Organo-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 1.27 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). 

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

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

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. 

Um JM, Gutierrez O, Schoenebeck F, Houk KN, MacMillan DWC (2010) Nature of Intermediates in Organo-SOMO Catalysis of a-Arylation of Aldehydes. J Am Chem Soc 132 6001... 

A new mode of oxidative organocatalytic activation has been reported, termed organo-SOMO catalysis, which has been successfully applied using an enantioselective intramolecular a-arylation of aldehydes via catalytic oxidative radical cyclization (Eq. 9.25) [101]. In this approach, the exposure of an aryl-tethered aldehyde (124) to a chiral secondary amine catalyst 125 and a suitable oxidant leads to enantio-enriched 126 ... 

Pham, P. V., Ashton, K., MacMillan, D. W. C. (2011). The intramolecular asymmetric allylation of aldehydes via organo-SOMO catalysis a novel approach to ring construction. Chemical Science, 2, 1470-1473. 

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... 

Kim H, MacMillan DWC (2008) Enantioselective organo-SOMO catalysis the a-vinylation of aldehydes. J Am Chem Soc 130 398-399... 

Even shorter, and certainly less conventional, is the synthesis of (—)-tashiromine ent-929) by MacMillan s group (Scheme 121). " This route rehed on the ortho-selective intramolecular a-arylation of the pyrrole-aldehyde 979 mediated by the chiral amine catalyst 980 in conjunction with ceric ammonium nitrate as a single-electron oxidant in a process that MacMillan has termed organo-SOMO catalysis. The reaction is thought to proceed via an imine intermediate that undergoes oxidation to the radical... 

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