The convergent enantioselective synthesis of a protected C1-C18 building block for the total synthesis of (-)-lytophilippine A was achieved. A catalytic asymmetric Gosteli-Claisen rearrangement and an Evans aldol reaction served as key C/C-connecting transformations during the assembling of the C1-C7 subunit (10 steps from 4, 29%). The synthesis of the C8-C18 segment was achieved utilizing d-galactose as inexpensive ex-chiral-pool starting material (15 steps, 15%). The merger of the subunits was accomplished by a remarkably efficient sequence consisting of esterification and ring-closing metathesis (five steps, 56%).

The ambivalent reactivity of 2-alkoxycarbonyl-substituted propargyl vinyl ethers has been explored. Depending on the conditions, the catalyzed and uncatalyzed Gosteli-Claisen rearrangement triggers downstream transformations that cascade from initially formed γ-allenyl α-keto esters to highly substituted furanes and cyclopentenes. In support of a mechanistic hypothesis, the results of a DFT study using the B1B95 and B3LYP functionals are revealed.

The synthesis of a diastereomer of lytophilippine A required 22 longest linear steps using known building blocks. Cross-metathesis/asymmetric aldol addition and regioselective esterification/ring-closing metathesis served as efficient combi tools for scaffold construction. Detailed NMR investigations in different solvent (systems) provide evidence for a deep-seated configurational misassignment of the molecule named lytophilippine A.

The title compound, C16H18F6O4, was obtained through an unprecedented one-pot reaction sequence involving a Gosteli–Claisen rearrangement and a cyclo­isomerization. The constitution and relative configuration were determined by single-crystal X-ray diffraction analysis. In the crystal, mol­ecules are connected via O—H ⋯ O hydrogen bonds.

Gosteli-Claisen Rearrangement of Propargyl Vinyl Ethers: Cascading Molecular Rearrangements. -2-Alkoxycarbonyl-substituted propargyl vinyl ethers are used as substrates for the unprecedented rearrangements. They lead to cyclopentene and cyclobutane derivatives and furans along with the expected α-ketoesters (II), depending on the reaction conditions. The reaction proceeding in the presence of HFIP (III) requires dry conditions since water prevents the cycloalkene formation. Gold--catalyzed Gosteli-Claisen rearrangement is superior to the reaction carried out using TfOH as a catalyst. In the case of (Ie) small amount of (IX) is obtained. -(GILLE, A.; REHBEIN, J.; HIERSEMANN*, M.; Org. Lett. 13 (2011) 8, 2122-2125, http://dx.