Diels-Alder reaction between substituted

In Chapter 2 the Diels-Alder reaction between substituted 3-phenyl-l-(2-pyridyl)-2-propene-l-ones (3.8a-g) and cyclopentadiene (3.9) was described. It was demonstrated that Lewis-acid catalysis of this reaction can lead to impressive accelerations, particularly in aqueous media. In this chapter the effects of ligands attached to the catalyst are described. Ligand effects on the kinetics of the Diels-Alder reaction can be separated into influences on the equilibrium constant for binding of the dienoplule to the catalyst (K ) as well as influences on the rate constant for reaction of the complex with cyclopentadiene (kc-ad (Scheme 3.5). Also the influence of ligands on the endo-exo selectivity are examined. Finally, and perhaps most interestingly, studies aimed at enantioselective catalysis are presented, resulting in the first example of enantioselective Lewis-acid catalysis of an organic transformation in water. 

SCHEME 2 Diels-Alder reaction between substituted furan 7 and TBCP. 

Recently, chiral bis-phosphoric acid 77 bearing a new chiral scaffold with triple axial chirality assisted by intramolecular hydrogen-bonding between two phosphoric acid moieties was designed as a new chiral Bronsted acid catalyst by the Terada group [33], Application of this catalyst in the Diels-Alder reaction between substituted acroleins 66 and amido-dienes 76 produced the corresponding cycloadducts 78 with excellent enantioselectivities (Scheme 38.22). In comparison with the mono-phosphoric acid, bis-phosphoric acid 77 showed obviously higher catalytic activity and selectivity. 

Finally, in Chapter 5, micellar catalysis of Diels-Alder reactions is discussed. In view of the nonpolar nature of most Diels-Alder reactants, efficient micellar catalysis of this reaction was anticipated However, this has not been observed. The results for the Diels-Alder reaction between cyclopentadiene and substituted 3-phenyl-l-(2-pyridyl)-2-propene-l-one dienophiles, discussed in... 

Experimentally, the rates of Diels-Alder reactions between electron-rich dienes and electron-poor dienophiles generally increase with increased alkyl substitution on the diene. This is because alkyl groups act as electron donors and lead to buildup of electron density on the diene. An exception to this is the reaction of Z,Z-hexa-2,4-diene with tetracyanoethylene (TCNE), which is actually slower than the corresponding addition involving E-penta-1,3-diene. 

Melles and Backer " found, from a study of the oxidation of substituted thiophenes with perbenzoic or peracetic acid, that sulfones could be obtained from polysubstituted methyl- and phenyl-thiophenes and that the presence of electron-attracting groups, such as nitro, hindered the oxidation. Oxidation of thiophene - led to a product which was formed through a Diels-Alder reaction between the intermediate thiophene sulfoxide (211) and thiophene sulfone (212) and for which two alternative structures, (213) or (214), were suggested. Similar sesquioxides were also obtained from 2- and 3-methylthiophene and 3-phenylthiophene. The structures were not proved. Bailey and Cummins synthesized thiophene-1,1-dioxide... 

A key transformation in Corey s prostaglandin synthesis is a Diels-Alder reaction between a 5-(alkoxymethyl)-l,3-cyclopenta-diene and a ketene equivalent such as 2-chloroacrylonitrile (16). As we have already witnessed in Scheme 3, it is possible to bring about a smooth [4+2] cycloaddition reaction between 5-substituted cyclopentadiene 15 and 2-chloroacrylonitrile (16) to give racemic 14 as a mixture of epimeric chloronitriles. Under these conditions, the diastereomeric chloronitriles are both produced in racemic form because one enantiotopic face of dienophile 16 will participate in a Diels-Alder reaction with the same facility as the other enantiotopic face. In subsequent work, Corey s group demonstrated that racemic hydroxy acid 11, derived in three steps from racemic 14 (see Scheme 3), could be resolved in a classical fashion with (+)-ephe-... 

Substituted 3,4-dihydropyranes were also prepared by Diels-Alder reactions between (E)-4-oxobutenoate 80 and vinylethers [80] under iron(III) 2-ethylhex-aonate, a mild and economical catalyst (Equation 3.26). Diastereomeric excess as high as 98 % was observed. Cycloadducts with a 2,4-cw-configuration were preferred. 

In the same area, a (5)-tryptophan-derived oxazaborolidine including a p-tolylsulfonylamide function has been used by Corey et al. to catalyse the enantioselective Diels-Alder reaction between 2-bromoacrolein and cyclo-pentadiene to form the corresponding chiral product with an unprecedented high (> 99% ee) enantioselectivity (Scheme 5.27)." This highly efficient methodology was extended to various 2-substituted acroleins and dienes such as isoprene and furan. In addition, it was applied to develop a highly efficient total synthesis of the potent antiulcer substance, cassiol, as depicted in Scheme 5.21... 

A Lewis acid-induced aza-Diels-Alder reaction between the /3-lactam-imine 295 and 3,4-di hydro-2//-pyran gives the two diastereomeric pyranoquinolines 296 and 297. Under basic conditions, these products rearrange to the amino-substituted pyranoindolizinones, 298 and 299, respectively, with retention of stereochemistry (Scheme 74) <2003CEJ3415>. 

The Diels-Alder reaction between DEAZDand 1,4-substituted butadienes occurs rapidly, and the adducts are obtained in high yield, retaining the initial configuration of the diene substituents in the product i.e., diene 100 gives adduct 101 exclusively.155 This is in accord with the expected concerted, stereospecific nature of the Diels-Alder reaction. These initial adducts... 

