Organoboron chemistry is increasingly important in large-scale production as well as laboratory-scale synthesis of pharmaceuticals due to the widespread use of boronic acid derivatives in transition metal- catalyzed C-C coupling. In particular, palladium or nickel catalyzed Suzuki-Miyaura coupling of boronic acids is revolutionizing the way that experimental drugs are made due to its excellent catalyst efficiency and compatibility with numerous heterocyclic environments of medicinal interest. The proposed studies will access synthetically important boronates using new procedures for boron activation. The emphasis is on conversion of simple Lewis base-borane complexes into versatile borane and boronic acid derivatives. A variety of heterocyclic boronic acid environments will be prepared using directed hydroboration methodology, and palladium catalyzed coupling chemistry of these intermediates will be confirmed under recently developed conditions for boronic acids that contain a secondary C-B bond. Specific applications of amine directed hydroboration will study stereocontrol and the synthesis of a pyrrolidine subunit common to the HIV1 inhibitor batzelladine F and batzelladine K. Newly developed N-directed ionic hydrogenations of amine and phosphite boranes will be used to control relative and absolute stereochemistry, and to explore applications to dihydroretinoid synthesis. The new amine borane activation methods also allow intramolecular and intermolecular electrophilic borylation of heterocyclic substrates. This technique will be applied to substrates where alternative methods are not suitable and the interface between mechanism and synthesis will be studied to improve the reactivity of boron reagents and to develop related organoaluminum reagents.

Public Health Relevance

Relevance Access to new organoboron environments is important because boronic acid coupling technology is revolutionizing large-scale as well as lab-scale synthesis of pharmaceuticals and experimental drugs. Boronic acids are also of interest as biologically active agents, and as carbohydrate sensors. Heterocyclic substrates are common building blocks for pharmaceuticals, and the derived organoboron structures are among the most useful tools for heterocycle assembly and functionalization.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Synthetic and Biological Chemistry A Study Section (SBCA)
Program Officer
Lees, Robert G
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Michigan Ann Arbor
Schools of Arts and Sciences
Ann Arbor
United States
Zip Code
Miller, Daniel K (2013) Facile conversion of chromane-6-triflate to chromane-6-alanines under Palladium conditions. Tetrahedron Lett 54:811-813
Prokofjevs, Aleksandrs; Jermaks, Janis; Borovika, Alina et al. (2013) Electrophilic C-H Borylation and Related Reactions of B-H Boron Cations. Organometallics 32:
Cazorla, Clement; De Vries, Timothy S; Vedejs, Edwin (2013) P-directed borylation of phenols. Org Lett 15:984-7
Prokofjevs, Aleksandrs; Kampf, Jeff W; Solovyev, Andrey et al. (2013) Weakly stabilized primary borenium cations and their dicationic dimers. J Am Chem Soc 135:15686-9
De Vries, Timothy S; Prokofjevs, Aleksandrs; Vedejs, Edwin (2012) Cationic tricoordinate boron intermediates: borenium chemistry from the organic perspective. Chem Rev 112:4246-82
De Vries, Timothy S; Majumder, Supriyo; Sandelin, Angela M et al. (2012) Mechanistic variations in ionic hydrogenation of unsaturated phosphine and amine boranes. Org Lett 14:688-91
Prokofjevs, Aleksandrs; Vedejs, Edwin (2011) N-Directed aliphatic C-H borylation using borenium cation equivalents. J Am Chem Soc 133:20056-9
Prokofjevs, Aleksandrs; Kampf, Jeff W; Vedejs, Edwin (2011) A boronium ion with exceptional electrophilicity. Angew Chem Int Ed Engl 50:2098-101
De Vries, Timothy S; Prokofjevs, Aleksandrs; Harvey, Jeremy N et al. (2009) Superelectrophilic intermediates in nitrogen-directed aromatic borylation. J Am Chem Soc 131:14679-87
Wang, Guoqiang; Vedejs, Edwin (2009) Stereocontrol in N-directed hydroboration: synthesis of amino alcohols related to the piperidine alkaloids. Org Lett 11:1059-61

Showing the most recent 10 out of 16 publications