First, we examined NH-azole nucleophiles, which are essential components in drug structures (Scheme 2a). Azoles containing electron-withdrawing groups were of particular interest, which may be mimicked by the electron-withdrawing nature of the oxetane. A range of substituted pyrazoles was well tolerated, providing oxetano-pyrazoles in moderate to excellent yields (39-46, 60 °C, 1.2 equiv pyrazole). Pyrazoles bearing 4-bromo and 4-Bpin groups were well tolerated, introducing an additional synthetic handle. The reaction with 3-methylpyrazole was regioselective at the less hindered nitrogen atom. OTIPS OSF 2 gave phenolic product 44 in quantitative yield, with similar regioselectivity. Azole oxetane derivatives 45, 46, and 60' were further characterized by X-Ray crystallography. Unlike typical conjugated diarylketones, the non-conjugated π systems in oxetanes 45 and 60' are rotated nearly 90° (dihedral angles 89.9° and 79.1° respectively) to minimize steric interactions, inducing a twisted conformation and creating an atropisomeric axis in the solid state, with one atropisomer crystallizing as a conglomerate. Slightly elevated temperatures (70 °C) improved the reactivity with imidazole nucleophiles, yielding oxetano-imidazoles 47-52 from the corresponding PMP and OTIPS OSF reagents. Interestingly, a significant change in regioselectivity was observed when reacting OTIPS OSF 2 in comparison to PMP OSF 1 (49: r.r. 53:47; 50: r.r. 90:10), which is seen also in later examples (53, 54). This may be explained through formation of a different intermediate from OTIPS OSF 2 proceeding through the quinone methide rather than the carbocation intermediate, which changes the angle of attack of the nucleophile from ca. 90° to the arene plane in the carbocation (p orbital) to ca. 107° in the quinone methide (Bürdi-Dunitz angle; LUMO p* orbital). Benzimidazole and theophylline were also reactive (51, 52), as well as 1,2,4-and 1,2,3-triazoles and benzotriazole, which generated the corresponding oxetano-triazoles in high yields (53-58). TMSN3, in the absence of K2CO3, afforded oxetane azide 59 in 85% yield, whereby the liberated fluoride anion presumably activates the azide nucleophile and in the process is effectively scavenged as TMSF. Substituted NHtetrazoles gave a mixture of regioisomers with a general preference for the 3-substituted product due to steric influence of the carbon substituent (60-63). Notably, the corresponding carbonyl derivatives of such N-heterocycles are unstable and represent intermediates in acylation processes by acting as an effective leaving group, often with the azole providing a catalyst, including histidine catalysis. As such, these stable oxetane-heterocycle derivatives may mimic acylation intermediates previously unusable for drug discovery purposes. f Reaction performed on a 0.15 mmol scale. g Tf2O (1.08 equiv), pyridine (2.0 equiv), CH2Cl2 (0.5 M), 0-25 °C, 3 h. h Pd2(dba)3 (1.5 mol%), tBuBrettPhos (4.5 mol%), KCl (2.0 equiv), KF (0.5 equiv), 1,4-dioxane (0.25 M), 130 °C, 16 h. Sulfoximines, the mono-aza-analogues of sulfones, have themselves become of significant interest in medicinal chemistry. The imine nitrogen can introduce a stereogenic center and has been shown to instill properties beneficial to drug compounds, including improved solubility, increased polarity and hydrogen-bond donor and acceptor capabilities. Functionalization of this imine nitrogen can tune the chemical and biological features of sulfoximine derivatives. Pleasingly, the sulfoximine nitrogen trapped the oxetane carbocation to generate the corresponding N-oxetane-sulfoximine fragments (Scheme 2b). High yields were achieved with excess nucleophile (3.0 equiv, 60 °C, 85% 73), though the reverse stoichiometry gave a similar yield (87%, 73). A wide variety of sulfoximines were amenable to the deFS coupling, including bulky bis-alkyl-(64), cyclic-(65), alkyl-aryl-(66) and diarylsulfoximines (67). Saturated heterocycles (68, 69) and electron poor pyridyl (70) groups were well tolerated. Moreover, potentially reactive sites including a sensitive BCB sulfoximine (72) were unaffected and successfully coupled under the mild thermal conditions. 4-Bromophenylmethyl sulfoximine reacted readily with different OSF reagents (7 and 132, see Scheme 6), providing a handle for further diversification. N-Oxetanesulfoximine 75 was characterized by X-ray crystallography, revealing a turn conformation about the Ar-C-N=S bond with a gauche arrangement (67.3°) with respect to the oxetane ring, stabilized by p-stacking interactions (d = 3.676 Å) between the oxetane and sulfoximine aryl groups in the solid state. Sulfonimidamides (the mono-aza analogues of sulfonamides) and sulfilimines (the aza-analogue of sulfoxides) also reacted successfully, to afford new oxetane functionalized derivatives (76, 77).