The construction of carbon-carbon bonds is of paramount importance in organic synthesis. As such, the development of new methods which allow for mild and selective C-C bond formation are highly desirable, especially in the context of the syntheses of natural products and pharmaceuticals. 1,2-additions of carbon nucleophiles into carbonyl compounds is a premier method for constructing carbon-carbon bonds. Common reagents employed in these transformations are Grignards, organolithium or organozinc reagents. Drawbacks of these reagents include low functional group tolerance, air and moisture sensitivity, high basicity and limited bench stability. An alternative approach is the metal catalyzed 1,2-addition of organoboron compounds into carbonyls. Organoboron reagents are advantageous in many ways including their ready availability, low basicity, stability to air, moisture and chromatography. To date, only highly activated carbonyls have been shown to undergo 1,2- additions with organoboron compounds under rhodium-catalysis. We wish to extend the scope of this reaction to include additions of pinacolboronic esters into unactivated ketones using Rh(I) catalysis. Initial goals will include establishing proof of concept for this type of addition and optimization of the reaction conditions as well as investigating the scope of both intra- and intermolecular variants of this transformation. Upon the successful completion of this investigation, an asymmetric variant will be developed allowing access to enantio-enriched tertiary alcohols. Preliminary results have shown aromatic and heteroaromatic pinacolboronic esters have undergo 1,2-addition into ketones, to smoothly afford the desired tertiary alcohols.

Public Health Relevance

The construction of carbon-carbon bonds is of paramount importance in organic synthesis. As such, the development of new methods which allow for mild and selective C-C bond formation are highly desirable, especially in the context of the syntheses of natural products and pharmaceuticals. Herein, we propose a novel Rh(I)-catalyzed 1,2-addition of arylpinacolboronic esters into unactivated ketones. The success of the initial goals will provide a pathway for the development of catalytic, enantioselective 1,2-additions of pinacolboronic esters.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31GM095238-01A1
Application #
8257341
Study Section
Special Emphasis Panel (ZRG1-F04A-G (20))
Program Officer
Hagan, Ann A
Project Start
2012-04-01
Project End
2015-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
1
Fiscal Year
2012
Total Cost
$34,741
Indirect Cost
Name
University of California Berkeley
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704