Diastereoselective Synthesis of Unsaturated Vicinal Amino Alcohols via Diels-Alder Reactions of iV-Sulfinyl Dienophiles

A novel diastereoselective route for the synthesis of α-hydroxy-β,γ-unsaturated amine derivatives is described. The protocol starts with a 3,6-dihydrothiazine 1-oxide, which is obtained stereoselectively by a Diels-Alder [4 + 2] cycloaddition of a N-sulfinyl dienophile and a 1,3-diene of known geometry. Fission of the S-N bond of the adduct with a Grignard reagent leads to an allylic sulfoxide which is converted stereoselectively to an allyl alcohol via an allylic sulfoxide/sulfenate ester [2,3]-sigmatropic rearrangement. (E,E)-2,4-Hexadiene (4) and (E,Z)-2,4-hexadiene (7) were stereoselectively transformed to threo amino alcohol (9) and erythro amino alcohol (11), respectively. Intermediates in these transformations have been investigated by ¹H NMR experiments. The configuration and conformation of Diels-Alder adduct 5a have been determined by X-ray crystallography and ¹H NMR lanthanide induced shift experiments. A variation of this strategy incorporating intramolecular N-sulfinyl Diels-Alder reactions has been used in total synthesis of the sphingolipid bases erythro- and threo-sphingosine. (E,E)-Diene carbamate 31 was converted to threo-sphingosine (25) in four steps in 52% overall yield. Similarly, (E,Z)-diene carbamate 46 was transformed to erythro-sphingosine (27) in 55% overall yield. Interestingly, the N-sulfinyl compound obtained from (E,Z)-diene carbamate 39 did not cyclize, probably for conformational reasons.