Cycloaddition of activated alkenes

A review of the mechanism of thermal 2 + 2-cycloadditions of activated alkenes to allenes and ketenes has been published. " Stereoselective intramolecular 2 + 2-cycloadditions of alkene-keteniminium salts (19) derived from L-glutamic salts yield... 

It appears likely that transient metallacyclobutanes are involved in a variety of organic reactions which are catalyzed by transition metal complexes. Thus, cycloadditions of activated alkenes to strained hydrocarbons such as quadricyclane and bicyclo[2.1.0]pentane are catalyzed by complexes such as Ni(CH2=CHCN)2 and probably involve initial formation of a nickelacyclobutane (Scheme 2) (79MI12200). The nature of the organometallic intermediates in related metal-catalyzed rearrangements (72JA7757) and retro-cyclo-addition reactions (76JA6057) of cyclopropanoid hydrocarbons, e.g. bicyclo[n.l.O]alkanes, has been discussed. 

Various unsaturated compounds, such as CO2, isocyanates and aldehydes, undergo Pd-catalysed cycloaddition with vinyl epoxides. Reaction of CO2 with 127 affords cyclic carbonates 128 with retention of the configuration at C(3), offering a method of cis hydroxylation of epoxides [66], and has been used for the synthesis of the side-chain unsaturated (—)-exo-brevicomin (129) [67], The tetrahydrofuran 131 was prepared by [3+2] cycloaddition of activated alkenes such as benzylidene malononitrile (130) with vinyl epoxide via Michael addition and allylation [68],... 

A general synthesis of heterofused 2tf-thiopyrans involves the cycloaddition of activated alkenes possessing a good leaving group with beteroaromatic thioketones. The products are themselves dienes with the potential for further elaboration (94S727). 

The complementary relationship between thermal and photochemical reactions can be illustrated by considering some of the same reaction types discussed in Chapter 11 and applying orbital symmetry considerations to the photochemical mode of reaction. The case of [2ti + 2ti] cycloaddition of two alkenes can serve as an example. This reaction was classified as a forbidden thermal reaction (Section 11.3) The correlation diagram for cycloaddition of two ethylene molecules (Fig. 13.2) shows that the ground-state molecules would lead to an excited state of cyclobutane and that the cycloaddition would therefore involve a prohibitive thermal activation energy. 

Recently, Burger devised an improved method of carrying out mild, regiospecific cyclizations that involve an intermediate that acts as a synthon for a nitrile ylide of HCN [47 (equation 48). With this methodology, cycloadditions with activated alkenes, alkynes, and azo compounds were earned out [47] (equation 49). All such reported reactions were regiospecific and had the same orientational preference... 

Attempts to liberate l-methyl-l-aza-2,3-cyclohexadiene (329) from 3-bromo-l-methyl-l,2,5,6-tetrahydropyridine (326) by KOtBu in the presence of [18]crown-6 and furan or styrene did not lead to products that could have been ascribed to the intermediacy of 329 (Scheme 6.70) [156], Even if there is no doubt as to the allene nature of 329 on the basis of the calculations on the isopyridine 179 and 3d2-lH-quinoline (257), it is conceivable that the zwitterion 329-Za is only a few kcal mol-1 less stable than 329. This relationship could foster the reactivity of 329 towards the tert-butoxide ion to an extent that cycloadditions to activated alkenes would be too slow to compete. On the other hand, the ultimate product of the trapping of 329 by KOtBu could have been an N,0-acetal or a vinylogous N,0-acetal, which might not have survived the workup (see, for example, the sensitivity of the N,0-acetal 262 [14], Scheme 6.57). 

By chance, the existence of the borane complex 330 of 329 was discovered. The liberation of 330 occurred with the best efficiency with sodium bis(trimethylsilyl)-amide from the borane complex 327 of 326. When styrene or furan was used as the solvent, three diastereomeric [2 + 2]-cycloadducts 328 and [4 + 2]-cycloadducts 331, respectively, were obtained in 30and 20% yield (Scheme 6.70) [156]. With no lone pair on the nitrogen atom, 330 cannot be polarized towards a zwitterionic structure, which is why its allene subunit, apart from the inductive effect of the nitrogen atom, resembles that of 1,2-cydohexadiene (6) and hence undergoes cycloaddition with activated alkenes. It is noted that the carbacephalosporin derivative 323 (Scheme 6.69) also does not have a lone pair on the nitrogen atom next to the allene system because of the amide resonance. 

