Nitroso aldol reactions

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). 

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

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... 

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... 

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

Scheme 24.20 Enantioselective nitroso aldol reaction catalysed by (S)-l-naphthyl glycolic acid 61.

The proline-catalyzed nitroso aldol reaction of aldehydes with nitrosobenzene derivatives, simultaneously reported by MacMillan, Zhong, and Hayashi in 2003... 

This process, like the proline-catalyzed nitroso aldol reaction, has been shown to exhibit the unusual characteristics of a rising reaction rate and a positive nonlinear effect [31]. An autoinductive reaction resulting in selective formation of a proline-product species in the catalytic cycle, analogous to that depicted in Scheme 2.3, has been invoked by Blackmond [32] to account for these results. 

Xu, Y.-J., Liu, Q.-Z., Dong, L. (2007). Copper-catalyzed enantioselective tandem conjugate addition/A-nitroso aldol reaction. Synletf 273-277. 

The reaction of silyl and tin enolates with nitrosobenzene, the so-called nitroso aldol reaction, was studied by Yamamoto and coworkers aiming at an overall enantioselective hydroxylation [254, 255]. This approach faces, however, the problem that in a noncatalyzed reaction, the nucleophilic silyl and stannyl enol ethers 514 attack the nitrogen atom of the ambident electrophile nitrosobenzene 515 so that the formation of hydroxyamino ketones 516 results [254a]. Fortunately, the authors developed suitable procedures wherein, under catalysis by chiral silver-bisphosphane complexes, aminooxy ketones 517 result in high ambidoselectivity. Alternatively, a controlled attack at nitrogen under formation of hydroxyamino ketones also became feasible by tuning of the catalytic system [254b,c] (Scheme 5.127). 

In 2003, Rawal reported the use of TADDOLs 177 as chiral H-bonding catalysts to facilitate highly enantioselec-tive hetero-Diels-Alder reactions between dienes 181 and different aldehydes 86 (Scheme 6.29A) [82], and also BINOL-based catalysts 178 were found to facilitate this reaction with excellent selectivities [83]. TADDOLs were also successfully used as organocatalysts for other asymmetric transformations like Mukaiyama aldol reactions, nitroso aldol reactions, or Strecker reactions to mention a few examples only [84]. In addition, also BINOL derivatives have been employed as efficient chiral H-bonding activators as exemplified in the Morita-Baylis-Hilhnan reaction of enone 184 with different carbaldehydes 86 [85]. The use of chiral squaramides for asymmetric reactions dates back to 2005 when Xie et al. first used camphor-derived squaric amino alcohols as ligands in borane reductions [86]. The first truly organocatalytic application was described by Rawal et al. in 2008 who found that minute amounts of the bifunctional cinchona alkaloid-based squaramide 180 are... 

Scheme 1.31 Regioselective synthesis of N- or O-adduct in enantioselective Nitroso aldol reactions.

The hydrogen bonding catalyst turned out to be effective also for the enantiose-lective nitroso aldol reaction of enamine. Yamamoto et al. reported that treatment of enamine and nitrosobenzene with (29) furnished N-nitroso aldol products in 77-91% ee. In striking contrast, the glycolic acid derivative (31) furnished O-nitroso aldol products in 70-93% ee (Scheme 2.76) [142]. 

Yamamoto et al reported nitroso Diels-Alder type reaction of diene with nitrosobenzene by a binaphthol derivative (39). Bicyclo ketones were obtained with excellent diastereo- and enantioselectivity (Scheme 2.82) [151]. The cyclization reaction involved the sequential N-nitroso aldol reaction followed by the Michael reaction. Optically active l-amino-3,4-diols are synthesized. 

Scheme 10.7 Regio- and enantioselective nitroso aldol reaction of enamines.

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