2-Nitrosopyridine

Cycloaddition of 2-nitrosopyridine 48 with nitrile oxides can give either di-A -oxides such as 49 or 3-mono-A -oxides such as 50 (93JHC287). In general, greater electron withdrawing character in the aromatic substituent appears to favor formation of the di-A -oxides. Sulfur ylides such as compound 51 are obtained from aryl isothiocyanates and l-amino-2-methylthiopyridinium iodides (84JCS(P1)1891) nitrogen ylides can be obtained from a similar reaction (86H(24)3363). 

Reactions of 2-nitrosopyridine with nitrile oxides afford, depending on structure of the latter, either l,2,4-triazolo[l,5-a]pyridine 1,3-di-N-oxides (370) or the corresponding 1.2.4-triazolo, 5-a Ipyridine 3-oxides (371) (419). 

Ready addition of 2-nitrosopyridine to 1,3-dienes gives 3,6-dihydro-1,2-oxazines, e.g. (774) — (773), and condensation with aromatic amines gives azo compounds, e.g. (774) — (775). Nitroso compounds are oxidized by ozone or sodium hypochlorite to the corresponding nitro compounds. 5-Nitrosopyrimidines can be reduced to the 5-amino derivatives or condensed with activated methylene groups. 

The 4 + 2-cycloaddition of 2-substituted 1,2-dihydropyridines with nitrosoben-zene produces [2.2.2]bicycloadducts, which are readily reduced by alane to trans-2-substituted 3-amino-l,2,3,6-tetrahydropyridines stereospeciflcally.123 The intramolec- (g) ular nitroso-Diels-Alder reaction of a-acetoxynitroso derivatives in aqueous medium produces 3,6-dihydro-l,2-oxazines in high yield.124 The nitroso-Diels-Alder reaction of acyclic OTIPS-dienes (115) and 6-methyl-2-nitrosopyridine (114) in the presence of (g) [Cu(MeCN)4(difluorosegphos)]PF6 yielded the dihydro 1,2-oxazine cycloadduct (116) with high yield and enantioselectivity (Scheme 33). 125 (Fe)... 

Methyl-2-nitrosopyridine reacted with (lZ,3Z)-cycloocta-l,3-diene to give the iV-pyridyl-l,2-oxazocine 132. Such a Diels-Alder reaction was conducted in the presence of a catalytic amount of an asymmetric bidentate ligand and a metal to provide an enantiomerically enriched cycloadduct however, the ee observed was only 4% (Equation 11) <2005WO068457>. 

Reactions which formally involve the oxidation of azides have been reviewed by Boyer. Other oxidations with useful synthetic applications include two which start from nitrogen ylides. Sulfimides (50) derived from electron-deficient aromatic and heterocyclic amines are oxidized to the corresponding nitroso compounds by MCPBA. - This is a very useful method of preparation of some otherwise inaccessible nitroso compounds such as 2-nitrosopyridine and 1-nitrosoisoquinoline. They can be further oxidized, for example by ozone, to the nitro compounds. Phosphimides (51) are oxidized directly by ozone to the nitro compounds, although the nitroso compounds are intermediates. Isocyanates can also be oxidized to the corresponding nitro compounds, by dimediyldioxiraiK (1). ... 

The second example of enantiodiveregent hetero-Diels-Alder reaction is shown in Scheme 6.28. Thus, racemic cyclohexadiene 132 was reacted with 2-nitrosopyridine 133 in the presence of a copper(I) source and the chiral phosphine ligand 134 to afford regioisomeric hetero-Diels-Alder products 135 (48% and 97% ee) and 136 (52% and 92% ee) [49b]. The Cu(I) complex of 134 functions as a chiral Lewis acid that catalyses the 2-1-4 cycloaddition. 

In the field of metal-catalyzed asymmetric cycloadditions, [2+2] cycloaddition seems to be relatively rare due to the ring strain force of the products. In 2010, Studer and co-workers presented the first Cu(I)/Walphos-catalyzed enantioselective [2+2] cycloaddition of 2-nitrosopyridine with various ketenes to afford synthetically valuable 1,2-oxazetidine-3-ones with good enantioselectivity (Scheme 33) [58]. Density function theory (DPT) calculations give evidence that the reaction occurs via a concerted pathway. 

Scheme 33 Asymmetric [2+2] cycloaddition of 2-nitrosopyridine with ketenes...

It is widely appreciated that the 1,3-cycloaddition is a pericyclic reaction, which proceeds through a concerted mechanism. However, many other cycloaddition reactions do not perform via a concerted manner, which could be called formal cycloaddition reactions. Studer and coworkers reported the first examples of highly enantioselective formal [3-1-2] cycloadditions of allyltin derivatives 48 with 2-nitrosopyridine 49 to give substituted isoxazolidines 50 [26]. It was found that the use of [Cu(MeCN)4]PF6 and Walphos-CFj ligand 51 was essential for obtaining high yield and enantioselectivity (Scheme 2.14). 

Chatterjee, L, Frdhlich, R., Studer, A. (2011). Formation of isoxazolidines by enantioselective copper-catalyzed annulation of 2-nitrosopyridine with allylstannanes. Angewandte Chemie International Edition, 50, 11257-11260. 

Chateijee I, Jana CK, Steinmetz M, Grimme S, Studer A. Copper-catalyzed enantioselective [2+2] cycloadditions of 2-nitrosopyridine with ketenes. Adv. Synth. Catal. 2010 352 945-948. 

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