Regioselective Mg-Promoted C-Acylation of Stilbene and Acenaphthylene Derivatives

Ikuzo Nishiguchi; Yoshimasa Yamamoto; Masahiro Sakai; Toshinobu Ohno; Yoshio Ishino; Hirofumi Maekawa

doi:10.1055/s-2002-25372

LETTER

Regioselective Mg-Promoted C-Acylation of Stilbene and Acenaphthylene
Derivatives

Ikuzo Nishiguchi*, Yoshimasa Yamamoto, Masahiro Sakai, Toshinobu Ohno, Yoshio Ishino, Hirofumi Maekawa
Department of Chemistry, Nagaoka University of Technology, 1603-1, Kamitomioka-cho, Nagaoka, Niigata 940-2188, Japan
Fax: +81(258)479300; e-Mail: nishiiku@vos.nagaokaut.ac.jp;

Abstract

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Abstract

Treatment of stilbene and acenaphthylene derivatives with Mg turnings in the presence of aliphatic acid anhydrides and trimethylsilyl chloride (TMSCl) in N,N-dimethylformamide (DMF) brought about a facile and efficient cross-coupling to give C-acylation products in moderate to good yields. The reaction may be initiated by electron transfer from magnesium to the carbon-carbon double bonds of the substrates to generate the corresponding anionic species which are subsequently subjected to regioselective electrophilic acylation with acid anhydrides.

Key words

acylation - electron transfer - magnesium - cross-coupling - regioselectivity

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References

1

Osaka Municipal Technical Research Institute.

2 Kleemann A. Engel J. Pharmazeutische Wirkstoffe: Synthesen, Patente, Anwendungen Georg Thieme Verlag; Stuttgart: 1982.

For electrochemical acylation, see :

3a Lund H. Degrand C. Acta Chem. Scand. 1979, B33: 57

3b Degrand C. Mora R. Lund H. Acta Chem. Scand. 1979, B37: 429

3c Lund H. Degrand C. Tetrahedron Lett. 1977, 3593

For electrochemical carbonation, see:

4a Wawzonek S. Blaha EW. Berkey R. Runner ME. J. Electrochem. Soc. 1955, 102: 235

4b Derien S. Dunach E. Perichon J. J. Am. Chem. Soc. 1991, 113: 8447

5a Shono T. Nishiguchi I. Ohmizu H. J. Am. Chem. Soc. 1977, 99: 7396

5b Ohno T. Aramaki H. Nakahiro H. Nishiguchi I. Tetrahedron 1996, 52: 1943

6a Ohno T. Sakai M. Ishino Y. Shibata T. Maekawa H. Nishiguchi I. Org. Lett. 2001, 3: 3439

6b Kyoda M. Yokoyama T. Maekawa H. Ohno T. Nishiguchi I. Synlett 2001, 1535

7

Commercially available Mg turnings for Grignard reaction was used without any pre-treatment.