The Diels-Alder reaction between azonianthracene (61) and bis-substituted olefins to give 6,ll-ethanobenzo-[fo]-quinolizinium salts 62 was greatly accelerated by the action of microwave irradiation and, consequently, the reaction might be applicable to... 

The key reaction in Jung et al. s proposed assembly of Plaunol B (81a) and C (81b) was an intermolecular Diels-Alder reaction between a diene and an allenic lactone that should give the exo-methylene group in the natural product (Scheme 19.16) [20], The phenyl-substituted lactone 83 was prepared as a model for the eventual furan lactone of the plaunols. Cydoaddition of 82 possessing a TBS enol ether and... 

An extensive review of the use of chiral Lewis acid catalysts in Diels-Alder cycloadditions has been presented. Brpnsted acid-assisted chiral Lewis acids have been shown to be highly efficient catalysts for the enantioselective Diels-Alder reactions of a- and /3-substituted-Q, /i-enals with numerous dienes. The chiral Lewis acid-catalysed Diels-Alder reaction between cyclopentadiene and alkenoyloxazolidi-nones can be catalysed by bis(oxazolone)magnesium catalysts. ... 

An extensive review of the hetero-Diels-Alder reactions of 1-oxabuta-1,3-dienes has been published. Ab initio calculations of the Diels-Alder reactions of prop-2-enethial with a number of dienophiles show that the transition states of all the reactions are similar and synchronous.Thio- and seleno-carbonyl compounds behave as superdienophiles in Diels-Alder reactions with cyclic and aryl-, methyl-, or methoxy-substituted open-chain buta-1,3-dienes.The intramolecular hetero-Diels-Alder reactions of 4-benzylidine-3-oxo[l,3]oxathiolan-5-ones (100) produce cycloadducts (101) and (102) in high yield and excellent endo/exo-selectivity (Scheme 39). A density functional theoretical study of the hetero-Diels-Alder reaction between butadiene and acrolein indicates that the endo s-cis is the most stable transition structure in both catalysed and uncatalysed reactions.The formation and use of amino acid-derived chiral acylnitroso hetero-Diels-Alder reactions in organic synthesis has been reviewed. The 4 + 2-cycloadditions of A-acylthioformamides as dienophiles have been reviewed. ... 

Extensive reviews of Diels-Alder reactions and hetero-Diels-Alder reactions in aqueous media have been presented. " " " " Micelles in the presence of catalytically active transition-metal ions catalyse the Diels-Alder reaction between 3-(/ -substituted phenyl)-l-(2-pyridyl)prop-2-en-l-ones with cyclopentadiene by a factor of 1.8 x 10 compared with the uncatalysed reaction in MeCN. " Diels-Alder reactions have been shown to be accelerated by encapsulation of both reactants by pseudospherical capsules assembled from self-complementary molecules (103). " ... 

Inverse type hetero-Diels-Alder reactions between p-acyloxy-a-phenylthio substituted a, p-unsaturated cabonyl compounds as 1-oxa-1,3-dienes, enol ethers, a-alkoxy acrylates, and styrenes, respectively, as hetero-dienophiles result in an efficient one step synthesis of highly functionalized 3,4-dihydro-2H-pyrans (hex-4-enopyranosides). These compounds are diastereospecifically transformed into deoxy and amino-deoxy sugars such as the antibiotic ramulosin, in pyridines having a variety of electron donating substituents, in the important 3-deoxy-2-gly-culosonates, in precursors for macrolide synthesis, and in C.-aryl-glucopyranosides. 

Recently, the first examples of catalytic enantioselective preparations of chiral a-substituted allylic boronates have appeared. Cyclic dihydropyranylboronate 76 (Fig. 6) is prepared in very high enantiomeric purity by an inverse electron-demand hetero-Diels-Alder reaction between 3-boronoacrolein pinacolate (87) and ethyl vinyl ether catalyzed by chiral Cr(lll) complex 88 (Eq. 64). The resulting boronate 76 adds stereoselectively to aldehydes to give 2-hydroxyalkyl dihydropyran products 90 in a one-pot process.The diastereoselectiv-ity of the addition is explained by invoking transition structure 89. Key to this process is the fact that the possible self-allylboration between 76 and 87 does not take place at room temperature. Several applications of this three-component reaction to the synthesis of complex natural products have been described (see section on Applications to the Synthesis of Natural Products ). 

As can be seen in the intramolecular cycloaddition (Section 8.03.5.1), the intermolecular Diels-Alder reactions between functionalized 2(l/f)-pyrazinones 83 and dimethyl acetylenedicarboxylate (DMAD) forming bicyclo adducts 84 has been shown to be significantly rate enhanced and increased in yields by using controlled microwave irradiation compared to the conventional thermal protocols (Scheme 21) <2002JOC7904>. The microwave-assisted Diels-Alder reactions of substituted 2(l//)-pyrazinones with ethene are significantly more effective utilizing prepressurized (up to 10 bar) reaction vessels <20040BC154>. 

The Diels-Alder reaction between l,3-diarylbenzo[c]furans and simple alkenes and alkynes has been much investigated kinetically. Glass and Smith found a remarkable enhancement of dienophilicity by the trifluoromethane sulfonyl group in a series of substituted phenylacetylenes of type 205 with 205 (R = SiMcj) no reaction occurred. 

Oxidation of thiophene with perbenzoic acid,373,376 or peracetic acid,377, 378 affords the adduct (111), or its isomer (112) (the available evidence supports structure ni 377-378), by a Diels-Alder reaction between the intermediates thiophene-1,1-dioxide and thiophene-1-oxide. Similar reactions have been observed with substituted thiophenes.376 When a solution of thiophene-1,1-dioxide is allowed to stand, the adduct (113), or its isomer (114), is formed.373 378... 

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