Molecular orbitals enamines

Some electrophile-nucleophile reactions are guided more by orbital interactions than by electrostatics. The key interaction involves the donor orbital on the nucleophile, i.e., the highest-occupied molecular orbital (HOMO). Examine the HOMO of enamine, silyl enol ether, lithium enolate and enol. Which atom is most nucleophilic, i.e., which site would produce the best orbital overlap with an electrophile ... 

The slightly lower lowest unoccupied molecular orbital (LUMO) energy of pyrido[3,4-r71pyridazine 5 compared to its isomer [2,3-r7] 6, calculated by the AMI method <1985JA3902>, explained the shorter time required for the pyrido[3,4-r7j-pyridazine to complete the [4+2] cycloaddition reaction with cyclic enamines of different ring sizes <1995M211, 2001ARK21>. 

A similar polar cyclization of an enamine and a thioketene derivative is shown in equation (87) (76TL4283), but electron-deficient alkenes and alkynes react in a concerted fashion. Concerted cyclizations may be subdivided into those in which the sulfur atom is part of the enophile or the dienophile. Into the first category fall the dimerizations of a,( - unsaturated thioaldehydes (equation 88) which may be shown to closely follow frontier molecular orbital predictions of regioselectivity (79JOC486). Related to this are the thiochalcones (equation... 

Ab initio molecular orbital calculations, coupled with activation energies and entropies from experimental data, have been employed to determine the nature of the intermediates in the reaction of singlet oxygen with alkenes, enol ethers, and enamines.214 Allylic alkenes probably react via a perepoxide-like conformation, whereas the more likely pathway for enamines involves a zwitterionic cycloaddition mechanism. The reactions of enol ethers are more complex, since the relative stabilities of the possible intermediates (biradical, perepoxide, and zwitterionic) here depend sensitively on the substituents and solvent polarity. 

Theoretical analysis of this [4% + 27r]-cycloaddition reaction by consideration of frontier-orbital interactions between the electron-rich olefin (highest occupied molecular orbital, HOMO) and the electron-poor 5-nitropyrimidine (LUMO) has shown that the FMO perturbation theory correctly predicts an exclusive regiospecific addition of the enamine to N-l and C-4 of the pyrimidine ring (86JOC4070). 

Molecular orbital calculations of rotation barriers around the carbon-nitrogen bond in thioamides, amidinium salts, amidines and enamines have been described by Sandstrom61. 

In the following a few recent molecular orbital calculations concerned with conformer energies and geometries of acceptor-substituted enamines will be discussed in conjunction with known crystal structures. 

Recently, it has been shown1 by molecular orbital calculations that the ionized vinylamine 34 (Scheme 26) is more stable than the ionized ethylideneimine isomer 35 by 122 kJ mol"The reverse is true for neutral compounds, the imine being more stable than enamine by 22 kJ mol-1. Moreover, the conversion of 34 to 35 by 1,3 H-transfer requires 265 kJ mol-1 of critical energy. 

The present chapter is dedicated to the cycloaddition reactions of enamines, which include transformations that, independently of the mechanism, create a new ring1. The cycloadditions may proceed via a concerted mechanism (following Woodward-Hoff-mann rules) or a two-step mechanism which may involve zwitterionic or diradical intermediates. Due to their low ionization potentials and asymmetric molecular orbital... 

Dienamines differ from simple enamines in that (i) there is an additional nucleophilic site at the -position and (ii) an equilibrium mixture of three isomeric dienamines is frequently formed, consisting of the linear s-trans isomer 1, the linear s-cis isomer 2 and the cross-conjugated isomer 31 (Scheme 1). A variety of factors influence the outcome of electrophilic attack on such an equilibrium system. Hiickel molecular orbital calculations indicate a significantly higher electron density at the -positions compared to the -positions of the dienamine system2 (Figure 1). 

A few molecular orbital calculations have been reported for these metallacycles. An ab initio study of a postulated azoniumrhodacyclopropane produced a structure in good agreement with known azoniummetallacyclopropanes. This as yet unknown heterocycle was studied because it has been proposed as an intermediate in the stereoselective isomerization of allyl amines to enamines... 

Theoretical studies indicate that these transition structures are probably influenced by frontier molecular orbitals (in addition to steric effects), as indicated in Scheme 5.34c [182]. For the reaction of aminoethylene (a primary enamine) and acrolein, the enamine HOMO and the enone LUMO have the most attractive interactions when aligned in the chair configuration shown, which has the enone in an 5-cis conformation. Note that this orientation places the NH and the electrophile a-carbon in close proximity for proton transfer via the ene transition structure. 

The use of secondary amine catalysis in combination with radical chemistry was first introduced by MacMillan in 2007 in a process he termed as organo-SOMO catalysis [32]. hi this system, the enamine that is generated in the condensation of a chiral secondary amine and a carbonyl, is oxidized via a single electron process. This generates a three-7i-electron radical cation with a singly occupied molecular orbital (SOMO) which can react asymmetrically in a variety of different processes (Scheme 1.25). 

As mentioned, the applications of chiral secondary amines in domino processes have been numerous, mainly because of the dual mechanism of activation allowing easy incorporation of other reactions [7, 8]. The first of these processes involves an iminium-enarnine (Scheme 7.1a), and the second an enamine-iminium activation (Scheme 7.1b), both of which can be in operation in domino reactions involving Michael reactions. These modes of action rely on the lower energy lowest unoccupied molecular orbital (LUMO) for the iminium ion and a rise in the highest occupied molecular orbital (HOMO) energy for enamine activation, which are discussed in further detail in Chapter 10 of this book [9, 10]. In the... 

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