This project dealing with the use of electrochemical techniques in organic synthesis is being supported by the Organic and Macromolecular Chemistry Program. Linear molecules containing two or more distal functional groups are being subjected to electrolysis to generate a radical anion at one site which will react by carbon-carbon bond formation at the other functional group resulting in the formation of ring-containing compounds. This research is centered on an attempt to understand the various factors which govern the cyclization process. Electroreductive cyclization reactions are being studied in detail with a special emphasis placed upon an examination of the following items: A. 1. Can substituents positioned at "strategically important locations" on the tether be used as stereocontrol elements allowing for the regulation of both relative and absolute stereochemistry? 2. Can proton donor surrogates (e.g., Me3SiCl) and/or captodative effects be used to facilitate cyclization at the expense of the unwanted C-C pi bond hydrogenation which occasionally accompanies electroreductive cyclizations involving ketones? 3. Can electroreductive cyclizations be conducted using a substrate wherein the alpha, beta-unsaturated ester unit is tethered to an ester (a lactone), an acid anhydride, or an acid halide? 4. Can the results of these investigations be used to design and implement a rational synthesis of the biologically important and architecturally interesting phorbol esters? B. Can mediators such as vitamin B12 or cobaloxime be used in electroreductive cyclization reactions and, if so, can the reactions be conducted catalytically? The results of these studies are being applied to model studies directed toward construction of bicyclo?5.3.O!undecane framework common to a host of natural products. C. Finally, the synthetic utility of electroreductive cyclization reactions involving systems containing the carbon-carbon triple bond (e.g., alkynones and alkynoates) linked to an easily reduced alkylidene malonate or an alkylidene Meldrum's acid subunit is being examined. In this way, the initially formed alpha, beta-unsaturated carbonyl compound should be inert to the conditions under which the reduction is conducted and will consequently be available for further elaboration. Additional studies focusing upon the use of a cyclopropyl Meldrum's acid subunit (a spiroacylal) are being carried out.

Agency
National Science Foundation (NSF)
Institute
Division of Chemistry (CHE)
Application #
8719617
Program Officer
George M. Rubottom
Project Start
Project End
Budget Start
1988-05-01
Budget End
1992-04-30
Support Year
Fiscal Year
1987
Total Cost
$202,580
Indirect Cost
Name
University of California Santa Barbara
Department
Type
DUNS #
City
Santa Barbara
State
CA
Country
United States
Zip Code
93106