Small molecule functionalization by metal-mediated borylene transfer chemistry
Lead Research Organisation:
University of Oxford
Department Name: Oxford Chemistry
Abstract
Reactions of saturated and unsaturated organic molecules with boron-containing reagents represent a very powerful and versatile range of methodologies for the introduction of functionality into organic substrates, which have been widely exploited, e.g. in the syntheses of pharmaceuticals, natural products and functional materials. The resulting boron-derivatized products can be exploited directly for further synthesis (e.g. aryl boronate esters in Suzuki-Miyaura C-C coupling), or converted to a range of more useful functional groups (e.g. alcohols, amines, etc.) using established protocols. Landmark reactions in which borane reagents have been used to introduce functionality into organic substrates include (i) hydro- and diboration of multiple bonds; (ii) palladium-catalysed conversion of aryl halides to aryl boronates; and (iii) direct C-H bond functionalization of alkanes and arenes catalysed by rhodium or iridium complexes. For each of these methodologies, control of the B-C bond-forming step can be achieved within the coordination sphere of a transition metal, in some cases opening up the possibility for enantio-/diastereoselective syntheses via the use of chiral ligand sets. Transition metal boryl complexes, LnM-BX2, are widely implicated in the delivery of the BX2 fragment to organic substrates (e.g. in both hydro-/diboration and C-H activation processes) and as such have been the subject of intense recent investigation.By contrast, the chemistry of the borylene fragment (:BX) has not been exploited to any great extent in the formation of C-B bonds, despite obvious parallels with carbene (:CR2) and silylene (:SiR2) fragments, and the wide range of useful reactivity in which these subvalent group 14 systems have been implicated. Thus, for example, the applications of carbenes in metathesis, cyclopropanation and insertion chemistries, and of silylenes in C-C bond formation, have been widely investigated. In part, the lack of analogous boron chemistry reflects the extremely labile nature of 'free' borylene and its indiscriminate reactivity, e.g. towards C-H/C-C bonds. A strategy which has been successfully adopted to modulate reactivity in the cases of carbenes and silylenes is to confine the reactive fragment to the coordination sphere of a transition metal. We intend to exploit this approach to develop controlled bond-forming chemistry based on metal complexes containing the borylene fragment. In part, this will build on previous work within the Aldridge group which has opened up synthetic routes to borylene complexes analogous to Fischer carbenes/vinylidenes, and uncovered aspects of their fundamental chemistry. Crucially, these studies have identified cationic complexes containing the aminoborylene fragment as achieving the balance between being sufficiently robust for ease of synthesis/handling, but displaying clean room temperature reactivity towards archetypal organic and inorganic bonds.We intend to build on this preliminary work to develop new methodologies for introducing boron-containing fragments in to organic molecules, primarily concentrating (in the first instance) on developing insertion and cycloaddition protocols which are not possible (or are very difficult to achieve) using existing borylation methodologies. Initially we will explore issues of mechanism and selectivity by examining processes which are stoichiometric in the metal borylene complex, with the ultimate aim of incorporating these fundamental steps into catalytic processes. This second goal will require parallel developments leading, in particular, to the development of direct synthetic approaches utilizing readily-available borane precursors. Thus, these two goals: side-by-side development of synthetic methodology and exploitation of reactivity patterns will form the basis for the proposed work.
Organisations
People |
ORCID iD |
Simon Aldridge (Principal Investigator) |
Publications
Vidovic D
(2009)
Coordination and activation of the BF molecule.
in Angewandte Chemie (International ed. in English)
Vidovic D
(2011)
Coordination chemistry of group 13 monohalides
in Chemical Science
Vidovic D
(2011)
Probing the intrinisic structure and dynamics of aminoborane coordination at late transition metal centers: mono(s-BH) binding in [CpRu(PR3)2(H2BNCy2)]+.
in Journal of the American Chemical Society
Vidovic D
(2010)
Synthesis and structural characterization of terminal (diisopropylamino)borylene complexes of group 8 metals
in Main Group Chemistry
Protchenko AV
(2021)
Approaching a "Naked" Boryl Anion: Amide Metathesis as a Route to Calcium, Strontium, and Potassium Boryl Complexes.
in Angewandte Chemie (International ed. in English)
Protchenko AV
(2013)
A generic one-pot route to acyclic two-coordinate silylenes from silicon(IV) precursors: synthesis and structural characterization of a silylsilylene.
in Angewandte Chemie (International ed. in English)
Protchenko AV
(2014)
Stable GaX2, InX2 and TlX2 radicals.
in Nature chemistry
Protchenko A
(2020)
Approaching a "Naked" Boryl Anion: Amide Metathesis as a Route to Calcium, Strontium, and Potassium Boryl Complexes
in Angewandte Chemie
Pierce G
(2009)
Half-Sandwich Group 8 Borylene Complexes: Synthetic and Structural Studies and Oxygen Atom Abstraction Chemistry
in Organometallics
Pandey KK
(2011)
Nature of M-Ga Bonds in cationic metal-gallylene complexes of iron, ruthenium, and osmium, [(?5-C5H5)(L)2M(GaX)]+: a theoretical study.
in Inorganic chemistry
Description | Reactions of saturated and unsaturated organic molecules with boron-containing reagents represent a very powerful and versatile range of methodologies for the introduction of functionality into organic substrates, which have been widely exploited, e.g. in the syntheses of pharmaceuticals, natural products and functional materials. this research has developed new methodologies for carrying out the synthesis of these key intermediates. |
Exploitation Route | Initially through academic dissemination and use of methodologies by others in synthesis; in the medium term - within fine chemical synthesis |
Sectors | Chemicals |
Description | The findings from this work have been utilised in developing new methods for the synthesis of key types of intermediate relevant to chemical manufacture. |
First Year Of Impact | 2009 |
Sector | Chemicals |
Impact Types | Economic |
Description | Leverhulme Trust |
Amount | £124,502 (GBP) |
Funding ID | F/08 699/E |
Organisation | The Leverhulme Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 08/2009 |
End | 09/2012 |