Stereoselective Synthesis of Nitrogen Containing Compounds from Hydroxy Allylic Azides

This thesis describes research conducted since September 2006 in Prof. Robert Batey’s laboratory. The thesis is divided into four chapters. Chapter one presents a general introduction of domino reactions, sigmatropic rearrangements, and the allylic azide rearrangement. Several factors affecting the allylic azide rearrangement along with some respective examples are presented. Chapter two describes an efficient synthesis of azido unsaturated ester compounds using a microwave-assisted domino allylic azide / Johnson-Claisen rearrangement. The domino rearrangement reaction proceeds to give the azido ester compounds in good yield and excellent diastereoselectivity. The synthesis of vinyl epoxides and hydroxy allylic azides starting materials are also presented. In addition, other variants of Claisen rearrangements are briefly discussed. Chapter three describes a microwave-assisted domino allylic azide / Overman rearrangement process. The scope of the domino rearrangements, including an example involving an enantioenriched compound, is presented. The product of the domino rearrangements can be used as precursors to 1,2-vicinal diamines. Several functional group transformations and potential application of the product of the domino rearrangement are also described. Chapter four provides the synthesis of cis-2,5-disubstituted pyrrolidines from domino reduction / cyclization of γ-azido-α,β-unsaturated ketones. The overall process involves hydrogenation of the alkene and the azido group, followed by intramolecular cyclization and loss of H2O to form an imine, which is further reduced to give cis-2,5-disubstituted pyrrolidines. The reaction proceeds cleanly to give the products in high yield and with a very high diastereoselectivity ratio. In addition, the formation of pyrrolidinones via domino reduction / cyclication of γ-azido esters are also reportedPh