Research Group of Prof. Declan G. Gilheany
Prof. Declan G. Gilheany
Professor of Chemistry University College Dublin |
Research Group 2017
|
Research Activity.
My interests lie in the area of synthetic chemistry, for the construction of both useful and theoretically interesting molecules, particularly: stoichiometric and catalytic enantioselective synthesis; organophosphorus chemistry; organo-Main group chemistry; medium rings, small multicyclic heterocycles; theories of chemical bonding:
Author of 82 original research articles, reviews & patents in the area of organic synthesis, catalysis and phosphorus chemistry. H-Index 26; Total citations 2105; Total refereed publications >120. To date, approx. €7.6M research funding (Irish government, EU & Irish industry). A breakthrough technology commercialised via a start-up company (CelticCatalysts.com), restricted publication in the period 2007-2010). Supervised 34 PhDs/24 PDRAs to date. Currently: 4 PhDs/3 PDRAs.
My interests lie in the area of synthetic chemistry, for the construction of both useful and theoretically interesting molecules, particularly: stoichiometric and catalytic enantioselective synthesis; organophosphorus chemistry; organo-Main group chemistry; medium rings, small multicyclic heterocycles; theories of chemical bonding:
Author of 82 original research articles, reviews & patents in the area of organic synthesis, catalysis and phosphorus chemistry. H-Index 26; Total citations 2105; Total refereed publications >120. To date, approx. €7.6M research funding (Irish government, EU & Irish industry). A breakthrough technology commercialised via a start-up company (CelticCatalysts.com), restricted publication in the period 2007-2010). Supervised 34 PhDs/24 PDRAs to date. Currently: 4 PhDs/3 PDRAs.
Overview of Novel Organophosphorus Methodologies
Dynamic resolution of P-Stereogenic phosphorus compounds. This unprecedented reaction enables easy construction of P-stereogenic phosphorus compounds (incl. phosphoramidites). It was run at kg scale and commercialized. It is based on an asymmetric version of the Appel conditions – I chose to look at this old reaction from the point of view of the unwanted by-product and realised that we could take advantage of its high selectivity to make much more desirable end-products. From initial promising results (publication P1) the project has matured to be a powerful and flexible method for the construction of a wide range of chiral phosphorus compounds (publication P2), which was patented (PCT/IB2005/002079 granted) and licensed for commercialization to Celtic Catalysts (our Campus Company set up for that purpose). We found interesting mechanisms and intermediates (Chem Commun, 2012, 48, 10040) and discovered fundamental insights into the rates of nucleophilic substitution at phosphonium centres notably: pentavalent transition states vs. pentavalent intermediates (Publication P3).
There are two entirely different uses for the compounds: as catalysts and as ProTide drug candidates. The latter have emerged recently as a powerful hepatitis C treatment.
· Synthesis of P-Stereogenic Phosphorus Compounds. Asymmetric Oxidation of Phosphines under Appel Conditions. E. Bergin, C.T. O'Connor, S.B. Robinson, E.M. McGarrigle, C.P. O'Mahony and D.G. Gilheany, Journal of the American Chemical Society, 2007, 129, 9566-9567.
· Turning Regioselectivity into Stereoselectivity: Dual Resolution of P-Stereogenic Phosphine Oxides via Bifurcation in the Reactivity of a Common Intermediate. K. Nikitin, K. V. Rajendran, H. Müller-Bunz and D. G. Gilheany, Angewandte Chemie International Edition, 2014, 53, 1906-1909.
· Degenerate Nucleophilic Substitution in Phosphonium Salts. E. V. Jennings, K. Nikitin, Y. Ortin and D. G. Gilheany, Journal of the American Chemical Society, 2014, 136, 16217–16226.
There are two entirely different uses for the compounds: as catalysts and as ProTide drug candidates. The latter have emerged recently as a powerful hepatitis C treatment.
· Synthesis of P-Stereogenic Phosphorus Compounds. Asymmetric Oxidation of Phosphines under Appel Conditions. E. Bergin, C.T. O'Connor, S.B. Robinson, E.M. McGarrigle, C.P. O'Mahony and D.G. Gilheany, Journal of the American Chemical Society, 2007, 129, 9566-9567.
· Turning Regioselectivity into Stereoselectivity: Dual Resolution of P-Stereogenic Phosphine Oxides via Bifurcation in the Reactivity of a Common Intermediate. K. Nikitin, K. V. Rajendran, H. Müller-Bunz and D. G. Gilheany, Angewandte Chemie International Edition, 2014, 53, 1906-1909.
· Degenerate Nucleophilic Substitution in Phosphonium Salts. E. V. Jennings, K. Nikitin, Y. Ortin and D. G. Gilheany, Journal of the American Chemical Society, 2014, 136, 16217–16226.
Earlier Research Achievements
· At MIT: I found a significant improvement in the Sharpless asymmetric dihydroxylation (AD) reaction - patent recognition was granted for this contribution and still generates royalty income. I am honoured to note that this work formed a part of the body of work for which Sharpless won the 2001 Nobel Prize and gratified that he mentioned this in his Nobel Prize address.
· At UCD: chromium salen catalysed asymmetric alkene epoxidation. With over 90% ee for trans-epoxides from E-alkenes, this method is complementary to Jacobsen-Katsuki epoxidation but, uniquely, utilizes a different salen substitution pattern - bis (3-trifluoromethyl): (Org. Lett. 2001, 3, 663, 3435) and ours is still the definitive review of metal-salen catalysis: (McGarrigle & Gilheany, Chem. Rev. 2005, 105, 1563).
· I gave coherent theoretical descriptions of P=C/P=O and hypervalent phosphorus bonds in my influential review (Chem. Rev. 1994, 94, 1339) and am especially known for the final debunking of virtual d orbital involvement and for the use of Walsh diagrams.
· A novel synthesis of azulenes giving the rare 1,3,5,6-substitution pattern (Chem Commun 2004, 684)
· An easy & general route to 7-membered carbocycles & heterocycles containing O, N, P or S via entropy/strain reduction in the reactivity of Z,Z-hexadiene derivatives (Chem Commun, 1994, 67).
· First Stevens rearrangement at phosphorus & proof of through-conjugation via phosphonium (PhD).
· At MIT: I found a significant improvement in the Sharpless asymmetric dihydroxylation (AD) reaction - patent recognition was granted for this contribution and still generates royalty income. I am honoured to note that this work formed a part of the body of work for which Sharpless won the 2001 Nobel Prize and gratified that he mentioned this in his Nobel Prize address.
· At UCD: chromium salen catalysed asymmetric alkene epoxidation. With over 90% ee for trans-epoxides from E-alkenes, this method is complementary to Jacobsen-Katsuki epoxidation but, uniquely, utilizes a different salen substitution pattern - bis (3-trifluoromethyl): (Org. Lett. 2001, 3, 663, 3435) and ours is still the definitive review of metal-salen catalysis: (McGarrigle & Gilheany, Chem. Rev. 2005, 105, 1563).
· I gave coherent theoretical descriptions of P=C/P=O and hypervalent phosphorus bonds in my influential review (Chem. Rev. 1994, 94, 1339) and am especially known for the final debunking of virtual d orbital involvement and for the use of Walsh diagrams.
· A novel synthesis of azulenes giving the rare 1,3,5,6-substitution pattern (Chem Commun 2004, 684)
· An easy & general route to 7-membered carbocycles & heterocycles containing O, N, P or S via entropy/strain reduction in the reactivity of Z,Z-hexadiene derivatives (Chem Commun, 1994, 67).
· First Stevens rearrangement at phosphorus & proof of through-conjugation via phosphonium (PhD).