Cycloisomerization double

With regard to the mechanism of the cycloisomerization, Fiirstner et al. found strong evidence of a metallacyclic intermediate. By labeling the allylic position of enynes 46 and 48, they showed that reactions yielding traws-annulated rings 47 transferred the deuterium atom to the exocychc double bond (eq. 1 in Scheme 10), whereas c -annulated rings 49 formed with complete preservation of the position of the deuterium atom (eq. 2 in Scheme 10). This corresponds well to a metallacycUc... 

Using a protocol for tandem carbonylation and cycloisomerization, Mandai et al.83 were able to synthesize cyclopentene and cyclohexene derivatives in high yield, including fused and 5/>/>0-bicycles (Scheme 25). The cyclohexene Alder-ene products were not isolable methanol addition across the exocyclic double bond (in MeOH/ toluene solvent) and olefin migration (in BuOH/toluene solvent) were observed. The mechanism of methanol addition under the mild reaction conditions is unknown. In contrast to many of the other Pd conditions developed for the Alder-ene reaction, Mandai found phosphine ligands essential additionally, bidentate ligands were more effective than triphenylphosphine. 

This system was described in one report and has been synthesized by a copper-assisted cycloisomerization of alkynyl imines. The authors proposed the following mechanism at first, 372 could undergo a base-induced propargyl-allenyl isomerization to form 373 next, coordination of copper to the terminal double bond of the allene (intermediate 374) would make it subjected to intramolecular nucleophilic attack to produce a zwitterion 375. The latter would isomerize into the more stable zwitterionic intermediate 376, which would be transformed to the thiazole 377 (Scheme 55) <2001JA2074>. 

Brummond [28] was the first to illustrate that cross-conjugated trienes could be obtained via an allenic Alder-ene reaction catalyzed by [Rh(CO)2Cl]2 (Eq. 14). Selective formation of the cross-conjugated triene was enabled by a selective cycloisomerization reaction occurring with the distal double bond of the aUene. Typically directing groups on the allene, differential substitution of the aUene termini, or intramolecularization are required for constitutional group selectivity. However, rhodium(f), unlike other transition metals examined, facihtated selective cyclization with the distal double bond of the allene in nearly aU the cases examined. 

Double cyclization of iodoenynes is proposed to occur through a Rh(I)-acetylide intermediate 106, which is in equilibrium with vinylidene lOS (Scheme 9.18). Organic base deprotonates the metal center in the course of nucleophilic displacement and removes HI from the reaction medium. Once alkenylidene complex 107 is generated, it undergoes [2 + 2]-cycloaddition and subsequent breakdown to release cycloisomerized product 110 in the same fashion as that discussed previously (Scheme 9.4). Deuterium labeling studies support this mechanism. 

In a recent report, Shi et al. developed a valuable tool for the synthesis of 2,6-trans substituted morpholines by addition of water and alcohol to epoxy alkynes [109]. The procedure involved a domino three-membered ring opening, 6-exo-cycloisomerization, and subsequent intra-or intermolecular nucleophilic addition or a double-bond sequence. 

Double cyclization was observed with siloxy enynes when a new cycloisomerization mechanism was used that involved a cascade of 1,2- alkyl shifts [154]. 

The same products are accessible by silver-catalyzed cycloisomerization of allenic ketones. Marshall and Bartley327 used AgNOs/silica gel in hexane to convert the allenic ketones 384 into the furans 386 with excellent yields (Scheme 112). Deuterium labeling experiments were interpreted in terms of the intermediate 385 which seems to arise from the coordination of silver catalyst to the allenic double bond distal to the carbonyl group. Again, gold precatalysts can be used with much lower catalyst loadings than their silver counterparts (see Section 9.12.4.3). 

Potassium hydride catalyzes cyclization of cycloocta-dienes at 190° to form 84-94 of (37), while 1,4,7-cyclo-nonatriene undergoes in the presence" potassium tert-butoxide in dimethyl sulfoxide double cycloisomerization to 327"... 

