Internal alkynes cycloadditions

The strong o-donor property of NHC ligands enhances the catalytic activity in [3+2] cycloaddition by promoting the activation of internal alkynes (i.e. 26), which proceeds by the formation of a ti-alkyne complex 25 (Scheme 5.7). 

Scheme 5.7 Proposed mechanism of [3+2] cycloaddition reaction of internal alkynes...

Scheme 5.8 [3+2] Cycloaddition reaction between diphenylcyclopropenone and internal alkynes...

Rhodium also has been reported as a catalyst for [2+2+2] alkyne cycloaddition in water. Uozumi et al. explored the use of an amphiphilic resin-supported rhodium-phosphine complex as catalyst (Eq. 4.60). The immobilized rhodium catalyst was effective for the [2+2+2] cycloaddition of internal alkynes in water,113 although the yields of products were not satisfactory. 

Another route involves a palladium-copper-catalyzed tandem carbon-carbon formation/cycloaddition sequence (Equation 12) <2005TL8531>. Notably, cycloadditions of azide to the internal alkynes failed under click chemistry reaction conditions <2003DDT1128>. Cyclization under oxidative conditions has been reported from dithioacetal 163 (Equation 13) <1996TL3925>. The formation of 164 as a single diastereoisomer has been explained by stereoelectronic effects. 

Complex 93 was tested in a variety of [5+2] cycloaddition reactions and compared, where relevant, with some other effective catalysts (Tab. 13.6). Excellent results were obtained with VCPs tethered to terminal and internal alkynes, alkynoates, and aUcenes. 

Aryl acetylenes undergo dimerization to give 1-aryl naphthalenes at 180 °C in the presence of ruthenium and rhodium porphyrin complexes. The reaction proceeds via a metal vinylidene intermediate, which undergoes [4 + 2]-cycloaddition vdth the same terminal alkyne or another internal alkyne, and then H migration and aromatization furnish naphthalene products [28] (Scheme 6.29). 

A novel microwave-mediated three-component coupling of a-acyl bromides, pyridine and internal alkynes was carried out in the absence of a solvent on activated basic alumina to provide a collection of indolizines (Scheme 3.5)7. It was proposed that the reaction proceeded via in situ generation of a dipole from an N-acyl pyridinium salt, followed by a [3+2] cycloaddition reaction. A dedicated laboratory microwave system was... 

The Rh-catalysed intermolecular [4+2] cycloaddition of a diene and a terminal alkyne affords the l,4-disubstituted-l,3-cyclohexadiene 58 via 57 [18], The 1,2,6-trisubstituted-l,4-cyclohexadiene 60 is obtained by the Fe-catalysed [4+2] cycloaddition of dienes and internal alkynes. The catalyst 59 is prepared by the reaction of a 1,4-diaza-1,3-diene complex of FeCl2 59 with EtMgBr [19]. 

The bicyclo[4.2.1]nonatriene 323 was prepared by the [6+2] cycloaddition of internal alkyne with the complex 322 under irradiation [79]. Ligand exchange of 323 with toluene liberated 324. The complex 325 underwent the [6+2] cycloaddition with two moles of terminal alkyne to give the tetracyclic compound 327 via 326. The [6+2] cycloaddition of the complex 322 and 1,7-octadiyne (328) afforded 329 as a primary product, which was converted further to 330 in 56% yield by further intramolecular [6+2] cycloaddition [80]. The tropone complex 331 underwent intramolecular [6+2] cycloaddition under irradiation to give the strained tricyclic compound 332 in moderate yield [81]. 

A palladium(n)-mediated cycloaddition of 2-(2-iodophenyl)propan-2-ol with unsymmetrically substituted internal alkynes yields l,l-dimethyl-l//-isochromenes with high regioselectivity (Equation 74) <1995JOC3270>. 

One of the first examples of ruthenium-catalyzed C-C bond formation afforded the synthesis of cyclobutenes, from norbornene derivatives with dimethyl acetylenedicarboxylate, and was reported by Mitsudo and coworkers [45, 46] by using various catalysts such as RuH2(CO)[P(p-C6H4F)3]3 or RuH2(PPh3)4. More recently, the complex Cp RuCl(COD) has shown to be an excellent catalyst for the [2+2] cycloaddition of norbornenes with various internal alkynes [45] (Eq. 33) and with a variety of substituted norbornenes and norbornadienes [47]. The ruthenacycle intermediate, formed by oxidative coupling, cannot undergo /1-hydride elimination and leads to cyclobutene via a reductive elimination. 

Unsaturated lactones lacking substitution at C-4 are the simi est ones available via this general type of cycloaddition. Several syntheses of these lactones are of practical value, including two Pd-based meth-ods. However, the considerable utility of metal carbonyl anions in lactone synthesis is illustrated by a rhodium carbonyl anion catalyst system which gives very high yields upon reaction with a variety of internal alkynes under weakly basic aqueous conditions, essentially water-gas shift conditions. These conditions were established to maximize chemoselectivity with respect to other possible alkyne carbonylation products. Regioselectivity is modest in this process, but was not examined systematic ly (equation 13). ... 

The metallocene complex 27 containing a M=X double bond undergoes overall [2 + 2] cycloaddition with an internal alkynes to give heterometallacyclobutenes (28) [77], A formal [2 + 2] cycloaddition of CpjZr (=N Bu)(thf) with imine affords a 2,4-diazametallacyclobutane, whose further reaction with imines results in an imine metathesis reaction [78] azametallacyclobutene is an intermediate in the Cp2Zr(NHR)2-assisted hydroamination of alkynes and allene [79],... 

It is now usual to promote these cycloadditions by catalysts for example, reaction with A -tosyl-ynamides, using ruthenium or copper catalysts, giving 1-substituted 5- and 4-amino triazoles, respectively the formation of the 1,4-substitution pattern with copper catalysis and 1,5-pattem with ruthenium catalysis seems to be general. The latter metal will also promote addition to internal alkynes. ... 

In a general illustration of the Dotz reaction a terminal or internal alkyne reacts with a carbene 123 and one carbonyl ligand at a [Cr(CO)3] template in a formal [3 + 2+1] cycloaddition reaction producing a chromium-complexed naphthol (124) under mild reaction conditions via the vinylketene intermediate 125 (see Scheme 57). Terminal alkynes (R1C = CR2 R HjR H) react with total regioselectivity, while the regiocontrol in the reaction course of internal alkynes... 

---