Divergent Synthetic Access toE- andZ-Stereodefined All-Carbon-Substituted Olefin Scaffolds: Application to Parallel Synthesis of (E)- and (Z)-Tamoxifens.
A highly substrate-general synthesis of all-carbon-substitutedE- andZ-stereodefined olefins is performed. The method comprises two sets of parallel and stereocomplementary preparations of (E)- and (Z)-α,β-unsaturated esters involving two robust and distinctive reactions: 1) stereocomplementary enol tosylations using readily available TsCl/diamine/(LiCl) base reagents, and 2) stereoretentive Negishi cross-coupling using the catalysts [Pd(dppe)Cl2] (forE) and [Pd(dppb)Cl2] (forZ). The present parallel approach is categorized as both type I (convergent approach: 16 examples, 56-87 % yield) and type II (divergent approach: 18 examples, 70-95 % yield). The obtained (E)- and (Z)-α,β-unsaturated ester scaffolds are successfully transformed into variousE- andZ-stereodefined known and novel olefins (8×2 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.
Department of Chemistry School of Science and Technology Kwansei Gakuin University 2-1 Gakuen, Sanda Hyogo 669-1337 Japan.
Yuichiro
Y
Ashida
Department of Chemistry School of Science and Technology Kwansei Gakuin University 2-1 Gakuen, Sanda Hyogo 669-1337 Japan.
Atsushi
A
Honda
Department of Chemistry School of Science and Technology Kwansei Gakuin University 2-1 Gakuen, Sanda Hyogo 669-1337 Japan.
Yuka
Y
Sato
Department of Chemistry School of Science and Technology Kwansei Gakuin University 2-1 Gakuen, Sanda Hyogo 669-1337 Japan.
Hidefumi
H
Nakatsuji
Department of Chemistry School of Science and Technology Kwansei Gakuin University 2-1 Gakuen, Sanda Hyogo 669-1337 Japan.
Yoo
0000-0003-3265-4343
Y
Tanabe
cross-coupling reactions; enols; esters; parallel synthesis; tamoxifen