Catalytic activation of nitriles towards nucleophilic addition

• Main Author: Lester, Roy P.
• Published: University of Nottingham 2015
• Subjects: QD241 Organic chemistry
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.692700

The work presented in this thesis is focused on the development of a multifaceted approach to the catalytic activation of nitriles. To develop a versatile method for catalytic nitrile activation two probes were utilised; i) the development of a direct synthesis of allylic amides from the corresponding allylic alcohol and nitrile using a commercial platinum salt, together with a detailed mechanistic investigation into the process, ii) the direct synthesis of 2-bezoxazole from the corresponding 2-aminophenol and nitrile with the aid of a commercial platinum salt as well as the use of alcoholic solvents. In addition to nitrile activation a preliminary study on the application and further functionisation of 2-trichlorobenzoxazoles was undertaken. i) A novel multifaceted approach to the direct synthesis of allylic amides via the catalytic activation of di- and trichloroacetonitrile will be discussed. This one-pot methodology relies on the same platinum catalyst to activate a nitrile towards nucleophilic attack of allylic alcohol as well as activate the newly formed allylic imidate towards a [3,3]-sigmatropic rearrangement, which produced a number of allylic amides. In addition to the development of the one-pot allylic amide methodology a number of mechanistic studies including 1H, 13C{1H} and gas chromatography were under taken to better understand the process. ii) The second probe used to identify the versatility of this multifaceted catalyst approach to nitrile activation was the direct synthesis of 2-benzoxazoles. Within this study it was discovered that protic solvents were able to activate di- and trichloroacetonitrile efficiently towards nucleophilic attack of the nitrogen nucleophile. From this discovery a mild and effective synthesis of a variety of di- and trichlorobenzoxazoles was developed in which the solvent was acting as the activating agent towards nucleophilic attack. iii) Preliminary results will also be reported on the novel manipulation of the trichloromethyl moiety of benzoxazoles. Within this study two efficient methodologies for the selective synthesis of 2-(pyrrolidin-1-yl)benzo[d]oxazole and benzo[d]oxazol-2-yl(pyrrolidin-1-yl)methanone were developed from a single starting material. These results show a positive direction for the study into diversity oriented synthesis to form a number of different small molecules from a single starting material by altering the conditions of the reaction.