Methyl crotonate Diels-Alder reactions

Asymmetric Diels-Alder reactions. Unlike methyl crotonate, which is a weak dienophile, chiral (E)-crotonyl oxazolidinones when activated by a dialkylaluminum chloride (1 equiv.) are highly reactive and diastereoselective dienophiles. For this purpose, the unsaturated imides formed from oxazolidinones (Xp) derived from (S)-phenylalanol show consistently higher diastereoselectivity than those derived from (S)-valinol or (IS, 2R)-norephedrine. The effect of the phenyl group is attributed in part at least to an electronic interaction of the aromatic ring. The reactions of the unsaturated imide 1 shown in equation (I) are typical of reactions of unsaturated N-acyloxazolidinones with cyclic and acyclic dienes. All the Diels-Alder reactions show almost complete endo-selectivity and high diastereoselectivity. Oxazolidinones are useful chiral auxiliaries for intramolecular Diels-Alder... 

Scheme 15. Diels-Alder reactions of cyclopropylideneacetates 1-Me, 3-X with furan (57) and 6,6-dimethylfulvene (58) and relative reaction rates compared with methyl acrylate and methyl crotonate [19,46]...

However, the results should be taken as an exception, since in our understanding of enantioface differentiating transformations enantioselectivity is obtained by discrimination of one of the two enantiofaces of a molecule usually due to steric hindrance. Since under high pressure the sterically more crowded transition structure is preferred, a decrease in enantioselectivity should be observed under high pressure. This indeed was found for the intermolecular all-carbon Diels-Alder reaction of 2-methyl-1,3-butadiene to a crotonic acid derivative [552], A divergent result may be obtained if the differentiation is caused by electrostatic reasons. 

The Stereoselectivity of 1,3-Dipolar Cycloadditions. There is no endo mle for 1,3-dipolar cycloadditions like that for Diels-Alder reactions. Stereoselectivity, more often than not, is low, as shown by the reactions of C,/V-diphenylnitrone—both regioisomers 6.238 and 6.239 (R=C02Et) from the reaction with ethyl acrylate are mixtures of exo and endo isomers, only a little in favour of the exo product. Similarly, the reactions of methyl crotonate with nitrones favour the exo product 6.242 over the endo 6.243. In contrast, other reactions are endo selective, as in the cycloaddition 6.244 of an azomethine ylid to dimethyl maleate giving largely the endo adduct 6.245. 

Since the disclosures that the thermal dimerizations of acrolein and methyl vinyl ketone provide the 3,4-dihydro-2//-pyrans (1, 2) derived from 4ir and 2Tt participation of the a,3-unsaturated carbonyl compound in a Diels-Alder reaction, an extensive series of related observations have been detailed. This work has been the subject of several comprehensive reviews - - including the Desimoni and Tacco-ni extensive tabular compilation of work through 1974. Consequently, the prior reviews should be consulted for thorough treatments of the mechanism, scope, and applications of the [4 + 2] cycloaddition reactions of a,3-unsaturated carbonyl compounds. The [4 + 2] cycloaddition reactions of 1-oxa-1,3-butadienes with their 4-it participation in the Diels-Alder reaction exhibit predictable regioselectivity with the preferential or exclusive formation of 2-substituted 3,4-dihydro-2W-pyrans (equation 1). The exceptions to the predicted regioselectivity that have been observed involve the poorly matched [4 + 2] cycloaddition reaction of an electron-deficient l-oxa-l,3-butadiene with an electron-deficient dienophile, e.g. methyl crotonate or methacrolein. - Rigorous or simplified theoretical treatments of the [4 + 2] cycloaddition reaction of 1-oxa-1,3-butadienes predict the preferential formation of 2-substituted 3,4-dihy-dro-2f/-pyrans and accommodate the preferred endo approach of the reactants in which the carbon-carbon bond formation is more advanced than carbon-oxygen bond formation, i.e. a concerted but nonsynchronous [4 + 2] cycloaddition reaction. ... 

In the Diels-Alder reaction, the typical dienophile will display lower stereoselectivity with acyclic dienes than with cyclic dienes. This is the case for the reactions of both methyl ciotonate and the prope-nyl tungsten complex (52b) with Danishefsky s diene (Scheme 9). Carbene complex (52b) gives a 58 42 selectivity in favor of the exo adduct (66), while methyl crotonate gives a similar selectivity of 66 34 in favor of the exo adduct (63) (64 and 65 are both derived from elimination of methanol from the endo adduct). This example reveals that the Diels-Alder reactions of caibene complexes are viable with functionalized and highly electron rich dienes. Furthermore, although the reaction of the carbene complex (52b) with Danishefsky s diene is not stereoselective, it does occur with a much greater rate and efficiency than that for the organic ester for which it can serve as synthon. 

Hawkins et al. described a simple and efficient catalyst for the Diels-Alder reaction based on a chiral alkyldichloroborane (Eq. 15) [16]. A molecular complex between methyl crotonate and the chiral catalyst have been isolated for the first time. A study of the crystal structure of the complex enabled the authors to propose a model predicting the approach of the diene on one of the faces of the methyl crotonate, because the other face is protected by n-n donor-acceptor interactions. This secondary attractive substrate-catalyst interaction is the basis of the stereocontrol. 

Predictions based on rigorous or simplified theoretical calculations support the formation of the predominant 2-substituted 3,4-dihydro-2//-pyran regioisomer and accommodate a preferred endo approach of the reactants in which the carbon-carbon bond formation is more advanced than carbon-oxygen bond formation, i.e., a concerted but nonsynchronous [4 + 2] cycloaddition.5 15-20 Notable exceptions to the predicted regioselectivity of the Diels-Alder reactions of oxabutadienes have been observed, and without exception the examples have involved the poorly matched reaction of electron-deficient a,/3-unsaturated carbonyl compounds (An-component) with electron-deficient dienophiles (2tt component), e.g., methyl crotonate or methacrolein.5 2122... 

Hawkins et al. have reported a simple, efficient catalyst for the Diels-Alder reaction based on a chiral alkyldichloroborane (4, Equation 21) [21]. A molecular complex between methyl crotonate and the chiral catalyst has been isolated for the first time. 

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