Stereocontrolled Synthesis of Enantiopure cis-Fused Octahydroisoindolones via Chiral Oxazoloisoindolone Lactams

Abstract

Kinetically controlled cyclocondensation of stereoisomeric and ring–chain tautomeric mixture of (±)-hydroxylactone 1 and 0.5 equiv of (R)-phenylglycinol provided tricyclic oxazoloisoindolone lactam (3R,5aS,9aR,9bS)-2a, a versatile intermediate for further stereocontrolled transformations to access enantiopure cis-fused octahydroisoindolones. An extension of this methodology was successfully applied to the synthesis of the 5,6-dihydroxy derivative (3aR,5R,6S,7aS)-17.

Ru-NHC-Catalyzed Asymmetric, Complete Hydrogenation of Indoles and Benzofurans: One Catalyst with Dual Function

“…Octahydroindoles are important structural motifs, prevalent in many marketed drugs, , natural products, , bioactive molecules, and organocatalysts (Figure e). , Therefore the development of synthetic methods for chiral octahydroindoles is of high importance. − Although there are some reports on the asymmetric partial hydrogenation of indoles, − however, to the best of our knowledge, chiral octahydroindoles have not been accessed via complete, enantioselective hydrogenation of indoles despite the straightforwardness of the transformation. − Therefore, we proposed a novel enantioselective hydrogenation utilizing dual catalysis driven by a single metal complex to access chiral octahydroindoles. Our group previously developed a Ru-chiral carbene catalyst (Ru­(( R , R )-SINpEt) 2 ) with excellent reactivity and enantioselectivity in the hydrogenation of heterocyclic aromatic compounds. ,− Drawing on the reported literature and our research on carbene chemistry, we envisioned that metal–carbene complexes could be promising to fulfill the requirements for an in situ transformable catalyst since these complexes can be converted into nanosized heterogeneous particles. ,− We herein report highly enantioselective and diastereoselective complete hydrogenation of indoles, using Ru­(( R , R )-SINpEt) 2 as a dual functional catalyst, to synthesize a wide range of chiral octahydroindoles (Figure c).…”