Aldehydes organo-SOMO catalysis

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

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

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],... 

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. 

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]. 

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... 

Enantioselective intramolecular F-C-type a-arylation of simple aldehydes, based on the concept of organo-SOMO catalysis, paved the way to the synthesis of two natural products via very sophisticated and well-designed strategies (Section 35.2.1). In 2009, Nicolaou and coworkers published the synthesis of the antitumor natural product demethyl calamenene [50] and, independently, in the same year the group of MacMillan developed an elegant route to (—)-tashiromine (Scheme 35.29) [5b]. 

SOMO catalysis, which has been the subject of considerable attention in recent years, is a unique and versatile activation mode that can participate in bond construction with various n-rich nucleophiles. The first asymmetric intramolecular a-arylation of aldehydes was reported by Nicolaou in 2009 using organo-SOMO catalysis [17a]. The authors applied imidazolidinone 23 as catalyst and cerium ammonium nitrate (CAN) as the oxidant Various 5-oxopentylbenzenes 36, or indole derivatives 38, could furnish the cyclic products 37 or 39, respectively, in good yields and with excellent ees (Scheme 36.11). Later, MacMillan disclosed similar research [17b], and a theoretical study of the intramolecular a-arylation of aldehydes was also reported by the same group via density functional theory [17c],... 

Organo-SOMO catalysis has been successfully exploited to achieve the first asymmetric a-vinylation of aldehydes using vinyl trifluoroborate salts and the commercial Kim and MacMillan catalyst 191. " ° Vinyl potassium trifluoroborate salts participate in enantioselective and regioselec-tive carbon-carbon bond formation with the aldehyde-derived radical cation 192 to form a (3-borato-stabilized radical 193 (Scheme 25.90), which in the presence of a suitable oxidant will undergo rapid electron transfer to render the (3-cation (not shown). Subsequent Peterson elimination of the trifluoroborate group with tran.s-selectivity followed by iminium hydrolysis of 194 would then reveal an optically enriched R-( )-vinyl aldehyde (e.g., 195). 

Conrad JC, Kong J, Laforteza BN, MacMillan DWC. Enantioselective a-arylation of aldehydes via organo-SOMO catalysis. An ortho-selective arylation reaction based on an open-shell pathway. J. Am. Chem. Soc. 2009 131(33) 11640-11641. 

---