Access to enantioenriched 2,3- and 2,5-dihydrofurans with a fully substituted C2 stereocenter by Pd-catalyzed asymmetric intermolecular Heck reaction† †Electronic supplementary information (ESI) available: Experimental procedures, characterization of all new compounds, VCD studies and spectral data. See DOI: 10.1039/c5sc01460c Click here for additional data file.

During the past decades, building on the seminal contributions of Overman and Shibasaki, the asymmetric intramolecular Heck reaction has been successfully applied in natural product synthesis to install tertiary and quaternary stereocenters. In stark contrast, the intermolecular version of this asymmetric transformation has not reached the same level of development and its synthetic utility remains limited (Fig. 1). A survey of the literature following Hayashi's pioneering contribution indicates that this transformation has been used essentially as a benchmark reaction to validate the design of novel homotopic and heterotopic chiral ligands. While variations of the electronic and steric nature of the aryl halides and pseudo-halides has been investigated in detail, most of these studies have been focused on the use of dihydrofurans or N-protected dihydropyrroles to afford the corresponding coupling products with a C2 tertiary center. Systematic studies where emphasis has been placed on exploring the diversity of the olenic coupling partner are scarce, in particular for the construction of congested quaternary centers or related fully saturated centers. Very recently, Sigman has reported a series of elegant contributions for the redox-relay Heck arylations of acyclic alkenyl alcohols enabling the installation of remote tertiary and quaternary stereogenic centers. Despite these recent breakthroughs, it is apparent that the development of an intermolecular asymmetric Heck reaction to enable the construction of fully saturated stereocenters in cyclic systems constitutes an important synthetic challenge.