Introduction: Kinetic resolution is a widely developed process that has been extensively used for industrial and academic applications to allow the effective preparation of enantiomerically pure compounds. Despite its widespread use, a recognised inherent drawback is that the theoretical maximum yield of a single product enantiomer from a racemate is 50%. This limitation can be overcome by a using a dynamic kinetic resolution (DKR) approach, that necessitates the individual enantiomers of the racemic starting material to interconvert (enantiomerization) at a timescale compatible with a subsequent enantioselective derivatization event (such as acylation). Current state-of-the art DKRs commonly use secondary alcohols or tri-substituted lactols (that contain a H-substituent at the carbinol carbon), with enantiomerization promoted through reversible dehydrogenation/hydrogenation (Fig 1A&B) or intramolecular ring closure/ring opening (Fig 1C&D). As representative examples of these approaches, Bäckvall has shown that a Ru-based catalyst can promote the enantiomerization of racemic secondary alcohols (Fig 1A) via a planar carbonyl intermediate, which is compatible with the subsequent enzymatic acylative KR. Alternatively treatment of racemic tri-substituted lactol with an isothiourea catalyst and anhydride leads to ester product in high yield and enantioselectivity with enantiomerization achieved via an achiral ring-opened intermediate (Fig ). The widely recognized remaining challenge in this area that has not been realized to date is to extend the DKR approach to tetra-substituted lactol substrates (where none of the substituents at the carbinol are H) (Fig 1C). To the best of our knowledge only a single report from Ye and co-workers utilising NHC catalysed enantioselective acylative DKR of benzosultam derived trifluoromethyl substituted hemi-aminols has been reported in this area to date. Although excellent enantioselectivity was observed, this methodology was limited by the need for C(3)-perfluorinated substituents at the carbinol centre, and requires a stoichiometric oxidant (3,3′,5,5′tetra-tert-butyldiphenoquinone, DQ) for reactivity (Fig 1D). Nitrogen-containing heterocycles are core features within biologically relevant pharmaceuticals, agrochemicals, and natural products with 59% of US FDA approved small-molecule drugs containing a nitrogen heterocycle. Within this field, the morpholine skeleton is widely considered a privileged scaffold for medicinal chemistry, and is recognised as being in the top 25 carbo-and heterocyclic ring systems that are incorporated within drug molecules. Within the morpholine family the morpholin-3-one lactol motif is a core constituent of various natural products such as Acortatarin A but is also present in σ1and μ-opioid receptor binding molecules, as well as neurokinin receptor antagonists (Fig ). Benzannulation of morpholine leads to benzoxazine derivatives that are known to possess antimicrobial, and antibacterial activity among others. They are of significant medicinal interest with derivatives displaying anti-Alzehimer and anticancer properties among others, as well as being of agricultural interest. Similarly, 1,4-benzoxazine derived lactols are the core heterocycle of Tonghaoxu analogues and plant growth inhibitors, while hydroxylated benzoxazinones such as GHDM2BOA are natural products found in their glycoside form. As such the development of new methods for the preparation of enantioenriched morpholine and benzoxazine derivatives is of widespread interest. In recent years the use of isothioureas as enantioselective Lewis base catalysts has been well established and applied to a range of reactions employing acyl ammonium, C(1)-ammonium enolates, and a,b-unsaturated acyl ammonium intermediates. In previous work we have applied the isothiourea HyperBTM in the KR of both tertiary heterocyclic and acyclic alcohols. In the heterocyclic alcohol case the reactivity and selectivity observed in were rationalised by a combination of computation and experimental evidence, that identified the significance of a key substrate C=O•••isothiouronium interaction (alongside 1,5-O•••S and C-H•••O contacts) as being essential to achieve effective enantiodiscrimination in this KR process (Fig ). Utilising this precedent, we considered that an effective acylative DKR of tetra-substituted morpholinones and benzoxazinones could be achieved using isothiourea catalysis. Reversible intramolecular ring-opening/ring closing of the heterocyclic scaffold would be used as an enantiomerization strategy, combined with isothiourea-promoted enantioselective acylation (incorporating the key substrate C=O•••isothiouronium interaction for selectivity) to generate medicinally relevant N-heterocycles in enantiomerically pure form (Fig 2C). At the onset of these studies the key challenges to overcome for an effective solution were (i) potential competition between acylation of the primary alcohol of the ring-opened species with acylation of the sterically hindered tetra-substituted lactol; (ii) the acylation catalyst is required to discriminate between enantiomers bearing three non-hydrogen substituents at the tetra-substituted carbinol centre; (iii) enantioselective acylation needs to be coupled with efficient enantiomerization for a DKR to work effectively. In this manuscript the DKR of a range of morpholinone and benzoxazinone derived tetra-substituted lactols is developed, with the scope and limitations of this process fully explored with respect to competitive acylation of a ring-opened derivative as well as enantioselectivity. DFT computational studies highlight the importance of the adjacent carbonyl group to the carbinol stereocentre as a key enantiorecognition motif that leads to products in high er.