Synthesis of 5-(2-methoxy-1-naphthyl)- and 5-[2-(methoxymethyl)-1-naphthyl]-11H-benzo[b]fluorene as 2,2'-disubstituted 1,1'-binaphthyls via benzannulated enyne–allenes

5-(2-Methoxy-1-naphthyl)- and 5-[2-(methoxymethyl)-1-naphthyl]-11H-benzo[b]fluorene were synthesized by treatment of the corresponding benzannulated enediynes with potassium tert-butoxide in refluxing toluene to give benzannulated enyne–allenes for the subsequent Schmittel cascade cyclization reactions. The structures of these two 5-(1-naphthyl)-11H-benzo[b]fluorenes could be regarded as 2,2'-disubstituted 1,1'-binaphthyls with the newly constructed benzofluorenyl group serving as a naphthyl moiety.

We also investigated the possibility of using the benzannulated enediynes bearing a 1-naphthyl, a 2-methoxy-1-naphthyl, or a 2-(methoxymethyl)-1-naphthyl substituent at one of the alkynyl termini for the cascade cyclization reaction.Using a slightly different synthetic sequence from that shown in Scheme 3 but reminiscent of a sequence developed for the synthesis of 4,5diheteroarylphenanthrenes [21], the benzannulated enediynes 19a and 19b were obtained (Scheme 4).It was gratifying to observe that on treatment with potassium tert-butoxide, 19a and 19b were smoothly converted to 20a and 20b, respectively.Similarly 20c was obtained via the synthetic sequence outlined in Scheme 5.It is worth noting that the synthetic sequences outlined in Scheme 4 and Scheme 5 represent new routes to 2,2'-disubstituted 1,1'-binaphthyls with the newly constructed benzofluorenyl serving as one of the naphthyl groups.The 1 H NMR spectrum of 13a in C 6 D 6 recorded on a 600 MHz NMR spectrometer exhibited an AB system with signals at δ 4.21 (J = 21.0Hz) and 4.13 (J = 21.0Hz), attributable to the methylene hydrogens on the five-membered ring.AB systems from the methylene hydrogens were also observed in other similar 11H-benzo[b]fluorenyl structures [7,[22][23][24].The AB pattern remained unchanged at 70 °C, suggesting a relatively slow rate of rotation, on the NMR time scale, around the carbon-carbon single bond connecting the 2-methoxyphenyl substituent to the C5 of the benzofluorenyl moiety.The rotational barrier was calculated to be at least 16.7 kcal/mol at 70 °C on the basis of the lack of coalescence of signals at this temperature.This lowest possible rotational barrier is significantly higher than that of 1-phenylnaphthalene, which was calculated by MM2' to be 12.4 kcal/mol [25,26].Similarly, the 1 H NMR spectrum of 13b taken in CDCl 3 showed a clear AB system at δ 4.07 (J = 13.8Hz) and 4.04 (J = 13.8Hz), attributable to the methylene hydrogens on the carbon attached to the methoxy group.The signals of the methylene hydrogens on the five-membered ring could barely be discerned as an AB system with the two inner signals overlapped at δ 4.51 and two small outer signals at δ 4.55 and 4.47.
The rotational barrier of the parent 1,1'-binaphthyl in N,Ndimethylformamide was determined to be 23.5 kcal/mol at 50 °C, corresponding to a half-life of 14.5 minutes for racemization [27,28].Because the structure of 20a could be regarded as a 2,3,4-trisubstituted 1,1'-binaphthyl, the rate of rotation can be expected to be even slower.Again, in C 6 D 6 recorded on a 600 MHz NMR spectrometer, the signals of the methylene hydrogens on the five-membered ring could be discerned as an AB system at δ 4.27 (J = 21 Hz) and 4.25 (J = 21 Hz).
The rotational barrier of BINOL as a member of the 2,2'-disubstituted 1,1'-binaphthyls was determined to be 37.2 kcal/mol at 195 °C in naphthalene, corresponding to a half-life of 4.5 hours for racemization [28].The high stability of the configuration even at such an elevated temperature allows BINOL to be used in a variety of synthetic applications.The configurational stability of 20b and 20c, which could be regarded as 2,2'-disubstituted 1,1'-binaphthyls with two additional substituents at the 3 and 4 positions, could also be expected to be high.AB patterns were observed for the methylene hydrogens on the five-membered ring of 20b and on the carbon bearing the methoxy group of 20c.
Treatment of 20b with boron tribromide converted the methoxy group to the hydroxy group, providing a handle for resolution of 24 with (1S)-(−)-camphanoyl chloride (Scheme 6) [29].It was possible to achieve partial separation of a small fraction of the two diastereomeric (1S)-camphanates in a 5:1 ratio by silica gel column chromatography.

Conclusion
In conclusion, the use of benzannulated enediynes as precursors to 2,2'-disubstituted 1,1'-binaphthyls represents a new synthetic approach to these sterically hindered molecules.The assembly of the enediynyl precursors from separate aromatic fragments allows the possibility of placing a variety of functional groups at various positions of the 1,1'-binaphthyl system.Transformation of the methoxy group in 20b to a hydroxy group provides a handle for resolution with optically active reagents.

Benzannulated enediyne 19c.
To a mixture of 0.242 g of 23 (0.812 mmol), Pd(PPh 3 ) 2 Cl 2 (0.030 g, 0.043 mmol), and copper(I) iodide (0.015 g, 0.080 mmol) in 6 mL of triethylamine, was added via cannula a solution of 0.265 g of 22 (0.974 mmol) in 2 mL of triethylamine.After stirring at 60 °C for 12 h, 15 mL of a saturated ammonium chloride solution and 15 mL of diethyl ether were added.The organic layer was separated and the aqueous layer back extracted with diethyl ether.The combined organic layers were washed successively with brine and water, dried over sodium sulfate, and concentrated.Purification of the residue by flash column chromatography (silica gel/5% methylene chloride in hexanes) afforded 0.255 g of 19c (0.577 mmol, 71%) as a colorless liquid: 1

5-(2-Methoxy-1-naphthyl)-10-(1,1-dimethylethyl)-11Hbenzo[b]fluorene (20b).
To 0.295 g of 19b (0.689 mmol) in 10 mL of anhydrous toluene under a nitrogen atmosphere, was added 0.77 mL of a 1.0 M solution of potassium tert-butoxide (0.77 mmol) in 2-methyl-2-propanol.The reaction mixture was then heated under reflux for 6 h.After the reaction mixture was allowed to cool to room temperature, 10 mL of water and 40 mL of methylene chloride were introduced.The organic layer was separated, dried over sodium sulfate and concentrated.The residue was purified by flash column chromatography (silica gel/5% methylene chloride in hexanes) to provide 0.263 g of 20b (0.614 mmol, 89%) as a light yellow liquid: IR 1267, 1250, 766 cm Recrystallization from a mixture of isopropyl alcohol and methylene chloride produced a crystal for X-ray structure analysis.Although the weakly diffracting crystal limited the amount of observed data, the analysis of these data supports the structural assignment of 20b.