Diels—Alder chemistry

The problems associated with predicting regioselectivity in quinone Diels-Alder chemistry have been studied, and a mechanistic model based on frontier molecular orbital theory proposed (85). In certain cases of poor regioselectivity, eg, 2-methoxy-5-methyl-l,4-ben2oquinone with alkyl-substituted dienes, the use of Lewis acid catalysts is effective (86). 

Synthesis of multisubstituted furan rings using silyl protection 99CSR209. Synthetic applications of furan Diels-Alder chemistry 97T14179. Transformation of furans to N-heterocycles by aza-Achmatovicz reaction 98SL105. 

Some of the developments of catalytic enantioselective cycloaddition reactions of carbonyl compounds have origin in Diels-Alder chemistry, where many of the catalysts have been applied. This is valid for catalysts which enable monodentate coordination of the carbonyl functionality, such as the chiral aluminum and boron complexes. New chiral catalysts for cycloaddition reactions of carbonyl compounds have, however, also been developed. 

The Diels-Alder cycloadditions of both 2-vinylindoles and 3-vinylindoles are very attractive methods for preparing [bjannelated indoles to serve as lead substances and as building blocks for alkaloids. Pindur and coworkers [84] have extensively studied the vinylindole Diels Alder chemistry. 

Aqueous intermolecular Diels-Alder chemistry vernolepin revisited [16e]... 

Kappe C. O., Murphree S. S., Padwa A. Synthetic Applications of Fnran Diels-Alder Chemistry Tetrahedron 1997 53 14179-14233... 

Schildknegt K., Aube J. Ionic Diels-Alder Chemistry Contemporary Interpretations of the Gassman Reaction Chemtracts Org. Chem. 1996 9 237 241 Keywords interpretations of Gassman reaction and ionic Diels-Alder chemistry... 

Boger and coworkers [51] have also extended their very useful pyrrole methodology to the preparation of ningalin D (Scheme 20). A tetrasubsti-tuted pyrrole (100) is prepared in the usual manner (see Scheme 3) via Diels-Alder/retrograde Diels-Alder chemistry involving azines that undergo... 

Levofloxacin, 27 223, 225 year of disclosure or market introduction, 3 6t Levoglucosan, 4 705 Lewis acid catalysts, 72 162 Lewis acid mediated Diels—Alder chemistry, 27 257... 

Quinone Diels—Alder chemistry, regioselectivity in, 21 255 Quinonediimine (QDI), 19 249, 251 in chromogenic chemistry, 19 245—246... 

An area of Diels-Alder Chemistry that has received a good deal of attention recently is in the synthesis of polycyclic natural products. This involves intramolecular variant. Thus a pseudotropine has been synthesized. The oxygen-nitrogen bond of isoxazoline can be cleaved by reduction. 

Apart from cydopentadiene 309a, furan [151, 165, 321-323, 327, 329] and pyrrole derivatives [158, 325] 309b and 309c, respectively, are also often used as dienes. Recently, the synthetic applications of furan Diels-Alder chemistry were reviewed comprehensively [330]. In the case of a,/3-unsaturated hydrazones 312, isomerization and elimination of dimethylamine convert the Diels-Alder products 314, which... 

In recent years, supramolecular chemistry has produced a number of systems which have been shown to be able to effectively catalyze a Diels-Alder reaction. Most systems selectively afforded only one diastereomer because of a pre-organized orientation of the reactants. These systems include cyclodextrines, of which applications in Diels-Alder chemistry have recently been reviewed89. Some other kinds of non-Lewis acid catalyzed Diels-Alder reactions, including catalysis by proteins and ultrasound, have been discussed by Pindur and colleagues90. 

The most important development within the field of Diels-Alder chemistry during the past two decades must be considered to be the design and application of chiral Lewis acid catalysts. From the mid 80s on, the number of literature reports about the design and application of chiral Lewis acids in the synthesis of chiral Diels-Alder adducts from achiral precursors grew exponentially, but it started to level off and decrease again in the mid 90s. Several excellent reviews about the application of chiral Lewis acids in Diels-Alder reactions have been published41,43 44. In this section, the recent literature about the chiral Lewis acid catalyzed all-carbon Diels-Alder reactions of dienes with dienophiles is reviewed, which, as such, has not been reviewed before. 

Scheme 71. The application of methyl 2-chloro-2-cyclopropylideneacetate (1-Me) in domino Heck-Diels-Alder chemistry [122,123]...

To arrive at racemic coriolin, Danishef sky and coworkers chose to add an acetonyl fragment to a bicyclic enedione by Diels-Alder chemistry (Scheme LXXIII) Treatment of the resulting adduct 695 sequentially with a series of conventional reagents produced the key intermediate 696. Suitable aldolization deUvered 697, the functionality in which was adjusted by deconjugation and reduction. Fiuther reduction of dPSiwith lithium in liquid ammonia and methanol followed by epoxidation afforded 699. Selective oxidation of the more accessible hydroxyl group and phenyl-sulfenylation gave 700 which experiences smooth elimination to 701 after conversion to the sulfoxide. As before, epoxidation completed the sequence. 

A second set of comparisons assesses the consequences of use of approximate reactant and transition-state geometries for relative activation energy calculations, that is, activation energies for a series of closely related reactions relative to the activation energy of one member of the series. Two different examples have been provided, both of which involve Diels-Alder chemistry. The first involves cycloadditions of cyclopentadiene and a series of electron-deficient dienophiles. Experimental activation energies (relative to Diels-Alder... 

