Author: Sin, Ka Yu Andy
Title: Development of nickel-catalyzed hydroamidation of arylalkenes with 1,4,2-dioxazol-5-ones
Advisors: Yu, Wing-yiu Michael (ABCT)
Degree: M.Phil.
Year: 2021
Subject: Organic compounds -- Synthesis
Transition metal catalysts
Hong Kong Polytechnic University -- Dissertations
Department: Department of Applied Biology and Chemical Technology
Pages: xvii, 156 pages : color illustrations
Language: English
Abstract: The synthesis of amides is of a great importance for manufacturing of many bioactive natural products and pharmaceutical compounds. Amides are commonly prepared by the coupling of activated carboxylic acids with amines. Recently, transition metal-catalyzed hydroamidation of alkenes, whereby the N-H bond of amines is formally added across the carbon-carbon π-bond, is an attractive strategy for the amides synthesis because this transformation provides a direct access to amides from simple precursors. It is anticipated that the σ-alkyl metal species formed by the hydrometallation of alkenes are active for the further functionalization by amidating reagents to offer the amide products. Moreover, an enantioselective synthesis of chiral amides is conceivable if chiral ligands are employed. In this thesis, we describe the development of the Ni-catalyzed hydroamidation of arylalkenes with 1,4,2-dioxazol-5-ones and 4,4,5,5-tetramethyl-1,3,2-dioxaborolane. Reacting arylalkenes (0.2 mmol) with 1,4,2-dioxazol-5-ones (0.4 mmol), 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.3 mmol), 6,6'-dimethyl-2,2'-dipyridyl (12 mol%) and Ni(ClO4)2·6H2O (10 mol %) offered the desired amide compounds in up to 91% yields with good functional groups tolerance. Moreover, this reaction shows Markovnikov regioselectivity exclusively. In addition, the preliminary mechanistic study revealed that the carboradical intermediates were unlikely to be involved. As for the study of the enantioselective nickel-catalyzed amidation of arylalkenes, a series of chiral bis(oxazoline) ligands was tested. Treating 4-tert-butylstyrene (0.2 mmol), 3-phenyl-1,4,2-dioxazol-5-one (0.4 mmol), 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.3 mmol), (+)-2,2′-isopropylidenebis(4R)-4-phenyl-2-oxazoline (12 mol%) and Ni(ClO4)2·6H2O (10 mol%) in DCE at 40°C for 12 h furnished the corresponding amide products in up to 82% yields with 84:16 enantiomeric ratio (er). The linear free energy relationship between the para-substituted alkenes and enantioselectivities was explored to imply that the migration of Ni-H species to alkenes was unlikely to be the enantioselectivity-determining step (EDS).
Rights: All rights reserved
Access: open access

Files in This Item:
File Description SizeFormat 
5957.pdfFor All Users5.97 MBAdobe PDFView/Open

Copyright Undertaking

As a bona fide Library user, I declare that:

  1. I will abide by the rules and legal ordinances governing copyright regarding the use of the Database.
  2. I will use the Database for the purpose of my research or private study only and not for circulation or further reproduction or any other purpose.
  3. I agree to indemnify and hold the University harmless from and against any loss, damage, cost, liability or expenses arising from copyright infringement or unauthorized usage.

By downloading any item(s) listed above, you acknowledge that you have read and understood the copyright undertaking as stated above, and agree to be bound by all of its terms.

Show full item record

Please use this identifier to cite or link to this item: