Tetraarylphosphonium Salt-Catalyzed Synthesis of Oxazolidinones from Isocyanates and Epoxides

Abstract

Preparation of a range of oxazolidinones, including enantioenriched N-aryl-substituted oxazolidinones, in which tetraarylphosphonium salts (TAPS) catalyze the [3 + 2] coupling reaction of isocyanates and epoxides effectively, is described. The key finding is a Brønsted acid/halide ion bifunctional catalyst that can accelerate epoxide ring opening with high regioselectivity. Mechanistic studies disclosed that the ylide generated from TAPS, along with the formation of halohydrins, plays a crucial role in the reaction with isocyanates.

Squaramide–Quaternary Ammonium Salt as an Effective Binary Organocatalytic System for Oxazolidinone Synthesis from Isocyanates and Epoxides

“…The lower yields by electron‐deficient isocyanates strongly suggests that the rate of the whole process is determined by the ring‐closing step, which corroborates the previously reported studies. [21b], To broaden the scope of this binary catalytic system, a variety of more challenging isocyanates including alkyl isocyanates 3g–h and tosyl isocyanate 3i were tested under the optimized reaction conditions. As shown in Table , entries 7, and 14–16, the reaction was not limited to only aromatic isocyanates whereas tosyl and aliphatic isocyanates were also tolerated.…”

“…As shown in Schemeàb, the applicability of this process was further expanded to the synthesis of Toloxatone ( 4z ), an antidepressant agent that acts as a selective and reversible inhibitor of monoamine oxidase‐A (MOA) using previously reported strategy. [21b]…”

“…1 H NMR and 13 C NMR spectra were in agreement with the previously reported spectrum . [21b] IR (neat) 3067, 2980, 1749 cm– 1 ; 1 H NMR (300 MHz, CDCl 3 ) δ H = 7.51 (d, J = 8.1 Hz, 2H), 7.33 (t, J = 7.9 Hz, 2H), 7.09 (t, J = 7.4 Hz, 1H), 5.84 (ddt, J = 17.2, 10.9, 5.6 Hz, 1H), 5.28–5.22 (dd, 17.2, 1.3 Hz, 1H), 5.17 (dd, J = 10.9, 1.3 Hz, 1H), 4.72 (dq, J = 10.9, 4.7 Hz, 1H), 4.05–3.98 (m, 3H), 3.88 (dd, J = 8.6, 6.4 Hz, 1H), 3.65 (d, J = 4.5 Hz, 2H); 13 C NMR (126 MHz, CDCl 3 ) δ C = 154.7, 138.4, 134.0, 129.1, 124.0, 118.2, 117.8, 72.7, 71.4, 70.1, 47.2; Anal. Calcd for C 13 H 15 NO 3 : C, 66.94; H, 6.48; N, 6.00.…”

“…1 H NMR and 13 C NMR spectra were in agreement with the previously reported spectrum. [21b] M.p. 65–67 °C; IR (neat) 1741, 1610, 1489 cm –1 ; 1 H NMR (600 MHz, CDCl 3 ) δ H = 7.36 (s, 1H), 7.31 (d, J = 7.8 Hz, 1H), 7.25 (t, J = 7.8 Hz, 1H), 6.97 (d, J = 7.8 Hz, 1H), 4.81 (dq, J = 9.1, 5.8 Hz, 1H), 4.07 (t, J = 9.1 Hz, 1H), 3.87 (dd, J = 9.1, 5.8 Hz, 1H), 3.76–3.69 (m, 2H), 2.36 (s, 3H); 13 C NMR (151 MHz, CDCl 3 ) δ C = 154.1, 139.1, 137.8, 128.9, 125.2, 119.1, 115.6, 71.0, 48.1, 45.0, 21.6; HRMS (ESI) calcd.…”

“…[21a] A pioneering work was accomplished by Toda and co‐workers in which a bifunctional tetraarylphosphonium salt catalyzes the title reaction (Schemeàa). [21b] An alternative process is a binary catalytic system – composed of a HBD molecule and quaternary ammonium salt as co‐catalyst – that have recently become highly favored in catalyzing reactions of carbon dioxide . They establish (a network of) hydrogen‐bonds ideally tailored for the catalytic opening of epoxides in addition to stabilization of the essential transition states via distinct hydrogen‐bonding interactions.…”