Cycloaddition of acrylates

Hawkins and Loren225 reported simple chiral arylalkyldichloroborane catalysts 352 which were effectively used in the cycloadditions of acrylates lib and 350 to cyclopen-tadiene, affording adducts 351a and 351b, respectively (equation 99). A crystal structure of the molecular complex between methyl crotonate and the catalyst allowed the authors to rationalize the outcome of the reaction. One face of methyl crotonate is blocked by tt-tt donor-acceptor interactions, as becomes clear from the structure of complex 353. The cycloadduct of methyl acrylate and cyclopentadiene (5 equivalents) was obtained with 97% ee, using the same catalyst. Three years later, the authors reported that the cycloadduct was obtained with 99.5% ee in the presence of 10 equivalents of cyclopentadiene226. 

Recently, Koizumi et al. reported that the use of high pressures allows exclusion of Lewis acids (which are not compatible with many dienes and/or adducts) in the cycloadditions of acrylates [43]. Thus, methyl 3-alkylsulfinyl acrylate 29 is able to react with cyclopentadiene, furan, and 2-methoxyfuran at 12.6 Kbar (Scheme 14). Both 7r-facial and endo/exo selectivities are very high in reactions with cyclopentadiene (only one adduct was obtained), whereas with furan derivatives the endo/exo selectivity is clearly lower. In reactions with cyclopentadiene it could be established that high pressures do not have a significant influence on the diastereoselectivity. The transformation into (-)-COTC of the major adduct obtained from 2-methoxyfuran was carried out in order to confirm its absolute configuration. 

Cycloadditions of Acrylate Derivatives. Acrylate derivatives undergo highly stereoselective Diels-Alder cycloadditions with 1,3-dienes when promoted by a Lewis acid, Dichlorotitanium Diisopropoxide or Jitanium IV) Chloride (eq 2). With the latter, care must be taken to avoid... 

While metallocenes are ubiquitous in organometallic and polymer chemistry, few such complexes have been reported to catalyze the Diels-Alder process in high enantioselectivity [127,128,129]. Thebis(tetrahydroindenyl)zirconium tri-flate 60 and the corresponding titanocene are electrophilic to the extent that they catalyze the low-temperature cycloadditions of acrylate and crotonate imides with cyclopentadiene with good diastereoselectivity and excellent enantioselec-tion (Scheme 48). The reactivity of 60 is noteworthy since the corresponding reaction using the crotonyl imide with highly reactive catalysts 31a or 44 requires temperatures of -15 and 25 °C, respectively. 

The efficiency of haloboranes as Lewis add catalysts and the sensitivity of the boron atom environment to steric hindrance (see Chapter 6) make boron compounds useful chiral catalysts. Hawkins and Loren [779] prepared enantiopure chloroborane (17 ,2I )-3.6, and they showed that the complex 3.6 with methyl crotonate lies under the s-trans conformation 9.40 both in the solid state and in solution. This conformation is also the reactive one, and [4+2]-cycloadditions of acrylates with cyclopentadiene or cydohexadiene catalyzed by (17 ,2i )-3.6 lead highly selectively to the product resulting from the attack of the diene on the unshielded face of complex 9.40 (Figure 9.15). 

The cycloaddition of acrylate 28a to 2-quinodimethanes, generated thermally from cyclobutane 53 or the sulfone 54 gives a single product 51a, and in the same manner 50b (90%) is produced by the thermal reaction of the fumarate 38b with cyclobutane 5312. Thermal cycloaddition of 38b to z-hydroxy-T-phenyl-o-quinodimethane (56) (generated from sulfone 55) yields adduct 57 and its isomer of an unknown structure in a d.r. 95 5. The major adduct has been converted into a podophyllotoxin analog12. 

Arabinose derived secondary alcohols have been reported as new cheap auxiliaries accessible in both enantiomerically pure forms. [4+2] Cycloadditions of acrylates la and lb to acyclic and cyclic dienes proceed with moderate diastereoselectivity25. 

