Application of L ‐Erythrose‐Derived Nitrones in the Synthesis of Polyhydroxylated Compounds via 3,6‐Dihydro‐2 H ‐1,2‐oxazine Derivatives

Enantiopure 3,6‐dihydro‐2 H ‐1,2‐oxazines were prepared by [3+3] cyclisations starting from lithiated methoxyallene and the L ‐erythrose‐derived nitrones 1′ and 3 . The role of the side‐chain protective group, which steers the highly selective formation of either anti ‐ or syn ‐configured products, was demonstrated. A hydroboration/oxidation protocol smoothly converted 1,2‐oxazine derivative syn ‐ 5 into secondary alcohol 6 . After deprotection, polyhydroxylated tetrahydro‐2 H ‐1,2‐oxazine 11 , which can be regarded as an azasugar, was isolated. Analogous treatment of 1,2‐oxazine anti ‐ 5 with the borane not only provided the expected secondary alcohol 7 , but it also induced reduction of the C=C bond and ring opening. Treatment of syn ‐ 5 and anti ‐ 2 with hydrochloric acid in methanol induced deprotections and cyclisations leading to bicyclic tetrahydro‐2 H ‐1,2‐oxazine derivatives. The second ring can be either a furan or a pyran ring. In the syn series, furan derivative 12 was formed exclusively, and its hydrogenolysis led to enantiopure aminofuran derivative 14 . Acid‐promoted rearrangement of unprotected anti ‐ 2 led to a mixture of bicyclic compounds with furan or pyran rings fused to the 1,2‐oxazine core. However, when TBDPS‐protected compound 20 was used it cleanly led to 1,2‐oxazine 21 with a fused furan ring and then to aminofuran 22 . Alternatively, the N–O bond in unprotected anti ‐ 2 was chemoselectively reduced with samarium diiodide, efficiently generating highly functionalized allylic alcohol 23 . Acid‐promoted cyclisation and deprotection furnished furan derivative 24 . Mechanistic suggestions to explain the different outcomes of the acid‐induced transformations are provided. Overall, it is demonstrated that the stereodivergent addition of lithiated alkoxyallenes to L ‐erythrose‐derived nitrones allow flexible access to a series of enantiopure amino polyols, including aminofuran derivatives.