Organoboron and Organosilicon Chemistry

Organoboron Chemistry

Currently in the Lloyd-Jones Group we are interested in studying the protodeboronation of organoboranes, and in the Arase-Hoshi R2BH-catalysed hydroboration of alkynes. Insights from in situ reaction monitoring, kinetic simulation, isotopic labelling studies and computational analysis have allowed us to establish quantitative mechanistic regimes for these reactions.

The Lloyd-Jones Group have previously invested significant research efforts into understanding the mechanism of protodeboronation of a diverse range of arylboronic acids including polyfluorinated and heteroaromatic systems.1,2 Boronic acids and boronic esters are indispensable building blocks in modern synthetic chemistry. The improved stability of boronic esters, usually assumed to be a consequence of the reduced Lewis acidity at the boron centre, has led to a surge in both their availability and use as alternative reagents in organic synthesis. Hence, a greater insight into the impact of polyols on the protoboronation of boronic acids is desirable, and underpins a prominent theme of research within the group.

  

R2BH-catalysed hydroboration of alkynes by 1,3,2-dioxaborolanes is another compelling area of organoboron chemistry to which the Lloyd-Jones Group has dedicated recent research efforts.3 By virtue of insights garnered from in situ 19F NMR spectroscopy, kinetic simulation, isotope entrainment, single-turnover labelling (10B/2H), and density functional theory (DFT) calculations, we have established the central importance of B-H/C-B metathesis in these transformations.

Past research endeavours for the Lloyd-Jones Group in this field include MIDA boronate hydrolysis and organotrifluoroborate hydrolysis.4,5 The mechanism for the hydrolysis of MIDA boronates was shown to differ depending on whether the nature of the process was rapid or slow.

Generation of boronic acids (RB(OH)2) via hydrolysis of the corresponding potassium organotrifluoroborates (RBF3K) was investigated in connection with Suzuki-Miyaura cross-coupling reactions.

Organosilicon Chemistry

Studies on the reactivity and resulting reaction mechanisms of organosilicon reagents, such as trifluoromethyltrimethylsilane (known as Ruppert’s reagent) and trimethylsilyldiazomethane, is an active field of research within the Group.

The methyl esterification of carboxylic acids by trimethylsilyldiazomethane has been investigated in detail, where isotopic labelling experiments and kinetic measurements elucidated the previously unknown mechanism of this reaction, which is now proposed to proceed through methanolytic protodesilylation of trimethylsilyldiazomethane to generate diazomethane in situ.6

Further work has been carried out on trimethylsilyldiazomethane to devise a method for efficient and versatile 13C labelling of various functional groups.7 The high-yielding synthesis of this labelling reagent starts from 13CH3OH, a cheap and readily available source of 13C.

The kinetics and mechanism of the TMSCF3 mediated CF3 transfer to ketones and aldehydes have been studied in detail by the Lloyd-Jones group, where information obtained from kinetic measurements (stopped-flow NMR and IR), kinetic isotope effects of 13C and 2H, and density functional theory (DFT) calculations helped elucidate the mechanistic picture of this widely used synthetic transformation.8 In this work, we have established that the direct transfer of CF3- by siliconate anions is unfavourable compared to a two-step CF3 dissociation and subsequent nucleophilic addition pathway.

References

  1. P. A. Cox; A. G. Leach; A. D. Campbell and G. C. Lloyd-Jones, J. Am. Chem. Soc., 2016, 138, 9145-9157.
  2. P. A. Cox; M. Reid; A. G. Leach; A. D. Campbell; E. J. King and G. C. Lloyd-Jones, J. Am. Chem. Soc., 2017, 139, 13156-13165.
  3. E. Nieto-Sepulveda, A. D. Bage, L. A. Evans, T. A. Hunt, A. G. Leach, S. P. Thomas, G. C. Lloyd-Jones, J. Am. Chem. Soc., Just Accepted Manuscript, DOI: 10.1021/jacs.9b10114, 2019.
  4. J. A. Gonzalez, O. Maduka Ogba, G. F. Morehouse, N. Rosson, K. N. Houk, A. G. Leach, P. H.-Y. Cheong, M. D. Burke, G. C. Lloyd-Jones, Nature Chem., 2016, 8, 1067–1075.
  5. A. J. J. Lennox, G. C. Lloyd-Jones, J. Am. Chem. Soc., 134, 7431-7441, 2012.
  6. E. Kühnel, D. D. P. Laffan, T. M. del Campo, I. R. Shepperson, J. L. Slaughter, G. C. Lloyd-Jones, Angew. Chem. Int. Ed., 2007, 46, 7075-7078.
  7. C. Nottingham, G. C. Lloyd-Jones, Org. Synth., 2018, 95, 374-402.
  8. C. P. Johnston, T. H. West, R. E. Dooley, M. Reid, A. B. Jones, E. J. King, A. G. Leach,  G. C. Lloyd-Jones, J. Am. Chem. Soc., 2018, 140, 11112-11124.