8

Typical procedure is as follows: Into a N,N-dimethylformamide (DMF, 20 mL) solution containing commercially available Mg turnings (40 mmol) for Grignard reaction and H₂O (5.6 mmol) was added dropwise a DMF solution (40 mL) of stilbene (1a, 10 mmol), trimethylsilyl chloride (TMSCl, 20 mmol), and acid anhydride(2a-d: 100 mmol) at 15-20 °C with magnetic stirring under nitrogen atmosphere during a period of 45 min. After the addition, the mixture was stirred at room temperature overnight. Treatment of the reaction mixture according to usual work-up gave 2-acyl-1,2-diphenylethanes (3a-d) in 73-59% yields accompanying a small amount (4-9%yield) of dibenzyl as a by-product. The products, 3,4-diphenyl-2-butanone(3a), [3a] 1,2-diphenyl-3-pentanone(3b), [9] 4-methyl-1,2-diphenyl-3-pentanone(3d), [10] 3-methyl-3,4-diphenyl -2-butanone(4a), [11] 2-methyl-1,2-diphenyl-3-pentanone(4b), [12] and 1-acetylacenaphthene(6a) [3a] were identified by comparison of their gas chromatography and spectroscopic behaviors with those of their authentic samples. The other products were characterized by spectroscopic methods (¹H- and ¹³C NMR, IR, MASS) and elemental analysis.
1,2-Diphenyl-3-hexanone(3c): ¹H NMR (400 MHz, CDCl₃) δ 0.71 (t, J = 7.6 Hz, 3 H), 1.39-1.50 (m, 2 H), 2.17-2.35 (m, 2 H), 2.90 (dd, J = 7.3 Hz, J = 13.7 Hz, 1 H), 3.42 (dd, J = 7.3 Hz, 13.7 Hz, 1 H), 3.91 (t, J = 7.3 Hz, 1 H) and 7.03-7.35 (m, 10 H) ppm. ¹³C NMR (CDCl₃) δ 13.43, 17.01, 38.69, 44.28, 60.82, 126.05, 127.24, 128.21, 128.33, 128.79, 128.99, 138.59, 139.82 and 209.77 ppm.. IR(neat): 3010, 2960, 1720, 1600, 1490, 1450, 1380 and 1110 cm^-1. EI-MS: m/z 252 (M⁺). Anal. Calcd for C₁₈H₂₀O: C, 85.67; H, 7.99. Found: C, 85.25; H, 8.01.
2-Methyl-1,2-diphenyl-3-hexanone(4c): ¹H NMR (400M Hz, CDCl₃) δ 0.77 (t, J = 7.3 Hz, 3 H), 1.41 (s, 3 H), 1.48-1.58 (m, 2 H), 2.14-2.25 (m, 2 H), 3.17 (d, J = 13.7 Hz, 1 H), 3.22 (d, J = 13.7 Hz, 1 H) and 6.65-7.33 (m, 10 H) ppm. ¹³C NMR (CDCl₃) δ 13.63, 17.73, 19.89, 40.06, 44.39, 56.35, 125.97, 126.94, 127.02, 127.46, 128.44, 130.53, 137.84, 141.76 and 212.49 ppm.. IR(neat): 3020, 2950, 1710, 1590, 1490, 1450, 1380 and 1120 cm^-1. EI-MS: m/z 266 (M⁺). Anal. Calcd for C₁₉H₂₂O: C, 85.67; H, 8.32. Found: C, 85.43; H, 8.45.
2,4-Dimethyl-1,2-diphenyl-3-pentanone(4d): ¹H NMR (400 MHz, CDCl₃) δ 0.85 (d, J = 6.8 Hz, 3 H), 1.02 (d, J = 6.8 Hz, 3 H), 1.45 (s, 3 H), 2.65 (sept, J = 6.8 Hz, 1 H), 3.16 (d, J = 13.7 Hz, 1 H), 3.22 (d, J = 13.7 Hz, 1 H) and 6.61-7.36 (m, 10 H) ppm. ¹³C NMR (CDCl₃) δ 19.23, 21.02, 21.17, 36.26, 44.27, 56.94, 125.92, 127.09, 127.46, 127.49, 128.37, 130.53, 137.94, 140.71 and 216.99 ppm. IR(neat): 3020, 2960, 1720, 1600, 1490, 1450, 1380 and 1110 cm^-1. EI-MS: m/z 266 (M⁺). Anal. Calcd for C₁₉H₂₂O: C, 85.67; H, 8.32. Found: C, 85.66; H, 8.32. Mp: 66-68 °C.
