For substrate 30 (R = t-Bu) a difference in free energy of the key stereodetermining transition states (TS1) arising from acylation of the (R)-and (S)-substrate enantiomers of 2.1 kcal/mol is calculated, reflecting a predicted 98:2 er, consistent with the 99:1 er observed experimentally (Figure ). In the favoured pathway using the (R)-substrate enantiomer, the O-heteroatom within the lactone interacts with the isothiouronium intermediate, whereas in the (S)-pathway, the aryl ring is orientated above the catalyst, instead exhibiting a cation-p type stabilising interaction. This preference is consistent with previous observations where an N-C=O carbonyl donor is the preferred recognition motif compared to an aromatic group in isothiourea catalysed acylation.