Zinc Chloride cycloaddition reactions

Cycloaddition of 2-cyanoalk-2-enones with several conjugated dienes proceeded under zinc chloride catalysis.636 Zinc halides have also shown reactivity with phenylacetylenes.637 Zinc chloride is an effective Lewis acid catalyst in the Diels Alder reactions of the keto esters and the effects on stereochemistry of catalysts used have been examined.638... 

The cycloaddition of allenyl cations with 1,3-dienes results in a number of intermediate cations from which different products result. The allenyl cations 38 are generated first by the reaction of propargyl chlorides with zinc chloride and are then allowed to react with cyclopentadiene or other 1,3-dienes. The products of cycloaddition depend on the substituents on the allenyl cations32,35. The products formed with cyclopentadiene are given in equation 14. 

Hsung and co-workers described the first epoxidation of 1-amidoallenes leading to highly reactive intermediate 292 (Scheme 8.76) [159]. Formation of bicyclic products 291 occurs via iminium enolate 293, which was trapped by cyclopentadiene 290 (X = CH2) or furan 290 (X = 0). [4+3] Cycloaddition of the intermediate 293furnished 291 in good yield as a mixture of mdo-diastereoisomers (-75 25). The best dia-stereoselectivity was found when the reaction was performed in the presence of 2 equiv. of zinc chloride (>96 4). 

Lewis acids such as zinc chloride, boron trifluoride, aluminum chloride, and diethylaluminum chloride catalyze Diels-Alder reactions.8 The catalytic effect is the result of coordination of the Lewis acid with the dienophile. The complexed dienophile is more electrophilic and more reactive toward electron-rich dienes. The mechanism of the cycloaddition is still believed to be concerted, and high stereoselectivity is observed.9 10 Lewis acid catalysts also usually increase the regioselectivity of the reaction. 

Zinc chloride-doped natural phosphate was shown to have catalytic behavior in the 1,3-dipolar cycloadditions of nucleoside acetylenes with azides to form triazolonucleosides <99SC1057>. A soluble polymer-supported 1,3-dipolar cycloaddition of carbohydrate-derived 1,2,3-triazoles has been reported <99H(51)1807>. 2-Styrylchromones and sodium azide were employed in the synthesis of 4(5)-aryl-5(4)-(2-chromonyl)-1,2,3-triazoles <99H(51)481>. Lead(IV) acetate oxidation of mixed bis-aroyl hydrazones of biacetyl led to l-(a-aroyloxyarylideneamino)-3,5-dimethyl-l,2,3-triazoles <99H(51)599>. Reaction of 1-amino-3-methylbenzimidazolium chloride with lead(fV) acetate afforded l-methyl-l/f-benzotriazole <99BML961>. Hydrogenation reactions of some [l,2,3]triazolo[l,5-a]pyridines, [l,2,3]triazolo[l,5-a]quinolines, and [l,2,3]triazolo[l,5-a]isoquinolines were studied <99T12881>. 

Allenyl cations. In the presence of a zinc chloride-ether complex allenyl cations (a) can be generated from a propargyl halide such as (1). The cation can undergo either [3 + 2]- or [2 + 2]cycloaddition with an alkene. When the R group is aryl, [2 + 2]cycloaddition is the major pathway (2) when R is CHj or C,H3, [3 + 2]-cycloaddition becomes the major reaction (3) (equation 1).1... 

Lewis acid-catalyzed [2+2] cycloaddition reactions of Ar-pivaloylaldiruincs 181 gave azetidines 182 and 183 (Scheme 38) <1995CL789>. Boron trifluoride etherate proved to be a better catalyst than zinc chloride, affording azetidines 182 and 183 in better yields. This transformation has been explained through the intermediacy of a /3-silyl cation. 

Glycosyl imines are not very reactive dienophiles in [4 + 2] cycloaddition reactions. However, they can be subjected to cycloaddition reactions after activation with Lewis acids [51]. TV-Galactosyl imines 7 were shown to react with isoprene in the presence of zinc(II) chloride to give the corresponding 4-methyl piperidine derivatives 43 (Scheme 25). 

