The asymmetric annulation of a range of a,b-unsaturated acyl ammonium intermediates, formed from isothiourea HBTM 2.1 and anhydrides with either 1,3-dicarbonyls, b-ketoesters or azaaryl ketones gives either functionalised esters (upon ring opening), dihydropyranones or dihydropyridones in good yields (up to 93%) and high enantioselectivity (up to 97% ee).

Isothiourea-catalyzed annulations of 2-acyl benzazoles and α,β-unsaturated acyl ammoniums are tuned to form lactams or lactones (up to 99% ee). Computations highlight the governing roles of S···O and CH···O interactions.

A combination of experimental and computational studies have identified a C=O⋅⋅⋅isothiouronium interaction as key to efficient enantiodiscrimination in the kinetic resolution of tertiary heterocyclic alcohols bearing up to three potential recognition motifs at the stereogenic tertiary carbinol center. This discrimination was exploited in the isothiourea-catalyzed acylative kinetic resolution of tertiary heterocyclic alcohols (38 examples, s factors up to >200). The reaction proceeds at low catalyst loadings (generally 1 mol %) with either isobutyric or acetic anhydride as the acylating agent under mild conditions.

3-Cyano-1-naphthalenecarboxylic acid is an intermediate required for manufacture of tachykinin receptor antagonists. The 1,3-disubstitution pattern on the naphthalene skeleton complicates the synthesis of this cyano acid. Previous literature-based chemistry is unattractive for large-scale manufacture due to stoichiometric use of mercury salts, low yield, and other operational difficulties. An attractive new route has been developed by establishing the 1,3-substitution on the carbon atoms destined for only one-half of the naphthalene 2-ring system, via 3-bromocoumalate, and then building up the rest of the naphthalene ring system by Diels-Alder addition of 3-bromocoumalate to in situ-generated benzyne. The resulting 4-bromo-2-naphthoate was converted to the required cyanoacid by transformation of ester to nitrile followed by carbonylation of the bromo substituent. The new route has been scaled up successfully and offers significant advantages over previous literature chemistry in terms of improved process environmental implications, improved yield, lower cost, and improved robustness and ease of operation at larger scales of operation.

A combination of experimental and computational studies have identified a C=O•••isothiouronium interaction as key to efficient enantiodiscrimination in the kinetic resolution of tertiary heterocyclic alcohols bearing up to three potential recognition motifs at the stereogenic tertiary carbinol center. This discrimination was exploited in the isothiourea-catalyzed acylative kinetic resolution of tertiary heterocyclic alcohols (38 examples, s up to > 200). The reaction proceeds at low catalyst loadings (generally 1 mol%) using either isobutyric or acetic anhydride as the acylating agent under mild conditions.

A series of arylene ethynylene compounds has been generated in order to study the differences between strong and weak intramolecular halogen bonding in solution. With strong intramolecular halogen bonding, the presence of electron‐withdrawing fluorine substituents near the halogen‐bond donor has a significant impact on the halogen bond and consequently on 13C NMR chemical shifts. UV/Vis studies suggest increased conjugation of the arylene ethynylene backbone when strong halogen bonds are present. UV/Vis and NMR signatures of intramolecular halogen bonding are diminished significantly when electron‐withdrawing fluorine substituents are absent, however. This change in behavior is further illustrated by differences in crystallization tendencies with the presence or absence of electron‐withdrawing substituents. Calculations using the M06‐2X functional provide some insight into the energies associated with both strong and weak intramolecular halogen bonding.

A conjugated, pyridine-containing, phenylethynyl ligand that forms complexes with Ag I and Pd II has been developed. NMR titration studies with Pd II reveal a stoichiometric binding of the ligand to the metal atom, while similar studies with Ag I reveal a binding that is dynamic on the NMR timescale. Analysis of the NMR spectroscopic data by Job's plot analysis and non-linear curve fitting of a titration curve reveals a 1:1

Isothiourea HBTM 2.1 is utilized to generate functionalized chiral esters, dihydropyranones, or dihydropyridones in good yields and high enantioselectivities.