A chiral spiroborate anion from diphenyl-l-tartramide [B{l-Tar(NHPh)2}2]− applied to some challenging resolutions

Abstract

The chiral spiroborate anion [B{L-Tar(NHPh)₂}₂]⁻ has been prepared as simple salts K, NH₄, Na in high yield and purity. Its structural features have been examined by single crystal XRD and DFT calculations and indicate that conformational arrangements are dominated by intramolecular NH---OC inter-amide hydrogen bonds. These confer predictable shape, as well as a clear binding site for ion-pair formation. The potential of this anion for resolution by diastereomeric salt formation was then tested using five challenging racemic amines of type NH₂CHR₁R₂ with high shape similarity between their enantiomers. Organo-ammonium salts from these were made directly from a simple 1-pot reaction from racemic amine, boric acid and 2 eq. N,N′-diphenyl-L-tartramide in MeOH. The products are single phase crystalline solids with moderate to excellent enantioexcesses up to 95% ee. They show conserved NH₃R⁺ binding and layered packing arrangements, all with short 5.5 Å axes. Based on chiral HPLC the initial [B{L-Tar(NHPh)₂}₂] salt from rac-phenylglycinol has [S-NH₃CH(CH₂OH)Ph]⁺ with 95% ee and the salt from rac-1-phenylpropylamine is also well resolved (>91% ee) in a single step. Three disorder modes that limit resolution in the other salts were identified at the cation site – H/R₁ site exchange, R₁/R₂ site exchange or C–H re-pyramidalization. Extension to a family of such aryltartramide anions may allow crystal engineering of the cation binding pockets to overcome the disorder inherent to such resolutions.