Cycloaddition reactions Diels-Alder cycloadditions

Cycloaddition Reactions (Diels-Alder Type Reactions). 271... 

Figure 30.9 Interaction of diene LUMO and alkene HOMO in a suprafacial 14 - 2] cycloaddition reaction (Diels-Alder reaction).

Bis(oxazoline)-type complexes, which have been found useful for asymmetric aldol reactions, Diels-Alder, and hetero Diels-Alder reactions can also be used for inducing 1,3-dipolar reactions. Chiral nickel complex 180, which can be prepared by reacting equimolar amounts of Ni(C10)4 6H20 and the corresponding (J ,J )-4,6-dibenzofurandiyl-2,2 -bis(4-phenyloxazoline) (DBFOX/Ph) in dichloromethane, can be used for highly endo-selective and enantioselective asymmetric nitrone cycloaddition. The presence of 4 A molecular sieves is essential to attain high selectivities.88 In the absence of molecular sieves, both the diastereoselectivity and enantioselectivity will be lower. Representative results are shown in Scheme 5-55. 

This chapter deals with [2 + 2], [4 + 2], [6 + 4], [8 + 2] and [2 + 2 + 2] cycloaddition reactions of dienes and polyenes. Most attention is devoted to the [4 + 2] cycloaddition reaction (Diels-Alder reaction) which is likely to be the most studied reaction in the chemical literature. 

To date, hydrogen bond catalysis has been successfully utilized to facilitate enantioselective Michael additions, Baylis-Hillman reactions, Diels-Alder cycloadditions, and additions of 7i-nucleophiles to imines. 

Oxidation reactions, Diels-Alder cycloadditions (with subsequent dehydration of the adducts to benzanthrones) and nucleophilic substitution reactions have also been reported. Probably these condensed isobenzofu-... 

Annelation (see Cycloaddition reactions, Diels-Alder reactions, Ring-forming reactions)... 

Photosensitized Diels-Alder reactions. Diels-Alder reactions between electron-rich dienes and electron-rich dienophiles are generally unproductive. But in the presence of TCA or dicyanonaphthalene this cycloaddition can occur in reasonable yield. Thus 1,3-cyclohexadiene undergoes [4 + 2]cycloaddition with (3-methylstyrene to form endo-6-methyl-5-phenylbicyclo[2.2.2]oct-2-ene with retention of the styrene configuration. 

Another series of publications from Ken s group compared kinetic isotope effects, computed for different possible transition structures for a variety of reactions, with the experimental values, either obtained from the literature or measured by Singleton s group at Texas A M. These comparisons established the most important features of the transition states for several classic organic reactions — Diels-Alder cycloadditions, Cope and Claisen rearrangements, peracid epoxidations, carbene and triazolinedione cycloadditions and, most recently, osmium tetroxide bis-hydroxylations. Due to Ken s research, the three-dimensional structures of many transition states have become nearly as well-understood as the structures of stable molecules. 

Electrocyclic reactions Diels-Alder reactions Hetero-Diels-Alder reactions 1,3-Dipolar cycloadditions... 

Related reactions Diels-Alder cycloaddition Hetero Diels-Alder reaction ... 

Resin-bound nitroalkenes were synthesized via a Knoevenagel condensation of resin-bound nitro acetic acid with aryl and alkyl substituted aldehyde (Scheme 9.29). In this way an extra site of diversity can be introduced into the cycloaddition products of these nitroalkenes. Furthermore, the resin-bound nitroalkenes can serve as activated alkenes in other cycloaddition reactions (Diels-Alder, 1,3-dipolar cycloaddition, [2 + 2] cycloaddition) and therefore lead to the solid phase synthesis of other interesting compoimd classes (see also Scheme 9.3, Sect. 9.2). Formation of the resin-bound nitroalkenes 73a-e was realized in one step via a microwave-assisted condensation of aldehyde 72a-e (10 equiv.) with the resin-bound nitro acetic acid 71, followed by dehydration of the intermediate y -nitroalcohol [6] (Scheme 9.29). THF was used as the solvent in order to obtain optimal diffusion of the aldehyde in the polystyrene resin. 

The principle presented here on two pericyclic reactions (Diels-Alder cycloaddition and cyclobutene ring opening) can be successfully applied to studies of the reaction outcome for many other pericyclic reactions. 

Gollnick, K. and G. O. Schenk. 1967. In Hamer, J., Ed. 1,4-Cycloaddition Reactions Diels-Alder Reaction in Heterocyclic Synthesis. (New York, NY Academic Press), pp. 255-300. 

Other Uses. Reagent 1 has been used for enantioselec-tive enolborination, albeit with poor (1.1 1) selectivity. Similar bis-sulfonamide-derived boron Lewis acids have been used for aldol additions, " ester-Mannich reactions, Diels-Alder reactions,Ireland-Claisen reactions, and [2,3]-Wittig rearrangements. Similar bis-sulfonamide-derived aluminum Lewis acids have been used for aldol additions, Diels-Alder reactions, - [2 + 2] ketene-aldehyde cycloadditions, cy-clopropanation of allylic alcohols, and polymerization. ... 

