Aqueous media nitroso-Diels—Alder

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)... 

The nitroso functionality is a powerful dienophile and N-alkyl- and N-acylnitroso compounds give inter- and intrahetero Diels-Alder reactions easily. The cycloadditions also occur in aqueous medium although some nitroso compounds (i.e. N-acylnitroso derivative) are short-lived in the presence of water. The NO functionality is generated in situ by periodate oxidation of the hydroxylamine group and the cycloaddition with butadienes gives a 1,2-oxazine ring. Scheme 5.16 illustrates the utility of the nitroso Diels-Alder cycloaddition for the synthesis of (—l-swainsonine/ (—)-pumiliotoxin and BCX-1812... 

The intramolecular /zetero-Diels-Alder reactions of 4-O-protected acyl-nitroso compounds 81, generated in situ from hydroxamic acids 80 by periodate oxidation, were investigated under various conditions in order to obtain the best endo/exo ratio of adducts 82 and 83 [65h] (Table 4.15). The endo adducts are key intermediates for the synthesis of optically active swainsonine [66a] and pumiliotoxin [66b]. The use of CDs in aqueous medium improves the reaction yield and selectivity with respect to organic solvents. 

The nitroso moiety of the N-acylnitroso function is a powerful dienophile and therefore N-acylnitroso compounds are trapped rapidly, especially in an intramolecular reaction, with a diene allowing the Diels Alder reaction to occur also in water, although N-acylnitroso compounds are short-lived in aqueous medium. 

An intramolecular hetero-Diels-Alder reaction of enantiomerically pure iV-acyl nitroso derivatives 78, prepared from hydroxamic acids 77 by oxidation on treatment with Pr4NI04 in an aqueous medium, afforded a mixture of diastereomeric pyrido[l,2-A][l,2]oxazin-8-ones 79 and 80 (Scheme 5) <1996J(P1)1113, 20000L2955,... 

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