Cycloaddition of 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. 

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]. 

The [Rh(COD)Cl]2-catalysed 6 + 2-cycloaddition of internal alkynes with cyclo-... 

Hilt, G., Paul, A., Hengst, C. (2009). Cobalt-catalysed [6+2] cycloaddition of internal alkynes and terminal alkenes with cycloheptatriene. Synthesis, 3305-3310. 

Zhang, X., Wang, J., Zhao, H., Wang, J. (2013). Rhodium-catalyzed [6+2] cycloaddition of internal alkynes with cycloheptatriene catalytic study and DPT calculations of the reaction mechanism. Organometalhcs, 32, 3529-3536. 

The first report on rhodium-catalyzed [2 + 2 + 2] cycloaddifion of alkynes is the intermolecular cyclotrimerization of dimethyl acetylenedicarboxylate (DMAD) catalyzed by a neutral rhodacyclopentadiene/arsine complex in 1968 [6]. After this initial report, various neutral rhodium(I) complexes were developed for intermolecular [2 + 2 + 2] cycloaddition of internal alkynes (Scheme 4.1) [7-13], Among them, (T) -cyclopentadienyl)rhodium(I) complexes [7-9,13] are the best-investigated catalysts. Neutral rhodium(ni) complexes have also been employed as catalysts [14,15], A RhCls/amine system effectively catalyzes [2 + 2 + 2] cycloaddition of internal alkynes [15]. 

Scheme 48 Cycloaddition of internal alkynes with azides regioselectivity issue...

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...

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). ... 

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... 

The benzannulation reaction is a versatile method for the formation of polysubstituted aromatic compounds such as naphthoquinones. This three-component coupling involves the reaction between an a. unsaturated Fischer carbene, an acetylene, and a CO ligand, and initially proceeds by cycloaddition of the alkyne with the carbene complex. The regioselectivity of this step is highly dependent on the substituents on the acetylene moiety and is usually low in the case of internal acetylenes. 

Ru3(CO)i2 coordinated with 2-(diphenylphosphino)benzonitrile catalysed the regioselective 2 + 2 + 2-cyclotrimerization of trifluoromethyl-substituted aryl alkynes in high yields and with a high regio-selectivity4 The alkyne 2 + 2 + 2-cyclotrimerization reaction has been applied to the synthesis of the central 4,5,6-tricyclic core (94) of 4,5,6-trinems (Scheme 30)4 The NbC /DMI-catalysed intermolecular 2 + 2 + 2-cycloadditions of terminal alkynes, internal alkynes, and alkenes produced 1,3,4,5-tetrasubstituted 1,3-cyclohexadienes in excellent yields and with high chemo- and regio-selectivities. ... 

Reaction with Internal Alkynes to Give 4, 5- Disubstituted AtProtected Triazoles. The cycloaddition of TSE-N3 (2) with internal alkynes is facilitated by both the Cu(I) and Ru(I) catalytic systems. Treatment of symmetrical alkynes 8, 9 with azide 2 using Cu(I) catalysis affords 4,5-disubstituted triazoles 10, 11 respectively, in good yields (eq 4). Similarly, Ru(I) catalyzed cycloaddition of symmetrical alkyne 12 provides triazole 13 in moderate yield (eq 5). ... 

This catalytic system tolerates terminal alkynes bearing various functionalities such as ketone, sulfone, ester, ketal, ether, alcohol, imide, or nitrile, which are useful for further transformations. The reaction with ethynyltrimethylsilane allowed the formation of the expected [6-1-2] cycloadduct in 92% yield. Such a result could not be obtained with the use of [(CHT)Co(CO)3] as catalyst [41]. Later, Hilt expanded the scope of the [6-t-2] cycloaddition to internal alkynes with modified pre-catalysts such as CoBr2[P(0/Pr)3]2 [55]. 

BigeaulL J., Giordano, L., Buono, G. (2005). [2-1-1] cycloadditions of terminal alkynes to norbomene derivatives catalyzed by palladium complexes with phosphinous acid hgands. Angewandte Chemie, International Edition, 44, 4753-4757. 

In [2 + 2 + 2] cycloaddition of unsymmetric alkynes, it is difficult to control its regioselectivity. Some neutral rhodium(I) and rhodium(in) complexes were able to catalyze regioselective [2 + 2 + 2] cycloaddition of various unsymmetric internal alkynes (Scheme 4.3) [13,15a,b,16-18],... 

Selective intermolecular [2 - - 2 - - 2] cycloaddition of terminal alkynes is more difficult to achieve than internal alkynes, due to their various reactivities toward transition-metal complexes in addition to the regioselectivity problem. Indeed, a neutral rhodium(I)/phosphine complex such as RhCl(PPh3)3 generally reacts with terminal alkynes to give not cyclotrimers but linear dimers [20]. The neutral rhodium(I) and rhodium(III) complexes could be applied to intermolecular [2 - - 2 - - 2] cycloaddition of terminal alkynes (Scheme 4.5) [13,15a and b]. 

The use of ruthenium (CpRuCl(PPh3)2) or palladium salts (Pd(OAc)2/PPh3, PdCl2(dppf) and Pd(PPh3)4) to catalyze cycloadditions with internal alkynes has been recently compared. 

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). 

Cycloadditions have been reported for many combinations of diazo compounds and alkynes (5). A few recent examples are given in Table 8.2. An inspection of entries 2-4 shows that the regiochemical behavior of internal sulfonylalkynes is totally reversed when the second substituent (R ) is changed from Me or Ph to SiMe3. This difference was explained in terms of a steric effect of... 

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