In this subchapter, I summarized the intermolecular two-component cycloaddition reactions, which are able to construct benzenoid aromatic rings. Four types of transition metal-catalyzed [4-r2] cycloaddition reactions (Diels-Alder reactions, reactions of enynes with alkynes, reactions via pyrylium intermediates, and reactions via acylmetallacycles) are described. 

Cycloaddition Reactions. Diels-Alder reactions with maleic anhydride (eq 4) lead to cyclic allylsilanes, which can undergo further interesting elaborations. ... 

Robinson, J.M., Sakai, T., Okano, K., Kitawaki, T. and Danheiser, R.L. (2010) Formal [24-24-2] cycloaddition strategy based on an intramolecular propargylic ene reaction/Diels-Alder cycloaddition cascade. Journal of the American Chemical Society, 132(32), 11039-11041. 

Cycloaddition reactions (Diels-Alder) between dienes and alkenes yield cyclohexenes. The reaction works well only when the alkene bears at least one electron-withdrawing group. 

Breslow supported this suggestion by demonstrating that the cycloaddition can be further accelerated by adding anti cliaotropic salts such as lithium chloride, whereas chaotropic salts such as guanidium chloride led to a retardation " "" ". On the basis of these experiments Breslow excluded all other possible explanations for the special effect of water on the Diels-Alder reaction " . 

Alternatively, authors have repeatedly invoked the internal pressure of water as an explanation of the rate enhancements of Diels-Alder reactions in this solvent ". They were probably inspired by the well known large effects of the external pressure " on rates of cycloadditions. However, the internal pressure of water is very low and offers no valid explanation for its effect on the Diels-Alder reaction. The internal pressure is defined as the energy required to bring about an infinitesimal change in the volume of the solvents at constant temperature pi = (r)E / Due to the open and... 

Apart from the thoroughly studied aqueous Diels-Alder reaction, a limited number of other transformations have been reported to benefit considerably from the use of water. These include the aldol condensation , the benzoin condensation , the Baylis-Hillman reaction (tertiary-amine catalysed coupling of aldehydes with acrylic acid derivatives) and pericyclic reactions like the 1,3-dipolar cycloaddition and the Qaisen rearrangement (see below). These reactions have one thing in common a negative volume of activation. This observation has tempted many authors to propose hydrophobic effects as primary cause of ftie observed rate enhancements. 

Mechanistic investigations have focused on the two pericyclic reactions, probably as a consequence of the close mechanistic relation to the so successful aqueous Diels-Alder reaction. A kinetic inquest into the effect of water on several 1,3-dipolar cycloadditions has been performed by Steiner , van... 

Dramatic rate accelerations of [4 + 2]cycloadditions were observed in an inert, extremely polar solvent, namely in5 M solutions oflithium perchlorate in diethyl ether(s 532 g LiC104 per litre ). Diels-Alder additions requiring several days, 10—20 kbar of pressure, and/ or elevated temperatures in apolar solvents are achieved in high yields in some hours at ambient pressure and temperature in this solvent (P.A. Grieco, 1990). Also several other reactions, e.g, allylic rearrangements and Michael additions, can be drastically accelerated by this magic solvent. The diastereoselectivities of the reactions in apolar solvents and in LiClO EtjO are often different or even complementary and become thus steerable. 

As final examples, the intramolecular cyclopropane formation from cycloolefins with diazo groups (S.D. Burke, 1979), intramolecular cyclobutane formation by photochemical cycloaddition (p. 78, 297f., section 4.9), and intramolecular Diels-Alder reactions (p. 153f, 335ff.) are mentioned. The application of these three cycloaddition reactions has led to an enormous variety of exotic polycycles (E.J. Corey, 1967A). 

Indoles are usually constructed from aromatic nitrogen compounds by formation of the pyrrole ring as has been the case for all of the synthetic methods discussed in the preceding chapters. Recently, methods for construction of the carbocyclic ring from pyrrole derivatives have received more attention. Scheme 8.1 illustrates some of the potential disconnections. In paths a and b, the syntheses involve construction of a mono-substituted pyrrole with a substituent at C2 or C3 which is capable of cyclization, usually by electrophilic substitution. Paths c and d involve Diels-Alder reactions of 2- or 3-vinyl-pyrroles. While such reactions lead to tetrahydro or dihydroindoles (the latter from acetylenic dienophiles) the adducts can be readily aromatized. Path e represents a category Iley cyclization based on 2 -I- 4 cycloadditions of pyrrole-2,3-quinodimcthane intermediates. 

Two types of cycloaddition reactions have found application for the Synthetic elaboration of indoles. One is Diels-Alder reactions of 2- and 3-vinylindoles which yield partially hydrogenated carbazoles. The second is cycloaddition reactions of 2,3-indolequinodimethane intermediates which also construct the carbazole framework. These reactions arc discussed in the following sections. 

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