The Synthesis of Functionalized 3-Aryl- and 3-Heteroaryloxazolidin-2-ones and Tetrahydro-3-aryl-1,3-oxazin-2-ones via the Iodocyclocarbamation Reaction: Access to Privileged Chemical Structures and Scope and Limitations of the Method

3-Aryl- and 3-heteroaryloxazolidin-2-ones, by virtue of the diverse pharmacologic activities exhibited by them after subtle changes to their appended substituents, are becoming increasingly important and should be considered privileged chemical structures. The iodocyclocarbamation reaction has been extensively used to make many 3-alkyl-5-(halomethyl)oxazolidin-2-ones, but the corresponding aromatic congeners have been relatively underexplored. We suggest that racemic 3-aryl- and 3-heteroaryl-5-(iodomethyl)oxazolidin-2-ones, readily prepared by the iodocyclocarbamation reaction of N-allylated N-aryl or N-heteroaryl carbamates, may be useful intermediates for the rapid preparation of potential lead compounds with biological activity. We exemplify this point by using this approach to prepare racemic linezolid, an antibacterial agent. Herein, we report the results of our systematic investigation into the scope and limitations of this process and have identified some distinguishing characteristics within the aryl/heteroaryl series. We also describe the first preparation of 3-aryloxazolidin-2-ones bearing new functionalized C-5 substituents derived from conjugated 1,3-dienyl and cumulated 1,2-dienyl carbamate precursors. Finally, we describe the utility of the iodocyclocarbamation reaction for making six-membered tetrahydro-3-aryl-1,3-oxazin-2-ones.