The adoption and implementation of greener practices in the development and manufacture of pharmaceuticals has gained significant momentum over the past decade.  More recently, such considerations are increasingly being applied to medicinal chemistry strategies in the earlier drug discovery settings, where despite the smaller scale, synthesis methods and procedures utilized here are often carried through into development in total or in part.  Waste reduction and greener choices for solvents and reagents used in common transformations are routinely targeted, though growing attention is also being paid to efficiency of processes through novel bond connection sequences and strategies.  One manner in which more sustainable practices can be engineered into synthetic routes for the preparation of analogues in lead optimization settings is through the use of telescoped sequences, where more than one key synthetic step is carried out in a single reaction vessel.  Methyliminodiacetic acid (MIDA) protected boronates provide chemical inertness to a wide range of synthetic transformations available to substrates thusly functionalized, yet can be readily liberated in situ to provide boronic acids competent for a range of transition metal catalyzed reactions.  As such, chemical diversity and complexity can be rapidly and efficiently generated by combining synthetic steps using this versatile group.  Herein we describe a number of efficient methods for the utilization of telescoped sequences with MIDA boronates to enable molecular diversity, each involving cross-coupling reactions of heterocycles, and including regiospecific access to substitution patterns previously difficult to achieve.

Telescoped transition-metal catalyzed reaction sequences using MIDA boronates enable efficient preparation of diverse, pharmaceutically relevant molecules

247th National Meeting (2014)

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