Fortuitous Enantiomeric Self-Rectification of an Unreported Partial Racemisation in the Synthesis of a Chiral Phosphoric Acid: A Warning to Practitioners.

Racemisation without Consequence: MOM deprotection of an ether intermediate during a routine synthesis of phosphoric acid 1 promoted partial racemisation of the product BINOL 5. Surprisingly, however, after phosphorylation of the partially racemised BINOL, enantiopure acid 1 was isolated. Further inspection revealed that during phosphorylation, unhydrolysed racemic phosphorochloridate 6 precipitated, thus restoring homochirality in the product phosphoric acid 1. Moreover, MOM deprotection partial racemisation was avoided by conducting reactions at lower temperatures for no longer than the required deprotection time, and/or by application of other deprotection conditions from the literature.

Unravelling ionic liquid solvent effects for a non-polar Cope rearrangement reaction.

The impact of ionic liquids (ILs) on polar reactions is well recognised, however the impact of ILs on non-polar reactions is less well understood or explored. Pericyclic Cope rearrangements are highly concerted, exhibit minimal charge localisation and pass through an uncharged but well-defined transition state, and thus provide a good mechanism for exploring the impact of IL polarizability on chemical reactivity. Recently, a 10× rate enhancement has been observed for the Cope rearrangement of 3-phenyl-1,5-hexadiene in the IL 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide [C4C1im][NTf2] compared to benzene. In this work we undertake a DFT based computational study (B3LYP-D3BJ/6-311+G(d,p) and M06-2X-D3/6-311+G(d,p)) of the Cope rearrangement of 3-phenyl-1,5-hexadiene and 3-propyl-hexa-1,5-diene in molecular solvents (acetonitrile, benzene and ethanol) and the IL [C4C1im][NTf2] using the SMD solvation model. The impact of benzene and [C4C1im][NTf2] on the Cope rearrangement of 3-phenyl-1,5-hexadiene is studied in more detail and we provide insight into the reason for the rate enhancement in an IL. The volume of activation is evaluated and the potential impact of 'solvent pressure' is discussed. We identify two potential mechanisms for volume effects to contribute to the rate enhancement. Solvent association energies are evaluated at the DLNPO-CCSD(T) level. Specific solvent interactions are explored through atomic partial charge, molecular orbital and bond critical point analysis, as well as via non-colvalent interaction (NCI) plots, electrostatic potential (ESP) differences and density difference Δρ(r) plots. We find that the cation and anion together form an extensive van der Waals pocket in-which the transition state (TS) sits. Electron density within the TS is anisotropically polarised via a 'push-pull' effect due to the dual cation-anion nature of the IL, stabilising the TS relative to benzene. We also provide experimental evidence that these effects are generalisable to other ILs. Overall, our aim is to provide a deeper moleuclar level understanding of the impact of ILs on non-polar reactions.

Surmounting Byproduct Inhibition in an Intermolecular Catalytic Asymmetric Alkene Bromoesterification Reaction as Revealed by Kinetic Profiling.

Kinetic profiling has shown that a (DHQD)2PHAL-catalyzed intermolecular asymmetric alkene bromoesterification reaction is inhibited by primary amides, imides, hydantoins, and secondary cyclic amides, which are byproducts of common stoichiometric bromenium ion sources. Two approaches to resolving the inhibition are presented, enabling the (DHQD)2PHAL loading to be dropped from 10 to 1 mol % while maintaining high bromoester conversions in 8 h or less. Iterative post-reaction recrystallizations enabled a homochiral bromonaphthoate ester to be synthesized using only 1 mol % (DHQD)2PHAL.