1-Propionylacenaphthene(6b): ¹H NMR (400 MHz, CDCl₃) δ 1.04 (t, J = 7.2 Hz, 3 H), 2.48 (dq, J = 7.2 Hz, J = 16.0 Hz, 1 H), 2.64 (dq, J = 7.2 Hz, J = 16.0 Hz, 1 H), 3.53 (dd, J = 8.4 Hz, J = 17.4 Hz, 1 H), 3.70 (dd, J = 3.4 Hz, J = 17.4 Hz, 1 H), 4.57 (dd, J = 3.4 Hz, J = 8.4 Hz, 1 H), 7.29 (d, J = 7.5 Hz, 1 H), 7.33 (d, J = 7.5 Hz, 1 H), 7.44 (t, J = 7.5 Hz, 1 H), 7.45 (t, J = 7.5 Hz, 1 H), 7.60 (d, J = 7.5 Hz, 1 H) and 7.64 (d, J = 7.5 Hz, 1 H) ppm. ¹³C NMR (CDCl₃) δ 7.85, 33.37, 33.86, 56.34, 119.61, 119.85, 122.63, 123.80, 127.64, 128.10, 131.68, 138.56, 142.49, 143.37 and 209.31 ppm. IR(neat): 3040, 2940, 1710, 1600, 1490, 1450, 1370 and 1110 cm^-1. EI-MS: m/z 210 (M⁺).
1-( n -Butyryl)acenaphthene(6c): ¹H NMR (400 MHz, CDCl₃) δ 0.86 (t, J = 7.4 Hz, 3 H), 1.61 (sext, J = 7.4 Hz, 2 H), 2.45 (dt, J = 7.4 Hz, J = 17.2 Hz, 1 H), 2.58 (dt, J = 7.4 Hz, J = 17.2 Hz, 1 H), 3.54 (dd, J = 8.5 Hz, J = 17.5 Hz, 1 H), 3.70 (dd, J = 3.6 Hz, J = 17.5 Hz, 1 H), 4.57 (dd, J = 3.6 Hz, J = 8.5 Hz, 1 H), 7.31 (d, J = 7.5 Hz, 1 H), 7.34 (d, J = 7.5 Hz, 1 H), 7.45 (t, J = 7.5 Hz, 1 H), 7.46 (t, J = 7.5 Hz, 1 H), 7.61 (d, J = 7.5 Hz, 1 H) and 7.66 (d, J = 7.5 Hz, 1 H) ppm. ¹³C NMR (CDCl₃) δ 13.67, 17.09, 33.80, 42.03, 56.61, 119.67, 119.92, 122.68, 123.84, 127.68, 128.13, 131.75, 138.65, 142.45, 143.40 and 208.71 ppm. IR(neat): 3040, 2960, 1710, 1600, 1500, 1450, 1370 and 1120 cm^-1. EI-MS: m/z 224 (M⁺).
1-Acetyl-1-methylacenaphthene(7a): ¹H NMR (400 MHz, CDCl₃) δ 1.60 (s, 3 H), 1.92 (s, 3 H), 3.23 (d, J = 18.0 Hz, 1 H), 3.82 (d, J = 18.0 Hz, 1 H), 7.22 (d, J = 7.8 Hz, 1 H), 7.34 (d, J = 7.8 Hz, 1 H), 7.48 (t, J = 7.8 Hz, 1 H), 7.51 (t, J = 7.8 Hz, 1 H), 7.67 (d, J = 7.8 Hz, 1 H) and 7.69(d, J = 7.8Hz, 1 H) ppm. ¹³C NMR (CDCl₃) δ 24.04, 25.31, 43.46, 60.34, 118.95, 119.89, 122.94, 123.96, 128.02, 128.26, 131.74, 138.25, 142.27, 148.07 and 208.58 ppm. IR(neat): 3050, 2960, 1700, 1600, 1490, 1420 and 1350 cm^-1. EI-MS: m/z 210 (M⁺).
1-Methyl-1-propionylacenaphthene(7b): ¹H NMR (400 MHz, CDCl₃) δ 0.92 (t, J = 7.2 Hz, 3 H), 1.61 (s, 3 H), 2.14 (dq, J = 7.2 Hz, J = 17.6 Hz, 1 H), 2.29 (dq, J = 7.2 Hz, J = 17.6 Hz, 1 H), 3.23 (d, J = 17.6 Hz, 1 H), 3.79 (d, J = 17.6 Hz, 1 H), 7.20 (d, J = 7.5 Hz, 1 H), 7.33 (d, J = 7.5 Hz, 1 H), 7.47 (t, J = 7.5 Hz, 1 H), 7.50 (t, J = 7.5 Hz, 1 H), 7.66 (d, J = 7.5 Hz, 1 H) and 7.68 (d, J = 7.5 Hz, 1 H) ppm. ¹³C NMR (CDCl₃) δ 8.42, 24.28, 30.70, 43.66, 60.01, 118.95, 119.81, 122.90, 123.84, 128.00, 128.22, 131.70, 138.36, 142.42, 148.34 and 211.52 ppm. IR(neat): 3050, 2970, 1710, 1600, 1500, 1450 and 1370 cm^-1. EI-MS: m/z 224 (M⁺).
1-( n -Butyryl)-1-methylacenaphthene(7c):¹H NMR (400 MHz, CDCl₃) δ 0.71 (t, J = 7.4 Hz, 3 H), 1.43-1.53 (m, 2 H), 1.60 (s, 1 H), 2.10 (dt, J = 7.3 Hz, J = 17.0 Hz, 1 H), 2.24 (dt, J = 7.3 Hz, J = 17.0 Hz, 1 H), 3.21 (d, J = 17.8 Hz, 1 H), 3.80 (d, J = 17.8 Hz, 1 H), 7.20 (d, J = 7.4 Hz, 1 H), 7.34 (d, J = 7.4 Hz, 1 H), 7.47 (t, J = 7.4 Hz, 1 H), 7.51 (t, J = 7.4 Hz, 1 H), 7.66 (d, J = 7.4 Hz, 1 H) and 7.68 (d, J = 7.4 Hz, 1 H) ppm. ¹³C NMR(CDCl₃) δ 13.54, 17.40, 24.26, 39.29, 43.44, 60.10, 119.03, 119.81, 122.90, 123.84, 127.99, 128.21, 131.70, 138.39, 142.45, 148.23 and 210.65 ppm. IR(neat): 3050, 2950, 1710, 1600, 1490, 1460 and 1370cm^-1.EI-MS: m/z 238 (M⁺).

