Previously, we reported the development of a colorimetric ISES (In Situ Enzymatic Screening) approach to evaluating possible catalytic combinations for a transformation of interest. When applied to screen a set of 3 cyclization substrates, 64 candidate transition metal complexes and 6 halides (1152 combinations), an interesting Pd-mediated transformation was identified. This is formally a (pseudo)halometalation/carbocyclization process, in which both a C-X and a C-C bond are constructed in a single step. The title transformation accommodates both halide and pseudohalide nucleophiles, depending upon the system. Discussed here will be the latest results in our studies directed at establishing the scope of this chemistry with respect to nucleophile, bridging heteroatom and ring size. Also central to these efforts is the ability to control relative stereochemistry through installation of a pre-existing stereocenter at either the allylic or propargylic positions in the substrate. Finally, by establishing the absolute stereochemistry in the educt, one can utilize this transformation to gain access to bridged bicyclic, natural cores that are readily functionalizable.

Examining the scope of ISES hits: Pd-catalyzed halo- and pseudohalometalation/carbocyclization transformations

249th National Meeting (2015)

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