Premium
Lithium‐Catalyzed Thiol Alkylation with Tertiary and Secondary Alcohols: Synthesis of 3‐Sulfanyl‐Oxetanes as Bioisosteres
Author(s) -
Croft Rosemary A.,
Mousseau James J.,
Choi Chulho,
Bull James A.
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201705576
Subject(s) - sulfanyl , alkylation , thiol , lithium (medication) , catalysis , chemistry , organic chemistry , psychology , psychiatry
Abstract 3‐Sulfanyl‐oxetanes are presented as promising novel bioisosteric replacements for thioesters or benzyl sulfides. From oxetan‐3‐ols, a mild and inexpensive Li catalyst enables chemoselective C−OH activation and thiol alkylation. Oxetane sulfides are formed from various thiols providing novel motifs in new chemical space and specifically as bioisosteres for thioesters due to their similar shape and electronic properties. Under the same conditions, various π‐activated secondary and tertiary alcohols are also successful. Derivatization of the oxetane sulfide linker provides further novel oxetane classes and building blocks. Comparisons of key physicochemical properties of the oxetane compounds to selected carbonyl and methylene analogues indicate that these motifs are suitable for incorporation into drug discovery efforts.