Compound 4a

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Synthetic procedure: See article for the definitive version of this procedure and for full experimental details.

General procedure for the synthesis of 5,4-spirocycles (4): to a 10-mL oven-dried microwave vial containing a magnetic stirring bar was added anhydrous Cs₂CO₃ (195.5 mg, 0.6 mmol), the vial was then dried under vacuum with a heating gun for about 2 min. After cooling to room temperature, Pd(P^tBu₃)₂ (15.3 mg, 0.03 mmol) and substrate 1 (if solid) (0.3 mmol) were added to the vial sequentially. The vial was then sealed with a re-sealable silicone/PTFE crimp cap, followed by three evacuation/Ar backfill cycle. After that, CH₃CN or ⁱPrCN (2 mL) was added to the vial via the cap using syringe under argon (if substrate 1 is a liquid, it was dissolved in the solvent and added to the vial using syringe). The vial was purged with argon for 5 min before placing in a preheated oil bath at 100 ^oC. After the reaction was complete as monitored by TLC (1-24 h), the reaction mixture was allowed to cool to room temperature, diluted with ethyl acetate (20 mL), and filtered through a short pad of celite eluting with ethyl acetate (3×20 mL). After evaporation, the residue was purified by chromatography on silica gel (eluent: hexane/dichloromethane = 10/1) to afford the desired product 4.

The title compound 4a was prepared according to the general procedure outlined above. 4a (53.6 mg, 86%) was obtained as a colorless oil and became a white solid after storing in a -20 ^oC freezer overnight: m.p. 47-48 ^oC; ¹H NMR (400 MHz, CDCl₃) δ = 7.33-7.21 (m, 2 H, Ar-H), 7.21-7.13 (m, 2 H, Ar-H), 7.08-7.03 (m, 1 H, Ar-H), 6.98 (dd, J₁ = 7.4 Hz, J₁ = 1.0 Hz, 1 H, Ar-H), 6.90-6.81 (m, 2 H, Ar-H), 4.83 (d, J = 9.2 Hz, 1 H, one proton from OCH₂C), 4.77 (d, J = 9.6 Hz, 1 H, one proton from OCH₂C), 3.53 (d, J = 14.0 Hz, 1 H, one proton from CH₂C), 3.47 (d, J = 14.0 Hz, 1 H, one proton from CH₂C); ¹³C NMR (100 MHz, CDCl₃) δ = 160.0, 148.4, 143.2, 131.8, 128.8, 128.5, 127.9, 123.2, 123.0, 121.3, 120.9, 109.7, 80.1, 56.1, 48.0; IR (CHCl₃, cm^-1) 2954, 2920, 2877, 1597, 1478, 1457, 1283, 1255; HRMS (DART) calculated for C₁₅H₁₃O [M+H⁺]: 209.09664, found: 209.09712.