Robert S. Paley

Research Interests

List of Publications

[NOTE: Swarthmore College undergraduate co-workers denoted by*].
The sulfoxide functional group, readily available in enantiomerically pure form, has long been used as a chiral auxiliary by synthetic organic chemists.  That is, it is readily attached, in a covalent manner, to an organic substrate and is then utilized to control the absolute stereochemistry of incipient stereogenic centers.  The final step of this strategy involves removal of the sulfoxide unit to afford a chiral organic unit in enantioenriched form.  While the use of enantiomerically pure sulfoxides in the context of "classic" organic transformations is well-established, their use as chiral auxiliaries in transition metal-mediated reactions remains rare.  Our group at Swarthmore has been involved in developing this area of research, and our contribution is a still-evolving indirect approach in which the sulfoxide is used in combination with diene iron(0) tricarbonyl complexes.

We have been the first to prepare sulfinyl diene iron(0) tricarbonyl complexes (1, Figure 1).  Placement of a chiral sulfoxide group at the terminus of diene, with cis stereochemistry as shown, renders the two faces of the diene distinct.  Therefore upon pi-complexation of an Fe(CO)3 fragment to the diene there are two possible diastereomeric products that could be formed by coordination either above or below the chiral plane defined by the diene.  In our case, complexation to the sulfinyl dienes is highly diastereoselective; attachment to one face is greatly preferred as a result of conformational bias (Figure 1).  Thus we are able to control the installation of planar chirality, and considering the paucity of reliable methods for controlling the facial preference in complexations of acyclic diene systems as well as the well-known usefulness of Fe(CO)3 fragments for the installation of new stereocenters along the periphery of dienes, this methodology has great promise as a novel strategy the construction of enantiomerically pure highly functionalized natural product sub-units.

Having thus demonstrated that the chirality of the sulfoxide group could be used to form "planar chiral" organometallic complexes, more elaborate substrates were prepared (2).  The planar chirality was then used to direct the installation of new stereocenters along the periphery of the diene (i.e., 3, Figure 2).  New carbon chains added during this process were then joined to form ring systems using "ring-closing metathesis" chemistry; of particular interest was the unexpected ease in synthesizing an eight-membered ring system, 4.

We have also been exploring the conversion of dialdehydes (5 and 6) into diols via an intramolecular pinacol coupling (Figure 3).  This reaction is highly diastereoselective and allows us to prepare more complex ring systems from our sulfinyl iron diene templates.

Current work in our laboratories includes synthesizing a variety of related substrates in order to obtain crystals suitable for analysis by X-ray crystallography (in order to establish the stereochemistry of the pinacol products).  Also, we are exploring further manipulations of the sulfinyl iron diene functionality.

Finally, planar chiral organometallic complexes can offer unique opportunities for the design of catalysts for asymmetric reactions, or in the design of transition metal ligands for asymmetric metal-catalyzed processes.  This is due to the potential for three-dimensional engineering about the atom or atoms intimately involved in the reaction one seeks to control.  An advantage of such strategies, which can represent wholly synthetic mimics of enzyme active sites, is the potential for precise spatial control of the chiral environment about the transition state of the desired reaction.  Thus, there has been substantial recent interest in the development of this area of synthetic methodology.  Since we can now prepare sulfinyl iron(0) diene complexes in which a sterically demanding functional group can be essentially fixed in a defined position above a diene whose lower face is blocked, some modifications of our complexes could lead to an entirely new class of chiral bidentate ligands based on non-biaryl atropisomerism and planar chirality.

Our initial focus would be to develop a ligand or ligands suitable for use in the palladium-catalyzed asymmetric allylic alkylation reaction which would proceed via an intermediate p-allyl complex, 7 (Figure 4).  The challenge in this area has been to design a ligand which would force the symmetrical p-allyl complex to adopt a single position in order to allow only one of its two faces to be accessible to the incoming nuclophile.  Furthermore, one of the two terminal carbon atoms of the p-allyl complex must be distinguished from the other to avoid indiscriminate approach of the nucleophile.  The best successes in this area have been achieved with the utilization of systems in which the chelating atoms are different - typically N, P- or S, P-ligands, since it has been demonstrated that nucleophile approach trans to the phosphorous atom is preferred.

At all stages of this work, high-field NMR is heavily utilized to identify and characterize the synthesized compounds.

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