Cycloisomerization. An oxime function is liable to add to a double bond at an appropriate distance and the reaction is teaUzed by heating unsaturated oximes with Al(OTf)3 in MeN02-... 

Cycloisomerizfdion. Molecules containing two aUene units that are separated by four bonds undergo Rh-catalyzed cycloisomerization. Unsaturated 7-membeied ring compounds with two exocyclic double bonds are produced. ... 

Cycloisomerization. Activation of a C—H bond by the Rh complex for intramolecular hydrometallation of a proximal double bond can lead to valuable cyclic products. Examples for such reactions include elaboration of dehydrobenzosuberones from o-formylbenzylide-necyclopropanes and of cyclopentane derivatives through addition of an azadiene." ... 

An example of palladium-catalyzed furan synthesis utilizing allenes as starting materials was reported, in which 2,4-disubstituted-2,3-butadienoic acids and 1,2-propadienyl ketones were used and 2,4-disubstituted furans were produced. The reaction may proceed via a matched double oxypalladation-reductive elimination process <04CEJ2078>. In a similar cycloisomerization of substituted allenes to tri- and tetrasubstituted furans with regioselectivity, the allenes were produced in situ from acyloxy-, phosphatyloxy- and sulfonyloxy-substituted alkynylketones via a 1,2-migration of such substituents catalyzed by CuCl or AgBF <04AG(E)2280>. 

Cycloisomerizations. 2-Substituted pyridines in which the side chain contains two double bonds undergo a catalyzed cyclization. Enediynes give aromatic products in an analogous process involving (i-PrjPljRhCl. ... 

The cycloisomerization of 1,6-enynes proceeds smoothly in the presence of AcOH or HCO2H and the reaction is explained by the following mechanism (hydridopalladium acetate mechanism) [45]. Most importantly, oxidative addition of AcOH to Pd(0) generates H-Pd-OAc 143, and the cyclization of 1,6-enynes starts by insertion of the triple bond to 143 to afford the alkenylpalladium 144. Subsequent intramolecular insertion of the double bond gives the alkylpalladium 145. The termination step is (i-R elimination and either the diene 136 or 138 is formed with regeneration of H-Pd-OAc. It should be noted that the alkenylpalladium 144 is a similar species formed in a Heck reaction by oxidative addition of alkenyl halide to Pd(0). Based on this reaction, alkyne is a useful starter in domino cyclization of polyenynes. 

In the presence of a proton source, 1,6-heptadiene (57) undergoes cycloisomerization to afford 1,2-disubstituted cyclopentenes. Insertion of one of the double bonds of 57 to H-Pd-X generates 58. Further insertion of the double bond in 58 gives 59, and y3-H elimination affords 60, 61, and 62 depending on the reaction conditions [23]. 

A double cyclization of an aldehyde enol to the methylene malonate, followed by a cycloisomerization onto the triple bond, leads to a bicyclo[5.3.0] decane of a tris-norguaiane (Scheme 10) [45]. 

A cetophenonef irradiation Double ring closure by cycloisomerization 763. CeHg... 

Six-membered dienes with an exocyclic double bond can also be obtained by gold-catalyzed cycloisomerization of 1,6-enynes. This transformation is stereospecific i.e., substrates with defined double-bond geometries afforded the products as single stereoisomers (Scheme 4-23). Low temperatures and electron-withdrawing... 

Whereas these transformations require stoichiometric gold compounds, catalytic amounts of both gold and palladium are sufficient for the cycloisomerization of allyl allenoates to allyl-substituted butenolides. Blum and co-workers reported this tandem C-O/C-C bond formation, which is initiated by activation of the distal allenic double bond with PhaPAuOTf (Scheme 4-107). This induces cyclization to an allyl oxonium intermediate, which undergoes deallylation in the presence of Pd2dba3. Nucleophilic attack of the resulting a-vinylgold intermediate at the ti-allylpalladium species and reductive elimination furnish the allylated butenolide and regenerate both catalysts. 

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