Stereospecific, nickel-catalyzed cross-couplings of amine and alcohol derived substrates
Date
2017
Authors
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Journal ISSN
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Publisher
University of Delaware
Abstract
This dissertation focuses on nickel-catalyzed cross-couplings of amine and
alcohol derivatives to set stereogenic centers. Chapter 1 focuses on the cross-coupling
of benzylic ammonium triflates with aryl, heteroaryl, and vinyl boronic acids. This
method expands the scope of previous methods from our group, utilizing Ni(cod)2
without any additional phosphine or N-heterocyclic carbene (NHC) ligands. This
reaction allows for cross-coupling of both naphthyl and phenyl substituted
ammonium salts. The mild conditions of this reaction displays excellent functional
group tolerance. ☐ Chapter 2 focuses on the cross-coupling of benzylic ammonium triflates with
bis(pinacolato)diboron to afford secondary benzylic boronates with excellent chirality
transfer, This reaction utilizes Ni(cod)2 as a catalyst with either phosphine or NHC
ligands. The reaction proceeds with mild reaction conditions and excellent functional
group tolerance. It allows for the cross-coupling of both naphthyl and phenyl
substituted ammonium salts. This is the first example of a Miyaura borylation of a
non-allylic electrophile to deliver products in highly enantioenriched form. ☐ Chapter 3 describes the development of the cross-coupling of tertiary benzylic
acetates to form all-carbon quaternary stereocenters. This reaction prioritizes the use
of an air-stable nickel(II) catalyst and environmentally friendly 2-Me-THF. The mild
reaction conditions allow for excellent functional group tolerance. The reaction
provides an efficient route to both di-aryl and tri-aryl quaternary stereocenters in high
stereochemical fidelity. This method shows an expansion in transition metal catalysis
to go beyond electrophiles adjacent to functional groups such as carbonyls and
alkenes, and displays the possibility for tertiary benzylic electrophiles to under go
transition metal catalysis. ☐ Chapter 4 focuses on the cross-coupling of enantioenriched allylic pivalates
with aryl and heteroaryl borxines to form allylic, all-carbon quaternary stereocenters.
This utilizes an air-stable nickel (II) catalyst, and functional group tolerant boroxine
coupling partners to afford these quaternary stereocenters with high stereochemical
fidelity. This reaction provides a powerful way to readily access allylic quaternary
stereocenters with substituted internal alkenes and a variety of functional groups and
heteroatoms in high yield and enantioenrichment
Description
Keywords
Pure sciences, Benzylic ammonium triflates, Enantioenriched benzylic boronates, N-heterocyclic carbene