5-Endo-dig cycloisomerization

Type of reaction C-0 bond formation Reaction conditions Dichloromethane, room temperature Synthetic strategy 5-endo-dig cycloisomerization Catalyst ZnCl2... 

Keywords 1,4-Di- and 1,2,4-trisubstituted but-3-yn-l-ones, dichloromethane, ZnCl2, room temperature, 5-endo-dig cycloisomerization, 2,5- and 2,3,5-trisubstituted furans... 

Polystyrene-immobilized Au catalyst, PEG supported Au and Pt catalysts are foxmd to be efficient to synthesize furan derivatives from alkynyl-diol by intramolecular 5-endo-dig cycloisomerization. 

Polystyrene-supported Au catalysts 17 and 18 have been prepared using the route outlined in Scheme 40. Polystyrene bound triphenyl phosphine was treated with [(Me2S)Au]Cl in dichloromethane at room temperature for 6h to obtain 16. Two different heterogeneously supported Au catalysts, 17 and 18 were obtained by simple ion exchange reaction of AgOTf and AgNTf2 wifh 16. These two catalysts were used to provide the furan derivative by the intramolecular 5-endo-dig cycloisomerization of alkynyl-diol (Scheme 41) [63]. 

In the similar iodocyclization of a-amino ynones 41 (Scheme 24), PEG MOO was a less effective solvent and better yields of 42 were obtained at room temperature with acetonitrile as a solvent [47]. However, the a-amino ynones 41 underwent 5-endo-dig cycloisomerization in PEG 3400 rmder microwave irradiation in the presence of platinmn(ll) chloride affording pyrrolin-3-ones 43 [48]. In the presence of potassium carbonate, the reaction proceeded without substantial epimerization of the products 43. The recyclability of tiie catalytic system and PEG 3400 was also investigated. 

Furthermore, Yamamoto and coworkers illustrated that o-(alkynyl)phenylisocya-nates 159 could also be efficiently employed in a similar Pt( 11)-catalyzed cycloisomerization reaction, serving as surrogates of the corresponding carbamate derivatives 160, to provide N-(alkoxycarbonyl)indoles 161 in moderate to excellent yields (Scheme 9.60) [219]. It is believed that a dual-role catalysis with the Pt(II) salt first triggered the initial intermolecular nucleophilic addition of alcohol to isocyanate 159, affording the key transient carbamate 160, which, upon a subsequent Pt(II)-catalyzed 5-endo-dig cyclization, generated the desired product 161. 

Alkenes are also capable of acting as nucleophiles and can add intramolecularly to ruthenium vinylidenes. Liu and coworkers described the TpRu(PPh3) (CH3CN)2PF6-catalyzed cycloisomerization of substituted ortlio-alkynylethynyl-styrenes to give different naphthalenes or indenes depending on the nature of the alkene substituents (Scheme 29) [142,143]. In all cases the reaction begins with the formation of the ruthenium vinylidene I. Subsequent 6-endo-dig (path a) or 5-endo-dig (path b) cyclization by nucleophilic attack of the alkene moiety would afford ruthenium species II and HI, respectively. When monosubstituted iodoalkenes... 

Recently, pyrazole syntheses by 5-endo-dig cyclization of (Z)-alkynic hydrazines 274 were reported (Scheme 19.75). Cu(I)-mediated stoichiometric cycloisomerization of 274 in the presence of EtsN affords pyrazole derivatives 275 [135]. Qian et al. reported electrophilic fluorocyclization using a gold catalyst and Selectfluor to give 4-fluoropyrazole derivatives 276 [136]. 

Another rhodium vinylidene-mediated reaction for the preparation of substituted naphthalenes was discovered by Dankwardt in the course of studies on 6-endo-dig cyclizations ofenynes [6]. The majority ofhis substrates (not shown), including those bearing internal alkynes, reacted via a typical cationic cycloisomerization mechanism in the presence of alkynophilic metal complexes. In the case of silylalkynes, however, the use of [Rh(CO)2Cl]2 as a catalyst unexpectedly led to the formation of predominantly 4-silyl-l-silyloxy naphthalenes (12, Scheme 9.3). Clearly, a distinct mechanism is operative. The author s proposed catalytic cycle involves the formation of Rh(I) vinylidene intermediate 14 via 1,2-silyl-migration. A nucleophilic addition reaction is thought to occur between the enol-ether and the electrophilic vinylidene a-position of 14. Subsequent H-migration would be expected to provide the observed product. Formally a 67t-electrocyclization process, this type of reaction is promoted by W(0)-and Ru(II)-catalysts (Chapters 5 and 6). 

Functional 1,5-enynes containing a propargyl alcohol motive in their structure can be cycloisomerized in the presence of platinum and gold catalysts following the same endo-dig pathway and H-shift, to directly form [3.1.0]-hexanones (Eq. 7) [41,42]. 

Ramana CV, Mallik R, Gonnade RG (2008) The influence of electronic factors on palladium-mediated cycloisomerization a systematic investigation of competitive 5-exo-dig versus 6-endo-dig cyclizations of sugar alkynols. Tetrahedron 64 219-233... 

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