Construction of spirocarbocycles via gold-catalyzed intramolecular dearomatization of naphthols

A highly efficient, gold-catalyzed intramolecular dearomatization reaction of naphthols via 5-endo-dig cyclization is described. This facile and direct approach furnishes spirocarbocycles in excellent yields under mild conditions.


General procedure for the preparation of 1-naphthol derivatives (1a-1t)
To a solution of 4-hydroxy-1-naphthaldehyde [1] (14.15 g, 82 mmol) and imidazole (8.40 g, 123 mmol) in DCM (100 mL), triisopropylsilyl chloride (TIPSCl, 20 mL, 90 mmol) was added dropwise and the mixture was stirred at room temperature. After completion (monitored by TLC), the reaction mixture was quenched with saturated NH 4 Cl (100 mL) and extracted with DCM (50 mL x 3). The combined DCM extract was washed with brine, dried over anhydrous Na 2 SO 4 and filtrated. After the solvent was concentrated under reduced pressure, the crude product was purified by recrystallization (PE) and S1 was obtained in 77% yield (22.60 g).
To a dry two-necked, round-bottomed flask containing a solution of S1 (3.28 g, 10 mmol) in THF (50 mL), activated zinc powder (845.0 mg, 13 mmol) was added and 3-bromopropyne (1.65 g, 14 mmol) was added dropwise under argon. The mixture was stirred at room temperature. After completion (monitored by TLC), the reaction mixture was quenched with saturated NH 4 Cl (50 mL). THF was removed under reduced pressure. The mixture was extracted with EtOAc (50 mL x 3). The combined EtOAc extract was washed with brine, dried over anhydrous Na 2 SO 4 and filtrated. After the solvent was concentrated under reduced pressure, the crude product was dissolved in DCM (100 mL) and the mixture was cooled at 0 o C. After addition of HSiEt 3 (2.33 g, 20 mmol), CF 3 COOH (2.28 g, 20 mmol) was added dropwise. The mixture was warmed up to room temperature and stirred. After completion (monitored by TLC), the reaction mixture was quenched with saturated NaHCO 3 (100 mL) and extracted with DCM (50 mL x 3). The combined DCM extract was washed with brine, dried over anhydrous Na 2 SO 4 and filtrated. After the solvent was concentrated under reduced pressure, the crude product S2 was dissolved in THF (10 mL) and the S4 mixture was cooled at 0 o C. Tetrabutylammonium fluoride (TBAF) (7.7 mL, 1M in THF, 7.7 mmol) was added dropwise and the mixture was stirred at 0 o C for 10 min.
A flame-dried two-necked, round-bottomed flask was cooled down to room temperature under argon. After CBr 4 (2.76 g, 8.32 mmol) was dissolved in DCM (25 mL), PPh 3 (4.36 g, 16.64 mmol) was added at 0 o C. Then the above crude product in 10 mL DCM was added dropwise and the solution was warmed up to room temperature. After completion (monitored by TLC), the reaction mixture was quenched with saturated NaHCO 3 (100 mL) and extracted with DCM (10 mL x 3).
The combined DCM extract was washed with brine, dried over anhydrous Na 2 SO 4 and filtrated. After the solvent was concentrated under reduced pressure, the crude product was used without further purification.

General procedure for gold-catalyzed dearomatization of naphthols
A flame-dried Schlenk tube was cooled down to room temperature under argon.

Gram-scale reaction of 1g and transformations of 2f
A flame-dried Schlenk tube was cooled down to room temperature under argon.
A flame-dried Schlenk tube was cooled down to room temperature under argon.