The scope and limitations of the developed process were subsequently investigated. Variation of the steric and electronic properties of the C(2)-substituent was predicted to challenge competition between acylation of the primary alcohol of the ringopened species with acylation of the sterically hindered tetrasubstituted lactol (Figure ). This optimized reaction process was amenable to scale-up, with the DKR of lactol 1 carried out on a 4.5 mmol (1 g) scale, giving 2 in 78% isolated yield and 97:3 er. With aliphatic C(2)-substituents, variation of the carbon chain from C(2)-methyl to C(2)-ethyl maintained excellent product yield and enantioselectivity (17, 68%, 98:2 er) with 15% of the undesired acyclic product observed. The introduction of a C(2)allyl substituent was tolerated, giving 19 (86%, 94:6 er) with <5% of the corresponding acyclic product observed. A C(2)-benzyl substituent gave excellent product yield and enantioselectivity (85%, 99:1 er), with <5% of the corresponding di-acylated acylic product 22 observed. Variation of the benzylic aryl substituent was readily tolerated, with the corresponding 4-t-BuC6H4, 2-ClC6H4, 3-ClC6H4 and 4-ClC6H4 variants giving 23, 25, 27 and 29 with excellent product yield and selectivity in each case (75% to 89% yield, >96:4 er, <5% by-product). The absolute (R)configuration within ester product 23 was unambiguously confirmed by X-ray crystallography, with all other product configurations assigned by analogy. The corresponding 2naphthyl-substituted variant was insoluble in toluene, and sparingly soluble in CHCl3, so gave reduced conversion to product (~40%) after extended reaction times, giving 31 in 35% yield but excellent enantioselectivity (99:1 er). Further investigations probed the effect of steric hindrance of the C(2)substituent. It was postulated that equilibration between ringopened and ring-closed lactols would be perturbed by steric hindrance of the substituent, leading to variation in product distributions upon catalytic acylation. A b-branched C(2)-i-Bu substituent led to preferred acyclic by-product formation (65%), but allowed the isolation of 33 in 33% yield and 99:1 er. The effect of a a-branched substitution was probed, with C(2)-cyclopentyl 35 isolated in 15% yield (99:1 er) as the minor product with 73% acyclic product observed. Under the standard reaction conditions, a C(2)-i-Pr substituent gave a similar product distribution, giving the preferred formation of the acyclic product in 70% yield and 37 in 15% yield and 99:1 er. In previous work we have shown that use of the selenium catalyst variant (2S,3R)-HyperSe 16 can lead to enhanced reactivity in tertiary alcohol acylation, and application of this catalyst (20 mol %) with acetic anhydride as acylating agent gave ester 39 in an improved 40% yield (98:2 er). With C(2)-vinyl and C(2)-phenyl substituents formation of the acylic acylated products was significantly favoured (55% and 93% respectively), with products 41 and 43 isolated in 20% (93:7 er) and 5% (93:7 er) yield. Given the conjugating effect of the aryl substituent, the incorporation of an electron-withdrawing substituent was predicted to bias the product distribution to the cyclic ester product. The use of a C(2)-4-F3CC6H4-substituent gave the desired cyclic ester 45 in a much improved 55% yield (92:8 er), while a C(2)-2-pyridyl substituent still gave preferential formation of the acylic product but also 47 in 25% yield (89:11 er).