Ester derivatives are also capable of forming carbonyl ylides and can undergo traditional cycloaddition with activated alkenes and alkynes and can even undergo reactions with heterodipolarophiles. Padwa was able to generate ester derived... 

The carbonyl ylides are trapped in a [2-1-3]-cycloaddition with activated alkenes or alkynes. For example, the reaction of the a-chloro ether 3.56 with cesium fluoride (CsF) in the presence of dimethyl fumarate gives only the trans cycloaddition product 3.57, while the reaction with dimethyl maleate gives exclusively the cis-isomer 3.58 (Scheme 3.24). 

The cycloaddition of an alkene across the C=N bond of an isocyanate is a useful method of synthesis of p-lactams (equation 50). 4,iS2 j, g reaction requires the activation of the alkene by electron-releasing... 

A second class of activated alkenes capable of undergoing intramolecular cycloadditions contains crotonate moieties from a topological point of view and thus exhibits enhanced stability with respect to polymerization. Additionally, the spacer between the methylenecyclopropane and the alkene only consists of s p -hybridized atoms in the case of substrates 8 and 11 so that the whole side chain should behave less rigidly than that of 3. In accordance with these predictions, moderate to high yields of the cycloaddition products, methyl c 5-3-melhylene-octahydropentalene-l-carboxylate (9) and methyl 3-methylenehexahydroindan-l-carboxylate (12), are obtained. From 8, however, a product 10 of a formal alkylation reaction is additionally formed. ... 

Tetrahydro-6-iodomethyl-2-one (224) is formed from 3-butenamine by coupling it with carbon dioxide in the presence of iodine and caesium carbonate (Equation (20)) <87AG(E)334> and in related chemistry 2-chloromethyloxirane (225) reacts with primary amines in the presence of carbon dioxide to give 5-hydroxytetrahydro-l,3-oxazin-2-ones (226) (Equation (21)) <86NKK1196>. Cycloadditions with activated alkenes can also be used. Thus, 6-alkoxytetrahydro-l,3-oxazin-... 

From Thione S-Imides (Type D). Further details of the cycloadditions between activated alkenes and thione S-imides (see Vol. 1, p. 112, ref 16) have been reported. ... 

The Lewis-acid promoted [4 + 2] cycloadditions are the most extensively smdied. However, nitroalkenes can react as heterodienes without Lewis acid activation under high pressure as well [100]. For example, the cycloaddition of nitro-alkene 44 (Scheme 16.18) with ethyl vinyl ether is accelerated in a pressure-dependent manner but does not stop after the [4 + 2] step [101]. The intermediate nitronate 67a undergoes a further [3 + 2] cycloaddition to form nitroso acetal 68a as the major product (67a/68a l/6). Complete conversion is observed at pressures above 8 kbar after only 1 h. For comparison, the same reaction requires a large excess (90 equiv) of the dienophile to reach completion at ambient pressure in ethanol after 5 days. Nitronate 67a is formed with... 

The two major methods of preparation are the cycloaddition of nitrile oxides to alkenes and the reaction of a,/3-unsaturated ketones with hydroxylamines. Additional methods include reaction of /3-haloketones and hydroxylamine, the reaction of ylides with nitrile oxides by activation of alkyl nitro compounds from isoxazoline AT-oxides (methoxides, etc.) and miscellaneous syntheses (62HC(i7)i). 

The regio- and stereoselectivities of cycloadditions of trifluoroacetonitrile oxide, which is generated m situ by treatment of the tnfluoroacetohydroxamyl bromide etherate with tnethylamine in toluene (equation 31), have been determined in a senes of studies by Tanaka [55, 36, 37, 5 ]. The highly reactive nitnle oxide reacts regioselectively with a variety of activated terminal alkenes and alkynes (equations 32 and 33)... 

A simple approach for the formation of 2-substituted 3,4-dihydro-2H-pyrans, which are useful precursors for natural products such as optically active carbohydrates, is the catalytic enantioselective cycloaddition reaction of a,/ -unsaturated carbonyl compounds with electron-rich alkenes. This is an inverse electron-demand cycloaddition reaction which is controlled by a dominant interaction between the LUMO of the 1-oxa-1,3-butadiene and the HOMO of the alkene (Scheme 4.2, right). This is usually a concerted non-synchronous reaction with retention of the configuration of the die-nophile and results in normally high regioselectivity, which in the presence of Lewis acids is improved and, furthermore, also increases the reaction rate. 

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