Off-campus UNL users: To download campus access dissertations, please use the following link to log into our proxy server with your NU ID and password. When you are done browsing please remember to return to this page and log out.

Non-UNL users: Please talk to your librarian about requesting this dissertation through interlibrary loan.

1. Catalytic palladium-mediated carbocyclizations: The [3+2] cycloaddition mode. 2. Chemistry of weak pronucleophiles: Mitsunobu alkylation and palladium-catalyzed dienylation of bis(2,2,2-trifluoroethyl) malonates

Alexei P Leonov, University of Nebraska - Lincoln

Abstract

Palladium(0)-mediated carbocyclizations of bisdienes provide a convenient access to functionalized 5- and 6-member-ring carbocycles and heterocycles. The reaction mode selectivity is controlled chiefly by the reaction conditions, but in some instances—by the bisdiene substituents as well. We found that aryl-substituted bisdienes readily undergo carbocyclization in a novel [3+2] cycloaddition reaction mode in preference to the other two carbocyclization modes: cyclization trapping, or cycloisomerization. The products of the cycloaddition are functionalized trans-bicyclo[4.3.0]nonanes. The reaction is diastereoselective, and occurs with the formation of 4 contiguous stereocenters located on the five-member ring of the product. The reaction is tolerant to a range of aryl substituents, and facile. During the work on the [3+2] cycloaddition, two new synthetic methodologies based on alkylation chemistry of bis(2,2,2-trifluoroethyl) malonates emerged in the Takacs group. Bis(2,2,2-trifluoroethyl) malonate has a pKa of <13, and unlike other simple malonates, such as diethyl malonate, readily undergoes Mitsunobo dehydrative alkylattion with a variety of primary alcohols; some secondary alcohols can be employed as well. In contrast to other stabilized carbon-based pronucleophiles that do undergo the Mitsunobo reaction with alcohols, bis(2,2,2-trifluoroethyl) malonate successfully undergoes monoalkylation with one equivalent of the alcohol partner, little competing dialkylation is observed. Due to their acidity, bis(2,2,2-trifluoroethyl) malonates exhibit improved regio- and stereo selectivity in the Pd-catalyzed dienylation reactions. Thus, bis(2,2,2-trifluoroethyl) malonates can be dienylated by 5-substituted 2,4-dienyl-alcohols, or their corresponding divinyl alcohols, to give dienylation products of higher regio- (the external, α position is alkylated only) and stereoisomeric purity (the reaction predominantly gives the E,E-dienes) than the analogous reaction of simple dialkyl malonates with the corresponding acetates and carbonates. The alkylation methodologies described above provide a convenient means for the rapid assembly of unsaturated substrates, including the bisdiene substrates for the Pd-catalyzed bisdiene carbocyclizations.

Subject Area

Organic chemistry

Recommended Citation

Leonov, Alexei P, "1. Catalytic palladium-mediated carbocyclizations: The [3+2] cycloaddition mode. 2. Chemistry of weak pronucleophiles: Mitsunobu alkylation and palladium-catalyzed dienylation of bis(2,2,2-trifluoroethyl) malonates" (2004). ETD collection for University of Nebraska-Lincoln. AAI3142091.
https://digitalcommons.unl.edu/dissertations/AAI3142091

Share

COinS