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Synlett 2006(7): 1080-1084  
DOI: 10.1055/s-2006-939075
LETTER
© Georg Thieme Verlag Stuttgart · New York

Two Protocols for the Conversion of Biphenol to Binaphthol: Synthesis of Diospyrol

Nopporn Thasanaa, Somchai Pisutjaroenponga, Somsak Ruchirawat*a,b
a Chulabhorn Research Institute, Vipavadee Rangsit Highway, Bangkok 10210, Thailand
Fax: +66(2)5740616; e-Mail: somsak@cri.or.th;
b Programme on Research and Development of Synthetic Drugs, Institute of Science and Technology for Research and Development, Mahidol University, Salaya Campus, Nakornpathom 73170, Thailand
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Publication History

Received 11 July 2005
Publication Date:
24 April 2006 (online)

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Abstract

The application of directed orthometallation (DoM), Fries rearrangement and transmetallation followed by allylation and cyclization is reported for the conversion of biphenol to binaphthol as a means for the synthesis of diospyrol. Furthermore, the same transformation can be accomplished by the reaction of the dienolate anion of an α,β-unsaturated amide with an aryne intermediate.

Key words

arynes - biaryls - ring closure - directed orthometallation - Fries rearrangement

14

Directed Orthometallation (DoM) and Fries Rearrangement.
To a solution t-BuLi (1.7 M, 30 mL, 50 mmol) and TMEDA (7.5 mL, 50 mmol) in dry THF (100 mL) was slowly added a solution of 2,2′-N,N-diethylcarbamoyl-1,1′-biphenyl (10, 7.68 g, 20 mmol) in THF (50 mL) at -78 °C under N2 atmosphere. The stirred reaction mixture was allowed to attain r.t. overnight and treated with a sat. NH4Cl solution. The organic solvent was removed in vacuo and the remaining solution was extracted with CH2Cl2. The combined organic layer was washed with H2O, brine, dried (anhyd Na2SO4), and evaporated to give a viscous oil. After purification by flash column chromatography using EtOAc-hexane as eluent, 2,2′-dihydroxybiphenyl-3,3′-dicarboxylic acid bisdiethyl amide(4) was obtained (6.14 g, 80%) as a white solid; mp 140-141 °C (EtOAc-hexane). IR (KBr): 3428, 2981, 1600, 1572, 1488, 1450, 1408, 1353, 1311, 1259, 1141 cm-1. 1H NMR (200 MHz, CDCl3): δ = 1.27 (t, J = 7.0 Hz, 12 H), 3.53 (q, J = 7.0 Hz, 8 H), 6.99 (t, J = 7.2, 7.8 Hz, 2 H), 7.31 (dd, J = 1.8, 7.8 Hz, 2 H), 7.38 (dd, J = 2.0, 7.7 Hz, 2 H). 13C NMR (50 MHz, CDCl3): δ = 13.4, 41.2, 119.3, 120.8, 127.1, 127.2, 133.7, 149.0, 171.0. MS (EI): m/z (%) = 385 (20) [M+ + 1], 384 (72) [M+], 383 (51), 313 (78), 312 (46), 311 (82), 310 (45), 295 (21), 285 (72), 283 (38), 240 (27), 239 (100). HRMS (FAB): m/z calcd for C22H28N2O4 [M + H+]: 385.2127; found: 385.2128.

15

Yield of 3b was improved to 53% using CuBr·SMe2.

17

Representative Procedure for the Double Ring Closure.
To a stirred THF (5 mL) solution of 2,2′-dimethoxy-4,4′-bis(2-methylallyl)biphenyl-3,3′-dicarboxylic acid bisdiethyl amide (3a, 0.1316 g, 0.25 mmol) at -78 °C under Ar was added a solution of MeLi (1.4 M, 1.1 mL, 1.5 mmol) in Et2O. The solution turned deep violet and was allowed to warm to r.t. and stirred at this temperature overnight. The reaction was quenched by the addition of 20 mL of sat. NH4Cl and extracted with CH2Cl2. The organic layer was combined, washed with H2O, brine and dried (anhyd Na2SO4). The crude product obtained after evaporation of CH2Cl2 was purified by PLC using CH2Cl2-hexane (2:1) as eluent to give white solid as 1,1′-dimethoxy-6,6′-dimethyl-2,2′-binaph-thalenyl-8,8-diol (1a, 0.0699 g, 75%); mp 234-236 °C (EtOAc-hexane). IR (KBr): 3321, 2926, 1637, 1573, 1460, 1378, 1354, 1058 cm-1. 1H NMR (400 MHz, CDCl3): δ = 2.47 (s, 6 H), 3.58 (s, 6 H), 6.82 (d, J = 1.4 Hz, 2 H), 7.17 (br s, 2 H), 7.50 (d, J = 8.5 Hz, 2 H), 7.58 (d, J = 8.5 Hz, 2 H). 13C NMR (100 MHz, CDCl3): δ = 21.7, 61.8, 112.9, 115.5, 118.4, 123.7, 124.3, 129.1, 136.5, 138.7, 153.4, 154.1. MS (EI): m/z (%) = 374 (61) [M+], 356 (15), 343 (23), 342 (81), 329 (36), 328 (100). HRMS (micro-TOF, ESI): m/z calcd for C24H22O4 [M + H+]: 375.1591; found: 375.1584.

19

Representative Procedure for the Aryne Annulation. A solution of lithium 2,2,6,6-tetramethylpiperidine (LTMP, 6.4 mmol) was prepared at 0 °C from 2,2,6,6-tetramethyl-piperidine (1.1 mL) and n-BuLi (4.95 mL) in dry THF (20 mL). After 30 min, the solution was cooled to -78 °C and a solution of N,N-diethyl seneciomide (7a, 0.66 g, 4.3 mmol) in dry THF (5 mL) was added and stirred at this temperature for 1 h. A solution of tetrabromo-2,2′-dimethoxybiphenyl (6, 0.57 g, 1.1 mmol) in dry THF (15 mL) was added drop-wise, the reaction turned to dark red. After the addition was complete, the reaction was slowly warmed to r.t. and stirred overnight. Then, sat. NH4Cl was added and the mixture was extracted with CH2Cl2. The combined organic layer was washed with H2O, brine and dried (Na2SO4) and evaporated to dryness. Further purification was carried out by PLC (SiO2, 4% EtOAc-hexane) to obtain binaphthol 12 (0.117 g, 20%).
Compound 12: mp 249-250 °C (EtOAc-hexane). IR (CHCl3): 3344 (OH), 3010, 1636, 1369, 803 cm-1. 1H NMR (200 MHz, CDCl3): δ = 2.55 (s, 6 H), 3.61 (s, 6 H), 6.91 (d, J = 1.3 Hz, 2 H), 7.56 (d, J = 0.9 Hz, 2 H), 7.84 (s, 2 H), 9.76 (s, 2 H). 13C NMR (50 MHz, CDCl3): δ = 22.0, 62.3, 114.3, 116.3, 118.2, 118.3, 123.1, 132.1, 134.4, 140.4, 153.4, 154.4. MS (EI): m/z (%) = 534 (50) [M+ + 2], 532 (100) [M+], 530 (48), 488 (41), 486 (84), 484 (42). Anal. Calcd for C24H20Br2O4: C, 54.16; H, 3.79. Found: C, 54.27; H, 3.76.