The synthesis and application of spiro-cations and anions for chiral resolution

Abstract

Spiro- molecules have the common feature of a quaternary atom at the junction of two rings. If the rings are asymmetric these types of molecules can exhibit chirality at the tetrahedral spiro center. Spiroammonium and spiroborates are cationic and anionic spiro molecules respectively that are easily prepared by using dihaloalkanes and oxy-based ligands. This thesis serves to study and investigate both families of these spiro molecules with either asymmetric rings or with permanent C-chiral centres as resolving agents. A total of over 50 new compounds and salts are reported, and their molecular and solid-state structures determined by single crystal X-ray diffraction. Chapter 1 provides a background and overview of the topic, the scope of using spiroammonium or spiroborate systems for challenging resolutions in diastereomeric salt formation. This will be explored especially for a new self-associating bis(L-tartramido) borate anion [B(L-TarNH₂)₂]^-. Chapter 2, the scope and limitation of spiroammonium cations application as resolving agent are investigated. Halide salts of aliphatic spiroammonium cations can be synthesized by cyclization reaction of α,ω-dihaloalkanes with simple cyclic amines. The bromide salts of such cations are observed to have hygroscopic properties. Metathesis to more stable forms could be achieved but severe ring disorder commonly observed. This will hamper their application as resolving agent, as well as attempts to resolve chiral methylated spiroammonium cations. The nature of these compounds may lead to their preferential use as chiral ionic liquids. Initial work on a new system of spirophosphonium cations formed by reaction of diarylamines with PCl₃ appears more promising for their application as crystallizing and resolving agents due to the semi-rigidity of these cations. In previous work in our group, we have studied chiral spiroborates with either B-based chirality, C-based chirality or both. Our group has shown that spiroborates derived from aryltartramide are promising resolving agents for even highly challenging resolutions such as 1,2-diaminopropane. In Chapter 3, we extend this to study of the simpler bis(L-tartramido) borate system. One pot reaction of inorganic and organic bases with boric acid and L-tartramide result in formation of [B(L-TarNH₂)₂]^- salts. The anions self-associate through H-bonds into 2D network, segregating space into chiral cation and anion spatial components. In the findings, the 2D network results in a typical 10 x 15 Å metric for the unit cells of the crystals of these salts. The metrics of the cation layer is affected by the separation of anionic layer, registration of anionic layer and corrugation of the anionic layer, to allow accommodation of cations with different charge, size and shape. The geometry of [B(L-TarNH₂)₂]^- anions adopt a conformation which is more energetically preferable with all four -NH₂ pointed internally to the core diolate oxygen atom, hereafter termed the (4,0) conformation. Although (4,0) appears the most common arrangement and may form most stable H-biond network in self-association, eventually other [B(L-TarNH₂)₂]^- anion conformations such as (3,1) and (2,2) were also found in other salts. Such altered configurations naturally lead to different self-associations and a number of the resulting networks are discussed in Chapter 4. The application of [B(L-TarNH₂)₂]^- as resolving agent is discussed in Chapter 5. We attempted to use the networks for challenging diastereomeric salt resolutions in which the mirror image cations are spatially similar and so tend to be disordered in a single product phase. Successful resolutions of 1-phenylpropylamine (96%ee), 2-phenylglycinol (95%ee) and R-2-amino-1-butanol (94 %ee) were achieved in a single crystallization step. As most of the salt’s are solvated with alcohol in the cation layers and channels, attempt to resolve racemic neutral alcohol molecules by their enantioselective inclusion in the chiral salts was attempted. Partial resolution of racemic alcohols such as 1,2-propanediol and 1-phenylpropanol were also demonstrated using the 2D layer salt [SpaH][B(L-TarNH₂)₂]. Chapter 6 discusses the future directions of this research including use as stationary phase in via a chiral column chromatography application. separations of racemic neutral molecules. Formation of double salts with different cationic building blocks is forming offers further scope for expansion of this work and the control of chiral spaces for preferential inclusion of chiral solvents. Finally, previous work on borates and saccharide solids have shown promise in non-linear optical materials. We will study the Second Harmonic Generation of laser light from these compounds to establish whether any of these inorganic-organic hybrids show promising optical conversions, combining high laser damage threshold with phase matchability.

Date of Award	2021
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology
Supervisor	Ian Duncan WILLIAMS (Supervisor)