Solid State Auto-Inversion of C-Centrochirality: Enantioselective Total Synthesis of Furocarbazolones (−)-epi-Claulansine D and (−)-Claulansine D and Pyranocarbazolone (+)-epi-Claulansine C

Abstract

Starting from dimethyl (E)-2-{[(1-tert-butoxycarbonyl)-1H-indol-3-yl]methylene}succinate and (R)-2,2,5,5-tetramethyl-1,3-dioxolane-4-carbaldehyde, facile synthesis of (-)-epi-claulansine D was accomplished via condensation and two intramolecular cyclizations. The (-)-epi-claulansine D in the solid state exists in a metastable form, and after an induction period of 30-90 days, it underwent complete epimerization to exclusively deliver the desired natural product (-)-claulansine D in quantitative yield. The witnessed inversion of C-centrochirality in the solid state is conceptually novel and takes place for relatively higher crystal stability reasons. Base-catalyzed ring expansion of both (±)/(-)-epi-claulansine D and (±)/(-)-claulansine D resulted in (±)/(+)-epi-claulansine C in very good yields.

State of the Art in Crystallization‐Induced Diastereomer Transformations

“…A fascinating and possibly the first example of CIDT proceeding in the solid phase was described by Markad and Argade (Scheme 82). [150] They prepared a solid sample of (−)‐ epi ‐claulansine D ( 215 ) and serendipitously detected that it cleanly transformed into (−)‐claulansine D ( 216 ) just on standing at rt for nearly two months. Repetitive experiments with both racemic and enantiomerically pure samples of 215 confirmed their complete conversion to 215 after 30 to 90 days.…”

Investigation of isomerization of dexibuprofen in a ball mill using chiral capillary electrophoresis

“…However, the ibuprofen enantiomers were found to be highly stable under acidic conditions. Furthermore, isomerization processes in solid state have been described in the scope of asymmetric synthesis or using thermal or irradiating stress [14][15][16][17][18][19].…”

Chemoselective Ring Closure of 4-(3-Methyl-2-oxo-2,5-dihydro-1H-pyrrol-1-yl)butanal Leading to Pandalizine A

“… , However, synthesis of pandalizines D and E bearing an additional hydroxyl group at two different positions in ring-B is still awaited. To date, we have accomplished the total synthesis of a large number of bioactive natural products using cyclic anhydrides and their derivatives as the potential precursors. − Now we report the total synthesis of pandalizine A via the regioselective reduction of citraconimide followed by a substrate-specific chemoselective ring closure as crucial reactions (Schemes and ).…”