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Synthesis of an (±)‐Estrone Precursor: The Scope of Zr‐ and Co‐Mediated Cycloannulations
Author(s) -
Betík Robert,
Herrmann Pavel,
Kotora Martin
Publication year - 2010
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200900937
Subject(s) - chemistry , estrone , ketone , steroid , ring (chemistry) , stereochemistry , geminal , conjugated system , natural product , total synthesis , enone , derivative (finance) , organic chemistry , hormone , biochemistry , financial economics , economics , polymer
The synthesis of an estrone intermediate based on a new approach was studied. The construction of the basic framework was carried out in three steps from a simple styrene derivative. The crucial reaction sequence for the steroid skeleton construction relied on a Zr‐mediated cyclization (Zr‐ene reaction)/propargylation followed by a Co‐mediated diastereoselective Pauson–Khand reaction that afforded various D ‐ring‐substituted tetracyclic ketones 11 with natural trans ‐ anti stereochemistry. The conjugated addition reaction of Me 2 CuLi to tetracyclic ketone 11a aiming at the installation of the angular methyl group in the 13‐position gave rise exclusively to product 12 with unnatural trans‐anti‐cis stereochemistry The successful synthesis of known estrone intermediate 4 with natural trans‐anti‐trans stereochemistry was accomplished by chemoselective reduction of the carbonyl group of ketone 11b . Attempts to use other metallo‐ene reactions to affect the synthesis of steroid B‐ring are also described.