A Novel Nickel(0)-Catalyzed Cascade Ullmann-Pinacol Coupling: From o-Bromobenzaldehyde to trans-9,10-Dihydroxy-9,10-dihydrophenanthrene

Abstract

Using 5 mol% of (Ph₃P)₂NiCl₂ as a catalyst, Zn powder as a reductant, ortho-carbonyl-substituted aryl halides could be ­coupled to form trans-9,10-dihydroxy-9,10-dihydrophenanthrenes in a one-pot cascade reaction.

Key words

Nickel catalysis - Ullmann-pinacol coupling - cascade reaction - trans-selectivity - trans-9,10-dihydroxy-9,10-dihydrophenanthrene

References and Notes

• 1a Seebach D. Beck AK. Heckel A. Angew. Chem. Int. Ed.  2001,  40:  93 
• 1b Blaser HU. Chem. Rev.  1992,  92:  935 
• 2 Chen Y. Yekta S. Yudin AK. Chem. Rev.  2003,  103:  3155 
• 3 For application of phendiol derivatives in asymmetric catalysis, Suzuki’s group has reported a valuable work recently. See: Ohmori K. Furuya S. Yamanoi S. Suzuki K. Chem. Lett.  2007,  36:  328 
• 4a Kitamura M. Ohmori K. Kawase T. Suzuki K. Angew. Chem. Int. Ed.  1999,  38:  1229 
• 4b Kelly TR. Li Q. Bhushan V. Tetrahedron Lett.  1990,  31:  161 
• 5a Cortex C. Harvey RG. Org. Synth., Coll. Vol. VI   Wiley and Sons; New York: 1988.  p.887 
• 5b Okajima M. Suga S. Itami K. Yoshida J. J. Am. Chem. Soc.  2005,  127:  6930 
• 6a Ohmori K. Kitamura M. Suzuki K. Angew. Chem. Int. Ed.  1999,  38:  1226 
• 6b Taniguchi N. Hata T. Uemura M. Angew. Chem. Int. Ed.  1999,  38:  1232 
• 6c Yamamoto Y. Hattori R. Itoh K. Chem. Commun.  1999,  825 
• 6d Yamamoto Y. Hattori R. Miwa T. Nakagai Y.-i. Kubota T. Yamamoto C. Okamoto Y. Itoh K. J. Org. Chem.  2001,  66:  3865 
• 6e Li C.-J. Meng Y. Yi X.-H. Ma J.-H. Chan T.-K. J. Org. Chem.  1998,  63:  7498 
• 7a Hassan J. Sévignon M. Gozzi C. Schulz E. Lemaire M. Chem. Rev.  2002,  102:  1359 
• 7b Bringmann G. Mortimer AJP. Keller PA. Gresser MJ. Garner J. Breuning M. Angew. Chem. Int. Ed.  2005,  44:  5384 
• 8a Chatterjee A. Joshi NN. Tetrahedron  2006,  62:  12137 
• 8b Tanaka K. Kishigami S. Toda F. J. Org. Chem.  1990,  55:  2981 
• 9a Scherf group reported a similar reaction to cis-phendiol with excess Ni(COD)₂ in 1999: Reisch HA. Enkelmann V. Scherf U. J. Org. Chem.  1999,  64:  655 
• 9b

  The trans-structure of 2a was determined by the J _9,10 = 8.1 Hz and the singlet for acetate at δ = 2.11 ppm of trans-9-acetoxy-10-hydroxy-9,10-dihydrophenanthrene (Scheme [4] ).

