Aryl Alcohol Derivatives

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Summary: Recently, researchers in the laboratory of Dr. Neil Garg, of the Department of Chemistry & Biochemistry at UCLA, have completed the first amination reactions of aryl O-sulfamates. In addition, the researchers have discovered that aryl carbamates are also excellent substrates for Ni-catalyzed amination reactions. Though relatively unexplored, these electrophilic cross-coupling partners possess a number of benefits compared to more conventional phenol based electrophiles. They are easy to prepare, exhibit pronounced stability to a variety of reaction conditions, show low reactivity toward Pd(0), and are able to direct ortho metalation. In combination, these characteristics make aryl O-sulfamates and aryl O-carbamates ideal partners for the multistep synthesis of polysubstituted aromatics. Applying this novel amination methodology, UCLA researchers were able to derive a concise synthesis of the antibacterial drug linezolid.   Background: Transition metal-catalyzed amination reactions are amongst the most powerful methods available for accessing the carbon nitrogen based motifs ubiquitously found in medicinal agents and natural products. Recently, efforts have focused on the amination of classically “inert” simple phenolic derivatives to synthesize these structures more readily. Towards this goal, a number of groups have searched for alternative phenol based amination partners, which can be used to direct the assembly of functional groups onto an aromatic ring. Resulting polysubstituted aryl amine motifs are commonly encountered in drug scaffolds, naturally occurring small molecules, pesticides, ligands for catalysis, and materials chemistry. Given the ubiquity of carbon-nitrogen bonds in medicinal agents, more efficient and cost-effective cross-coupling reactions will provide significant economic advantages to therapeutic development and manufacturing.