Synthesis of Oxazolidinones by using Carbon Dioxide as a C₁ Building Block and an Aluminium‐Based Catalyst

Abstract

Oxazolidinone synthesis through the coupling of carbon dioxide and aziridines was catalysed by an aluminium(salphen) complex at 50–100 °C and 1–10 bar pressure under solvent‐free conditions. The process was applicable to a variety of substituted aziridines, giving products with high regioselectivity. It involved the use of a sustainable and reusable aluminium‐based catalyst, used carbon dioxide as a C1 source and provided access to pharmaceutically important oxazolidinones as illustrated by a total synthesis of toloxatone. This protocol was scalable, and the catalyst could be recovered and reused. A catalytic cycle was proposed based on stereochemical, kinetic and Hammett studies.

Bypassing the Inertness of Aziridine/CO2 Systems to Access 5‐Aryl‐2‐Oxazolidinones: Catalyst‐Free Synthesis Under Ambient Conditions

“…This direct synthesis of 5‐aryl‐2‐oxazolidinones from 1 – 7 appears more convenient than the two‐step route via isolation of aryl‐aziridines and subsequent catalyzed aziridine/CO 2 coupling (Scheme ), since it avoids high‐temperature and ‐pressure conditions, saves solvents and materials otherwise necessary for the synthesis of a catalyst and the isolation/purification of the intermediate aziridine, and may be favourable in terms of E‐factor metric. For sake of comparison, calculated E‐factor for the synthesis of 8 c from 1 /NH 2 Et in isopropanol is approximately 2.2, while it is approximately 2.6 following the procedure recently reported by Sengoden et al . (see Supporting Information for details).…”

“…Furthermore, the catalytic systems may present some critical issues in terms of catalyst loading and the need for a halide co‐catalyst (Lewis base) and toxic solvents . It is quite common in the literature that aziridines employed for the cyclization reaction with CO 2 are prepared with a convenient procedure whereby a sulfonium bromide salt, derived from styrene or related ring‐substituted species, provides the C 2 unit of the three membered heterocycle (Scheme ) . This protocol allows to access a variety of 2‐aryl‐aziridines, and the catalyzed conversion into the corresponding aryl‐oxazolidinones follows.…”

Recent Advances in the Chemistry of Metal Carbamates

“…The formation of carbamato complexes is considered a key step in metal-mediated reactions such as the CO 2 /aziridine coupling [ 306 , 307 , 308 ] and the CO 2 cycloaddition to propargyl amines [ 113 , 309 , 310 , 311 , 312 ] or aminoalcohols [ 306 ]. The production of oxazolidinones (cyclic carbamates) via CO 2 /aziridine coupling is one of the most widely investigated carbon dioxide fixation processes, and many species have been evaluated as catalytic precursors, such as Al(III) [ 313 ], Cr(III) [ 314 ] and Co(III) [ 315 ] salen complexes, and Cu(II) [ 316 ] and Zn(II) [ 317 ] porphyrin complexes. Regarding the cycloadditon of CO 2 to propargylamines, catalysts based on late transition metals are privileged since they offer the possibility to activate the alkyne reactant via η 2 -coordination [ 113 , 318 ].…”

Unlocking the Potential of Substrate‐Directed CO2 Activation and Conversion: Pushing the Boundaries of Catalytic Cyclic Carbonate and Carbamate Formation

“…At a later stage, however, the same authors reported the formal synthesis of Toloxatone through an intermediate hydroxymethyl aziridine species mediated by a bimetallic aluminum‐salen complex [30] . This aziridine could be converted into the desired oxazolidinone at 100 °C, and according to the proposed mechanism occurs via a double inversion manifold (Scheme 8a) as supported by formal retention of configuration using a chiral aziridine substrate.…”