Professor Peter O'Brien
Development and Use of New Methods in Asymmetric Synthesis
We develop novel methodology for the synthesis of single enantiomers of chiral molecules. Our ultimate target molecules are biologically active natural products and their analogues,pharmaceutical compounds and chiral ligands and catalysts. All of the group's research focuses on developing selective and synthetically useful methods. We aim to develop catalyticasymmetric synthesis protocols that are technically simple, high yielding and robust.
The main research themes in the group revolve around organolithium reagents and chiraldiamines, with a developing emphasis on catalytic asymmetric synthesis using organolithiums.The three main themes in the group are:(i) (+)-Sparteine Surrogate: a chiral diamine that is almost the mirror image of (–)-sparteine hasbeen introduced and the group continues to develop new synthetic applications using the (+)-sparteine surrogate.(ii) Catalytic Asymmetric Synthesis with Organolithiums: we continue to optimise one-ligandand two-ligand methodology for catalytic asymmetric deprotonation using organolithiumreagents and chiral diamines (eg (–)-sparteine and the (+)-sparteine surrogate).(iii) New Methodology Using Three-membered Ring Heterocycles: the group has on ongoinginterest in developing new reactions of aziridinium ions and lithiated aziridines.In all examples, we exemplify the utility of our new methodology by applying it to the totalsynthesis of biologically active natural products and compounds of pharmaceutical interest.
Selected recent publications
- Enantioselective, Palladium-Catalyzed α-Arylation of N-Boc Pyrrolidine: In Situ React IR Spectroscopic Monitoring, Scope and Synthetic Applications, J. Org. Chem. 2011, 76, 5936.
- One-ligand Catalytic Asymmetric Deprotonation of a Phosphine Borane: Synthesis of P-Stereogenic Bisphosphine Ligands, J. Org. Chem. 2011, 76, 4794.
- Synthesis of the Azaphilones (+)-Sclerotiorin and (+)-8-OMethylsclerotiorinamine Utilizing (+)-Sparteine Surrogates in Copper-Mediated Oxidative Dearomatization, J. Org. Chem. 2011, 76, 2577.
- Asymmetric Deprotonation using s-BuLi or i-PrLi and Chiral Diamines in THF: the Diamine Matters, J. Am. Chem. Soc., 2010, 132, 15445.
- Synthesis of P-Stereogenic Compounds via Kinetic Deprotonation and Dynamic Thermodynamic Resolution of Phosphine Sulfides: Opposite Sense of Induction using (–)-Sparteine, J. Am. Chem. Soc., 2010, 132, 13922.
- Diamine-free Lithiation-Trapping of N-Boc Heterocycles using s-BuLi in THF, Org. Lett. 2010, 12, 4176.
- Asymmetric Deprotonation of N-Boc Piperidine: React IR Monitoring and Mechanistic Aspects, J. Am. Chem. Soc., 2010, 132, 7260.
- Catalytic Asymmetric Synthesis of Piperidines from Pyrrolidine: Concise Synthesis of (+)-L-733,060, Org. Lett., 2009, 11, 1935.
- Catalytic Asymmetric Deprotonation of Phosphine Boranes and Sulfides as a Route to P-Stereogenic Compounds, Chem. Commun. 2008, 3750.
- Palladium-Catalyzed Enantioselective Oxidation of Chiral Secondary Alcohols: Access to Both Enantiomeric Series, Angew. Chem. Int. Ed. 2008, 47, 6367.
- Basic Instinct: Design, Synthesis and Evaluation of (+)-Sparteine Surrogates for Asymmetric Synthesis”, Chem. Commun., 2008, 655 (Feature Article).
- A New Sparteine Surrogate for Asymmetric Deprotonation of N-Boc Pyrrolidine, Org. Lett. 2008, 10, 1409.