Synthesis of an Optically Active Decahydro‐6‐isoquinolone Scaffold with a Quaternary Stereocenter

A straightforward synthesis of optically active decahydro‐6‐isoquinolone derivative 3, containing a quaternary stereocenter, is reported. The starting (R)‐configured enantiopure enone 2, which is readily accessible through a copper‐catalyzed, L‐valine amide mediated Michael reaction and a subsequent Robinson annulation, was hydrogenated with Pd/C in iPrOH to give the decahydroisoquinolone 4. Treatment of 4 with ethyleneglycol in the presence of PPTS yielded the dioxolane‐protected derivative 7. A sequence of ester reduction with LiAlH4 and subsequent Ley oxidation of the resulting primary alcohol 10 accomplished the synthesis. Enantiomerically pure aldehyde 3, with three groups for further functionalization, was thus obtained in 63% overall yield. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)