Chiral 9-phenyl-9H-fluoren-9-amines in asymmetric induction

Research output: ThesisDoctoral ThesisMonograph

Researchers

  • Essi Karppanen

Research units

Abstract

Chiral amines are present in numerous active pharmaceutical ingredients, bioactive natural products and pharmaceutical building blocks. Therefore the sustainable and selective production of chiral amines is a key research priority in the pharmaceutical industry. Access to enantiopure compounds is needed in other areas of organic chemistry as well. Enantiopure compounds can be obtained through different methods such as resolution, crystallization, enzymatic methods and asymmetric synthesis. In asymmetric synthesis, the asymmetric information may originate from either the starting material or the reagents. The work presented in this thesis is based on internal asymmetric induction, using amino acids as the starting materials and the source of chiral information. Common carbamate-based nitrogen protecting groups do not always fare particularly well in protecting the enantiomeric purity of alpha-chiral amino carbonyl compounds. The 9-phenyl-9H-fluoren-9-yl group has proven to be an outstanding choice for protecting the alpha-center of the amino acid derivatives and it is used as the nitrogen-protecting group throughout the work presented in this thesis, while examining its applicability to different synthetic methods. A number of chiral amines were prepared in the first part of this thesis, including phenethylamine derivatives. Phenethylamines are endogenous compounds exhibiting important roles as neurotransmitters, and the deviations in their production and/or biochemistry causes neurological diseases. Stereoselective synthesis of phenethylamines is of great importance for the evaluation and investigation of their effect on these diseases, and for the development of proper treatments. Several phenethylamines are indeed used in the treatment of neurological diseases, such as ADHD and Parkinson's disease. In this dissertation, two novel transition metal catalyzed routes to access phenethylamines were developed, which produced the desired products in enantiomerically pure form. A number of other selected chiral amines were also synthesized. In the second part of the thesis, the potential of the aerobic copper-TEMPO oxidation was elucidated and developed into an environmentally friendly and economically feasible process. Substrate scope for the oxidation was examined.

Details

Translated title of the contributionKiraaliset 9-fenyyli-9H-fluoren-9-amiinit asymmetrisessä induktiossa
Original languageEnglish
QualificationDoctor's degree
Awarding Institution
Supervisors/Advisors
Publisher
  • Aalto University
Print ISBNs978-952-60-6667-7
Electronic ISBNs978-952-60-6668-4
Publication statusPublished - 2016
MoE publication typeG4 Doctoral dissertation (monograph)

    Research areas

  • asymmetric synthesis, chiral amines, phenylfluorenyl, phenethylamines, asymmetric hydrogenation, catalytic aerobic oxidation

ID: 18990737