• 9c For cis-9-acetoxy-10-hydroxy-9,10-dihydrophenanthrene, J _9,10 = 3.8 Hz and the singlet for acetate is at δ = 1.92 ppm, see: Jerina DM. Selander H. Yagi H. Wells MC. Davey JF. Mahadevan V. Gilbson DT. J. Am. Chem. Soc.  1976,  98:  5988 
• 13 The phendiol 2a is stable in solid. But, in our observation, it could be oxidized to phenanthrenequinone in solution. The colorless solution of phendiol 2a changed to yellow in several hours, indicated that some phenanthrenequinone was formed. This conversion could be accelerated by silica gel or light, see: Barbas JT. Sigma ME. Dabestani R. Environ. Sci. Technol.  1996,  30:  1776 ; thus, the diol products must be separated as quickly as possible after ceasing the reaction to assure high yields
• Prepared from β-naphthol according to literature procedure:
• 18a Russell A. Lockhart LB. Org. Synth., Coll. Vol. III   Wiley & Sons; New York: 1955.  p.463 
• 18b Shoesmith JB. Mackie A. J. Chem. Soc.  1930,  1584 
• Prepared from 2-methylnaphthalene according to literature procedure:
• 19a Oi S. Matsunaga K.-i. Hattori T. Miyano S. Synthesis  1993,  895 
• 19b Smith JG. Dibble PW. Sandborn RE. J. Org. Chem.  1986,  51:  3762 
• 22 Sarobe M. van Heerbeek R. Jenneskens LW. Zwikker JW. Liebigs Ann./Recl.  1997,  2499 
• 23 Prepared from 3,4,5-trimethoxybenzaldehyde according to literature procedure: Molander GA. George KM. Monovich LG. J. Org. Chem.  2003,  68:  9533 
• 24a Shi L. Fan C.-A. Tu Y.-Q. Wang M. Zhang F.-M. Tetrahedron  2004,  60:  2851 
• 24b Ogoshi S. Kamada H. Kurosawa H. Tetrahedron  2006,  62:  7583 

10

The zinc powder was purchased from SCRC (Sinopharm Chemical Reagent Co., Ltd). The activation procedure was conducted as follows: The zinc powder was stirred in 1 M HCl for a few minutes to remove the oxide, then filtered and washed successively with H₂O, EtOH, and Et₂O. The material was dried in vacuum for 24 h and then stored in a sealed bottle.

11

Synthesis of (Ph ₃ P) ₂ NiCl ₂ from NiCl ₂ ·6H ₂ O and PPh ₃ Nickel(II) chloride hexahydrate and PPh₃ were purchased from SCRC and used as available. Then, PPh₃ (10.50 g, 40 mmol) was dissolved in 100 mL of warm AcOH, and then cooled to r.t. To this solution, NiCl₂·6H₂O (4.76 g, 20 mmol) in H₂O (4 mL) was added dropwise. The mixture was stirred at r.t. for 48 h. The dark green solution was filtered, yielding deep green solid, which was washed successively with AcOH, EtOH, and Et₂O. The material was dried in vacuum for 24 h and then stored in a sealed bottle.

12

Addition of PPh₃ seems to accelerate the Ullmann coupling step. When 28 mol% of PPh₃ was added and the reaction was ceased in 53 min, the biphenyl-2,2′-dialdehyde can be isolated with 80% yield. But the second step of pinacol coupling was not affected by PPh₃.

14

In solution, 2b and 2c were oxidized faster than 2a in our observation. That resulted in lower yield of 2b and 2c.

15

The coordination of the Zn²⁺ with both the carbonyls, which brings the two carbonyls together, is essential to the intramolecular pinacol coupling. In the reaction of heterocyclic 1h, this effect may be disturbed by the competitive coordination of the nitrogen atom on the heterocycle.

16

Typical Procedure for the (Ph ₃ P) ₂ NiCl ₂ -Catalyzed Ullmann-Pinacol Coupling To a mixture of (Ph₃P)₂NiCl₂ (33 mg, 0.05 mmol) and zinc powder (196 mg, 3 mmol) in anhyd DMF (0.5 ml) was added the 2-bromobenzaldehyde (1a, 185 mg, 117 µL, 1 mmol) at 60 °C under a nitrogen atmosphere. This mixture was stirred for 7 h. After cooling to ambient temperature, 5 mL 1 M HCl and 10 mL CH₂Cl₂ were added. The mixture was stirred for 10 min, and then filtered to remove the unreacted zinc powder. The phases were separated and the aqueous phase was extracted with CH₂Cl₂ (3 × 5 mL). The combined organic extracts were dried over MgSO₄ for 1 h and concentrated. Purification of the residue by chromatography gave the phendiol 2a (85 mg, 80% yield).

