Asymmetric synthesis of pharmaceutically relevant 1-aryl-2-heteroaryl- and 1,2-diheteroarylcyclopropane-1-carboxylates
This study describes general methods for the enantioselective syntheses of pharmaceutically relevant 1-aryl-2-heteroaryl- and 1,2-diheteroarylcyclopropane-1-carboxylates through dirhodium tetracarboxylate-catalysed asymmetric cyclopropanation of vinyl heterocycles with aryl- or heteroaryldiazoacetat...
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Veröffentlicht in: | Chemical science (Cambridge) 2021-08, Vol.12 (33), p.11181-1119 |
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Hauptverfasser: | , , , , , , |
Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | This study describes general methods for the enantioselective syntheses of pharmaceutically relevant 1-aryl-2-heteroaryl- and 1,2-diheteroarylcyclopropane-1-carboxylates through dirhodium tetracarboxylate-catalysed asymmetric cyclopropanation of vinyl heterocycles with aryl- or heteroaryldiazoacetates. The reactions are highly diastereoselective and high asymmetric induction 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 Rh
2
(
R-p
-Ph-TPCP)
4
. In the case of
ortho
-substituted aryl- or heteroaryldiazoacetates, the optimum catalyst was Rh
2
(
R
-TPPTTL)
4
. For a highly enantioselective reaction with the
ortho
-substituted substrates, 2-chloropyridine was required as an additive in the presence of either 4 Å molecular sieves or 1,1,1,3,3,3-hexafluoroisopropanol (HFIP). Under the optimized conditions, the cyclopropanation could be conducted in the presence of a variety of heterocycles, such as pyridines, pyrazines, quinolines, indoles, oxadiazoles, thiophenes and pyrazoles.
The dirhodium tetracarboxylate-catalysed asymmetric cyclopropanation has been applied to the enantioselective syntheses of pharmaceutically relevant 1-aryl-2-heteroaryl- and 1,2-diheteroarylcyclopropane-1-carboxylates. |
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ISSN: | 2041-6520 2041-6539 |
DOI: | 10.1039/d1sc02474d |