Carbocyclic rings are structural units present in most pharmacologically active compounds. As a consequence, the development of cyclization reactions for the efficient construction of molecules containing these units is essential. Several well-known ring-forming processes (e.g. the Diels-Alder and Robinson annulation reactions) have been highly developed and extensively utilized. Other processes which might be complimentary to these and perhaps more general in scope have seen comparatively little development. We propose a systematic study of intramolecular reductive coupling reactions in an effort to examine their scope for the construction of carbocyclic rings. The first part of the proposal outlines fundamental research in carbocyclic ring-forming reactions. A variety of difunctional organic substrates will be investigated for their ability to undergo intramolecular reductive coupling reactions. A number of metal-based reductants will be utilized to effect these cyclizations. The goal of these studies is to determine the conditions under which effective cyclization will occur, as well as to assess the chemo- and stereoselectivity of the processes developed. The second phase of the study will focus on the use of chelation-control in these intramolecular reductive coupling reactions to bring about the cyclization with complete stereochemical control. Once again, several systems will be evaluated for their effectiveness in this process. Nearly all of the proposed substrates can be prepared in optically active form, and thus this represents an extremely efficient process for the synthesis of chiral carbocyclic materials from acyclic substrates.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Colorado at Boulder
Schools of Arts and Sciences
United States
Zip Code
Presset, Marc; Fleury-Brégeot, Nicolas; Oehlrich, Daniel et al. (2013) Synthesis and minisci reactions of organotrifluoroborato building blocks. J Org Chem 78:4615-9
Molander, Gary A; Traister, Kaitlin M; Barcellos, Thiago (2013) Palladium-catalyzed ?-arylation of 2-chloroacetates and 2-chloroacetamides. J Org Chem 78:4123-31
Tschaen, Brittany A; Schmink, Jason R; Molander, Gary A (2013) Pd-catalyzed aldehyde to ester conversion: a hydrogen transfer approach. Org Lett 15:500-3
Molander, Gary A; Cavalcanti, Livia N (2013) Synthesis of trifluoromethylated isoxazolidines: 1,3-dipolar cycloaddition of nitrosoarenes, (trifluoromethyl)diazomethane, and alkenes. Org Lett 15:3166-9
Presset, Marc; Oehlrich, Daniel; Rombouts, Frederik et al. (2013) Complementary regioselectivity in Rh(III)-catalyzed insertions of potassium vinyltrifluoroborate via C-H activation: preparation and use of 4-trifluoroboratotetrahydroisoquinolones. Org Lett 15:1528-31
Molander, Gary A; Barcellos, Thiago; Traister, Kaitlin M (2013) Pd-catalyzed cross-coupling of potassium alkenyltrifluoroborates with 2-chloroacetates and 2-chloroacetamides. Org Lett 15:3342-5
Argintaru, O Andreea; Ryu, DaWeon; Aron, Ioana et al. (2013) Synthesis and applications of ?-trifluoromethylated alkylboron compounds. Angew Chem Int Ed Engl 52:13656-60
Molander, Gary A; Traister, Kaitlin M (2013) Pd-catalyzed alkynylation of 2-chloroacetates and 2-chloroacetamides with potassium alkynyltrifluoroborates. Org Lett 15:5052-5
Colombel, Virginie; Presset, Marc; Oehlrich, Daniel et al. (2012) Synthesis and reactivity of solid-supported organotrifluoroborates in Suzuki cross-coupling. Org Lett 14:1680-3
Devulapally, Rammohan; Fleury-Bregeot, Nicolas; Molander, Gary A et al. (2012) Synthesis and cross-coupling reactions of imidomethyltrifluoroborates with aryl chlorides. Tetrahedron Lett 53:1051-1055

Showing the most recent 10 out of 72 publications