Boehringer Ingelheim – UCLA Lectureship

Thu, Oct 6 5:00pm
CS24 Young Hall
Speaker Professor Larry E. Overman
Hosted by
UCLA Department of Chemistry and Biochemistry

The 2016 Boehringer Ingelheim – UCLA Lectureship


1:30 PM Lecture

Cram Conference Room – 3440 Molecular Sciences Bldg

“Development of Efficient Asymmetric Syntheses of a Chiral Quaternary FLAP Inhibitor and an Atropisomeric HIV Integrase Inhibitor”

Dr. Keith R. Fandrick

Principal Scientist, Chemical Development

Boehringer Ingelheim Pharmaceuticals, Inc.

Abstract.  Practical and Efficient Asymmetric Syntheses of two structurally challenging drug substances possessing rare chiral structural motifs has been accomplished. A practical sequence involving a non-cryogenic stereospecific boronate rearrangement followed by a robust formylation with an in-situ generated DCM anion have been developed for the asymmetric construction of an all-carbon quaternary stereogenic center of a FLAP inhibitor. The key boronate rearrangement was rendered noncryogenic and robust by using LDA as the base and instituting an in-situ trapping of the unstable lithiated benzylic carbomate with the boronic ester. A similar strategy was implemented for the DCM formylation reaction. It was found that the 1,2-boronate rearrangement for the formylation reaction could be temperature controlled thus preventing over addition of the DCM-anion and rendering the process reproducible. The robust stereospecific boronate rearrangement and formylation were utilized for the practical asymmetric synthesis of a chiral quaternary FLAP inhibitor. A practical and efficient synthesis of a complex chiral atropisomeric HIV integrase inhibitor has been accomplished. The combination of the copper catalyzed acylation along with the implementation of the BI-DIME ligands for the ligand controlled Suzuki cross coupling and the unprecedented bis(trifluoromethane)-sulfonamide catalyzed tert-butylation rendered the synthesis of this complex molecule robust, safe and economical. In addition, the overall synthesis was rendered asymmetric and diastereoselective with respects to the imbedded atropisomer.


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5:00 PM Lecture

CS24 Young Hall

“Fragment Coupling Using Carbon Radicals”

Professor Larry E. Overman

Distinguished Professor of Chemistry

Department of Chemistry

University of California, Irvine

Abstract.  Reactions that allow complex molecular fragments to be combined in high yield occupy an exalted position in organic synthesis because they are fundamental to convergent synthesis strategies. Recent discoveries from our laboratories show that bimolecular reactions of structurally elaborate tertiary carbon radicals and electron-deficient alkenes can unite complex fragments by forming a new sp3–sp3 in good yield using near equimolar amounts of the two coupling partners. Reflecting the large steric bulk of tertiary carbon radicals, these reactions can take place with high stereoselectivity to form new quaternary and secondary carbon stereocenters. Tertiary carbon radicals are generated conveniently using visible-light photocatalysis, which offers distinct advantages over older less-green methods for forming carbon radicals.


Thursday, October 6, 2016