Cyclizations 1,5-enynes

A variety of metal catalysts, based on metals such as Mo, W, Ru, Rh, Pd, and Pt, are available to cyclize enyne ketones (Equation 21). Initially, furan intermediates with a metal carbenoid substituent in the 2-position are formed which can be subjected to subsequent reactions furnishing furans with vinyl ether- <1998JOC4564>,... 

Significant differences have also been observed for the cyclization of 1,6-enynes substituted in the 3,4, or 5 position, Eq. (16). A variety of different 4-sub-stituted enynes (Table 3, entries 1,2,3, and 6) have been converted to cyclopen-tenones with high levels of enantioselectivity. However, attempts to cyclize enynes substituted at the 3- (Fig. 7, 29 and 30) or 5- (Fig. 7, 31) position have failed. As with the bulky R groups, these failures likely arose from unfavorable steric interactions between these proximal substituents and the EBTHI ligand. 

Electrophilic Au(I) complexes or their halide AuX analogoues typically cyclize enynes (I, Scheme 58) (475) by a 5-exo-dig pathway to give a variety of cycloisomerization and addition derivatives. The mechanism is proposed to involve formation of a cyclopropyl gold-carbene intermediate... 

Propargyl alcohols add to allylic indium sesquihalides, but the mechanism of the process is not known. Molybdenum complexes have been used to cyclize enynes and dienynes . ... 

Earlier in this chapter different ways of cyclizing enyne-allenes were considered (Scheme 3.4). Depending on the sites of the newly formed carbon-carbon bond, they are classified as C -C (Schmittel) and C -C (Myers-Saito) cyclizations. Schmittel and coworkers [18] performed modern computational analysis of the cyclization mechanism and estimated various effects on the regioselectivity. 

Under the similar reaction conditions the catalyst 113 is able to cyclize enynes in the presence of CO into the corresponding cyclopentenone deriva-... 

In the alkylative cyclization of the 1,6-enyne 372 with vinyl bromide, formation of both the five-membered ring 373 by exn mode carbopalladation and isomerization of the double bonds and the six-membered ring 374 by endo mode carbopalladation are observed[269]. Their ratio depends on the catalytic species. Also, the cyclization of the 1,6-enyne 375 with /i-bromostyrene (376) affords the endo product 377. The exo mode cyclization is commonly observed in many cases, and there are two possible mechanistic explanations for that observed in these examples. One is direct endo mode carbopalladation. The other is the exo mode carbopalladation to give 378 followed by cyclopropana-tion to form 379, and the subsequent cyclopropylcarbinyl-homoallyl rearrangement affords the six-membered ring 380. Careful determination of the E or Z structure of the double bond in the cyclized product 380 is crucial for the mechanistic discussion. 

The benzene derivative 401 by the intermolecular insertion of acrylate[278], A formal [2 + 2+2] cycloaddition takes place by the reaction of 2-iodonitroben-zene with the 1,6-enyne 402. The neopentylpalladium intermediate 403 undergoes 6-endo-lrig cyclization on to the aromatic ring to give 404[279],... 

The cyclic 2,4-dienoate 184, formed by the Pd-catalyzed cyclization of the 1,6-enyne 183, reacted with 154 to form the azulene derivative 185[118], The 3-methylenepyrrolidine 188 is formed by the reaction of the Zn reagent 186 with the chiral imine 187 with high diastereomeric excess. The structure of the allylic ethers is important for obtaining high diastereoselectivity[l 19],... 

Depending on the substituents of l,6-enynes, their cyclization leads to 1.2-dialkylidene derivatives (or a 1.3-diene system). For example, cyclization of the 1,6-enyne 50 affords the 1.3-diene system 51[33-35]. Furthermore, the 1.6-enyne 53, which has a terminal alkene, undergoes cyclization with a shift of vinylic hydrogen to generate the 1,3-diene system 54. The carbapenem skeleton 56 has been synthesized based on the cyclization of the functionalized 1,6-enyne 55[36], Similarly, the cyclization of the 1,7-enyne 57 gives a si -mem-bered ring 58 with the 1,3-diene system. 

The cyclization of l-alkoxybut-l-en-3-ynes with hydrazine was first achieved by Franke and Kraft (55AG395). By heating 1-methoxybut- l-en-3-yne with hydrazine sulfate in an aqueous alcohol medium they obtained 3(5)-methylpyrazole (13) in high yield. Winter (63HCA1754) used the cyclization of 1-methoxybut-l-en-3-yne with hydrazine hydrate and phenylhydrazine to establish the structure of the initial enyne ether [in this case a mixture of l-phenyl-3(5)-propylpyrazoles was obtained]. The reaction with hydrazine sulfate gives only one product, 3(5)-propyl-pyr azole. 

