Cycloaddition acrylate esters

Enamines have been observed to act both as dienophiles (46-48) and dienes (47,49) (dienamines in this case) in one-step, Diels-Alder type of 1,4 cycloadditions with acrylate esters and their vinylogs. This is illustrated by the reaction between l-(N-pyrrolidino)cyclohexene (34) and methyl t/-a i-2,4-pentadienoate (35), where the enamine acts as the dienophile to give the adduct 36 (47). In a competitive type of reaction, however, the... 

However, most asymmetric 1,3-dipolar cycloaddition reactions of nitrile oxides with alkenes are carried out without Lewis acids as catalysts using either chiral alkenes or chiral auxiliary compounds (with achiral alkenes). Diverse chiral alkenes are in use, such as camphor-derived chiral N-acryloylhydrazide (195), C2-symmetric l,3-diacryloyl-2,2-dimethyl-4,5-diphenylimidazolidine, chiral 3-acryloyl-2,2-dimethyl-4-phenyloxazolidine (196, 197), sugar-based ethenyl ethers (198), acrylic esters (199, 200), C-bonded vinyl-substituted sugar (201), chirally modified vinylboronic ester derived from D-( + )-mannitol (202), (l/ )-menthyl vinyl ether (203), chiral derivatives of vinylacetic acid (204), ( )-l-ethoxy-3-fluoroalkyl-3-hydroxy-4-(4-methylphenylsulfinyl)but-1 -enes (205), enantiopure Y-oxygenated-a,P-unsaturated phenyl sulfones (206), chiral (a-oxyallyl)silanes (207), and (S )-but-3-ene-1,2-diol derivatives (208). As a chiral auxiliary, diisopropyl (i ,i )-tartrate (209, 210) has been very popular. 

As exemplified in Eq. 8.38, thermal [2 + 2] cycloadditions of 4-vinylidene-2-oxazoli-dinone 287 and alkynes such as phenylacetylene result in the formation of 3-phenyl-substituted methylenecyclobutene 288 [149]. The authors confirmed by NMR analysis that only the Z-configuration isomer was formed. It is worth noting that the [2 + 2] cycloaddition of allenes 287 is not restricted to alkynes even olefins such as acrylic esters or silyl enol ethers furnish the corresponding methylenecyclobutanes... 

Cyclic amino acids 139, when heated in acetic anhydride, probably form initially mesoionic oxazolium 5-oxides (munchnones) subsequent 1,3-dip olar cycloaddition of 1,2-dicyanocyclobutene, loss of carbon dioxide, and opening of the cyclobutane ring lead to dinitriles 140 (80JHC1593). Pyridone 141 is the by-product (together with an indolizine) of the mono-cyclic pyridone dicarboxylate and acrylic ester (73JHC77). 

Another (4+2)-cycloaddition, not accompanied with fragmentation, was observed by Martin et al.I60> when 1-formyl hexahelicene (87) was treated with the ylid of (Et0)2P0CH2C02Et in boiling benzene for 12 h. Two racemic stereoisomers (88 a) and (88 b) were formed in 80 and 12%, respectively. At room temperature only one isomer (88a) was obtained in 90%. The obvious intermediate P-(l-hexahelicycl)acrylic ester, could not be isolated (Scheme 23). 

Cycloaddition of a-nitroso acrylic esters (749) to alkenes followed by base hydrolysis provides a route to 5,6-dihydro-4//-l,2-oxazine-3-carboxylic acids (750). These heterocycles on heating above 150 °C decarboxylate to furnish y-hydroxynitriles (thus the overall c/s-addition of OH and CH2CN to a double bond), which can be transformed further to y-lactones (751) by treatment with methanolic hydrochloric acid (Scheme 172) (79CC1090). The adducts were also reduced to a-amino esters (752) by the action of aluminum amalgam (Scheme 173) (79CC1089). 

Pyrazolo[l,2- ]pyrazole systems 166 can be obtained by the reaction of hydrazine with acrylic esters (Scheme 99) <2001J(P2)243, CHEC-III(12.10.12.1)406>. The betaines 167 reacts with dimethyl acetylenedicarboxylate to give products 168 which easily undergo thermal fragmentation to 169 followed by another cycloaddition to form 170 (Scheme 100) <1981JA7743>. Criss-cross addition of azines, e.g. 171, also involves two successive 1,3-dipolar cycloadditions to give pyrazolo[l,2-. 

