A Stereoselective and Short Total Synthesis of the Polyhydroxylated gamma-Amino Acid (-)-Detoxinine, Based on Stereoselective Preparation of Dihydropyrrole Derivatives from Lithiated Alkoxyallenes

摘要

Based on our earlier results employing lithiated methoxyallene 2 as C_3 building block and imines 3 for the synthesis of dihydropyrrole derivatives synthesis of dihydropyrrole derivatives 5, we have investigated chiral imines 6, 10, and 15 as electrophilic components. Combined with lithiated alkoxyallenes, these imines provide the corresponding primary adducts and finally the dihydro-pyrrole derivatives 8, 12, 17, 20, and 22 in good yields and with high to excellent syn selectivities. This stereochemical outcome is interpreted as a result of alpha-chelate control. Treatment with hydrochloric acid converted syn-8 and syn-12 into bicyclic compounds 9 and 13, where- as under more mildly acidic conditions adduct syn-17 was transformed into diol syn-18. The total synthesis of the un-common gamma-amino acid (-)-detoxinine could be achieved by starting from (S)-malic acid, which was converted into imine 15 in four steps. Lithiated benzyl-oxyallene added to imine 15 and efficiently furnished the crucial dihydropyr-role derivative syn-22. The hydrogenol-ysis of this compound did not directly provide the protected triol 29 as anticipated, but a stepwise protocol made the triol available in a fairly satisfactory manner. A second crucial step of the synthesis was the selective oxidation of 29, which could be achieved by employing platinum dioxide and oxygen. The resulting bicyclic lactone 30 was smoothly transformed into enantiopure (-)-detoxinine. Thus, a fairly short synthesis of this natural product based on a lithiated alkoxyallene could be per-formed, demonstrating the potential of these intermediates for syntheses of interesting functionalized heterocyclic compounds.