New methods for catalytic enantioselective construction of C-C bonds are fundamentally significant. In the right context, such methods can prove to be lynchpin reactions for total synthesis and they can offer new and more efficient routes to useful therapeutic agents. Along these lines, single enantiomer chiral compounds are vitally important as new materials and as medicinally relevant therapies. Indeed, one recent review article established that as of 2003, fully 50% of new drugs brought to market are single enantiomer chiral entities. Further, it was estimated that 500-1000 single enantiomer compounds are in the global drug pipeline at any one time. Clearly, our ability to prepare such chiral therapeutic agents can be enhanced substantially by the introduction of catalytic enantioselective chemical transformations that result in fundamentally new synthetic disconnections. The proposed research will extend our fruitful studies on catalytic conjugate allylation reactions to a much broader range of enantioselective cross-coupling reactions.

Public Health Relevance

Enantiomerically-enriched chiral compounds are important structures in modern health care. The chirality that accompanies these types of compounds may enable them to fit into physiological drug targets better than flat structures thereby offering more potent therapeutics. The proposed research aims to develop new reactions that will provide more accessible routes to such chiral molecular entities.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM064451-09
Application #
8599469
Study Section
Special Emphasis Panel (ZRG1-BCMB-B (02))
Program Officer
Lees, Robert G
Project Start
2002-07-01
Project End
2016-11-30
Budget Start
2013-12-01
Budget End
2014-11-30
Support Year
9
Fiscal Year
2014
Total Cost
$267,615
Indirect Cost
$96,615
Name
Boston College
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
045896339
City
Chestnut Hill
State
MA
Country
United States
Zip Code
02467
Schuster, Christopher H; Coombs, John R; Kasun, Zachary A et al. (2014) Enantioselective carbocycle formation through intramolecular Pd-catalyzed allyl-aryl cross-coupling. Org Lett 16:4420-3
Le, Hai; Batten, Amanda; Morken, James P (2014) Catalytic stereospecific allyl-allyl cross-coupling of internal allyl electrophiles with AllylB(pin). Org Lett 16:2096-9
Yu, Zhiyong; Ely, Robert J; Morken, James P (2014) Synthesis of (+)-discodermolide by catalytic stereoselective borylation reactions. Angew Chem Int Ed Engl 53:9632-6
Ardolino, Michael J; Morken, James P (2014) Congested C-C bonds by Pd-catalyzed enantioselective allyl-allyl cross-coupling, a mechanism-guided solution. J Am Chem Soc 136:7092-100
Le, Hai; Kyne, Robert E; Brozek, Laura A et al. (2013) Catalytic enantioselective allyl-allyl cross-coupling with a borylated allylboronate. Org Lett 15:1432-5
Zhang, Ping; Roundtree, Ian A; Morken, James P (2012) Ni- and Pd-catalyzed synthesis of substituted and functionalized allylic boronates. Org Lett 14:1416-9
Poe, Sarah L; Morken, James P (2011) A boron-based synthesis of the natural product (+)-trans-dihydrolycoricidine. Angew Chem Int Ed Engl 50:4189-92
Zhang, Ping; Le, Hai; Kyne, Robert E et al. (2011) Enantioselective construction of all-carbon quaternary centers by branch-selective Pd-catalyzed allyl-allyl cross-coupling. J Am Chem Soc 133:9716-9
Brozek, Laura A; Sieber, Joshua D; Morken, James P (2011) Catalytic enantioselective conjugate allylation of unsaturated methylidene ketones. Org Lett 13:995-7
Brozek, Laura A; Ardolino, Michael J; Morken, James P (2011) Diastereocontrol in asymmetric allyl-allyl cross-coupling: stereocontrolled reaction of prochiral allylboronates with prochiral allyl chlorides. J Am Chem Soc 133:16778-81

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