Table 6.5. Examples of asymmetric cycloadditions of acrylates with acyclic dienes. The Xc column refers to Figure 6.12.

The enantioselective intramolecular formal 2+4-cycloaddition of acrylates and a, -unsaturated imines (99) catalysed by chiral phosphines (100), derived from amino acids, produced A-heterocycles (101) (Scheme 31). Chiral dirhodium(II) carboxamidates (102) catalysed the hetero-Diels-Alder reactions between 2-aza-3-silyloxy-l,3-butadienes and aldehydes to yield all cw-substituted l,3-oxazinan-4-ones in high yields and high enantioselectivity (98% ee)P The nickel-catalysed 4 + 2-cycloaddition of a, -unsaturated oximes with alkynes yielded 2,3,4,6-tetrasubstituted pyridine derivatives. The reaction of isoquinoline, an activated alkyne, and 4-oxo-4//-l-benzopyran-3-carboxaldehyde (103), in ionic solvents, produced 9a//,15//-benzo[a][l]benzopyrano[2,3-/t]quinolizine derivatives (105) via the zwitterion (104) selectively and in good yields (Scheme 32).The Diels-Alder cycloaddition of ethyl 3-(tetrazol-5-yl)-l,2-diaza-l,3-butadiene-l-carboxylates with -rich heterocycles, nucleophilic olefins, and cumulenes formed 3-tetrazolyl-l,4,5,6-tetrahydropyridazines regioselectively. The silver-catalysed formal inverse-electron-demand Diels-Alder... 

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],... 

Two-step 1,4 cycloaddition of enamines, such as was observed with methyl vinyl ketone, is not possible with acrylate or maleate esters. This is due to the fact that, following the initial simple substitution, no side-chain carbanion is available for nueleophilic attack on the a carbon of the iminium ion. Likewise two-step 1,3 eycloaddition, such as that found when alicyclic enamines were treated with acrolein, is impossible with acrylate or maleate esters because transfer of the amine moiety from the original enamine to the side chain to form a new enamine just prior to the final cyclization step is not possible. That is, the reaction between a seeondary amine and an ester does not produce an enamine. 

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... 

Vinyl ethers undergo many cycloaddition reactions similar to those which take place with enamines. In general, however, these cycloaddition reactions with vinyl ethers take place less readily than those with enamines. These reactions include cycloaddition of vinyl ethers with ketene (200-205), phenyl isocyanate (206), sulfene (207,208), methyl acrylate (209), diethyl acetylenedicarboxylate (210), and diphenylnitrilimine (183). 

Evans s bis(oxazolinyl)pyridine (pybox) complex 17, which is effective for the Diels-Alder reaction of a-bromoacrolein and methacrolein (Section 2.1), is also a suitable catalyst for the Diels-Alder reaction of acrylate dienophiles [23] (Scheme 1.33). In the presence of 5 mol% of the Cu((l )-pybox)(SbF5)2 catalyst with a benzyl substituent, tert-butyl acrylate reacts with cyclopentadiene to give the adduct in good optical purity (92% ee). Methyl acrylate and phenyl acrylate underwent cycloadditions with lower selectivities. 

Other examples of acrylate additions have been reported298 and analogous [6 + 2] cycloadditions of the corresponding ethyl 17/-azepine-1-carboxylate-tricarbonylchrominium complex with alkynes have been achieved in good yields (63-68%).299... 

Danishefsky and coworkers using the same approach have synthesized substituted cyclohexadienones 563s65,666 (equation 361). A highly stereoselective (96%) cycloaddition of diastereoisomerically pure (Ss)-menthyl 3-(3-trifluoromethylpyrid-2-ylsulphinyl)acrylate 564 to 2-methoxyfuran 565 leads to the cycloadduct 566 which was elaborated by Koizumi and coworkers to glyoxalase I inhibitor 567667 (equation 362). 

