Mild and efficient boronic acid catalysis of Diels-Alder cycloadditions to 2-alkynoic acids

The concept of boronic acid catalysis (BAC) for the activation of unsaturated carboxylic acids is applied to the Diels-Alder cycloaddition between 2-alkynoic acids as dienophiles and various dienes. These [4+2] cycloadditions produce cyclohexadienyl carboxylic acids, which can be oxidized in situ to produce polysubstituted aromatic carboxylic acids. The boronic acid catalyst is suspected to provide activation by a LUMO-lowering effect of the unsaturated carboxylic acid likely via a covalent, monoacylated hemiboronic ester intermediate.     

Syntheses of polyfluoro-α-amino acids

Some fluorine-containing amino acids have been known to inactivate certain enzymes selectively and irreversibly. We have synthesized β-(polyfluoro ethyl)alanines and β-(trifluorovinyl)alanine from polyfluoroiodoethanes and acrylate.The synthetic schemes of β-(polyfluoroethyl)- alanines are shown below.

Using similar procedures, we have also prepared β-(polyfluoroethyl)-β-methylalanines, CF₂XCFX′CH(CH₃)- CH(NH₂)CO₂H from polyfluoroiodoethanes and ethyl crotonate.β-(Trifluorovinyl)alanine was synthesized in a good yield from the ester of β-(dichlorotrifluoro ethyl)alanine as follows:

The reactive trifluorovinyl group in the amino acid allows us to synthesize various kinds of fluorine- containing amino acids with a functional group through radical and ionic addition reactions. Some reactions of the ester of N-acetylated β-(trifluorovinyl)alanine with alkoxides (nucleophilic addition) and alcohols (radical addition) will be mentioned.

     

A novel regio-and stereo-specific hydrohalogenation reaction of 2-alkynoic acids and their derivatives

The nucleophilic hydrohalogenation of 2-alkynoic acids anti their derivatives byheating with lithium halides iu HOAc afforded the thermodynamically unfavorable 3-halo-2 (Z)-alkenoic acids and their derivatives stereospecifically     

2-Nitrofurans as dienophiles in Diels-Alder reactions

α-Nitrofuran derivatives are studied in Diels-Alder reactions under thermal conditions. In contrast to α-acylfurans, they proved to be efficient dienophiles.     

Dual inhibition of mycobacterial fatty acid biosynthesis and degradation by 2-alkynoic acids

2-Hexadecynoic acid and 2-octadecynoic acid have cidal activity against Mycobacterium smegmatis and Mycobacterium bovis BCG. At subinhibitory concentrations, M. smegmatis rapidly transformed [1-(14)C]-2-hexadecynoic acid into endogenous fatty acids and elongated them into mycolic acids. Toxic concentrations of 2-hexadecynoic acid resulted in accumulation of 3-ketohexadecanoic acid, which blocked fatty acid biosynthesis, and 3-hexadecynoic acid, an inhibitor of fatty acid degradation. The combination of these two metabolites is necessary to achieve the inhibition of M. smegmatis. We conclude that 2- and 3-hexa/octadecynoic acids inhibit mycolic acid biosynthesis, fatty acid biosynthesis, and fatty acid degradation, pathways of significant importance for mycobacteria.     

Diastereo- and regioselective Diels-Alder reactions of 2-phosphaindolizines

1,3-Bis(alkoxycarbonyl)-2-phosphaindolizines undergo Diels-Alder reactions at the CP- functionality with 2,3-dimethylbutadiene and with isoprene in the presence of sulfur with complete diastereoselectivity. The reaction with isoprene occurs with 100% regioselectivity as well. 3-Ethoxycarbonyl-1-methyl-2-phosphaindolizine, however, fails to undergo Diels-Alder reaction under these conditions. Difference in the dienophilic reactivities of mono- and bis(alkoxycarbonyl) substituted 2-phosphaindolizines and the observed regioselectivity in the Diels-Alder reaction has been rationalized on the basis of DFT calculations. The relative stabilities of the transition structures have been explained on the basis of the NBO analysis.     

Aza Diels-Alder reactions utilizing 4-iodo-2-trimethylsilyloxy-butadiene

The aza Diels-Alder reaction is described for a novel diene. Imines bearing benzyl and aromatic protecting groups both work well. Moderate diastereoselectivities can be obtained using the simple α-methylbenzyl chiral auxiliary.     

