Pericyclic reactions with substituents

Mechanistically the all-carbon Diels-Alder reaction is generally considered a concerted, pericyclic reaction with an aromatic transition state, but there is also evidence for a stepwise (diradical or diion) process. For HDA reactions, theoretical studies revealed that the transition states are usually concerted, but less symmetrical. Depending on the reaction conditions and the number and type of substituents on the reactants, the HDA reaction can become stepwise, exhibiting a polar transition state. 

The way the substituents affect the rate of the reaction can be rationalised with the aid of the Frontier Molecular Orbital (FMO) theory. This theory was developed during a study of the role of orbital symmetry in pericyclic reactions by Woodward and Hoffinann and, independently, by Fukui Later, Houk contributed significantly to the understanding of the reactivity and selectivity of these processes. ... 

As a consequence of the pericyclic reaction path, the addition of a-stereogenic allylmctals to carbonyl compounds is accompanied by an effective 1,3-chirality transfer in the allylic moiety combined with 1,4-chira induction at the prostereogenic carbonyl group3032. The scheme also demonstrates the importance of the orientation of the substituent X in the six-membered transition state. By changing from a pseudo-axial to a pseudo-equatorial position, the cation-induced sy/i-attack addresses opposite faces of both prostereogenic moieties, leading to a Z-and an -isomer, these being enantiomeric in respect to the chiral moiety. 

Danshefsky s diene [19] is the 1,3-butadiene with amethoxy group at the 1-position and a trimethylsiloxy group at the 3-position (Scheme 18). This diene and Lewis acids extended the scope of hetereo-Diels-Alder reactions with aldehydes [20], This diene reacts with virtually any aldehyde in the presence of Lewis acids whereas dienes usually react with only selected aldehydes bearing strongly electron accepting a-substituents. There are two (Diels-Alder and Mukaiyama aldol) reaction pathways (Scheme 18) identified for the Lewis acids catalyzed reactions of Danishefsky diene with aldehydes [21, 22]. The two pathways suggest that these reactions occur on the boundary between the delocahzation band (the pericyclic... 

The problem comes with the insertion of a carbene into a double bond, which is well known to be stereospecifically suprafacial with singlet carbenes like dichlorocarbene (p. 28). This is clearly a forbidden pericyclic reaction, if it takes place in the sense 3.49 —> 3.50, This is known as the linear approach, in which the carbene, with its two substituents already lined up where they will be in the product, comes straight down into the middle of the double bond. The two reactions above, 3.47 and 3.48, are also linear approaches, but these are both allowed, the former because the total number of electrons (6)... 

The X-ray crystal structure for AZ-28 has a variety of structural features that are consistent with the proposed mechanism operative for the oxy-Cope rearrangement. The antibody binds the transition stage analog in a chair-like conformation, consistent with the preferred chair transition state for this pericyclic reaction (Doering and Roth, 1962). The positions of the C-2 and C-5 atoms are fixed in the antibody-bound hapten molecule in a similar fashion, the C-2 and C-5 positions in the hexadiene substrate should be held in a fixed position by conserved van der Waals interactions locking in the two phenyl substituents in the antibody combining site. This bound conformation of the acyclic (47T + 2er) system of the hexadiene substrate should enforce a molecular conformation close to the transition state for the rearrangement reaction, consistent with the catalysis observed for AZ-28. 

Since they are equivalent to homobutadienes, cyclopropanes interacting directly with an olefin unit display a particularly rich chemistry. Pericyclic reactions come into play in this specific area. Similar to other cyclopropane derivatives, the reactivity of vinylcyclopro-panes with nucleophiles, electrophiles and radicals as well as their general chemical behaviour will be governed by substituents at the cyclopropane core and at the double bond. ... 

Nevertheless, frontier orbital theory, for all that it works, does not explain why the barrier to forbidden reactions is so high. Perturbation theory uses the sum of all filled-with-filled and filled-with-unfilled interactions (Chapter 3), with the frontier orbitals making only one contribution to this sum. Frontier orbital interactions cannot explain why, whenever it has been measured, the transition structure for the forbidden pathway is as much as 40 kJ mol 1 or more above that for the allowed pathway. Frontier orbital theory is much better at dealing with small differences in reactivity. We shall return later in this chapter to frontier orbital theory to explain the much weaker elements of selectivity, like the effect of substituents on the rates and regioselectivity, and the endo rule, but we must look for something better to explain why pericyclic reactions conform to the Woodward-Hoffmann rules with such dedication. 

It is more difficult to explain the effect of substituents on the rates, and on the regio- and stereoselectivities of the unimolecular pericyclic reactions. We cannot strictly look at the HOMO and LUMO of each component, as we could with bimolecular reactions, and therefore cannot properly use frontier orbitals to explain the effects of electron-donating and electron-withdrawing substituents on the rates.905 The effects are profound, sometimes even strong enough to override the Woodward-Hoffmann rules.906... 

Abstract The control elements that did not find mention in the earlier chapters are dealt with here. The prominent among these elements are spiroconjugation, peris-electivity in pericyclic reactions, torquoselectivity in conrotatory-ring openings, ambident nucleophiles and electrophiles, a-effect in nucleophilicity, carbene addition to 1,3-dienes, Hammett s substituent constants, Hammond postulate, Curtin-Hammett principle, and diastereotopic, homotopic, and enantiotopic substituents. 

In this case, Cucurbituril (53) reveals a number of enzymelike features The reaction exhibits saturation behaviour, it becomes independent of substrate concentration with sufficient amounts of 54 and 55, high concentrations of 54 retard the cycloaddition (substrate inhibition), and release of product 56 from its complex with Cucurbituril (53) is the rate determining step. NMR spectroscopic data suggest that both starting materials of the cycloaddition are hydrogen bonded to the carbonyl groups of 53 with their ammonium moiety and that the reactive substituents extend into the interior of Cucurbituril (53). In this cavity the pericyclic reaction takes place to form the 1,2,3-triazole 56. Kinetic data indicate that the formation of the ternary complex of Cucurbituril (53) with the two starting materials 54 and 55 is not strainless. Since the reaction is still accelerated very much it is assumed that the transition state of the reaction corresponds to the size of the cavity more closely than the substrates. This is a further indication that this case is a useful enzyme model. 

The Meerwein-Eschenmoser-Claisen rearrangement is one of the most useful pericyclic reactions. In its basic form, it involves the conversion of an allylic alcohol 1 to a ketene N, 0-acetal 2, which undergoes rapid [3,3]-sigmatropic rearrangement to yield a y,d-unsaturated amide 3 (Scheme 7.1). In accordance with the general electronic effects observed in Claisen rearrangements, the presence of an electron-donating amino substituent on the ketene acetal intermediate substantially increases the rate of the pericydic step. 

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