An efficient asymmetric synthesis of an estrogen receptor modulator by sulfoxide-directed borane reduction.
An efficient asymmetric synthesis of a selective estrogen receptor modulator (SERM) that has a dihydrobenzoxathiin core structure bearing two stereogenic centers is reported. The stereogenic centers were established by an unprecedented chiral sulfoxide-directed stereospecific reduction of an alpha,beta-unsaturated sulfoxide to the saturated sulfide in one step. Studies to elucidate the mechanism for this reduction are reported. Highly efficient Cu(I)-mediated ether formation was used to install the ether side chain, and selective debenzylation conditions were developed to remove the benzyl protecting groups on the phenols.
Song
Zhiguo J
ZJ
Department of Process Research, Merck Research Laboratories, P.O. Box 2000, Rahway, NJ 07065, USA. zhiguo_song@merck.com
King
Anthony O
AO
Waters
Marjorie S
MS
Lang
Fengrui
F
Zewge
Daniel
D
Bio
Matthew
M
Leazer
Johnnie L
JL
Javadi
Gary
G
Kassim
Amude
A
Tschaen
David M
DM
Reamer
Robert A
RA
Rosner
Thorsten
T
Chilenski
Jennifer R
JR
Mathre
David J
DJ
Volante
R P
RP
Tillyer
Richard
R
D001880:Boranes / Q000737:chemistry*; D020847:Estrogen Receptor Modulators / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D012451:Safrole / Q000031:analogs & derivatives* / Q000737:chemistry*; D013237:Stereoisomerism
D001880:Boranes; D020847:Estrogen Receptor Modulators; D012451:Safrole; C005746:sulfoxide