The application of MIDA boronates (MIDA = N-methyliminodiacetic acid) in Suzuki- Miyaura reactions has increased over the last years. This is mainly because in many cases, the replacement of the boronic acid for the respective MIDA boronate has a positive result in the reaction yield. The key feature that makes MIDA boronates efficient coupling partners is that they can undergo a slow hydrolysis reaction under Suzuki-Miyaura conditions, which generates the boronic acid in situ. The control of the hydrolysis rate is crucial to keep a low concentration of the boronic acid to avoid some of the side reactions frequently observed. The kinetics of the hydrolysis reaction from a range of alkyl, aryl, and heteroaryl MIDA boronates have been determined under different reactions conditions. In addition, competition experiments and computational calculations have resulted in the proposal of three distinct mechanisms for the hydrolysis of MIDA boronates: ‘base-promoted’, ‘water-promoted’, and ‘acid-promoted’. The base and acid mediated processes occur at faster rates than the neutral pathway and involves a rate-limiting addition at the MIDA carbonyl carbon by hydroxide or water, respectively. Whilst the 'neutral' hydrolysis requires neither base nor acid and involves ratelimiting B-N bond cleavage by a water cluster. Under certain conditions the neutral mechanism can operate in parallel with the base or with the acid mediated mechanism; relative rates are easily quantified by 18O incorporation in the MIDA, after this is released from the hydrolysis reaction. This insight is expected to assist informed application and optimisation of MIDA boronates in synthesis as well as the design of new MIDA boronate derivatives.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:723879 |
| Date | January 2017 |
| Creators | González González, Jorge Augusto |
| Contributors | Lloyd-Jones, Guy ; Cockroft, Scott |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/23461 |
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