Clay-catalyzed asymmetric Diels-Alder reactions were investigated by using chiral acrylates [10]. Zn(II)- and Ti(IV)-K-10 montmorillonite, calcined at 55 °C, did not efficiently catalyze the cycloadditions of cyclopentadiene (1) with acrylates that incorporate large-size chiral auxiliaries such as cA-3-neopentoxyisobornyl acrylate (2) and (-)-menthyl acrylate (3, R = H) (Figure 4.1). This result was probably due to diffusion problems. 

Pagni and coworkers [18] have conducted in-depth investigations on the cycloadditions of cyclopentadiene with methyl acrylate on alumina of varing activity (200 300 400 800 °) showing that the diastereoselectivity of the... 

Good yields and high diastereoselectivities were obtained by using zeolites in combination with Lewis-acid catalyst [21]. Table 4.7 illustrates some examples of Diels-Alder reactions of cyclopentadiene, cyclohexadiene and furan with methyl acrylate. Na-Y and Ce-Y zeolites gave excellent results for the cycloadditions of carbocyclic dienes, and combining these zeolites with anhydrous ZnBr2 further enhanced the endo diastereoselectivity of the reaction. An exception is the cycloaddition of furan that occurred considerably faster and with better yield, in comparison with the classic procedure [22], when performed in the presence of sole zeolites. 

The importance of the relationship between the macrocycle cavity and the binding of two reagents is shown by the cycloadditions of cyclopentadiene with diethyl fumarate and ethyl acrylate in aqueous solution. The presence of jS-CD strongly accelerates the first cycloaddition, while it slows down the reaction rate of the second, probably because the cavity favors the binding of two molecules of either diene or dienophile [65c]. 

The aqueous medium also has beneficial effects on the diastereoselectivity of the Diels-Alder reactions. The endo addition that occurs in the classical cycloadditions of cyclopentadiene with methyl vinyl ketone and methyl acrylate is more favored when the reaction is carried out in aqueous medium than when it is performed in organic solvents (Table 6.4) [2b, c]. 

Indium trichloride [30] and methylrhenium trioxide [31] catalyze the aqueous Diels-Alder reaction of acrolein and acrylates with cyclic and open-chain dienes. Some examples of the cycloaddition of methyl vinyl ketone with 1,3-cyclohexadiene are reported in Scheme 6.18. MeReOs does not give satisfactory yields for acroleins and methyl vinyl ketones with substituents at the jS-position and favors the self-Diels-Alder reaction of diene. 

The results of Diels-Alder reactions of cyclopentadiene with diethyl fumarate, diethyl maleate and ethyl acrylate carried out in SC-H2O are reported in Scheme 6.32 [79]. The cycloaddition of diethyl fumarate occurred with low yield. 

The diastereoselectivity of the cycloaddition of cyclopentadiene with methyl acrylate in SC-CO2 at 40 °C and subcritical liquid CO2 at 22 °C is practically the same endojexo = 75 25 and 76 24 respectively) and is comparable to that found in hydrocarbon solvents (73 27 and 75 25 in heptane and cyclohexane, respectively). This shows that CO2, in these states, behaves like an apolar solvent with very low polarizability [82]. 

Pyrrolidines have been prepared by 1,3-dipolar cycloaddition of N-(benzyli-dene)trimethylsilylamine/TMSOf 20 and methyl acrylate, N-methylmaleimide, or dimethyl maleate [35]. More recently, methyl trans-3-cyanociruiamate 1479 was reacted with N-benzyl-N-(trimethylsilylmethyl)aminomethyl methyl ether 1480 and trifluoroacetic acid in CH2CI2 at 0°C and 24°C to afford, via 1481, the pyrrolidine derivative 1482 in high yield and MeOSiMe3 13a [35a] (Scheme 9.20). Several... 

The Diels-Alder cycloaddition of furan and acrylic acid, in the presence of hydroquinone as a polymerization inhibitor, provided enrfo-7-oxabicy-clo[2.2.1]hept-5-ene-2-carboxylic acid - (29) in a yield of 45%. Compound 29 was found to be the most accessible and important starting-material for the synthesis of various racemic carba-sugars, as well as their enantiomers. 

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