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
Stereodefined oxygen‐substituted 1,2‐oxazines were prepared by three different routes. The cycloaddition of enol ethers such as 1 with α‐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...
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Veröffentlicht in: | European Journal of Organic Chemistry 2010-07, Vol.2010 (21), p.4111-4121 |
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Zusammenfassung: | Stereodefined oxygen‐substituted 1,2‐oxazines were prepared by three different routes. The cycloaddition of enol ethers such as 1 with α‐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 1,2‐amino 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 1,2‐oxazin‐6‐one 28b. Overall, the results demonstrate the remarkable potential of suitably substituted 1,2‐oxazine derivatives for the stereoselective synthesis of amines.
Oxygen‐substituted 1,2‐oxazines were prepared from 6H‐1,2‐oxazines. 1,4‐Additions of alcohols provided 5‐alkoxy‐substituted derivatives. Use of hydroperoxides furnished epoxides. Reduction of these substituted 1,2‐oxazines gave hydroxyproline derivatives or 1,2‐amino alcohols. |
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ISSN: | 1434-193X 1099-0690 |
DOI: | 10.1002/ejoc.201000425 |