Efficient methods for the synthesis of chiral 2‐oxazolidinones as pharmaceutical building blocks

Abstract

Although the wide variety of heterocyclic compounds is common knowledge, chiral 2‐oxazolidinones are recognized as some of the most important heterocycles in medicinal chemistry. Many important pharmaceutical molecules have been constructed based on the chiral 2‐oxazolidinone backbone. Therefore, the development of even more efficient catalytic methods for the synthesis of chiral 2‐oxazolidinones remains a very important pursuit in the field of synthetic organic chemistry. This review summarizes the coupling reactions of epoxides and isocyanates for the preparation of 2‐oxazolidinones. Both metal catalysts and organocatalysts promote these reactions. Optically pure 2‐oxazolidinones are prepared from optically pure epoxide substrates via these catalytic methods. A synthetic example of a commercially available pharmaceutical compound utilizing this method is also introduced.

Engineering of halohydrin dehalogenases for the regio- and stereoselective synthesis of (S)-4-aryl-2-oxazolidinones

“…[17][18][19] Because of these important properties, the synthesis of enantiopure 2-oxazolidinones has already attracted considerable attention, and searching effective methods for the synthesis of enantiopure 2-oxazolidinones remains a focus of organic synthesis. 2,[20][21][22] The conventional methods for preparing enantiopure 2-oxazolidinone and its derivatives are based on enantiopure raw materials derived from β-amino alcohols and their derivatives, via carbonylation reactions using electrophilic "CO" reagents. However, this method often involves the use of highly toxic and dangerous carbonylation reagents such as phosgene and its derivatives, carbon monoxide, or carbon dioxide as a carbonyl source under harsh reaction conditions.…”

“…[22][23][24][25][26] The coupling of epoxides and isocyanates is currently the most efficient and convenient method for the synthesis of enantiopure 2-oxazolidinones due to the wide availability of both starting materials. 2,27 The coupling reactions of epoxides and isocyanates can be catalyzed by both metals and organic compounds, 2,4,[28][29][30] and more efficient organocatalysts are expected in the near future. The ring-opening of epoxides by isocyanate/cyanate has the disadvantages of poor regio-and stereoselectivity, high cost, strict reaction temperature and long reaction time.…”

“…Oxazolidinones are an important class of five-membered heterocyclic compounds containing oxygen and nitrogen. 1 Enantiopure 2-oxazolidinones play a prominent role in modern organic synthesis, known as Evans' chiral auxiliaries, 2,3 which allow a wide range of asymmetric transformations for the synthesis of chiral building blocks of natural products and novel candidate drugs. 4 Furthermore, the enantiopure 5-substituted 2-oxazolidinones are highly valuable building blocks for many pharmaceutical compounds.…”

Catalytic asymmetric CO2 utilization reaction for the enantioselective synthesis of chiral 2-oxazolidinones

“…It is noteworthy that the resultant chiral 2-oxazolidinone products 4 from the halocyclizations of in situ generated carbamic acids are important building blocks for pharmaceutical development. 9…”

Tetraarylphosphonium salt-catalyzed formal [3+2] cycloaddition between epoxides and trichloroacetonitrile for the synthesis of β-amino alcohol derivatives

“…, bromide or iodide ions) to activate the epoxides. 1,2 In general, acid/halide ion combined catalysis involves an epoxide ring opening step and a heterocumulene capture step (Scheme 1a, top). In 2016, our group uncovered a novel bifunctional tetraarylphosphonium salt (TAPS) catalyst, possessing a hydroxyl group at the ortho -position, that could facilitate the [3+2] reaction of epoxides with carbon dioxides.…”