Organic chemists have a variety of strategies which they can pursue in order to improve product selectivity. Some of these like temperature and reaction time rest on the balance between thermodynamic and kinetic reaction pathways (see discussion in Chapter 1). Others such as solvent and external additives (catalysts) may as well lead to changes in the relative stabilities of competing transition states. Because it has been so widely explored, Diels-Alder chemistry provides a good opportunity to examine these variables and, in addition, to survey the use of calculations in anticipating changes in product distributions. 

All in all, this is not very encouraging as it would lead to less selective Diels-Alder chemistry. 

Dihydro-l,2,4-tetrazine 49 reacts with trimethylaluminium to produce mono 5 a and diketones 50b depending upon the reaction conditions. Borohydride reduction of 50a gives alcohol 50c. Aromatization of 50a-c by exposure to nitrous gases affords tetrazines 51a-c which have proved to be very good electron-defficient heteroatomic azadienes for inverse electron demand Diels-Alder chemistry. Numerous examples are described with symmetric and nonsymmetric electron rich dienophiies <98JOC10063>. 

The use of a chiral dienophile or enophile in the Diels-Alder reaction effects asymmetric induction. This asymmetric Diels-Alder chemistry, pioneered by Korolew and... 

Case study pyrazinone Diels-Alder chemistry... 

The reaction of norbomene yields the cis exo diester (equation 66).93 This exo isomer is not obtained directly by Diels-Alder chemistry. Other cyclic alkenes such as cyclopentene yield cis diesters, but isomers are obtained as a result of (3-hydride elimination-readdition from intermediates such as (23) prior to CO insertion (equation 67). Thus the palladium walks around the ring to some extent, but always stays on the same face. The extent of rearrangement can be minimized by higher CO pressures since CO insertion becomes more competitive with (3-elimination. This rearrangement becomes a critical problem in the dicarboxylation of 1-alkenes, since a variety of diesters are formed and the reaction is not particularly useful. These reactions were carried out with catalytic amounts of palladium and stoichiometric amounts of copper chloride. 

In keeping with a mechanistic emphasis, the book was reorganized. The chapter on mechanism is now Chapter 5 instead of Chapter 10. Thus the first six chapters focus on the mechanistic and structural underpinnings of organic chemistry. Synthetic aspects of organic chemistry are then discussed from a mechanistic and structural point of view. Several new sections have been added and others expanded. An expanded discussion of resonance and aromaticity is found in Chapter 1. A section on organopalladium chemistry and olefin metathesis has been added to Chapter 8 as they relate to current methods of carbon-carbon bond formation. Chapter 9 on free-radical reactions for carbon-carbon bond formation has been revised. The discussion of Diels-Alder chemistry has been moved to Chapter 10 and expanded. A number of new problems have been added which serve to further illustrate the principles developed in each chapter. Finally, thanks to input from many people who have read dris text and taught from it, the discussion has been further honed and errors corrected. 

Diels-Alder chemistry has been reviewed by several authors220,470-472. 

C. O. Kappe, S. S. Murphree, A. Padwa, Synthetic Applications of Furan Diels-Alder Chemistry Tetrahedron 1997, 53 14179-14231. 

Wiberg and coworkers published relative rate constants and the products of reaction of silene 6 with a number of alkenes and dienes in ether solution at 100 °C6 106-108. These data are listed in Table 2 along with an indication of the type of product formed in each case. As is the norm in Diels-Alder additions by more conventional dienophiles, the rate of [2 + 4]-cycloaddition of 6 to dienes increases with sequential methyl substitution in the 2- and 3-positions of the diene, as is illustrated by the data for 2,3-dimethyl-1,3-butadiene (DMB), isoprene and 1,3-butadiene. The well-known effects of methyl substitution at the 1- and 4-positions of the diene in conventional Diels-Alder chemistry are also reflected with 6 as the dienophile. For example, lruns-1,3-pen tadiene reacts significantly faster than the f/.v-isorrier, an effect that has been attributed to steric destabilization of the transition state for [2 + 4]-cycloaddition. In fact, the reaction of c/s-l,3-pentadiene with 6 yields silacyclobutane adducts, while the trans-diene reacts by [2 + 4]-cycloaddition108. No detectable reaction occurs with 2,5-dimethyl-2,4-hexadiene. The reaction of 6 with isoprene occurs regioselectively to yield adducts 65a and 65b in the ratio 65a 65b = 8.5 (equation 50)106,107. 

The first volume begins with a comprehensive review by Prof. Jose Luis Garcia Ruano and Dr. Belen Cid de la Plata of asymmetric cycloaddition mediated by sulfoxides, including dipolar and other processes in addition to Diels-Alder chemistry. It is followed by a discussion of the synthetic uses of thiocarbonyl compounds by Prof. Patrick Metzner. 

The somewhat neutral electronic properties of unactivated 1-aza-l,3-butadienes are responsible for their low reactivity towards dienophiles which requires drastic reaction conditions [216]. Another drawback is the inherent instability of the cyclic enamines resulting from the aza Diels-Alder reaction [217]. Therefore, 1-aza-l,3-butadienes have only sparingly been employed for a long period in hetero Diels-Alder chemistry. The main approach made to enhance the reactivity of these compounds is altering the electronical properties by introducing suitable electron-donating or electron-withdrawing substituents. 

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