Transition metal catalyzed C�H functionalization of sp3 centers has taken great strides in recent years. Pioneering work by Daugulis, Yu, Baran and others has demonstrated both auxiliary-assisted and ligand-enabled approaches to Pd-catalyzed functionalization of sp3 C�H bonds. This has enabled efficient access to novel structures, including the directed arylation of small carbocyclic structures. However, to date there are no examples of C�H arylation on heterocyclic derivatives .In this presentation we will describe the first C�H arylation of heterocycles, in the regio- and stereospecific synthesis of proline derivatives by Pd-catalyzed directed C�H functionalization. A range of novel, enantiopure C3�functionalized proline derivatives are synthesized on a substantial scale, in good to excellent yields (up to 91% ). The reaction tolerates a wide range of functional groups in the reacting iodide partner, and is suitable for the installation of aromatic, heteroaromatic and vinyl functionality. Following the C�H functionalization, removal or conversion of the directing group and/or N�R groups leads to fascinating unnatural amino acid structures with desirable fragment properties, which may provide excellent starting points for medicinal chemists. They may also find use in organocatalysis, where proline already holds an esteemed position.

Regio- and stereospecific synthesis of proline derivatives by palladium-catalyzed directed C(sp<sup>3</sup>)�H functionalization

248th National Meeting (2014)

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Regio- and stereospecific synthesis of proline derivatives by palladium-catalyzed directed C(sp3)�H functionalization

Regio- and stereospecific synthesis of proline derivatives by palladium-catalyzed directed C(sp³)�H functionalization