Total synthesis of a protected form of sphingofungin E using the [3,3]-sigmatropic rearrangement of an allylic thiocyanate as the key reaction.
An approach to the stereocontrolled synthesis of the protected form of sphingofungin E (32) starting from the known protected d-glucose derivative 3 is described herein. For the construction of a tetrasubstituted carbon atom that is substituted with nitrogen, the [3,3]-sigmatropic rearrangement of thiocyanate 8 was employed. Subsequent functional group interconversions afforded the highly functionalized fragment, allylic bromide 26. Its coupling reaction with the known C(12) hydrophobic segment 2, followed by further manipulation, completed the total synthesis.
gem-Diacetates as carbonyl surrogates for asymmetric synthesis. Total syntheses of sphingofungins E and F.
The equivalent of an asymmetric addition to a carbonyl group with a stabilized anion is accomplished by discriminating between the enantiotopic C-O single bonds of a gem-diacetate. In this way, enantioselective total syntheses of two antifugal agents, sphingofungins E and F, have been accomplished. The synthetic strategy is based on a series of catalytic processes whereby all of the chiral centers are created with high stereoselectivities. The first two stereocenters are introduced by an asymmetric allylic alkylation reaction of gem-diacetate 9 with azlactone 10. The complex of Pd(0) and ligand 14 efficiently catalyzes this key reaction, which differentiates both the enantiotopic leaving groups of a gem-diacetate and enantiotopic faces of the enolate of an azlactone in high enantiomeric excess and diastereomeric excess. From these two stereocenters, the configurations of the remaining two centers are set by a diastereoselective Os(VIII)-catalyzed dihydroxylation reaction with excellent stereocontrol. The trans-alkene is established by Cr(II)-mediated olefination, and a subsequent B-alkyl Suzuki coupling reaction conjoins the polar head unit and the nonpolar, 13-carbon lipid tail. The efficiency of our strategy is illustrated by the completion of syntheses of sphingofungins F and E in 15 and 17 steps, and in 17% and 5% overall yields, respectively.
Manipulation of substrate-controlled diastereoselectivities in hydroborations of acyclic allylamine derivatives
Racemic, and optically active, 2-methyl-3-(N-tosylamino)alkenes I were prepared and subjected to both catalyzed and uncatalyzed hydroborations. Data obtained for the catalyzed hydroborations of these allylamine derivatives are consistent with the theory of secondary orbital interactions in transition metal mediated processes presented in the preceding paper. Surprisingly, diastereoselectivities for conventional (uncatalyzed) hydroborations of the same substrates can be extremely sensitive to the borane used; anti products result when borane-tetrahydrofuran complex is reacted with substrates I (R'=Bn), while with 9-BBN (9-borabicyclo[3.3.1]nonane) these reactions are syn selective