Up to four stereocenters with a well-defined configuration are generated in a single synthetic step by cyclocondensation of (R)-phenylglycinol or (1S,2R)-1-amino-2-indanol with stereoisomeric mixtures (racemates, meso forms, diastereoisomers) of cyclohexanone-based δ-keto acid and δ-keto diacid derivatives in enantio-and diastereoconvergent processes that involve dynamic kinetic resolution and/or desymmetrization of enantiotopic groups. A detailed analysis of the stereochemical outcome of the process is presented. The methodology provides easy access to enantiopure 8-and 6,8-substituted cis-decahydroquinolines, including alkaloids of the myrioxazine group.

Cyclocondensation of (R)-phenylglycinol with stereoisomeric mixtures (racemates, cis/trans) of 3-substituted 2-oxocyclohexaneacetates stereoselectively afforded tricyclic oxazoloindolone lactams, from which straightforward procedures for the stereocontrolled formation of enantiopure 7-substituted octahydroindoles with a variety of stereochemical patterns have been developed. The methodology has been successfully applied to the synthesis of (+)-α-lycorane.Phenylglycinol-and other aminoalcohol-derived oxazolopiperidone and oxazoloquinolone lactams have proven to be versatile building blocks for the enantioselective synthesis of a wide variety of diversely substituted piperidine-containing heterocycles, including complex alkaloids belonging to different skeletal types. 1 The usefulness of these lactams lies in their easy preparation, by stereoselective cyclocondensation of the chiral nonracemic aminoalcohol with an appropriate δ-oxo acid derivative, and in their functionalization and conformational rigidity, which allow the stereocontrolled formation of C-C bonds at the different positions of the nitrogen heterocycle.Starting from 2-oxocyclohexanepropionate-based δ-keto esters, the cyclocondensation stereoselectively affords tricyclic oxazoloquinolone lactams, which can be easily converted to enantiopure cis-decahydroquinoline alkaloids. 2 Depending on the structural characteristics of the substrate, the cyclocondensation involves a dynamic kinetic resolution and/or differentiation of enantiotopic or diastereotopic ester groups.Bearing in mind that the octahydroindole nucleus is present in numerous natural bioactive compounds, for instance Amaryllidaceae alkaloids, we considered expanding the scope of the above stereoconvergent cyclocondensation reactions towards the generation of tricyclic oxazoloindolone lactams as precursors of this nucleus. This would require starting from appropriately substituted 2-oxocyclohexaneacetate derivatives (γ-instead of δ-keto esters).In this letter, we report a general straightforward procedure for the stereocontrolled access to enantiopure 7-substituted cis-and trans-octahydroindoles. The few precedents of the enantioselective synthesis of 7-substituted octahydroindoles all deal with 7-aryl cis-derivatives, 3 used as intermediates in the synthesis of lycorane-like structures. Scheme 1. Envisaged Access to Enantiopure 7-Substituted OctahydroindolesThe preparation of the target enantiopure octahydroindoles was envisaged as outlined in Scheme 1. Starting from a stereoisomeric mixture of 3-substituted 2-oxocyclohexane-acetates 1 (two racemates when R = alkyl or aryl; one racemate and a

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