Molecular transformations using a sodium hydride-iodide composite

• Main Author: Chan, Guo Hao
• Other Authors: Chiba Shunsuke
• Format: Theses and Dissertations
• Language: English
• Published: 2019
• Subjects: DRNTU::Science::Chemistry::Organic chemistry::Organic synthesis
• Online Access: https://hdl.handle.net/10356/103312; http://hdl.handle.net/10220/47383
• Institution: Nanyang Technological University

Sodium hydride is used exclusively as a strong Brønsted base for the deprotonation reactions in chemical synthesis. This thesis describes development of new protocol for use of sodium hydride in a variety of unique hydride reduction processes by its combined use with alkali metal iodides. In Chapter 1, various strategies for the manipulation of alkali and alkaline earth metal hydrides for the reduction of π-electrophiles are discussed. Chapter 2 describes serendipitous discovery and development of unprecedented hydrodecyanation of alpha-quaternary benzylcyanides by a NaH-iodide. This simple protocol bestows NaH with an unique hydride-donor chemical reactivity. The composite can reduce a cyano functional group at the benzylic position to its respective alkanes (via the iminyl intermediate) with a retention of the preinstalled α-chirality. Chapter 3 describes development of the sodium hydride-iodide composite for the selective hydride reduction of tertiary carboxamides into the corresponding aldehydes. This protocol displays interesting reactivity in the reduction of a wide variety of aryl, heteroaryl and aliphatic carboxamide amides into the aldehydes. Retention of α-chirality in α-enantioriched amides and chemoselective reduction of amides over ketones and tert-butyl esters feature prominently in the present reduction protocol. The chapter also describes the use of sodium deuteride as an economical alternative for the synthesis of various deuterated aldehydes in high deuterium incorporation. In Chapter 4, discovery and development of the amide-directed C-H sodiation by the NaH-iodide composite are discussed. It was found that unique Lewis acidity is installed on sodium hydride in the presence of NaI or LiI, that enables amide-directed deprotonative sodiation of ortho-aromatic C-H or benzylic C-H bond to form nucleophilic organosodium intermediates. Subsequent transformations allowed for facile synthesis of ortho-secondary alkyl arylaldehydes, 2-indanones, and phenanthrenes. Chapter 5 describes the experimental procedures and characterization of the compounds synthesized in each Chapter.