Electrophilic Late Metal Catalysts
Since its discovery in the 1940's, no asymmetric variant of the Cope rearrangement of achiral 1,5-dienes has emerged, this despite the successes that have been achieved with its heteroatom variants (Claisen, aza-Cope, etc). The new gold(I) catalyst derived from double Cl—-abstraction of ((S)-3,5-xylyl-PHANEPHOS(AuCl)2), has been developed for the sigmatropic rearrangement of alkenyl-methylene cyclopropanes. The reaction proceeds at low temperature and the synthetically useful vinyl cyclopropane products are obtained in high yield and enantioselectivity, driven by the relief of ring strain in the cyclopropylidene moiety. Further investigations into the utilization of relief of ring strain in promoting otherwise thermodynamically unfavorable rearrangements are currently underway. We are pleased that this work has recently been accepted to Nature: Chemistry.
Mechanistic studies of gold(I)-catalyzed allene activation reactions has shown that "digold" and "gold-silver" complexes are key intermediates. Our efforts to understand this phenomenon has shed light on the role of polymetallic complexes in defining the mechanistic pathway to product and in defining how and where the catalyst rests in the cycle. These efforts have provided insights that we are now using to develop asymmetric variants of these reactions.
Weber, Tarselli, Gagné. Angew. Chem. Int. Ed. 2009, 48, 5733
Weber, Gagné. Org. Lett. 2009, 11, 4962
Weber, Jones, Adduci, Gagné. Angew. Chem. Int. Ed., 2012, accepted
We have previously demonstrated that phosphine-ligated dicationic platinum complexes are exceptionally efficient at initiating cation-olefin cascades, especially when the poly-ene is terminated with a protic trap. More recent studies have demonstrated that these catalysts can even tolerate replacing the protic trap with a bio-like alkene terminus. However, in contrast to protic terminators, the reaction proceeds more slowly, likely reflecting the kinetic cost of generating a discrete tertiary cation at the terminus. A number of poly-enes were examined that varied in the number of rings formed (two-three), the arrangement of the terminating alkene (endo versus exo-cyclic), and the ring size. Catalytic conditions are currently being optimized. These experiments represent the closest approaches that the community has developed for biomimetic cation-olefin cascade catalysis of sterols.
Sokol, Korapala, White, Becker, Gagné. Angew. Chem. Int. Ed., 2011, 50, 5658
For earlier efforts in protic terminators, see:
Cochrane, Brookhart, Gagné. Organometallics, 2011, 30, 2457
Mullen, Campbell, Gagné. Angew. Chem. Int. Ed., 2008, 47, 6011
Feducia, Gagné. J. Am. Chem. Soc., 2008, 130, 592
Mullen, Gagné. J. Am. Chem. Soc., 2007, 129, 11880
Chianese, Lee, Gagné. Angew. Chem. Int. Ed., 2007, 26, 2788
Koh, Gagnéé. Angew. Chem. Int. Ed., 2004, 43, 3459
Carbon-fluorine bonds have an integral role in pharmaceuticals, agrochemicals, materials and tracers for positron emission tomography. Despite a growing interest, selective C-F bond formation is still challenging. To address this deficiency we have developed several enantioselective Pt-catalyzed cyclization/fluorination reactions. Our early stoichiometric experiments demonstrated that F+ sources quickly converted (triphos)Pt-R+ complexes into R-F products with stereoretention. More recently we have found that P2Pt(II) and (P2P)Pt(II) dications (P2 = bidentate phosphine ligand; P = monodentate phosphine ligand) are excellent catalysts for the electrophilic cyclization/fluorination of polyene substrates. The catalyst in combination with XeF2, has given good results for the catalytic electrophilic fluorination of the dienephenol substrate. Current studies are underway to expand the substrate scope, develop asymmetric variants and investigate the mechanism.
Zhao, Becker, Gagné. Organometallics 2011, 30, 3926-3929
The poly-ene cyclization reactions mediated by Pt catalysts have allowed for the synthesis of a variety of polycyclic frameworks, enabling generation of a C3-organometallic. A number of natural products consist of similar polycyclic frameworks with C3-oxygenation (e.g. lanosterol, cholesterol and testosterone) but there are no asymmetric methodologies for accessing these classes of compounds. To address this deficiency we seek to develop methods to oxygenate the Pt-C bond of the C3-organometallic intermediates and thereby gain access to C3-oxygenated sterol skeletons.
