Oxazepines Michael additions

Another type of chiral Michael acceptor, the oxazepine derivatives (47), is prepared by condensation of the (-)-ephedrine-derived malonic acid derivative (46) with aldehydes (Scheme 18).51 52 Treatment of (47) with a variety of Grignard reagents in the presence of NiCh affords, after hydrolysis and decarboxylation, the 3-substituted carboxylic acids (48), in most cases with more than 90% ee. Diastereoselective Michael additions to (47) were also used for the preparation of optically active cyclopropane derivatives (49)53 and P-substituted-y-butyrolactones (50 Scheme 18).54 A total synthesis of indolmycin is based on this methodology.55... 

The chiral, nonracemic oxazepine derivative (46 Scheme 18) was studied as donor in the Michael addition to prochiral a,p-unsaturated carbonyl compounds.134-133 The products were obtained with 44-55% ee after removal of the chiral auxiliary group. With 1-nitrocyclohexene as acceptor, somewhat better se-lectivities (62% ee) were observed.136... 

The Michael addition of (2/ ,3S)-3,4-dimethyl-5,7-dioxo-2-phenylperhydro-1,4-oxazepine (236) to l-phenyl-2-buten-l-one (237) and 2-cyclopenten-l-one (238) in tetrahydrofuran at 0°C gave a mixture of diastereomeric... 

Variations in the 5-substituent of chiral oxazolines cause considerable fluctuations in the degree of asymmetrical alkylation of these substrates, showing that steric as well as chelation factors are important in this method of obtaining chiral carboxylic acids. An impressive example of asymmetric induction is the synthesis of 3-substituted-3-phenylpropionic acids (5) of ca. 99% optical purity, from the 1,4-oxazepine (4) (derived from a-ethoxycarbonylcinnamic acid and /-ephedrine hydrochloride), by Michael addition of Grignard reagents in the presence of nickel chloride, followed by hydrolysis and decarboxylation."... 

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). 

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. 

An unexpected result is observed when 2,6-dimethylhepta-2,5-dien-4-one 96 reacts with hydroxylamine (Scheme 2.24). Instead of forming 1-hydroxy-4-piperidone 98 or isoxazole 99, a double Michael-type addition of the OH and NH groups of hydroxylamine across the double bonds of 96 with formation of hexahydrol,2-oxazepine 97 occurs [101]. 

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See also in sourсe #XX -- [ ]

See also in sourсe #XX -- [ , ]

See also in sourсe #XX -- [ , ]

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