Three successive [2+4] cycloadditions were used in the synthesis of the pentacyclic methyl ether of G-2N by Kraus and Zhao [92] and later, by a slightly modified procedure, also of the natural product G-2N (118) [93] (Scheme 31). Thermal reaction of the cyclobutanol 112 with acrylic ester gave the dihydronaphthalene 113 which was demethylated by treatment with boron tribromide and converted into the exocyclic ketene acetal 114. This unstable diene was reacted in a second cycloaddition with 2,6-dichlorobenzoquinone (115) to afford the tetracyclic chloroquinone 116. In a last Diels-Alder reaction, ring E was anella-ted by treatment of 116 with l-methoxy-l,3-bis[(trimethylsilyl)oxy]-l,3-buta-diene (117) to yield the pentacyclic natural product G-2N (118) [93]. 

Section 1.1.2.12 (i) Acrylate esters. Narasaka and coworkers found that N-acryloyloxazolidinone undergoes a [2 + 2] cycloaddition with l,l-bis(methylthio)ethylene in the presence of TiCl2(OPr )2 and (213) to give 74% of the cyclobutane in 88% enantiomeric excess. ... 

The simple homochiral adduct from Diels-Alder cycloaddition of (/ )-pantolactone acrylate ester with cyclopentaidiene was hydrolyzed and converted to the methyl ketone in 89% yield through addition of 3... 

A considerable number of experiments with 1,3-cycloaddition were reported by Tartakovskii, Novikov and co-workers (181-1851- They reacted nitronic acid esters (esters of aciform of primary or secondary nitro alkanes) with dipole-philes such as styrene, vinyl chloride, acrylic esters and methyUvinyl ketone (36c). The reaction occurs at room temperature (or lower) with an excess of un-satured compound, the yield is 60-90%. 

Simpler, open-chain, chiral alkenes have also been employed in [3 + 2]-cycloaddition reactions in order to obtain face selectivity of the addition. The introduction of chiral alcohols such as ( —)-(l/ ,27 ,5S)-menthol into acrylic esters provides a simple entry into this field however, the conformational variability of such molecules allows for only relatively low stereoselectivities.The same is true for the (— )-(l /J,2i ,4i )-bornyl and (— )-(l 7 ,27 ,55)-8-phenylmenthyl derivatives. ... 

A tandem Claisen/Diels-Alder sequence was recently used to construct the tricyclic structure found in a series of Garcinia natural products, represented by more-llin. On heating at 140 °C, acrylate ester 113 underwent an initial [3,3]-sigmatropic rearrangement to provide intermediate 114 (Scheme 20) (020L909). A subsequent intramolecular Diels-Alder cycloaddition then produced 115 in 92% yield. 

The diastereoselectivity of transition metal catalyzed [2 + 2] cycloadditions has been investigated for several cases21,24. Thus, acrylonitrile or acrylic esters, upon irradiation in the presence of a nickel(O) complex, exclusively give the fra s-disubsti luted cyclobutanes 5, tram- 1,2-di-cyanocyclobutane (R = CN) or dialkyl tra s-l,2-cyclobutanedicarboxylate (R = COOalkyl), respectively24. 

The first applications of nickel-catalyzed [3 + 2] cycloaddition to asymmetric diastereose-lective synthesis of metbylenecyclopentanes employed acrylic ester substrates chirally modified with menthol-4 or camphor-derived41,42 auxiliaries. The adducts were obtained in good yield with diastereomeric ratios up to 99 141-42. After hydrolysis, optically active 3-methylene-l-cy-clopentanecarboxylic acids 4 were obtained. 

Diazo-5,5-dimethylcyclohexan-l,3-dione (140) with an excess of acrylate esters serving as both reactant and solvent in the presence of rhodium acetate afforded benzofuran 141 (98SC865). The formation of the dihydrofurans probably proceeded via a 1,3-dipolar cycloaddition of a metal carbenoid to the x,/)-unsa titrated ester (98SC865). Similarly, the reaction can take place with dihydrofuran, furan, and 1-acetyl indole to give 109,142, and 143, respectively (91JOC6269) (Scheme 24). 

Scheme 6.43. Acrylate ester cycloadditions using chelating auxiliaries (a) [6] ...

