Stereocontrolled Synthesis of Phosphoproline Analogues Containing a trans-Fused Octahydroindole Bicyclic System.

Herein we report for the first time the diastereoselective synthesis of (2R,3aR,7aS)- and (2S,3aS,7aR)-octahydroindole-2-phosphonic acid (OicP trans-fused stereoisomers) from diethyl (R)- and (S)-phosphopyroglutamate derivative. The key steps of this procedure are the ruthenium tetroxide oxidation of enantiomerically pure diethyl (R)- and (S)-phosphoprolinate obtained through Katritzky's benzotriazole-oxazolidine methodology, a highly diastereoselective successive double 4,5-diallylation of diethyl (R)- and (S)-phosphopyroglutamate with allyl bromide and allyltrimethylsilane with a trans-addition mode, and a ring-closing metathesis with Grubbs' first-generation ruthenium catalyst.

Enantiopure 4-oxazolin-2-ones and 4-methylene-2-oxazolidinones as chiral building blocks in a divergent asymmetric synthesis of heterocycles.

Enantiopure 3-((R)- and 3-((S)-1-phenylethyl)-4-oxazoline-2-ones were evaluated as chiral building blocks for the divergent construction of heterocycles with stereogenic quaternary centers. The N-(R)- or N-(S)-1-phenylethyl group of these compounds proved to be an efficient chiral auxiliary for the asymmetric induction of the 4- and 5-positions of the 4-oxazolin-2-one ring through thermal and MW-promoted nucleophilic conjugated addition to Michael acceptors and alkyl halides. The resulting adducts were transformed via a cascade process into fused six-membered carbo- and heterocycles. The structure of the reaction products depended on the electrophiles and reaction conditions used. Alternative isomeric 4-methylene-2-oxazolidinones served as chiral precursors for a versatile and divergent approach to highly substituted cyclic carbamates. DFT quantum calculations showed that the formation of bicyclic pyranyl compounds was generated by a diastereoselective concerted hetero-Diels-Alder cycloaddition.