17

Selective NMR Data of Products Compound 2a: ¹H NMR (300 MHz, CDCl₃): δ = 7.76 (dd, J = 6.2, 2.8 Hz, 2 H), 7.67 (dd, J = 9.4, 3.1 Hz, 2 H), 7.42-7.36 (m, 4 H), 4.76 (s, 2 H), 1.65 (br, 2 H). ¹³C NMR (75 MHz, CDCl₃): δ = 136.2, 132.6, 128.6, 128.5, 125.3, 123.9, 74.2.
Compound 2b: ¹H NMR (300 MHz, acetone-d ₆): δ = 8.41 (d, J = 8.4 Hz, 2 H), 8.21 (d, J = 8.7 Hz, 2 H), 8.02 (d, J = 8.7 Hz, 2 H), 7.95 (d, J = 7.8 Hz, 2 H), 7.64-7.51 (m, 4 H), 5.69 (s, 2 H), 3.13 (s, 2 H). ¹³C NMR (75 MHz, acetone-d ₆): δ = 134.3, 133.9, 132.1, 131.5, 129.8, 129.2, 127.5, 126.6, 124.8, 123.5, 67.9.
Compound 2c: ¹H NMR (300 MHz, CDCl₃): δ = 8.00 (d, J = 8.4 Hz, 2 H), 7.95-7.91 (m, 4 H), 7.56 (d, J = 8.4 Hz, 2 H), 7.46 (t, J = 7.5 Hz, 2 H), 7.27 (t, J = 6.6 Hz, 2 H), 4.73 (s, 2 H), 2.61 (br, 2 H). ¹³C NMR (75 MHz, CDCl₃): δ = 136.2, 133.8, 130.2, 129.1, 129.1, 128.5, 127.6, 125.6, 125.4, 121.4, 75.0.
(18) Compound 2e: ¹H NMR (300 MHz, acetone-d ₆): δ = 7.78-7.72 (m, 4 H), 7.34-7.29 (m, 4 H), 3.04 (s, 2 H), 1.24 (s, 6 H). ¹³C NMR (75 MHz, acetone-d ₆): δ = 144.8, 132.7, 128.8, 128.0, 125.1, 124.0, 77.3, 25.0.
Compound 2f: ¹H NMR (300 MHz, acetone-d ₆): δ = 7.71 (dd, J = 8.4, 6.0 Hz, 2 H), 7.60 (dd, J = 10.3, 2.5 Hz, 2 H), 7.13 (td, J = 8.6, 2.5 Hz, 2 H), 4.60 (s, 2 H), 3.12 (s, 2 H). ¹³C NMR (75 MHz, acetone-d ₆): δ = 163.7 (d, J = 241.0 Hz), 135.1 (d, J = 2.9 Hz), 134.7 (dd, J = 8.0, 2.3 Hz), 129.0 (d, J = 8.4 Hz), 115.6 (d, J = 21.5 Hz), 111.2 (d, J = 23.1 Hz), 73.416.
Compound 4: ¹H NMR (300 MHz, CDCl₃): δ = 8.48 (s, 4 H), 7.55 (d, J = 4.5 Hz, 2 H), 4.81 (s, 4 H), 2.96 (br, 2 H). ¹³C NMR (75 MHz, CDCl₃): δ = 148.7, 148.1, 147.8, 129.8, 122.08, 61.28.

20

Compound 1d was prepared from 9-bromophenanthrene in five steps (Scheme [5] ).

21

Pure diol product was not obtained. The most polar product was supposed to be the mixture of cis-diol and trans-diol by NMR analysis.

25

Preparation in multigram scale is feasible, the dosage of nickel catalyst can be reduced to 0.03 equiv: To a mixture of (Ph₃P)₂NiCl₂ (392 mg, 0.60 mmol) and zinc powder (3.930 g, 60.1 mmol) in anhyd DMF (10 mL) was added the 2-bromobenzaldehyde (1a, 3.70 g, 2.34 mL, 20 mmol) at 60 °C under nitrogen atmosphere. After stirring for 7 h, the mixture was poured into ice water (50 mL) and filtered. The filtrate was discarded. The filter residue was dissolved in hot EtOAc and filtered again. Concentration of the filtrate gave crude phendiol 2a, which is easily recrystallized in EtOAc or EtOH to afford pure product (1.683 g, 79% yield).

