LUMO activation

Recently, Chi and coworkers disclosed the formal LUMO activation of a,p-unsaturated esters by NHC catalysis for highly enantioselective reactions with enamides. NHCs D5 and H6 provided best results in terms of the yields and stereoselectivities for lactams 213 and 215 from p-disubstituted and a-substituted esters, respectively (Scheme 20.88). 

Comparing the activation mode of iminium and enamine catalysis, iminium catalysis is based on a LUMO-activation mode of the electrophile whereas enamine catalysis is based on a HOMO-activation of the nucleophile. Keeping in mind the fact that enamine and iminium species are rapidly interconverted via a two-electron redox process (proton abstraction of an iminium species results in an enamine), MacMillan and co-workers reasoned that it should be possible to interrupt this equilibrium chemically by carrying out just a one-electron oxidation of an enamine. This would then generate a three-7i-electron radical cation with a singly occupied molecular orbital (SOMO) that should be activated towards catalytic transfomiatirHis (racemic or asymmetric) not possible using classical enamine or iminium activation (Scheme 80) 316). 

LUMO activation HOMO activation SOMO activation... 

Chiral Lewis acid-catalyzed cycloadditions between NJf-cyclic azomethine imines and electron-deficient olefins by lowest unoccupied molecular orbital (LUMO) activation... 

Chiral Lewis acid LUMO activation Asymmetric induction Dual activation Chiral cycloadduct... 

The vast majority of organocatalysis involves HOMO activation (such as enamine catalysis) or LUMO activation (such as iminium catalysis). However, a third type of organocatalytic activation has been reported by the MacMillan group which involves the single electron oxidation of transiently produced enamines, which is known as singly occupied molecular orbital (SOMO) catalysis. 

Hydrogen bonding of water to the activating group of (for normal-electron demand Diels-Alder reactions) the dienophile constitutes the second important effect". Hydrogen bonds strengthen the electron-withdrawing capacity of this functionality and thereby decrease the HOMO-LUMO gap... 

Figure 10 12 shows the interaction between the HOMO of one ethylene molecule and the LUMO of another In particular notice that two of the carbons that are to become ct bonded to each other m the product experience an antibondmg interaction during the cycloaddition process This raises the activation energy for cycloaddition and leads the reaction to be classified as a symmetry forbidden reaction Reaction were it to occur would take place slowly and by a mechanism m which the two new ct bonds are formed m separate steps rather than by way of a concerted process involving a sm gle transition state... 

Let us focus attention on the unfavorable ring closures. Why, for example, should formation of a five-membered ring by an endo-trig process be difficult The answer is provided by a consideration of the trajectory of approach of the nucleophile." If Z is an electron-attracting conjugating group of the type necessary to activate the double bond to nucleophilic attack, the reaction would involve the LUMO of the conjugated system, a 7t ... 

This idea can be quantitatively expressed by defining activation hardness as the difference between the LUMO-HOMO gap for the reactant and that for the rr-complex intermedi-... 

The 1,3-dipolar cycloadditions offluonnatedallenes provide a rich and varied chemistry Allenes, such as 1,1-difluoroallene and fluoroallene, that have fluorine substitution on only one of their two cumulated double bonds are very reactive toward 1,3-dipoles Such activation derives from the electron attracting inductive and hyperconjugative effects of the allylic fluorine substituent(s) that give nse to a considerable lowering of the energy of the LUMO of the C(2)-C(3) n bond [27]... 

For example, in a 4-electron, 6-orbital CAS—specified as CASSCF 4,6)—performed on a singlet system, the active space would consist of the two highest occupied molecular orbitals (where the four electrons reside) and the four lowest virtual orbitals. Similarly, for a 6-electron, 5-orbital CAS on a triplet system, the active space would consist of the four highest occupied MO s— two of which are doubly-occupied and two are singly-occupied—and the LUMO (the keyword is CASSCF(6,5)). 

A simple approach for the formation of 2-substituted 3,4-dihydro-2H-pyrans, which are useful precursors for natural products such as optically active carbohydrates, is the catalytic enantioselective cycloaddition reaction of a,/ -unsaturated carbonyl compounds with electron-rich alkenes. This is an inverse electron-demand cycloaddition reaction which is controlled by a dominant interaction between the LUMO of the 1-oxa-1,3-butadiene and the HOMO of the alkene (Scheme 4.2, right). This is usually a concerted non-synchronous reaction with retention of the configuration of the die-nophile and results in normally high regioselectivity, which in the presence of Lewis acids is improved and, furthermore, also increases the reaction rate. 

Scheeren et al. reported the first enantioselective metal-catalyzed 1,3-dipolar cycloaddition reaction of nitrones with alkenes in 1994 [26]. Their approach involved C,N-diphenylnitrone la and ketene acetals 2, in the presence of the amino acid-derived oxazaborolidinones 3 as the catalyst (Scheme 6.8). This type of boron catalyst has been used successfully for asymmetric Diels-Alder reactions [27, 28]. In this reaction the nitrone is activated, according to the inverse electron-demand, for a 1,3-dipolar cycloaddition with the electron-rich alkene. The reaction is thus controlled by the LUMO inone-HOMOaikene interaction. They found that coordination of the nitrone to the boron Lewis acid strongly accelerated the 1,3-dipolar cycloaddition reaction with ketene acetals. The reactions of la with 2a,b, catalyzed by 20 mol% of oxazaborolidinones such as 3a,b were carried out at -78 °C. In some reactions fair enantioselectivities were induced by the catalysts, thus, 4a was obtained with an optical purity of 74% ee, however, in a low yield. The reaction involving 2b gave the C-3, C-4-cis isomer 4b as the only diastereomer of the product with 62% ee. 

The basic concept of activation in hetero-Diels-Alder reactions is to utilize the lone-pair electrons of the carbonyl and imine functionality for coordination to the Lewis acid. The coordination of the dienophile to the Lewis acid changes the FMOs of the dienophile and for the normal electron-demand reactions a decrease of the LUMO and HOMO energies is observed leading to a better interaction with... 

Thermal dimerization of ethylene to cyclobutane is forbidden by orbital symmetry (Sect 3.5 in Chapter Elements of a Chemical Orbital Theory by Inagaki in this volume). The activation barrier is high E =44 kcal mof ) [9]. Cyclobutane cannot be prepared on a preparative scale by the dimerization of ethylenes despite a favorable reaction enthalpy (AH = -19 kcal mol" ). Thermal reactions between alkenes usually proceed via diradical intermediates [10-12]. The process of the diradical formation is the most favored by the HOMO-LUMO interaction (Scheme 25b in chapter Elements of a Chemical Orbital Theory ). The intervention of the diradical intermediates impfies loss of stereochemical integrity. This is a characteric feature of the thermal reactions between alkenes in the delocalization band of the mechanistic spectrum. 

Modulation of the electron density on the frontier atomic orbitals centered on the active atom(s) with LUMO and HOMO character... 

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