Mechanistic Aspects of Diels‐Alder Reactions: A Critical Survey

Abstract

The question of concerted or consecutive bond formation arises in all types of cycloaddition reactions. Stereochemical investigations and studies of regiospecificity as well as intensive kinetic investigations with regard to substituent and solvent effects, and the dependence of the reaction on temperature and pressure permit in many cases mechanistic conclusions concerning the Diels-Alder reaction. Efforts towards a theoretical interpretation, ab initio and semiempirical calculations, the application of frontier molecular orbital theory (FMO) as well as thermochemical measurements permit a description of the energy hypersurface of these [4 + 21-c~cloadditions. An attempt is made here to draw a line of distinction between the mechanistic alternatives-one-step reaction versus two-step reaction-considering all experimental and theoretical criteria [4 + 2]-cy~loadditions[~~, named after their discoverers, were later joined by [2 + 11-, [2 + 21-, [3 + 21-cycloadditions (1,3-dipolar cycloadditions), and those leading to more extended ring systems. Diels and Alder were already able to identify essential characteristics of the [4 + 21-cycloaddition:1 . The addition reactions take a stereospecific course resulting in a cis-addition. 2. In the case of cyclic dienes the endo principle is often followed. 3. Unsymmetrically substituted reactants combine regiospecifically to give the cycloadduct. 4. With maleic acid anhydride, valued in those days as the most reactive test dienophile, electron releasing groups in the diene accelerate the reaction, while electron withdrawing groups in the diene retard it. Kinetic measurem e n t~~~ quantified the so-called "Alder-rule", formulated by Alder.A preparatively useful extension of the cycloaddition was provided by the discovery of its catalysis by Lewis-acids ['], which, with retention of stereospecificity, accelerates the rate of addition by several powers of ten. In the presence of Lewis-acids, endo-products and the normally favored regioisomers were formed even to a higher extent.Concepts of the mechanisms of the Diels-Alder reaction were most strongly influenced by the Woodward-Hoffmann rule^^'"-'^'. If in those days the experimental results were con-N atoms implies 3 N -6 degrees of freedom of vibration on a hypersurface of the same dimension-all methods of interpretation are limited from the outset, on the one hand by the selection of simple model reactions and, on the other, by the approximations which are necessary in the case of selected theoretical procedures. Also solvent effects are generally not considered, because theoretical models are normally developed for isolated molecules in in the gas phase. The fact that these limitations can lead to a false interpretation of experimental results, has been demonstrated on a number of occasions in recent years, particularly with regard to vapor phaseacidity and basicity experiments[431.Conclusions drawn from such investigations must always be examined carefully in the light of these approximations. Herndon[2'1 gives a survey of t...

Rolf Huisgen: Some Highlights of His Contributions to Organic Chemistry

“…The intermediate, bicycle B, is trapped from the equilibrium with C by d e. This rate law is observed for less-reactive dienophiles, for instance, maleic anhydride [58]. Tetracyanoethylene (TCNE) and dicyanomaleimide are record dienophiles [60]. Dilatometric rate measurements with COT using increasing dienophile concentrations furnished curves approaching a plateau as demonstrated in Fig.…”

“…The majority of 1,3-dipolar cycloadditions, when analyzed mechanistically, will, however, still follow a concerted ( p 4 s p 2 s ) pathway. This applies as well to the related ( p 4 s p 2 s ) Diels ± Alder cycloaddition [60]. In a recent plenary lecture [95] entitled 1,3-Dipolar Cycloadditions: Concertedness, Yes or No ?, Rolf Huisgen displays his present view on the mechanism of these reactions.…”

Stereoselective synthesis of cis-fused hexahydro-isoindolones

“…This observation contrasts the report by Mellor and Wagland 6 who described that the reaction of maleic anhydride with N-benzylhexa-2,4-dienylamine in toluene gave rise to the formation of a trans-fused hexahydroisoindolone (yield: 82 %) with a coupling constant of J 3a,7a = 12.5 Hz. Because Diels-Alder reactions generally show preference for the formation of endoproducts, 13 the observed cis-fusion of the bicyclic ring system in 8-12 can be rationalized by the two different reaction paths A and B in Scheme 5. …”

“…2 Maleic anhydride (> 99%, Fluka) and maleic imide (> 98 %, Merck) were used as purchased. 1 H NMR spectra (300, 400, or 600 MHz) and 13 C NMR spectra (75.5 or 100.6 MHz) refer to …”

Revisiting the stability of endo/exo Diels-Alder adducts between cyclopentadiene and 1,4-benzoquinone

“…[1][2][3][4][5][6][7][8] This cycloaddition is widely used to construct, in a regio-and stereo-controlled way, a six-membered ring with up to four stereogenic centers. [1][2][3][4][5][6][7][8] Historically, in 1906 Albrecht 9 published the reaction between the cyclopentadiene (1) and 1,4-benzoquinone (2) as a 1:1 adduct. However, Albrecht's considerations about the structure of the obtained adduct were inconsistent.…”