According to Scott isovincoside 41 is converted to stemmadenine 42 via several steps. Heterolytic ring opening and concomitant dehydration leads to the postulated intermediate dehydrosecodine 43. Starting from the acrylic ester 43 two [4-i-2]-cycloadditions are possible. If the 2-dehydropyridine system... 

The mesoionic 3-oxido-A-alkylpyridinium betaine 13 undergoes 1,3-dipolar cycloadditions as the dipoles a and b. Thus, acetylenedicarboxylate addition via O and C-2 is followed by electrocyclic cleavage of the pyridine N/C-2 bond in the intermediate 16, resulting in the formation of fiiran derivatives 17, In contrast, phenylacetylene and acrylic ester add to the betaine 13 via C-2 and C-6 producing 8-azabicyclo[3.2.1]octane derivatives 14 and 15 [85] ... 

Cycloaddition of diazomethane to the carbocyclic acrylic ester 323 gave the pyrazoline 324, which was elaborated to 325 (76CJC861) (Scheme 72). 

The case of azides is the one where the difference of orientation according to the polar character of Y is best defined These 1,3-dipoles behave as if they had a stable polarisation in the sense Ar-N-N=l, the nitrogen atom on the left receiving electrophilic attack by acrylic esters and acrylonitrile, the terminal atom nucleophilic attack by enamines and vinyl ethers. While it has been argued that the main factor controlling orientation in 1,3-cycloadditions to olehns and acetylenes is a steric one", phenyl azide can add in the usual orientation even to a bulky enamine viz-... 

Disubstituted acetylenes and 1,2-disubstituted olefins are comparatively bad dipolarophiles. If the introduction of the second substituent was expected to have a strong accelerating effect, this is lacking (fumaric ester is sometimes less reactive than acrylic ester) or is small, c.f. acetylene dicarboxylate with propiolates. When the second substituent is a phenyl group, it deactivates phenylpropiolate is less reactive than propiolate in reaction types (i) (ii) and (iv). Table 13. The introduction of methyl groups into the a or )3 position of acrylic ester, has a similar effect on the rate of several different 1,3-cycloadditions". Steric hindrance appears to intervene in these cases. 

The preceding study has demonstrated [2.2.1]bicycloheptenyl functionalized resins can be useful and interesting ene components in photoinitiated thiolene polymerizations. The addition of thiols to the unsaturation of this bicyclic system appears to be rapid and exothermic. The relative rates of this addition compared with allylic derivatives and vinyl ethers are quite favorable. The organic resins can be readily prepared from either polyols, f>olyamines, or acrylic precursors (Figure 10) and the yields are generally quite good. When acrylate esters are used as precursors, the cycloaddition reaction occurs spontaneously and no catalysis of the reaction is necessary. 

Supported liquid acrylic esters have been prepared from hydroxylated imidazolium-based TSILs and used neat in (4-1-2) Diels-Alder cydoadditions. First, Handy et al. [31] used a fructose-derived ionic liquid to support acryUc acid and performed the Diels-Alder cycloaddition with several dienes induding cydopenta-and cydohexadienes and butadiene derivatives at 120 °C for 12 h in the presence of hydroquinone (Scheme 5.5-25). 

This group " also diverted the usual Diels-Alder cycloaddition pathway of Reissert salts with olefinic esters to a 1,3-dipolar cycloaddition pathway by the addition of triethylamine. Thus treatment of munchnone imine 364 with ethyl acrylate and triethylamine affords the 1,3-dipolar cycloaddition product 366 (30%) as the major product, formed by fragmentation of cycloadduct 365 (Fig. 4.121). The Diels-Alder product (not shown) is formed in 15% yield. Similar products to 366 are formed with dimethyl and diethyl maleate and fumarate. Laude and coworkers " also were able to trap munchnone imine 367 with dipolarophiles to furnish 368 (Fig. 4.122). No Diels-Alder cycloadducts derived from the oxazolium salt were detected. In contrast, fumarate and acrylate esters give only Diels-Alder cycloadducts from the tautomeric oxazolium salt (not shown). However, benzo-quinones and 1,4-naphthoquinone react in a 1,3-dipolar fashion with munchnone imine 372 derived from Reissert compound 369 to give 373 (Scheme 4.11). " Diels-Alder cycloadducts derived from oxazolium salt 371 were not observed. In a... 

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