Synthesis of a novel enantiopure spiro-B-norestradiol analogue by multiple Pd-catalyzed transformations

The 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 spiro-cyclic 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. (C) Wiley-VCH Verlag GmbH Co.