For the two-stage strategy to be broadly useful the synthesis of the enantioenriched desymmetrized P(V) compounds would also need to be scalable. To our delight, our second-generation protocol could be carried out on gram scale employing just 2.5 mol% of B-1. After 48 hours, enantioenriched 2 was obtained in 82% yield and 96:4 e.r. which could be further boosted to 98.5:1.5 e.r. after a single recrystallization (Scheme 3). With a considerable amount of enantioenriched 2 (98.5:1.5 e.r.) in hand, the scope of the second stage of the strategy, namely the enantiospecific substitution of the second thiazolidinone leaving group, could then be explored. In the first instance the thiazolidinone was smoothly displaced with a series of complex, medicinally relevant 1° and 2° alcohols (Scheme 4, A). Employing 3.0 equiv. of nucleophile and 3.0 equiv. of DBU in THF or DMF at room temperature, the remaining leaving group could be displaced with: TBS-deoxycytidine (33), the anti-HIV drugs 175 stavudine (34), 176 AZT (35), abacavir (36) and didanosine (37), the nucleoside fragment of anti-hepatitis C drug sofosbuvir (38) 177,178 and the secondary 3'-OH of acetal protected D-glucose (39), all in good to excellent yields and with over >95:5 d.r. Subsequently, the use of phenols as nucleophiles in the second stage enantiospecific nucleophilic substitution was then investigated (Scheme 4, B). This was of particular importance as the resulting enantioenriched diaryl phosphonate esters represent a class of P(V) compounds previously inaccessible by both our first-generation method and that described by Jacobsen. When using 3.0 equivalents of nucleophile and 3.0 equivalents of DBU at in Et2O at 0 °C for 16 hours the remaining thiazolidinone could be replaced with a suite of phenols, including medicinally relevant ones. Carrying out the displacement with phenol afforded desired product 40 in 77% yield and 94:6 e.r. (91% enantiospecificity). When using sesamol as nucleophile the desired product 41 was obtained in 68% yield but with a minor erosion of enantiopurity (81% e.s.). Other biologically relevant nucleophiles were instead better tolerated, with the products derived from Boc-L-tyrosine methyl ester (42), eugenol (43) and the antibiotic clofoctol (44), which also exhibits considerable antiviral activity in Vero 81 cells against SARS-CoV-2 179,180 being isolated in 33-65% yield and ≥ 93% e.s. Product 42 was recrystallized to enantiopurity, and single crystal X-ray diffraction analysis revealed that the nucleophilic substitution proceeded with inversion of stereochemical configuration at the P(V) center. Following the displacement with alkyl alcohols and phenols, the use of amines to displace the thiazolidinone was examined (Scheme 4, C). When employing 1.5 equiv. of nucleophile (generated from 1.5 equiv. each of the amines and n-BuLi as base at -78 °C in THF) at -40 °C a range of phosphonamidates derived from acyclic (45) and cyclic amines (46-48) could be obtained in 50-60% yield and ≥ 95:5 e.r. In addition, the enantiospecific substitution could also be carried out with tricyclic H₁ inverse agonist desloratadine, with resulting product 49 being obtained in 43% yield and 97:3 e.r. (97% e.s.). X-Ray diffraction analysis of a single crystal of 46 revealed that nucleophilic substitution with amines proceeded with inversion of the P(V) stereocenter as well.