Cycloadditions. The reaction of-1 in CHjCl, with 1,3-dienes with zinc chloride as catalyst results in [3 + 4]cycloaddition to give cycloheptenones as major products. In some cases [3 + 2]cycloadducts are formed as minor products. Styrene derivatives react with 1 to form mainly cyclopentanones by [3 + 2]cycloaddition. 

P-Disubstituted a-chloroenamines are readily converted into the corresponding keteniminium salts (33) in the presence of a Lewis acid (equation 68). Silver tetrafluoroborate, zinc, tin and aluminum chlorides have been successfully used. 3-Disubstituted keteniminium salts have been isolated and characterized. " Unlike the corresponding ketenes, they do not dimerize or polymerize. However, they readily undergo [2 + 2] cycloaddition reactions with unsaturated substrates. ... 

Cycloalkenones generally perform poorly as dienophiles in Diels-Alder reactions but their reactivity can be enhanced by Lewis acids [105]. SnCU is effective in promoting the Diels-Alder reaction between simple 1,3-butadienes, for example isoprene and piperylene, and cyclopentenone esters (Eq. 67) [106], Cycloaddition does not, however, occur in the presence of SnCU when the diene contains an oxygen-bearing substituent such as an alkoxy or siloxy group. For such compounds, as is generally true for the Diels-Alder reactions of cycloalkenones, other Lewis acids such as zinc chloride are more effective. 

Under appropriate conditions, even unactivated alkenes will take part in intermolecular cycloadditions with 3- and 5-bromo-2-pyrones and with 3-methoxycarbonyl-2-pyrone. Reactions can be conducted at 100 °C, or at room temperature under 10-12 kbar and with zinc chloride catalysis. 

The efficiently chelated (zinc chloride, boron trifluoride diethyl ether complex), rigid five-mem-bered-ring dienophiles la and lb have been used in the enantioselective syntheses of several natural products. Thus, the reaction of (S)-l with 1,3-butadiene (5), promoted by zinc chloride (1 equiv) produces the cycloadduct ( + )-6 (83% d.r. 99 1), later converted to a precursor of (S)-sarkomycin (7). Cycloaddition of (S)-la with l,4-diacetoxy-l,3-butadicnc (8), catalyzed by boron trifluoride-diethyl ether complex (0.5 equiv) gives (-)-9 (72%) as a single diastercomer, further converted into (-)-shikimic acid (10) in a six-step procedure. Similarly, addition of (/ )-lb to 1,3-butadiene carbamate 11 in the presence of boron trifluoride-diethyl ether complex (1 equiv) produces ( + )-12 (95% d.r. 99 1), which was converted into ( + )-pumiliotoxin. 

Mechanistically, the cycloaddition reaction is rather complex. Depending on the catalyst or solvent used and the reaction substrates, pericyclic and/or Mukaiyama aldol-like pathways may be involved.43 The pericyclic mechanism, generally favored by zinc chloride and the lanthanide catalysts, tends to produce adducts having the cis relative stereochemistry at C-5,6. It is assumed that chelation of the aldehyde with the Lewis acid occurs in an anti fashion and that the steric bulk of R is less than that of the Lewis acid-solvent complex L [Eq. (11)], thus favoring a Diels-Alder transition state with R endo. 

The reaction proceeds under mild conditions and zinc chloride could be used to accelerate the rate of reaction. The observed regiospecificity of the [4 + 2] cycloaddition is not obvious, and the potential of an undetected reversible, kinetic [2 + 2] cycloaddition preceding the formation of the thermodynamically stable [4 + 2] cycloaddition products was not ruled out. 

Oxetanes hydroxy esters. Ketene acetals (1) react with aldehydes and ketones in the presence of zinc chloride to form 2,2-dialkoxyoxetanes (2). This reaction fails when R = R = H. The products are hydrolyzed under weakly acidic conditions to j3-hydroxy esters (3). The sequence can be carried out in one pot. Yields of 3 are 40-80% when R = H. Yields are lower in the case of ketones because the cycloaddition reaction is reversible and faster than hydrolysis with ketones. The method offers an alternative to the Reformatstky reaction, which often gives low yields with simple aldehydes. 

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