Enantioselective [1,3] O-to-C rearrangement: dearomatization of alkyl 2-allyloxy/benzyloxy-1/3-naphthoates catalyzed by a chiral π–Cu(ii) complex

An asymmetric [1,3] O-to-C rearrangement of alkyl 2-allyloxy/benzyloxy-1/3-naphthoates was realized under the catalysis of a chiral π–Cu(ii) complex to produce naphthalenone derivatives bearing an all-carbon quaternary stereogenic center in good to high yield with excellent enantioselectivity. The π–cation interaction of the complex was proved by X-ray diffraction analysis.


General Remarks
1 H NMR spectra were recorded on a JEOL ECS400 400 MHz spectrometer or a Bruker 500 MHz spectrometer in CDCl 3 . Chemical shifts are reported in ppm with the internal TMS signal at 0.0 ppm as a standard. The data are reported as (s = single, d = double, t = triple, q = quartet, m = multiple or unresolved, brs = broad single, coupling constant(s) in Hz, integration). 13 C NMR spectra were recorded on a JEOL ECS400 100 MHz or a Bruker 125 MHz spectrometer in CDCl 3 .
Chemical shifts are reported in ppm with the internal chloroform signal at 77.0 ppm.
Commercially obtained reagents were used without further purification. All reactions were monitored by TLC with silica gel-coated plates. Infrared (IR) spectra were recorded on a JASCO FT/IR 460 plus spectrometer. Enantiomeric ratios were determined by HPLC, using a chiralpak AS-3 column, chiralpak AD-3 column and chiralpak IA-3 column with hexane and i-PrOH as solvents. The racemic adducts were attained by using the complex of Cu(OTf) 2 and racemic ligand as the catalyst. The absolute configuration of 2l was determined unequivocally according to the X-ray diffraction analysis, and those of other adducts were deduced on the basis of this result.

General Procedure for the Synthesis of Ligands
To a solution of N-(tert-butoxycarbonyl)-L-norvaline (1.08 g, 5.0 mmol) in dichloromethane (DCM, 25 mL) were added 1-hydroxybenzotriazole (HOBt, 743 mg, 5.5 mmol), DCC (1.10 g 5.5 mmol) and butylamine (0.6 mL, 6.0 mmol) at 0 °C. Then the mixture was stirred at room temperature for 16 h before quenched with 10% w/w citric acid. After the mixture was filtered, the organic layer was separated and the aqueous layer was extracted with DCM. The combined organic layer was washed with brine, dried over Na 2 SO 4 , filtered and then concentrated under reduced pressure. tert-Butyl (S)-(1-(butylamino)-1-oxopentan-2-yl)carbamate was obtained and directly used in next step without further purification.
To a solution of the crude tert-butyl (S)-(1-(butylamino)-1-oxopentan-2-yl)carbamate in DCM (6.4 mL) was added trifliroacetic acid (TFA, 3.2 mL) dropwise at 0 °C. The mixture was then stirred at room temperature for 3 h. The mixture was neutralized with NaOH (1 M). The organic layer was separated, the aqueous layer was extracted with DCM. The combined organic layer was washed with brine, dried over Na 2 SO 4 , filtered and then concentrated under reduced pressure.
(S)-2-amino-N-butylpentanamide was obtained and directly used in next step without further purification.
Cinnamyl bromide 2 (or benzyl bromide) (8 mmol) was added by syringe and the reaction was heated to 60 °C until TLC revealed complete conversion of naphthols. The mixture was diluted with ethyl acetate and water after cooling. The organic layer was washed with brine, dried with anhydrous Na 2 SO 4 , and concentrated under vacuum. The residue was purified by silica gel chromatography to afford corresponding product.
To a solution of MOMO protected 1-allylnaphthalen-2-ol or 1-phenylnaphthalen-2-ol (5.00 mmol) in Et2O (20.0 mL) was added n-BuLi (6.25 mL, 10.0 mmol, 1.6M in hexane) at 0 oC. The reaction mixture was allowed to room temperature. After stirring for 1 h at room temperature, the reaction was quenched by dry ice (ca. 1 g) slowly, and then solvents were removed in vacuo. To the residue in Acetone (50.0mL) were added iodomethane (0.778 mL, 10.0 mmol) and Cs2CO3 (4.4 g, 12.5 mmol) at room temperature. After stirring for 2 h at 40 oC, the resulting mixture was poured into water and the aqueous layers were extracted with EtOAc (twice). The combined organic layers were washed with brine and dried over anhydrous MgSO4, then the solvents were removed in vacuo .The residue was purified by flash column chromatography on silica gel to give the corresponding ester.
To a solution of the corresponding ester intermidiate in MeOH (0.2 M) was added conc. HCl aq.
(a few drops). The reaction mixture was warmed to 50 ºC. After stirring for 2 h, water was added to the resulting mixture, and the aqueous layers were extracted with EtOAc. The combined organic layers were washed with brine and dried over anhydrous MgSO4, then the solvents were removed in vacuo. The residue was directly used in next step without further purification.
Then 3a and 3b could be synthesized by using the same procedure for the synthesis of methyl 2-allyloxy-and 2-Benzyloxy-1-naphthoates as we mentioned at the beginning of part 3.

2-Allyloxy-and 2-Benzyloxy-1-naphthoates
L8 (0.0165 mmol) and Cu(OTf) 2 (0.015 mmol) were stirred in 0.4 mL of DCM at room tempertaure for 0.5 h, then the reaction system was cooled to specific temperature. Naphthyl ethers 1 (0.15 mmol) was dissolved in 0.35 mL DCM and added to the system. The mixture was stirred at the same temperature until reaction completed. Then the solvent was removed, and the residue was purified by flash chromatography on silica gel (products 2s, 2t, 2u, 4a and 4b were purified using diol silica gel) to give the product 2, which was then directly analyzed by HPLC to determine the enantiomeric excess.

Prospect for Appropriate Substrate and Optimization of the Reaction Conditions
As shown in Scheme S1, compounds 1 are appropriate substrates for the [1,3] rearrangement.