Oxazepines addition reaction

A concise a-amino acid-based synthetic approach via sequential inter-molecular nucleophilic substitution and intramolecular Michael addition reactions starting from MBH acetates has also been described to synthesize disubstituted [l-4]oxazepin-2-ones 821. Such a synthetic method was operationally simple under ambient conditions, and gave 81-93% yields of the target [l,4]oxazepin-2-ones (Seheme 4.236). 

Interestingly, a study of the addition reactions of lithium dialkylcuprates revealed that the same product enantiomer 67 was formed regardless of the starting oxazepine olefin isomer employed (99% ee, Scheme 12.9). The intermediacy of a radical anion prone to configurational equilibration was suggested in order to account for this unanticipated stereoconvergent outcome [79]. 

The synthesis of perfluorinated 1,2-oxazepines 33 and 34 was carried out through unusual cyclocondensation process. The reaction of hydroxy lamine with excess of 16 resulted in the formation of 1 2 adduct—1,2-oxazepine 33 in 50% yield, along with smaller amount of by-product 34 (derived from 33 as the result of HF addition across the C=C bond (Fig. 10.15), while the expected 5-fluoro-3-(pentafluoroethyl)-4-trifluoromethylisoxazole is formed in this reaction only as a minor by-product. Several 2,2-bis(trifluoromethyl)-l,3-oxazepines were prepared using an interesting reaction of 2,2-bis(trifluoromethyl)-l,3-oxazolidin-5-ones (35) and 1-diethyla-minoprop-l-yne. This reaction results in a high-yield formation of the corresponding 2-bis(trifluoromethyl) l,3-oxazepin-5-ones 36 (Fig. 10.16). 

The reaction of ethanolamines with 16 has significantly higher selectivity for the formation of seven-membered heterocycles compared to the reactions of ethyleneglycol and catechol. In this reaction, 1,4-oxazepines 42 form as a major products, along with small amount of 43, resulting from HF addition across the double bond of 42 (Fig. 10.18). ... 

A low yield of the solid hexahydro-3,3,7,7-tetramethyl-l,2-oxazepin-5-one (38) (m.p. 50°C) can be obtained on reaction of phorone with hydroxylamine in the presence of base. The competing reaction is the formation of the five-membered ring compound, 3-isobutenyl-5,5-dimethyl-4,5-dihydroisoxazole by intramolecular 1,2-addition, rather than by 1,4-addition by nitrogen in the intermediate (37), followed by dehydration. Some of the oxime of (38) is also formed (Scheme 3) <81G279>. 

Asymmetric Michael addition of optically active perhydro-l,4-oxazepin-5,7-diones, and of thioglycollic acid in the presence of a cinchona alkaloid as catalyst, to a-nitro-olefins yields y-nitrocarboxylic acids and 2-nitrothio ethers, respectively, with reasonable enantiomeric excess. Allylsilanes add to a-nitro-olefins in the presence of aluminium chloride to give unsaturated nitronic acids, which are further transformed in a Nef-type reaction to give y,5-enones (Scheme 36).Nitro-compounds are also converted into the corresponding carbonyl compounds upon treatment with base and MoOs pyHMPA, a new modified Nef reaction. 

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