Nucleophilic attack of the C-3 atom of the 1,3-enyne by the primary amino group (intermediate 153) and cyclization of its tautomer (154) via the Michael-like attack at C-1 with the r XH elimination (formation of 2,6-isomer 148). 

The cyclization of the 1,3-enyne amines with cyanacetamide in the presence of bases (55°C, H2O, 2 h) leads to 3-cyano-6-methyl-2-pyridones (155), yield 77% (69ZOR1179). 

The cyclization pathway proposed (81UK1252) involves nucleophilic substitution of the hetero group (XR) by the formamide amino group to form either enyne formamide 157 or imine 158. 

The reactive structural element for the Myers cyclization is an enyne allene, the heptatrienyne 6, which reacts to form a diradical species 7 ... 

Hexacarbonyldicobalt complexes of alkynes have served as substrates in a variety of olefin metathesis reactions. There are several reasons for complex-ing an alkyne functionality prior to the metathesis step [ 125] (a) the alkyne may chelate the ruthenium center, leading to inhibition of the catalytically active species [125d] (b) the alkyne may participate in the metathesis reaction, giving undesired enyne metathesis products [125f] (c) the linear structure of the alkyne may prevent cyclization reactions due to steric reasons [125a-d] and (d) the hexacarbonylcobalt moiety can be used for further transformations [125c,f]. 

RCM of 132 to the medium-sized enyne 135, for example, appears to be highly unlikely. This transformation was achieved by conversion of 132 to the cobalt complex 133, which is cyclized to the protected cycloenyne 134. Deprotection yields 135, and a subsequent Pauson-Khand reaction yields the interesting tricyclic structure 136 (Scheme 27) [125c]. 

In 2009, Chirik reported a hydrogen-mediated reductive enyne cyclization catalyzed by the bis(imino)pyridine iron complex 5 (Scheme 37) [119]. In the... 

The catalytic cycle, which is supported by stoichiometric and labeling experiments, is shown in Scheme 38. Loss of 2 equiv. of N2 from 5 affords the active species a. Reaction of a with the 1,6-enyne gives the metallacycle complex b. Subsequently, b reacts with H2 to give the alkenyl hydride complex c or the alkyl hydride complex d. Finally, reductive elimination constructs the C-H bond in the cyclization product and regenerates intermediate a to complete the catalytic cycle. 

Scheme 38 Catalytic cycle for the hydrogen-mediated enyne cyclization...

Scheme 12 Mechanism of the titanium alkoxide catalyzed cyclization of enynes...

Similar reactivity is observed in the cyclization of enynes in the presence of the yttrium-based catalyst 70 and a silane reductant [53,54]. The 1,6- and 1,7-enynes 90 and 91 provide -E-alkylidene-cyclopentancs 92 and -cyclohexanes 93 in very good yield (Eq. 15, Scheme 20) [55]. These transformations likely proceed by syn hydrometallation of the 7r-basic alkyne, followed by insertion of the alkene and a-bond metathesis. The reaction of 1,6-enynes tolerated... 

Palladium complexes are effective catalysts for the reductive cydization of enyne substrates [53,54], The first report of catalytic cydization of 1,6- and 1,7-enynes 115a,b to cyclopentane 116a and cyclohexane 116b derivatives appeared in 1987 (Eq. 19) [70]. The authors proposed that the Pd(II) species 117 forms by oxidative addition of acetic acid to Pd(0) (Scheme 25). Complex 117 hydrometallates the alkyne to give 118, which cyclizes to provide... 

Cationic palladium complex 121 reductively coupled enynes (Eq. 20) using trichlorosilane as the stoichiometric reductant [71]. This combination of catalyst and silane afforded silylated methylenecyclopentanes such as 122 in good yield from enynes such as 123. Attempts to develop an enantioselective version of this reaction were not successful [71]. When enediyne 124 was cyclized in the presence of trichlorosilane, the reaction favored enyne cycli-zation 126 by a 3 1 ratio over diyne cyclization to 125 (Eq. 21). In contrast, when the more electron-rich dichloromethylsilane was used as the reductant, diyne cyclization product 125 was preferred in a ratio of 4 1 [71]. Selectivities of up to 10 1 for enyne cyclization were observed, depending on the substrate employed [72],... 

Scheme 26 Dependence of Pd(II)-catalyzed enyne cyclization upon solvent and added silane...

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