Synthesis of a Novel Enantiopure Spiro‐B‐norestradiol Analogue by Multiple Pd‐Catalyzed Transformations

Abstract

AbstractThe novel tetracyclic spiro compound 13 was synthesized by the use of two subsequent Pd‐catalyzed reactions. Firstly, the ortho‐bromobenzyl chloride 1 was coupled with the enantiopure boronic ester 8, obtained from the Hajos−Wiechert ketone in a chemoselective Suzuki‐type reaction to give 12 in 77% yield. Unexpectedly, the intramolecular Heck reaction then did not provide the annulated compound 6, but the spirocyclic compound 13, containing a quaternary carbon center, in 73% yield. The Heck reaction was also performed under microwave irradiation conditions, allowing a considerably shorter reaction time. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)