Spiroborate anions are boron compounds with two oxygen based chelating ligands which offer useful prospects for crystallization and chiral resolution. In particular the application and the rationale of using chiral spiroborates with either B-based or ligand-based chirality as a simple, cheap and effective auxiliaries for resolution are studied.

In Chapter 2 the scope and limitations of spiroborate formation and crystallization are explored through different classes by investigating their structures and properties. Structures of five different classes are described including spiroborates derived from various diols, catechols, α-hydroxy acids, hydroxybenzoic acids and hydroxyl oximes. The crystallizing abilities are demonstrated with successful isolation of stable product using differing...[ Read more ]

Spiroborate anions are boron compounds with two oxygen based chelating ligands which offer useful prospects for crystallization and chiral resolution. In particular the application and the rationale of using chiral spiroborates with either B-based or ligand-based chirality as a simple, cheap and effective auxiliaries for resolution are studied.

In Chapter 2 the scope and limitations of spiroborate formation and crystallization are explored through different classes by investigating their structures and properties. Structures of five different classes are described including spiroborates derived from various diols, catechols, α-hydroxy acids, hydroxybenzoic acids and hydroxyl oximes. The crystallizing abilities are demonstrated with successful isolation of stable product using differing cations. Both limitations and difficulties in each system are also discussed.

In chapter 3 chiral spiroborate anions bora-bis-mandelate [B(Man)₂] anions are introduced as highly effective auxiliary for resolution of various racemic chiral cations. The scope of their application is well exemplified by, though not limited to, three disparate examples; the pharmaceutically important natural alkaloid tetrahydropalmatine (THP) which forms a mono-cation, the small 1,2-diaminopropane (1,2-dap) which forms a dication and the metal-organic complex [Co(phen)₃]³⁺. The resulting salts with [B(R-Man)₂] are 1:1, 1:2 and 1:3 stoichiometry. The resolutions may be either by a facile one-pot solvothermal procedure or via counter-ion exchange in metathesis crystallizations using a pre-prepared salt such as Na[B(R-Man)₂]. High ee of > 90 % have been achieved in all three systems and confirmed by chiral chromatography and/or Circular Dichroism spectroscopy.

In Chapter 4 the investigation of spiroborate diastereomeric ion pairs using chiral [B(Man)₂] anions and chiral aminoalcohols were undertaken to better understand the structural issues of chiral resolution and predict the resolution result. Three other chiral chelating ligands are also introduced as further potential examples of new classes of spiroborate resolving agent, including substituted mandelates, hydrobenzoin and pinanediol. These anions have stable chirality conferred by the ligands themselves through chiral C-centers. The enantiostability of B-based chiral spiroborates such as bis-salicylates [B(Sal*)₂] is also reported. The stabilization of boron chirality in aprotic medium shows these anions may also have possible chiral resolving application.

In Chapter 5 three new directions for spiroborate systems are introduced. The phase pure and high yield synthesis of hetero-spiroborates is a synthetic challenge. Various successful syntheses and isolation of hetero-spiroborates are described. The possibility of extending the library of spiroborate anions as crystallizing agent with various shapes and sizes with different substituent groups is explored.

The successful isolation of anionic mono-chelated borates [B(OH)₂(Chelate)] increases our understanding in spiroborate formation mechanisms. Such intermediate species previously seen in NMR studies were confirmed through their solid state structures. Finally a novel anionic spiroborate chain polymer was isolated from pentaerythritolate as a bi-chelate and indicates engineering of extended structures are possible.

In conclusion several new spiroborate systems have been explored and offer excellent prospects for crystallization. Chiral spiroborate systems with mandelate ligands have been found to be a simple and effective auxiliary for resolution of various racemic chiral cations. Study of diasteromeric salts allows study and prediction of resolution mechanism. New classes of spiroborate resolving agent involving either labile B-based, or stable C-based chirality have been investigated. Heterogeneous spiroborates and anionic spiroborate polymers are among the new compounds that offer much scope for future research and development.