Organocatalytic asymmetric mannich, formal [4+1] and [4+2] annulation reactions
Date of Issue2011
School of Physical and Mathematical Sciences
In this doctoral thesis, the research work that was carried out during the last four years will be divided into 5 chapters. Firstly, an introduction to the field of organocatalysis will be described in chapter 1. This will be followed by the first example of an organocatalytic asymmetric Mannich reaction of α-isothiocynamide with tosyl imines. This methodology leads to the facile synthesis of protected α, β-diamino acid derivatives with excellent diastereo- and enantioselectivities. A simple quinine derivative was proven to be an efficient catalyst to promote this reaction, and only low catalyst loading (2.5 mmol%) was required. A wide substrate scope, involving aromatic and aliphatic aldehydes derived imines, was well tolerated. Isoxazoline N-oxides are intriguing synthetic targets as they can be readily converted into highly functionalized γ-hydroxy-α-amino acids or γ-amino-α-hydroxy acids. In chapter 3, a novel methodology for the preparation of optically active cis-isoxazoline N-oxides developed via a formal [4+1] annulation reaction of α-Iodoaldehydes with 2-nitroacyrates, in the presence of (S)-diphenyl trimethylsilyl ether pyrrolidine will be discussed. Additionally, a concise synthesis of chiral densely functionalized α-amino lactone from the isoxazoline N-oxide product will be demonstrated. In chapter 4, a new [4+2] annulation reaction of vinyl ketones with N-sulfonyl-1-aza-1, 3-dienes, using PPh3 as catalyst, will be presented. Phenol additives were found to improve reaction rates and diastereoselectivities. This protocol established a practical process to the preparation of highly substituted tetrahydropyridines, in good to excellent yields and diastereoselectivities, with broad substrates scope. Lastly, in chapter 5, the asymmetric version of this [4+2] annulation reaction was realized by chiral phosphines derived from amino acids. Good yields, moderate to good diastereo- and enantioselectivities were obtained. In addition, benzensulfonamide was proven to be effective in improving enantioselectivity.
DRNTU::Science::Chemistry::Organic chemistry::Organic synthesis