Singly Occupied Molecular Orbital SOMO Catalysis

Singly Occupied Molecular Orbital (SOMO) Catalysis... 

Singly occupied molecular orbital (SOMO) catalysis has been successfully employed in an enantioselective organocatalytic a-allylation of cyclic ketones, using commercially available allylsilanes. (g)... 

ORGANO-SINGLY OCCUPIED MOLECULAR ORBITAL (SOMO) CATALYSIS... 

Mastracchio A, Warkentin AA, Walji AM, MacMillan DWC. Direct and enantioselective a-allylation of ketones via singly occupied molecular orbital (SOMO) catalysis. Proc. Nat. Acad Sci USA 2010 107(48) 20648-20651. 

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. 

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). 

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). 

In 2007, the groups of MacMillan and Sibi almost simultaneously introduced a new mode of organocatalytic activation, termed SOMO (singly occupied molecular orbital) catalysis, which was founded upon the transient production of a 37r-electron radical cation species that could function as a generic platform of induction and reactivity. This new mode of organocatalytic activation, was founded upon the mechanistic hypothesis that one-electron oxidation of a transient enamine intermediate, derived from the aldehyde and the chiral amine catalyst, rendered a 37i -electron SOMO-activated species, which could readily participate in asymmetric bond construction. 

SOMO Activation Within the field of aminocatalysis, asymmetric organo-SOMO (singly occupied molecular orbital) catalysis has recently emerged as a powerful technique for the preparation of optically active compounds. In this context, MacMillan and coworkers described in 2008 the formation of y-oxyaldehydes from aldehydes and styrenes by organo-SOMO catalysis [25]. The condensation between the amine catalyst 46 and an aldehyde gave rise to an enamine intermediate, which was then oxidized by ceric ammonium nitrate (CAN) to give a radical cation. Reaction of this radical cation with a nonactivated olefin, namely styrene, led to the... 

The ability of enamines to form in situ generated radicals gives rise to an entirely new principle of activation and thus to a series of very usefijl and highly selective previously unknown C-C bond formation processes. Thus, enamine catalysis changed into SOMOsingly occupied molecular orbital) (Figure 4.2) [24]. For direct experimental evidence of an enamine radical cation in SOMO catalysis see Reference [25]. These types of transformations were extensively elaborated by the MacMillan group. The first steps in this new concept were accomplished by the formation of radicals of enamines of imidazoHdin-4-ones. 

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