The use of O-(diphenylphosphinyl)hydroxylamines and nitrogen-selenium ylides in transition-metal-free aminations of sp2 carbon centres
File(s)
Author(s)
Milner, Harry
Type
Thesis
Abstract
Due to their abundance in both natural products and synthetic pharmaceuticals, and their diverse and interesting biological properties, nitrogen containing compounds are of great importance to organic chemists. As such, synthetic methodology for the incorporation of nitrogen into organic compounds via the construction of C-N bonds is highly sought after. The research described in this thesis concerns the development of three methodologies for the synthesis of small nitrogen containing compounds via the amination of carbon sp2 centres:
1) Synthesis of N-Boc-aziridines
Building upon recent reported methodology utilising O-(diphenylphosphinyl) hydroxylamine (DppONH2) as a nitrogen source for NH-aziridinations, studies were undertaken into the use of N-Boc-O-(diphenylphosphinyl) hydroxylamine (DppONHBoc) in the synthesis of N- Boc-aziridines. Described herein are studies into the use of DppONHBoc as a nucleophilic nitrogen transfer agent (NNTA) for the aziridination of enones and vinyl sulfones under mildly basic conditions.
2) Amination of aromatic C-H centres
The use of a N-methyl morpholine (NMM)-derived aminimine as an aminating agent in the vicarious nucleophilic amination (VNA) of electron-deficient (hetero)arenes is also reported. Initial studies which used iodide hydrazinium salts as aminimines precursors in the amination of a range of electron-deficient substrates are described. An alternative reaction system utilising the in situ formation of NMM/DppONH2 hydrazinium salts, in-place of preformed hydrazinium salts, in the vicarious nucleophilic amination reaction was then developed.
3) Synthesis of enantioenriched allylic amines
Finally, the NCS-meditated amination/[2,3]-sigmatropic rearrangement of enantioenriched allylic selenides, utilising a range of amino acid derived and aryl amine nucleophiles, is used to access a wide range of novel vinyl glycine derived unnatural peptides and peptidomimetic products.
1) Synthesis of N-Boc-aziridines
Building upon recent reported methodology utilising O-(diphenylphosphinyl) hydroxylamine (DppONH2) as a nitrogen source for NH-aziridinations, studies were undertaken into the use of N-Boc-O-(diphenylphosphinyl) hydroxylamine (DppONHBoc) in the synthesis of N- Boc-aziridines. Described herein are studies into the use of DppONHBoc as a nucleophilic nitrogen transfer agent (NNTA) for the aziridination of enones and vinyl sulfones under mildly basic conditions.
2) Amination of aromatic C-H centres
The use of a N-methyl morpholine (NMM)-derived aminimine as an aminating agent in the vicarious nucleophilic amination (VNA) of electron-deficient (hetero)arenes is also reported. Initial studies which used iodide hydrazinium salts as aminimines precursors in the amination of a range of electron-deficient substrates are described. An alternative reaction system utilising the in situ formation of NMM/DppONH2 hydrazinium salts, in-place of preformed hydrazinium salts, in the vicarious nucleophilic amination reaction was then developed.
3) Synthesis of enantioenriched allylic amines
Finally, the NCS-meditated amination/[2,3]-sigmatropic rearrangement of enantioenriched allylic selenides, utilising a range of amino acid derived and aryl amine nucleophiles, is used to access a wide range of novel vinyl glycine derived unnatural peptides and peptidomimetic products.
Version
Open Access
Date Issued
2015-01
Date Awarded
2015-06
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Armstrong, Alan
Sponsor
Engineering and Physical Sciences Research Council
GlaxoSmithKline
Publisher Department
Chemistry
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)