9 Prashad M. Seth M. Bhaduri AP. J. Indian Chem. Soc. 1980, 1115

10 Sawaki Y. Ogata Y. J. Am. Chem. Soc. 1977, 99: 5412

11 Aranda A. Diaz A. Diez-Barra E. Antonio H. Moreno A. Sanchez-Verdu P. J. Chem. Soc., Perkin Trans. 1 1992, 2427

12 Maria CF.-M. Ruiz MP. J. Chem. Research 1990, 46

13

It may be assumed that presence of water played a role in restraint of formation of tarry material by rapid protonation to the benzylic anion generated in the reaction system.

14

This unique regioselectivity may be elucidated through higher reactivity of tertiary benzylic carbanion in the anion radical species 12 toward acylation, or preferential formation of more stable secondary carbanion species 13, generated by electrophilic acylation followed by almost concerted second electron transfer, although any clear-cut explanation has not been available as yet.

15

The reaction of stilbene(1a) with acid chlorides 10a-c was also carried out according to the similar procedure except use of larger excess of acid chloride (20 equiv mol), Mg (12 equiv mol) and H₂O (2 equiv mol), and reaction at lower reaction temperature (-10˜10 °C). The products, cyclopropanol esters (11a-c), were characterized by spectroscopic methods (¹H- and ¹³C NMR, IR, MASS) and elemental analysis.
1-Acetoxy-1-methyl-2,3- trans -diphenylcyclo-pro-pane(11a): ¹H NMR (400 MHz, CDCl₃) δ 1.38 (s, 3 H), 1.86 (s, 3 H), 2.51 (d, J = 7.6 Hz, 1 H), 2.87 (d, J = 7.6 Hz, 1 H) and 7.21-7.42 (m, 10 H) ppm. ¹³C NMR (CDCl₃) δ 18.30, 21.02, 33.57, 34.26, 64.84, 126.32, 126.69, 128.00, 128.28 ( × 2), 128.90, 136.56, 136.87 and 170.52 ppm. IR(neat): 3020, 2930, 1750, 1600, 1500, 1440, 1360, 1230, 1170 and 1100 cm^-1. EI-MS: m/z 223 (M - Ac)⁺, 43(Ac). Anal. Calcd for C₁₈H₁₈O₂: C, 81.17; H, 6.81. Found: C, 80.92; H, 6.85.
1-Propionyloxy-1-ethyl-2,3- trans -diphenylcyclo-propane(11b): ¹H NMR (400 MHz, CDCl₃) δ 0.95 (t, J = 7.3 Hz, 3 H), 0.98 (t, J = 7.7 Hz, 3 H), 1.28 (dq, J = 7.3 Hz, 15.4 Hz, 1 H), 1.93 (dq, J = 7.3 Hz, 15.4 Hz, 1 H), 2.17 (q, J = 7.7 Hz, 2 H), 2.50 (d, J = 7.8 Hz, 1 H), 2.90 (d, J = 7.8 Hz, 1 H) and 7.17-7.48 (m, 10 H) ppm. ¹³C NMR (CDCl₃) δ 8.90, 9.79, 24.88, 27.62, 32.21, 35.05, 68.55, 126.29, 126.63, 127.99, 128.22, 128.64, 128.99, 136.60, 137.00 and 174.16 ppm. IR(neat): 3030, 2920, 1750, 1610, 1490, 1440, 1360, 1230, 1160 and 1100 cm^-1. EI-MS: m/z 294 (M⁺) Anal. Calcd. for C₂₀H₂₂O₂: C, 81.60; H, 7.53. Found: C, 81.44; H, 7.54.
1-Butyryloxy-1-propyl-2,3- trans -diphenylcyclo-pro-pane(11c): ¹H NMR (400 MHz, CDCl₃) δ 0.82 (t, J = 7.3 Hz, 3 H), 0.84 (t, J = 7.1 Hz, 3 H), 1.07-1.15 (m, 1 H), 1.42-1.53 (m, 4 H), 1.93-2.01 (m, 1 H), 2.11-2.15 (m, 2 H), 2.50 (d,
J = 7.8 Hz, 1 H), 2.86 (d, J = 7.8 Hz, 1 H) and 7.21-7.49 (m, 10 H) ppm. ¹³C NMR (CDCl₃) δ 13.51, 13.96, 18.21, 19.01, 32.43, 33.66, 34.70, 36.24, 67.53, 126.29, 126.63, 127.99, 128.22, 128.64, 129.01, 136.56, 137.04 and 173.43 ppm. IR(neat): 3030, 2910, 1740, 1600, 1500, 1450, 1350, 1240, 1160 and 1090 cm^-1. EI-MS: m/z 322 (M⁺). Anal. Calcd for C₂₂H₂₆O₂: C, 81.95; H, 8.13. Found: C, 81.80; H, 8.18.