Asymmetric synthesis of pharmaceutically relevant 1-aryl-2-heteroaryl- and 1,2-diheteroarylcyclopropane-1-carboxylates
作者:Jack C. Sharland、Bo Wei、David J. Hardee、Timothy R. Hodges、Wei Gong、Eric A. Voight、Huw M. L. Davies
DOI:10.1039/d1sc02474d
日期:——
tetracarboxylate-catalysed asymmetriccyclopropanation of vinyl heterocycles with aryl- or heteroaryldiazoacetates. The reactions are highly diastereoselective and high asymmetricinduction could be achieved using either (R)-pantolactone as a chiral auxiliary or chiral dirhodium tetracarboxylate catalysts. For meta- or para-substituted aryl- or heteroaryldiazoacetates the optimum catalyst was Rh2(R-p-Ph-TPCP)4
本研究描述了通过四羧酸二铑催化乙烯基杂环与芳基或杂芳基重氮乙酸酯的不对称环丙烷化反应,对映选择性合成药学相关的 1-芳基-2-杂芳基-和 1,2-二杂芳基环丙烷-1-羧酸酯的一般方法。该反应具有高度非对映选择性,并且使用( R )-泛内酯作为手性助剂或手性四羧酸二铑催化剂可以实现高度不对称诱导。对于间位或对位取代的芳基或杂芳基重氮乙酸酯,最佳催化剂是Rh 2 ( Rp -Ph-TPCP) 4。在邻位取代的芳基或杂芳基重氮乙酸酯的情况下,最佳催化剂是Rh 2 ( R -TPPTTL) 4。为了与邻位取代的底物进行高度对映选择性反应,需要在 4 Å 分子筛或 1,1,1,3,3,3-六氟异丙醇 (HFIP) 存在下使用 2-氯吡啶作为添加剂。在优化条件下,环丙烷化反应可以在吡啶、吡嗪、喹啉、吲哚、恶二唑、噻吩、吡唑等多种杂环化合物存在下进行。
Synthesis of Highly Substituted Cyclobutanones by a One‐Pot Keteniminium‐Enamine Process
作者:Dylan Dagoneau、Amandine Kolleth、Pierre Quinodoz、Beyza Horoz、Saron Catak、Alexandre Lumbroso、Sarah Sulzer‐Mossé、Alain De Mesmaeker
DOI:10.1002/hlca.202100022
日期:2021.5
synthesis of highly substitutedcyclobutanones. This process relies on first a [2+2] cycloaddition involving a keteniminium salt intermediate with an alkene followed by isomerization of the resulting cyclobutaniminium salt into its cyclic enamine form and then reaction of the latter with an electrophile. The adduct can be either hydrolyzed or reduced to give the corresponding cyclobutanone or cyclobutanamine
A compound of the formula I or where W, X and Y are for example each CH; R
1
is H; R
2
is halogen; and R
6
is, for formula I, for example, OH, CN, C3-C8-cycloalkyl, C3-C8-cycloalkyl-C1-C6-alkyl, C2-C6-alkenyl, C2-C6-haloalkenyl, C2-C6-alkenyloxy, C2-C6-alkynyl, C2-C6-haloalkynyl, C2-C6-alkynyloxy, optionally substituted C1 to C3-alkyl, or optionally substituted C1-C6-alkoxy, or R
6
is, for formula II, for example, CN, C3-C8-cycloalkyl, or optionally substituted C3-C6-alkyl; and/or salts thereof; and their use as as pesticidal agents.
The invention described herein provides compounds of Formula (I) and pharmaceutical compositions thereof,
for use in, e.g. treating type 2 diabetes mellitus, pre-diabetes, obesity, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, and cardiovascular disease.