Enantioselective γ- and δ -Borylation of Unsaturated Carbonyl Derivatives: Synthesis, Mechanistic Insights, and Applications.

Authors

Gia L. Hoang, University of Nebraska-LincolnFollow

ORCID IDs

Gia L. Hoang

First Advisor

James M. Takacs

Date of this Version

8-2017

Document Type

Article

Citation

Hoang, G. L., Thesis Dissertation, University of Nebraska, 2017

Comments

A DISSERTATION Presented to the Faculty of The Graduate College at the University of Nebraska In Partial Fulfillment of Requirements For the Degree of Doctor of Philosophy, Major: Chemistry, Under the Supervision of Professor James M. Takacs. Lincoln, Nebraska: August, 2017

Copyright (c) 2017 Gia L. Hoang

Abstract

Chiral boronic esters are valuable synthetic intermediates widely used in a variety of stereospecific transformations. Transition metal-catalyzed asymmetric hydroboration (CAHB) of alkenes is among the most popular methods for their preparation. Enantioselective hydroboration of activated alkenes (i.e., vinyl arene derivatives or conjugated carbonyl compounds) have been extensively studied by many research groups. We, on the other hand, are interested in enantioselective hydroboration of unactivated alkenes utilizing coordinating functional groups (e.g., carbonyl derivatives) to give functionalized, chiral boronic esters. While conjugate addition and C–H activation methodologies provide efficient alternatives to CAHB for enantioselective beta-borylation of carbonyl compounds, direct gamma- and delta-borylations were essentially unknown prior to our wok on CAHB. The gamma-borylated products were used for understanding stereochemical aspects of Suzuki–Miyaura cross-coupling reactions resulting in stereoretention and in contrast to similar beta-borylated carbonyl derivatives reported in literature. Some other selected transformations were carried out to construct a number of biologically relevant structural motifs, such as lignan precursors, 1,4-amino alcohols, gamma-amino acid derivatives, 5-substitued-gamma-lactone and lactam ring systems. In addition, collaborative experimental and computational studies of the enantioselective desymmetrization via CAHB gain a better understanding of the mechanistic pathways.

Advisor: James M. Takacs