphthyl catalyst 95 at 0 °C afforded the cycloadduct 97 with 76% ee (Scheme 29). 

With the objective of stabilizing the initial intermediates formed after addition of dipolarophiles, a huge series of mono- and diphosphine-containing a-iminoketone starting compounds [Fe(RN=CHCR=0)(PR3)(C0)2] and [Fe(RN=CHCR=0)(dppe)(CO)] has been synthesized and subjected to cycloaddition with DMAD, MP, phenyl-acetylene, dimethyl maleate, and ArNCS. As can be inferred from the structures of the bicyclo[2.2.1]-adducts 81 and 82 depicted in Scheme 14, oxidative cycloaddition across the Fe-0=C dipole is preferred over Fe-N=C addition. 

Fig. 7.19 Phenyl azide and phenyl acetylene are coencapsulated to give a Michaelis complex with high molarity and effective molarity. The cycloaddition (click) reaction takes place without copper catalysis...

It has been reported that Cu on porous glass is a recyclable catalyst for the azide-alkyne cycloaddition in water under microwave irradiation (Jacob et al, 2013). This microwave-assisted cycloaddition of benzyl azide with phenyl acetylene in water gave 1,4-tviazole almost exclusively after 10 or 20 min at 120° or 100°C, respectively. 

Vinyl-l,2,3-triazoles have been synthesized in moderate yields by the cycloaddition of vinyl azides and phenyl acetylene, using acetone or dioxane as solvent, in a flow microreactor where copper wire was inductively heated. The copper metal was directly and instantaneously heated inside the reactor, which results in a higher reactivity than with conventionally heated elemental copper [88]. 

Analogously to ynamines and o, /3-acetylenic ketones, 4-aminobut-3-yn-2-ones react with 1,3-dipoles (68HCA443 73HCA2427 92KGS867). The reaction of 4-dimethylaminobut-3-yn-2-one with diphenylketene follows a route of [2-1-21-cycloaddition (30°C, THF, 1 h) to give 2-acetyl-3-dimethylamino-4,4-diphenyl-cyclobut-2-en-l-one (377) in 15% yield. With ethyl azidoformate (30°C, THF, 3 h), the tiiazole 378 is formed in 82% yield, whereas with phenyl isocyanate, the quinoline 379 is the product (by a [2- -4] scheme) in 70% yield (68HCA443). 

Diarylmethylenecyclopropa[6]naphthalenes 14, unlike their benzene parent counterparts which give cycloaddition reactions at the cyclopropene bridge bond [10a], react on the exo double bond in Diels-Alder cycloadditions (see Sect. 2.1.1) [10b]. The reactions of 14 with the highly electron-deficient acetylenic(phenyl)iodonium triflate 584 give products 586a and 587, which are believed to derive from unstable primary [2 + 2] cycloadducts 585 (Scheme 82) [10b],... 

Reduced isoindoles are formed when acetylenes are cooligomerized with N-phenyl- or N-methylmaleimide but the synthetic value of these processes is limited by competing secondary reactions of product cycloaddition (Scheme 51) and oxidation.87... 

A variety of triazole-based monophosphines (ClickPhos) 141 have been prepared via efficient 1,3-dipolar cycloaddition of readily available azides and acetylenes and their palladium complexes provided excellent yields in the amination reactions and Suzuki-Miyaura coupling reactions of unactivated aryl chlorides <06JOC3928>. A novel P,N-type ligand family (ClickPhine) is easily accessible using the Cu(I)-catalyzed azide-alkyne cycloaddition reaction and was tested in palladium-catalyzed allylic alkylation reactions <06OL3227>. Novel chiral ligands, (S)-(+)-l-substituted aryl-4-(l-phenyl) ethylformamido-5-amino-1,2,3-triazoles 142,... 

The thermal cycloaddition of azides to acetylenes is the most versatile route to 1,2,3-triazoles, because of the wide range of substituents that can be incorporated into the acetylene and azide components. The accepted mechanism for the reaction is a concerted 1,3-dipolar cycloaddition. The rates of addition of phenyl azide to several acetylenes have been measured the rates of formation of the aromatic triazoles are not appreciably different from the rates of cycloaddition to the corresponding olefins, indicating that the transition-state energy is not lowered significantly by the incipient generation of an aromatic system. 

Intramolecular [3- -2]-cycloadditions of thiocarbonyl ylides with nonactivated acetylenes have also been described. Most representative examples involved the use of mesoionic substrates. The initially formed polycyclic adducts of type 110 undergo spontaneous elimination of phenyl isocyanate (24,62,151). A typical example leading to compound 111 is shown in Scheme 5.40. 

N-Aryl analogs have been synthesized193 by cycloaddition of terminal-acetylenic sugar derivatives to azides, as exemplified by the conversion of the pentyne derivative 171a into l-phenyl-4-(D-threo-... 

Replacing the hydrogen in 68 with a phenyl group leads to the secondary acetylenic monomer 70. It was believed that this disubstituted acetylene would suppress the reaction of acetylene with itself and insure that there was an acetylene functionality available for reaction with the o-quinodimethane at 200 °G The DSC of 68 showed the presence of a single exothermic peak at 263 °C which the authors felt was adequate evidence for the occurrence of a Diels-Alder reaction between the acetylene and benzocyclobutene. Unfortunately they did not report on any control experiments such as that between diphenylacetylene and simple benzocyclobutene hydrocarbon or a monofunctional benzocyclobutene in order to isolate the low molecular weight cycloaddition product for subsequent characterization. The resulting homopolymer of 68 had a Tg of 274 °C and also had the best thermooxidative stability of all of the acetylenic benzocyclobutenes studied (84% weight retention after 200 h at 343 °C in air). 

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