Divergent Synthetic Access to E- and Z-Stereodefined All-Carbon-Substituted Olefin Scaffolds: Application to Parallel Synthesis of (E)- and (Z)-Tamoxifens.
ChemistryOpen
; 6(1): 73-89, 2017 Feb.
Article
em En
| MEDLINE
| ID: mdl-28168153
ABSTRACT
A highly substrate-general synthesis of all-carbon-substituted E- and Z-stereodefined olefins is performed. The method comprises two sets of parallel and stereocomplementary preparations of (E)- and (Z)-α,ß-unsaturated esters involving two robust and distinctive reactions 1)â
stereocomplementary enol tosylations using readily available TsCl/diamine/(LiCl) base reagents, and 2)â
stereoretentive Negishi cross-coupling using the catalysts [Pd(dppe)Cl2] (for E) and [Pd(dppb)Cl2] (for Z). The present parallel approach is categorized as both typeâ
I (convergent approach:
16â examples, 56-87 % yield) and typeâ II (divergentapproach:
18â examples, 70-95 % yield). The obtained (E)- and (Z)-α,ß-unsaturated ester scaffolds are successfully transformed into various E- and Z-stereodefined known and novel olefins (8×2â derivatization arrays). As a demonstration, application to the parallel synthesis of both (E)- and (Z)-tamoxifens, a representative motif of all-carbon-substituted olefins, is accomplished in a total of eight steps with an overall yield of 58 % (average 93 %) and 57 % (average 93 %), respectively.
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01-internacional
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MEDLINE
Idioma:
En
Revista:
ChemistryOpen
Ano de publicação:
2017
Tipo de documento:
Article