Synthesis of 2-ethoxyprop-2-enal dimethylhydrazone and its Diels-Alder reactions

Conditions were found for the preparation of 2-ethoxyprop-2-enal dimethylhydrazone by reaction of 2-ethoxypropenal with N,N-dimethylhydrazine. 2-Ethoxyprop-2-enal dimethylhydrazone reacted with methyl vinyl ketone and methyl acrylate according to the [4 + 2]-cycloaddition pattern with regioselective formation of substituted tetrahydropyridines. The major product in the reaction of 2-ethoxyprop-2-enal dimethylhydrazone with 1,4-benzoquinone was 5-hydroxy-1-benzofuran-2-carbaldehyde dimethylhydrazone formed as a result of [3 + 2]-cycloaddition; a small amount of the corresponding [4 + 2]-cycloaddition product was also obtained. Some spontaneous transformations of the primary cycloaddition products were revealed.     

对映选择催化 Diels-Alder 反应

本文综述了对映选择催化 Diels-Alder 反应的进展。     

Asymmetric synthesis of 2-aminonorbornane-2-carboxylic acids by Diels-Alder reaction

The reaction between methyl N-acetyl-,β-didehydroalaninate and cyclopentadiene in the presence of several chiral Lewis acids is studied and the results obtained are compared with those described for the reactions of the same diene with chiral N-acetyl-,β-didehydroalaninates. In the presence of the titanium complex 24d methyl (1R,2R,4R) 2-acetamido-5-norbornen-2-carboxylate is preferably obtained. Thus, the reaction between methyl N-acetyl-(,β-didehydroalaninate and cyclopentadiene is a good method for the synthesis of (1S, 2R, 4R) 2-aminonorbomane-2-carboxylic acid.     

Use of Lewis acids and high pressure to carry out extremely hindered Diels-Alder reactions

Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 3, pp. 743–744, March, 1989.     

Synthesis and Diels-Alder reactions of homochiral 2-sulfinylmaleates with cyclopentadiene

Enantiomerically pure 2-p-tolylsulfinylmaleates 1, 2 and 3 have been readily prepared by Knoevenagel reaction between (S)-menthyl p-toluenesulfinate and glyoxylic acid. Their asymmetric Diels-Alder reactions with cyclopentadiene have been studied under a wide range of uncatalyzed and catalyzed conditions and the stereochemical results have been explained by assuming a steric control approach, in term of S-cis or S-trans favoured conformations. Uncatalyzed Diels-Alder reactions of 1 and some Lewis acid catalyzed Diels-Alder reactions of 2 show high facial and endo selectivities. The facial selectivity of dienophile 2 highly depends on the Lewis acid, whereas reactivity of 1 and 3 is very sensitive to the solvent. These sulfinylmaleates 1, 2 and 3 act as synthetic equivalents of chiral acetylenedicarboxylates in Diels-Alder reactions after basic elimination of the sulfinylic moiety in the resulting adducts.     

Highly regioselective Diels-Alder reactions of 9-substituted anthracenes and 2-acetamidoacrylate: synthesis of conformationally constrained α-amino acids

The highly regioselective Diels-Alder reactions of 9-substituted anthracenes and 2-acetamidoacrylate afford a series of novel and conformationally constrained bicyclic bisaryl α-amino acids.     

Tandem Diels-Alder/ene reactions

[reaction: see text] The reactions of unsaturated aldehydes and triene 3 afford adducts via a tandem Diels-Alder/ene reaction.     

Enantioselective Diels-Alder reactions with N-hydroxy-N-phenylacrylamide

[reaction: see text] The use of hydroxamic acids as templates for Lewis acid catalyzed enantioselective Diels-Alder reactions has been examined. A very simple chiral Lewis acid, prepared by mixing optically pure binaphthol with 3 equiv of trimethylaluminum, catalyzes the [4 + 2] cycloaddition of N-hydroxy-N-phenylacrylamide with cyclopentadiene at 0 degrees C in high yield (>96%) and with a fairly good level of enantioselectivity (91% ee). Facile conversion of the products to the corresponding alcohols or aldehydes makes the hydroxamic acid intermediates particularly useful.     

Intramolecular Diels-Alder reactions of 4-vinylimidazoles

[reaction: see text] The synthesis of a variety of unsaturated ethers, esters, and amides derived from urocanic acid and their Diels-Alder reactions are reported. Propargylic ethers and esters cyclize with reasonable efficiencies, but the related mono- and unactivated olefins did not cyclize. On the other hand, the corresponding amines and amides, along with the doubly activated ester/amide derivatives participate in the cycloaddition reaction.