1243250-52-3Relevant academic research and scientific papers
1,2-oxazines as building blocks for stereoselective synthesis: Preparation of oxygen-substituted 1,2-oxazines, either by alcohol addition or by epoxidation, and subsequent hydrogenation leading to 1,2-amino alcohols and pyrrolidines
Zimmer, Reinhold,Buchholz, Monika,Collas, Markus,Angermann, Joerg,Homann, Kai,Reissig, Hans-Ulrich
supporting information; experimental part, p. 4111 - 4121 (2010/10/02)
Stereodefined oxygen-substituted 1, 2-oxazines were prepared by three different routes. The cycloaddition of enol ethers such as 1 with a-nitrosoalkenes generated in situ gave the heterocycles 3 and 4. Acid-catalysed additions of alcohols to the 6H-1, 2-oxazines 5 led to mixtures of the adducts 6 and the substitution products 7 with moderate chemoselectivity. Epoxidation of the 6H-1, 2-oxazines 5 proceeded more efficiently and furnished the corresponding epoxides 25 and 32 in reasonable to excellent yields. It was demonstrated that the resulting oxygen-substituted 1, 2-oxazines were suitable precursors for the preparation of cyclic or acyclic primary and secondary amines in racemic or enantiopure form. Hydrogenation of the 3-phenyl-substituted 1, 2-oxazines 3 and 25a and of (6S)- and (6R)-32 preferentially furnished the 1, 2amino alcohols 15, rac-29 and (2S)- and (2R)-29. On the other hand, reduction of the 3-ethoxycarbonyl-substituted 1, 2-oxazines 4, 6d and 20 led to the formation of the N-protected proline esters 21-24 in moderate yields. It was also found that the 5-methyl-6H-1, 2-oxazine 10 was a good precursor for the propargylic ether 11, which allowed a Pauson-Khand reaction leading to the tricyclic compounds 13 and 14. Hydrogen peroxide converted 10 into a hydroperoxide intermediate, which was further transformed into the l, 2-oxazin-6-one 28b. Overall, the results demonstrate the remarkable potential of suitably substituted 1, 2-oxazine derivatives for the stereoselective synthesis of amines.