26

The trans-structures of the phendiols in Table [1] were confirmed based on NMR analysis of the diols and the corresponding monoacetates (see ref. 9).
Typical Procedure for Phendiol Monoacetate Method A (2a, 2c, 2f): To a suspension of phendiol (0.05 mmol) and Na₂CO₃ (16 mg, 0.15 mmol) in anhyd EtOAc (0.5 mL), Ac₂O (15 mg, 14 µL, 0.15 mmol) was added at r.t. After the reaction was complete (monitored by TLC), the mixture was poured into 2 mL of cold H₂O and the phases were separated. The aqueous phase was extracted with EtOAc (3 × 1 mL). The combined organic extracts were concentrated. Purification of the residue by chromatography gave the monoacetate.
Method B (2b): To a solution of 2b (18 mg, 0.058 mmol) in 0.5 mL pyridine, Ac₂O (8.9 mg, 8.2 µL, 0.087 mmol) was added at r.t. The reaction was conducted for 10 h. Conventional procedures led to the isolation of the monoacetate (5 mg, 24.5%).
Selective NMR Data of Phendiol Monoacetates Monoacetate of 2a: ¹H NMR (300 MHz, CDCl₃): δ = 7.75 (m, 2 H), 7.55 (d, J = 7.2 Hz, 1 H), 7.41-7.22 (m, 5 H), 6.02 (d, J = 8.1 Hz, 1 H), 4.82 (d, J = 8.1 Hz, 1 H), 2.48 (s, 1 H), 2.11 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 171.3, 135.5, 133.1, 132.3, 132.0, 129.2, 128.9, 128.5, 128.1, 127.6, 127.1, 123.9, 123.8, 74.5, 71.1, 21.1.
Monoacetate of 2b: ¹H NMR (300 MHz, acetone-d ₆): δ = 8.38 (d, J = 8.4 Hz, 1 H), 8.28-8.25 (m, 3 H), 8.13-8.06 (m, 2 H), 8.00-7.96 (m, 2 H), 7.67-7.53 (m, 4 H), 7.06 (d, J = 2.4 Hz, 1 H), 5.66 (d, J = 2.4 Hz, 1 H), 3.07 (br, 1 H), 1.84 (s, 3 H). ¹³C NMR (75 MHz, acetone-d ₆): δ = 171.0, 134.5, 134.3, 133.6, 133.5, 133.4, 131.4, 131.3, 131.1, 130.3, 129.5, 129.3, 128.2, 127.8, 127.2, 126.9, 124.7, 124.0, 123.5, 123.4, 68.7, 65.1, 20.9.
Monoacetate of 2c: ¹H NMR (300 MHz, CDCl₃): δ = 8.00-7.90 (m, 5 H), 7.57-7.43 (m, 5 H), 7.29-7.24 (m, 2 H), 6.06 (d, J = 11.1 Hz, 1 H), 4.92 (d, J = 11.1 Hz, 1 H), 2.65 (br, 1 H), 2.38 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 172.0, 136.1, 133.9, 133.8, 132.8, 130.2, 130.0, 129.3, 129.0, 128.8, 128.44, 128.39, 127.6, 127.5, 125.8, 125.7, 126.5, 125.4, 121.6, 121.0, 76.6, 73.4, 21.1.
Monoacetate of 2f: ¹H NMR (300 MHz, acetone-d ₆): δ = 7.73-7.63 (m, 3 H), 7.45 (dd, J = 8.4, 5.7 Hz, 1 H), 7.19-7.07 (m, 2 H), 5.96 (d, J = 7.2 Hz, 1 H), 4.84 (d, J = 7.2 Hz, 1 H), 3.03 (s, 1 H), 2.09 (s, 3 H). ¹³C NMR (75 MHz, acetone-d ₆): δ = 170.9, 165.8 (d, J = 17.1 Hz), 162.6 (d, J = 16.2 Hz), 135.8 (dd, J = 8.2, 2.4 Hz), 134.7 (dd, J = 8.0, 2.2 Hz), 133.6 (d, J = 2.9 Hz), 131.3 (d, J = 8.6 Hz), 130.9 (d, J = 8.5 Hz), 130.0 (d, J = 3.0 Hz), 116.2 (d, J = 14.3 Hz), 115.8 (d, J = 14.5 Hz), 112.0 (d, J = 15.9 Hz), 111.6 (d, J = 15.9 Hz), 74.2, 70.1, 21.0.