Aldol nitroso

Yamamoto s group recently published a highly enantioselective chiral amine-catalyzed domino O-nitroso aldol/Michael reaction of 2-268 and 2-269 (Scheme 2.63) [141]. As products, the formal Diels-Alder adducts 2-271 were obtained with >98% 66, which is probably due to the selective attack of an enamine, temporarily formed from amine 2-270 and enone 2-268, onto the nitroso functionality. 

Scheme 2.63. Organocatalytic synthesis of 2-271 by a domino O-nitroso-aldol/Michael reaction.

Momiyama and Yamamoto" have further expanded the utility of H-bond-mediated reactions catalyzing nitrosobenzene addition to enamines using TADDOL 38 or hydroxy acid 39 as catalysts. Remarkably, the judicious selection of H-bond-catalyst/enamine combination resulted in the formation of only A-addition compounds with TADDOL 38 (Scheme 11.14e), while acid 39 furnished exclusively O-nitroso aldol products (Scheme 11.14f). 

Momiyama and Yamamoto have recently demonstrated that acid cocatalysts can even influence the outcome of enamine-mediated reactions [63]. In their studies of the acid-catalyzed O- and A-nitroso aldol reaction, they found that the nature of the acid catalyst dictates the regioselectivity of the reaction between preformed enamine species A carboxylic acid catalyst promoted the 0-nitroso aldol reaction whereas a hydrogen bonding catalyst catalyzed the formation of an A-adduct, both in high enantioselectivities(Scheme 10). 

Yamamoto and coworkers described a highly enantioselective asymmetric domino 0-nitroso aldol-conjugate addition seqnence using cyclic enones 221 and aromatic nitroso compounds 222 as depicted in Scheme 36 [346]. A related reaction with imines was also reported by Cdrdova and coworkers (Scheme 37) [228]. 

Scheme 36 Domino 0-nitroso aldol-conjugate addition...

Scheme 72 Asymmetric nitroso aldol reactions of achiral enamines...

Exclusive formation of the M-nitroso aldol product from similar starting materials was observed in the presence of 1-naphthyl TADDOL (30 mol%) in toluene (63-81%, 65-91% ee-, n=, 2). 

Nitroso-Aldol Reaction In the course of the Yamamoto group s studies on the nitroso-aldol (NA) reachon of enamines substantial rate increases were observed upon addihon of stoichiometric amounts of achiral Br0nsted acid. Furthermore, exclusive regioselective formation of the N- versus 0-adducts could be controlled by the choice of MeOH or AcOH, respechvely, as Br0nsted acids (Scheme 5.60) [113]. Subsequently, enantioselechve versions of both N- and 0-nitroso aldol... 

In direct nitroso aldol reactions of a-branched aldehydes, an L-prolinamide (50) catalyses to give a-hydroxyamino carbonyl compounds which are otherwise dis- favoured ees up to 64% were found.149 Another prolinamide derivative gives similar results in a nitrosobenzene reaction.150 For proline-catalysed cases involving highly substituted cyclohexanones, DFT calculations have highlighted the roles of electro- static and dipole-dipole interactions in the level of de achieved.151 (g)... 

Grignard additions, 9, 66 radical addition of zincs, 2, 401 zinc-containing reagent additions, 2, 398 Nitroolefins, enantioselective conjugate additions, 10, 382 (Nitrophenylthio)osmocenes, preparation, 6, 634 (Nitrophenylthio)ruthenocenes, preparation, 6, 634 Nitropyridines, reductive aminocarbonylation, 11, 543 Nitroso aldol reaction... 

Table 6.42 (S)-l-Naphthyl glycolic acid-catalyzed O-nitroso aldol reactions.

Table 6.43 Taddol-catalyzed N-nitroso aldol reactions.

The reaction of nitroso compounds with typical metal enolates, the nitroso aldol reaction, occurs in high yields to generate a-hydroxyamino carbonyl compounds. Exclusive iV-selectivity >99 1 is observed to give hydoroxyamino ketone in the reaction with tin enolates (Equation (70)).2... 

The use of Lewis acid drastically changes the regioselectivity. The highly enantioselective and O-selective nitroso aldol reactions of tin enolates with nitrosobenzene have been developed with the use of (i )-BINAP-silver complexes as catalysts. AgOTf and AgCICL complexes are optimal in the O-selective nitroso aldol reaction in both asymmetric induction (up to 97% ee) and regioselection (0/N= > 99/1), affording amino-oxy ketone. The product can be transformed to a-hydroxy ketone without any loss of enantioselectivity (Equation (71)).224... 

Silver salts or reagents have received much attention in preparative organic chemistry because they are useful catalysts for various transformations involving C-G and C-heteroatom bond formation.309 Especially, the silver(i)/ BINAP (2,2 -bis(diphenylphosphino)-l,T-binaphthalene) system is a very effective catalyst for a variety of enantio-selective reactions, including aldol, nitroso aldol, allylation, Mannich, and ene reactions. Moreover, silver salts are known to efficiently catalyze cycloisomerization and cycloaddition reactions of various unsaturated substrates. Recently, new directions in silver catalysis were opened by the development of unique silver complexes that catalyze aza-Diels-Alder reactions, as well as carbene insertions into C-H bonds. 

Recently, some extensive research has been devoted to exploring a diastereo-selective and enantioselective route for the synthesis of a-hydroxyaldehydes or a-hydroxyketones because they are important building blocks for the construction of complex natural products and biologically active molecules [91]. In parallel with the transition-metal-catalyzed asymmetric nitroso-aldol reaction [92], much interest has also been expressed towards the proline-catalyzed direct asymmetric a-aminoxylation of aldehydes or ketones for the synthesis of optically active a-hydroxyladehydes and a-hydroxyketones [93]. Wang [94] and Huang [95] independently reported an L-proline-catalyzed asymmetric a-aminoxylation reaction in ionic liquids, whereby it was found tliat aldehydes and ketones could undergo... 

Yamamoto and coworkers reported a tandem highly enantioselective 0-nitroso aldol-conjugate addition reaction catalysed by 5a. Cyclic enones and aromatic nitroso compounds afforded the corresponding bicyclic products with excellent enantioselectivity (Scheme 9.49). The results considerably extended the control of regio- and stereochemistry for the synthesis of nitroso Diels-Alder adducts. 

Scheme 11.12 Cu-catalyzed 1,4-addition/N-nitroso aldol reaction of 54 [23],...

In 2005 Yamamoto et al. reported the first example of asymmetric Bronsted acid-catalysed nitroso-aldol synthesis in particular 1-naphthyl-TADDOL 2a was particularly efficient in promoting the addition of achiral enamines 22 to nitrosobenzene with high regio- and enantioselectivities (Scheme 24.8). ... 

Scheme 24.8 As mimetric TADDOL-catalysed nitroso aldol nthesis.

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