Practical access to axially chiral sulfonamides and biaryl amino phenols via organocatalytic atroposelective N-alkylation

The importance of axial chirality in enantioselective synthesis has been widely recognized for decades. The practical access to certain structures such as biaryl amino phenols known as NOBINs in enantiopure form, however, still remains a challenge. In drug delivery, the incorporation of axially chir...

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Bibliographic Details
Published in:	Nature communications Vol. 10; no. 1; pp. 3061 - 10
Main Authors:	Lu, Shenci, Ng, Shawn Voon Hwee, Lovato, Kaitlyn, Ong, Jun-Yang, Poh, Si Bei, Ng, Xiao Qian, Kürti, László, Zhao, Yu
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 11-07-2019 Nature Publishing Group Nature Portfolio
Subjects:	140/131 140/58 639/638/403/933 639/638/77/883 639/638/77/889 Alkylation Aminophenols - chemical synthesis Antibiotics Aromatic compounds Catalysis Catalysts Chemical synthesis Chemistry, Pharmaceutical - methods Chirality Drug delivery Drug Delivery Systems Enantiomers Humanities and Social Sciences Molecular Structure multidisciplinary Phenols Science Science (multidisciplinary) Stereoisomerism Sulfonamides Sulfonamides - chemical synthesis
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Summary:	The importance of axial chirality in enantioselective synthesis has been widely recognized for decades. The practical access to certain structures such as biaryl amino phenols known as NOBINs in enantiopure form, however, still remains a challenge. In drug delivery, the incorporation of axially chiral molecules in systematic screening has also received a great deal of interest in recent years, which calls for innovation and practical synthesis of structurally different axially chiral entities. Herein we present an operationally simple catalytic N -alkylation of sulfonamides using commercially available chiral amine catalysts to deliver two important classes of axially chiral compounds: structurally diverse NOBIN analogs as well as axially chiral N -aryl sulfonamides in excellent enantiopurity. Structurally related chiral sulfonamide has shown great potential in drug molecules but enantioselective synthesis of them has never been accomplished before. The practical catalytic procedures of our methods also bode well for their wide application in enantioselective synthesis. NOBINs and other axially chiral entities have received a great deal of interest in recent years. Here, the authors report the kinetic resolution of racemic amino phenols and the enantioselective preparation of axially chiral N-aryl sulfonamides with excellent level of enantiopurity and broad substrate scope.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-019-10940-4