Aldol nitrosobenzene

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). 

It is true that highly enantioselective reactions are possible with proline in the asymmetric a-amination of aldehydes by azodicarboxylates and in a-oxidation with nitrosobenzene. However, good rather than excellent yields and enantioselectivities are more common in intermolecular Michael and aldol reactions. Moreover, the high catalyst loadings required for proline-catalyzed aldol reactions (up to 30%), and low TOFs (from hours to days to achieve a good conversion, even at a high catalyst... 

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)... 

Zhong rationalized the enantioselectivity by proposing an enamine mechanism which proceeds via the chair transition state shown in Figure 7.1 [11]. In this transition state, the Si face of an E enamine formed from the aldehyde and the catalyst L-proline approaches the less-hindered oxygen atom of nitrosobenzene leading to the chiral product with (R) configuration. This mechanism is in accordance with the proposed reaction mechanism for the aldol reaction (see chapter 6.2). 

Hydrogen bond-promoted asymmetric aldol reactions and related processes represent an emerging facet of asymmetric proton-catalyzed reactions, with the first examples appearing in 2005. Nonetheless, given their importance, these reactions have been the subject of investigation in several laboratories, and numerous advances have already been recorded. The substrate scope of such reactions already encompasses the use of enamines, silyl ketene acetals and vinylogous silyl ketene acetals as nucleophiles, and nitrosobenzene and aldehydes as electrophiles. 

Table 6.43). These authors proposed activation of nitrosobenzene to aldol addition through N-coordination when using chiral carboxylic acid catalyst 134 and through O-coordination when using the less-acidic taddol catalyst 119 to explain the observed regioselectivities.

In 2002, Yamamoto and Momiyama reported an unusual aldol-like reaction with silyl enol ethers and nitrosobenzene in the presence of a catalytic amount of TESOTf (nitrosoaldol reaction).29 Usually, nucleophiles react with nitrosobenzene without Lewis acid to give the N adduct predominantly. In contrast, they reported that the reaction of silyl enol ethers and nitrosobenzene catalyzed by TESOTf afforded the... 

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... 

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). ... 

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

The same group was able to perform a similar cycloaddition reaction but with complete reversal of the regioselectivity (Scheme 11.45) [126]. They revealed that the O vs. N selectivity is dependent on the presence or absence of a weak hydrogen-bond donor in the catalyst (OH group), which apparentiy coordinates the oxygen atom of nitrosobenzene to facilitate the formation of iV-nitroso aldol products. Nucleophilic attack of the preformed enamine is postulated to occur from the Re face as described in Scheme 11.45. For steric reasons the subsequent intramolecular 0-Michael addition just occurs when R are CH3 groups. 

Momiyama and Yamamoto [50] found that cyclic achiral enamines also react with nitrosobenzene in the presence of chiral carboxylic acids to produce the 0-nitroso aldol product (Scheme 12.3). The best result was obtained with piperidine enamine 16 and (S)-l-naphthyl glycolic acid 17. 

In analogy t 0 the Cu(II) complex systems, the silver(I) -catalyzed aldol reaction is also proposed to proceed smoothly through a Lewis acidic activation of carbonyl compounds. Since Ito and co-workers reported the first example of the asymmetric aldol reaction of tosylmethyl isocyanide and aldehydes in the presence of a chiral silver(I)-phosphine complex (99,100), the catalyst systems of sil-ver(I) and chiral phosphines have been applied successfully in the aldol reaction of tin enolates and aldehydes (101), Mukaiyama aldol reaction (102), and aldol reaction of alkenyl trichloroacetates and aldehydes (103). In the Ag(I)-disphosphine complex catalyzed aldol reaction, Momiyama and Yamamoto have also examined an aldol-type reaction of tin enolates and nitrosobenzene with different silver-phosphine complexes (Scheme 15). The catalytic activity and enantioselectivity of AgOTfi(f )-BINAP (2 1) complex that a metal center coordinated to one phosphine and triflate were relay on solvent effect dramatically (Scheme) (104). One catalyst system solves two problems for the synthesis of different O- and AT-nitroso aldol adducts under controlled conditions. 

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). 

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. 

Another way to carry out the electrophilic amination of a carbonyl compound is by the reaction of an enamine or enolate with a nitroso derivative, the so-called hydroxyamination, oxyamination, or N-nitroso aldol reaction. The regio- and enan-tioselectivity of the transformation have been studied by DFT calculations for the reaction between achiral enamines and nitrosobenzene (70a) promoted by a chiral Brmsted acid catalyst, such TADDOL [64]. The results suggested a transition state that involves the enamine, nitrosobenzene, and two or more organic acid molecules, forming a cluster-like structure, where hydrogen-bonds play an important role. 

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