Gold-catalyzed oxycyclization of allenic carbamates: expeditious synthesis of 1,3-oxazin-2-ones

Abstract

A combined experimental and computational study on regioselective gold-catalyzed synthetic routes to 1,3-oxazinan-2-ones (kinetically controlled products) and 1,3-oxazin-2-one derivatives (thermodynamically favored) from easily accessible allenic carbamates has been carried out.

Keywords: allenes; computational chemistry; gold; gold catalysis; heterocycles; reaction mechanisms.

Scheme 1

Preparation of allenic carbamates 2a–j. Reagents and conditions: (i) Propargylamine, MgSO₄, CH₂Cl₂, rt, 15 h. (ii) NaBH₄, MeOH, rt, 0.5 h. (iii) Boc₂O, Et₃N, CH₂Cl₂, rt, 2–15 h. (iv) (CH₂O)_n, iPr₂NH, CuBr, 1,4-dioxane, reflux, 1 h. (v) Ohira–Bestmann reagent, K₂CO₃, MeOH, rt, 15 h. (vi) Boc₂O, DMAP, CH₃CN, rt, 2 h. (vii) Dess–Martin periodinane, CH₂Cl₂, rt. PMP = 4-MeOC₆H₄.

Scheme 2

Controlled oxycyclization reactions of allenic carbamates 2 to 1,3-oxazinan-2-ones 3 and 1,3-oxazin-2-ones 4 under selective gold-catalyzed conditions. Reagents and conditions: (i) 2.5 mol % [AuClPPh₃], 2.5 mol % AgOTf, 10 mol % PTSA, CH₂Cl₂, rt, 3a: 6 h; 3b: 7 h, 3d: 6 h; 3e: 8 h; 3f: 7 h; 3g: 5.5 h; 3h: 5 h; 3i: 7 h; 3j: 2 h. (ii) 2.5 mol % [AuClPPh₃], 2.5 mol % AgOTf, 10 mol % PTSA, CH₂Cl₂, sealed tube, 130 °C, 4a: 1.5 h; 4b: 2 h, 4c: 4 h; 4d: 6 h; 4e: 4 h; 4f: 0.5 h; 4g: 5.5 h; 4i: 2 h. (iii) 2.5 mol % [AuClPPh₃], 2.5 mol % AgOTf, 10 mol % PTSA, CH₂Cl₂, sealed tube, 80 °C, 4j: 2 h. PMP = 4-MeOC₆H₄.

Scheme 3

Possible explanation for the gold-catalyzed isomerization reaction of 1,3-oxazinan-2-one 3a into 1,3-oxazin-2-one 4a. Reagents and conditions: (i) 2.5 mol % [AuClPPh₃], 2.5 mol % AgOTf, 10 mol % PTSA, CH₂Cl₂, sealed tube, 130 °C, 1.5 h.

Scheme 4

Mechanistic explanation for the gold-catalyzed oxycyclization reactions of allenic carbamates 2 into 6-methylene-1,3-oxazinan-2-ones 3 or into 3-substituted-3,4-dihydro-2H-1,3-oxazin-2-ones 4.

Figure 1

Computed reaction profile for the reaction of AuPMe₃⁺ and 1M. Numbers indicate the corresponding PCM-corrected ΔG₂₉₈ energies (in kcal/mol) using dichloromethane as solvent. Bond distances are given in angstroms. All data have been computed at the PCM-M06/def2-SVP//B3LYP/def2-SVP level.