HOMO-activation

Imidazofidinones Organ a catalysts for LUMO or HOMO Activation Motives... 

Aminocatalytic asymmetric Diels—Alder reactions via HOMO activation (in particular, preparation of a variety of O- or N-heterocycles with high optical purity) 12ACR1491. 

An interesting example of HOMO activation through catalytic chiral diene formation was reported by Christmann and co-workers [29]. They describe the intramolecular DA of bis-2-enals 38 catalyzed by prolinol ether salt 39 to give the fused ring systems 40 in moderate yields and high enantioselectivity (Scheme 6.9). 

The HOMO activation of dienophiles (reversed electron demand DA) was reported by Chen and co-workers [32]. They found that the catalytic reaction of crotonaldehyde with prolinol ether 46 resulted in formation of a 1,3-dieneamine 49 that selectively reacted as a dienophile on the terminal double bond in a reversed electron demand Diels-Alder reaction with electron-deficient dienes 48 to give access to highly diastereo- and enantioenriched cyclohexen derivatives 50 (Scheme 6.12). 

Following this, Chen and co-workers [43,44] successfully reported an aza-HAD (Scheme 6.16). They applied the J0rgensen-Hayashi catalyst 46 for catalytic HOMO activation of aldehydes 66 that readily underwent DA with enimine 73 to give optically active piperidine derivatives 74. The adducts 74 were obtained in moderate... 

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... 

The use of chiral primary or secondary amines as covalent catalysts allows for the activation of carbonyl componnds for different reactions. Either the initially formed imininm species are the reactive intermediate (LUMO lowering), which is mainly the case when using a,p-unsatnrated carbonyl compounds, or the derived enamine can be ntilized for enolate-type reactions (HOMO activation), or, after a single electron oxidation of the enamine, a singly occnpied molecular orbital (SOMO) activation is possible (Scheme 6.18) [14, 31, 32], In addition, by combining these complementary activation modes, it has been possible to carry out organocascade reactions with excellent control of... 

Asymmetric inverse-electron-demand Diels-Alder reactions controlled by the dienophile HOMO and the diene LUMO have seldom been reported. Through a HOMO-activation strategy by the formation of dienamine intermediate H between crotonaldehyde (2a) and chiral amine 36 to raise the dienophile HOMO energy, Chen and coworkers successfully developed the first organocatalytic aU-carbon-based inverse-electron-demand Diels-Alder reaction to produce multifunctional cycloadducts 35 with up to 99% ee (Scheme 38.11) [19]. 

Based on the success of dienamine catalysis in inverse-electron-demand Diels-Alder reactions, Jia et al. explored the possibility of applying the HOMO-activation mode to poly-conjugated enals, such as 2,4-dienals, to form a reactive dienamine... 

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. 

Chiral enamine, dienamine, and trienamine intermediates have been shown to catalyse asymmetric Diels-Alder reactions via HOMO activation. These Diels-Alder reactions generally occur with high chemo-, regio-, and stereo-selectivities. ° The effect of the viscosity of pyridinium-based ionic liquids, with tetrafluoroborate and bis(trifluorosulfonimide) anions, on the kinetics of intra- and inter-molecular Diels-Alder reactions has been investigated. Results show that the intramolecular cycloaddition reaction is less susceptible to viscosity variations than the intermolecular reaction. 

Based on these results the following reaction pathway can be assumed. Iminium catalysis is reahzed by the use of chiral imidazohdinones. The subsequent enamine catalysis (HOMO activation) is realized by deployment of prohne. The anti-configured products were detected by apphcation of L-prohne, whereas the use of D-prohne determines the syn[Pg.90]

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