Diels-Alder cycloaddition reaction substituent effects

Diels-Alder cycloadditions are sensitive to steric effects of two major types in the diene. Bulky substituents on the termini of the diene hinder approach of the two components to each other and decrease the rate of reaction. This effect can be seen in the relative reactivity of 1-substituted butadienes toward maleic anhydride.19... 

DFT calculations on the intramolecular Diels-Alder reaction of penta-l,3-dienyl acrylates predict stereoselectivities that are in good agreement with the experimen- (g) tal results.85 Another DFT study at the B3LYP/6-31G(d) level of the intramolecular Diels-Alder cycloaddition of 5-vinylcyclohexa-1,3-dienes has been reported. Reaction rates are influenced by dienophile twisting and substituent effects.86 The intramolecular dehydro-Diels-Alder reactions of ynamides (79) provides a new synthesis of benzo[fc]-, tetrahydrobenzo[fc]-, naphtho[l,2-/j -, and dibenzo[a,c]carbazoles... 

Only a few examples of a Diels-Alder type reaction of the valence tautomeric ketene of mesoionic 1,3-dithiolones are known. Thus the reactions of differently substituted mesoionic compounds (2) with o-chloranil give the unusual adducts (142), derived via [4 + 2] cycloaddition to the non-detectable valence tautomeric ketene (141) which is in equilibrium with (2). The reaction rate depends upon the nature of the substituents, for example substituents with —I and/or —M effects lower the reaction rates (81ZN(B)609). 

In addition to the [4 + 2] cycloadditions of oxazoles (Section 1) and substituted 1,2,4,5-tetrazines (Section 14), the Diels-Alder cycloadditions of substituted 1,2,4-triazines constitute one of the most thoroughly investigated heteroaromatic azadiene systems capable of 4tt diene participation.3,89 In contrast to the oxazole or sym-tetrazine series, two potential and observed modes of cycloaddition are open to 1,2,4-triazines cycloaddition across C-3/C-6 or C-5/N-2 of the 1,2,4-triazine nucleus, and the former is subject to 1,2,4-triazine substituent control of the observed regioselectivity.90 The complementary addition of electron-withdrawing substituents to the 1,2,4-triazine nucleus generally increases its rate of participation in inverse electron demand Diels-Alder reactions, influences the mode of [4 + 2] cycloaddition (C-3/C-6 versus C-5/N-2 cycloaddition), and controls the observed regioselectivity. In addition, the reactivity of the electron-rich dienophile as well as the reaction conditions, polar versus nonpolar solvent, have a pronounced effect on the observed course of the [4 -I- 2] cycloadditions.89... 

CONTENTS Facial Diastereoselection in Diels-Alder Cycloadditions and Related Reactions Understanding Planar Interactions and Establishing Synthetic Potential, A. G. Faille and Yee-Fung Lu. Substituent and Structural Effects in the Ozonolysis of Cyclic Vinylogous Esters. W. H. Bunnelle. N-Metalated Azomethine Ylides, S. Kanemasa and Otohiko Tsuge. Azomethine Ylide Cy-cloadditlons via 1,2- Prototropy and Metallo-Dipole Formation from Imines, R. Grigg and V. Sridharan. Index. 

Evans s bis(oxazolinyl)pyridine (pybox) complex 17, which is effective for the Diels-Alder reaction of a-bromoacrolein and methacrolein (Section 2.1), is also a suitable catalyst for the Diels-Alder reaction of acrylate dienophiles [23] (Scheme 1.33). In the presence of 5 mol% of the Cu((l )-pybox)(SbF5)2 catalyst with a benzyl substituent, tert-butyl acrylate reacts with cyclopentadiene to give the adduct in good optical purity (92% ee). Methyl acrylate and phenyl acrylate underwent cycloadditions with lower selectivities. 

The substituents at C-2, C-3 within diene 97 and those at C-1, C-2 within dienophiles 98-100 are electronically and/or sterically equivalent with respect to diene and dienophile reaction centers, respectively, and therefore cycloaddition should not display regiochemical bias in the absence of orientational effects. The Diels-Alder reactions of 97 prepared in situ with 98-100 gave an excess of 101 (Scheme 4.19) [70b], which are the expected regioisomers if the reagents react in their preferred orientations within a mixed micelle with an ammonium head group at the aggregate-water interface and the remainder in the micelle interior. 

The choice of the acyl substituent X for Diels-Alder reactions of l-N-acylamino-l,3-butadicnes depends on the particular synthetic problem. The acyl substituent has a moderate effect on the cycloaddition reactivity of these dienes, and also determines what amine unmasking procedures are required. As a result of their stability and the variety of amine deprotection procedures available, " the diene carbamates are the components of choice in most cases. A particularly attractive aspect of the diene synthesis detailed here is the ability to tailor the amino-protecting group... 

The final important category of [4 + 2] cyclization is the Diels-Alder and other [4 + 2] cycloaddition reactions. This topic has been the subject of intense study for many years and continues to attract the attention of many researchers, as in a great many instances the reactions involved constitute excellent procedures for the synthesis of both heterocyclic and non-heterocyclic compounds. The discussion in this section is restricted to processes which result in the formation of heterocyclic compounds from non-heterocyclic precursors, although of course a heterocycle may be present as a substituent in either the diene or ene component but have no significant or controlling effect in the cycloaddition reaction. 

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