SOMO-catalysis

Asymmetric CDC Reactions of Aldehydes via Organo-SOMO Catalysis... 

Chiral secondary amines have proven to be amongst the most dynamic and efficient of asymmetric catalysts. There are essentially two modes of activation by secondary amines whereby a nucleophilic enamine or an electrophilic imininm ion is generated. Figure 1.4 shows a generic scheme of these two modes of activation and how they would be used in asymmetric organocatalytic cyclizations. A third mode of catalysis, named Organo-SOMO catalysis is discussed in Sect 1.5.1.5. 

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). 

Scheme 1.25 MacMillan s SOMO catalysis introduced a further dimension to secondary amine catalysis...

Scheme 1.27 Ortho-selective a-arylation of aldehydes via Organo-SOMO catalysis. ML ...

Scheme 5.56 General strategy of organo-SOMO catalysis.

The most recent highlight in enantioselective radical domino processes can be attributed again to the MacMillan group, in their development of an efficient polyene domino cyclization via the organo-SOMO catalysis strategy [85] (Scheme 5.57). 

Scheme 5.57 Enantioselective domino cyclization via SOMO catalysis.

SOMO Catalysis. Organo-SOMO catalysis is an alternative pathway for... 

SCHEME 2.20. Representative mechanistic cycle for asymmetric organo-SOMO catalysis. 

FIGURE 2.22. MacMillan s transition state model for SOMO catalysis. 

FIGURE 2.23. SOMO catalysis for the a-chlorination of aldehydes, (a) Ground state conformation of the imidazolidinone catalyst, (b) Transition state model. 

SCHEME 8 9. Enantioselective a-alkylation of aldehydes via organo-SOMO catalysis reported by MacMUlan and co-workers [133,134]. 

Next the same group reported an interesting protocol for the enantioselective a-alkylation of aldehydes with styrenes, including an intermolecular trap of the supposed cationic intermediate by the nitrate anion, again via organo-SOMO catalysis (Scheme 8.31) [138], The corresponding y-nitrate a-alkyl aldehydes 109-111 were obtained in excellent yields (up to 95%) and enantioselectivities (up to 96% ee) but with moderate diastereoselectivities (a,y-anti/syn 3 1). 

In 2009, an enantioselective a-nitroalkylation of aldehydes as another example of use of organo-SOMO catalysis concept was described (Scheme 8.32) [139],... 

Further extension of organo-SOMO catalysis concept to ketones was reported also by MacMillan and co-workers. In 2010, they developed a family of oxidatively... 

In 2009, an interesting application of organo-SOMO catalysis into intramolecular Friedel-Crafts-type a-arylation of aldehydes was developed by Nicolaou et al. [141] (Scheme 8.34). 

Soon afterward, MacMillan and co-workers [142, 143] also reported enantio-selective intramolecular a-arylation of aldehydes via organo-SOMO catalysis. [Fe(Phen)3l [PFsl 3, instead of CAN, as a single-electron oxidant together with designed imidazolidinone catalysts LXVIII and LXIX were found to be optimal for reaction efficiency and enantioselectivity (Scheme 8.35). Moreover, ortho selectivity, when 1,3-disubstituted aromatic systems were used, was observed. Methodologies presented by Nicolaou and MacMillan represent a useful tool for the total synthesis of various naturally occurring compounds, such as dimethyl calamenene, tashiromine, and so on. 

Closely related methodology to organo-SOMO catalysis is an approach reported by Jang and co-workers [146], who developed environmentally friendly methodology... 

Ror more crucial features involved in the organo-SOMO activation process and experimental evidence of the radical cation itermediate formed in organo-SOMO catalysis, see (a) J. J. Devery, III, J. C. Conrad, D. W. C. MacMillan, R. A. Rlowers, II, Angew. Chem. Int. Ed. 2010,49, 6106-6110 (b) R. Beel, S. Kobialka, M. L. Schmidt, M. Rngeser, Chem. Commun. 2011, 47, 3293-3295. 

Metabolic cyclization routes of polyenes leading to terpenes [1] inspired chemists to synthesize steroids and polycyclic structures [2]. Metal catalysis, chiral auxiliaries, substrate control, and other stoichiometric methods reach some level of success [3], but only recently Rendler and MacMillan published independently two approaches using organo-SOMO catalysis to synthesize these features (Scheme 10.1) [4], as a continuation of their work on the asymmetric cyclization of aldehydes [5]. 

SCHEME 10.1. Stereoselective polycycUzation by organo-SOMO catalysis. 

SCHEME 10.2. Organo-SOMO catalysis mechanism for polycyclization. 

The asymmetric a-chlorination of aldehydes has also be achieved using SOMO catalysis (Scheme 13.21) [49]. In these reactions, saturated aldehydes condensed with MacMillan s imidazolidinone organocatalyst to form enamines. The oxidant combination of Cu(TFA)2 and Na2S20g oxidized the enamine to the radical cation (inset in Scheme 13.21), the reactive intermediate in this transformation containing... 

SCHEME 13.21. Enantioselective a-chlorination of aldehydes via SOMO catalysis. 

In all cases, enantioenriched a-chloroaldehyde products were isolable and could be subsequently readily functionalized. Alternatively, the enantioenriched a-chloroaldehyde products could be functionalized in situ (Scheme 13.22). Using the conditions developed by Jprgensen for the a-chlorination of aldehydes, in situ reductive amination and base-catalyzed intramolecular S 2 reaction generated chiral terminal aziridines in one-pot from achiral saturated aldehydes [50]. Enantioenriched terminal epoxides could be produced in one-pot from achiral saturated aldehydes using SOMO catalysis for the a-chlorination of aldehydes, followed by an in situ reduction and base-catalyzed Sff2 reaction [49]. 

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