New Synthetic Methods for Seven- and Eight-Membered Cyclic Ethers Based on the Ring-Expansion Reactions of Hydroxy or Lithioxy Methoxyallenylisochroman Derivatives

Yoshimitsu Nagao; Satoru Tanaka; Kazuhiko Hayashi; Shigeki Sano; Motoo Shiro

doi:10.1055/s-2004-815440

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Synlett 2004(3): 481-484
DOI: 10.1055/s-2004-815440

LETTER

New Synthetic Methods for Seven- and Eight-Membered Cyclic Ethers Based on the Ring-Expansion Reactions of Hydroxy or Lithioxy Methoxyallenylisochroman Derivatives

Yoshimitsu Nagao*^a, Satoru Tanaka^a, Kazuhiko Hayashi^a, Shigeki Sano^a, Motoo Shiro^b
^a Faculty of Pharmaceutical Sciences, The University of Tokushima, Sho-machi, Tokushima 770-8505, Japan
Fax: +81(88)6339503; e-Mail: ynagao@ph.tokushima-u.ac.jp;
^b Rigaku Corporation, 3-9-12 Matsubara-cho, Akishima-shi, Tokyo 196-8666, Japan

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Publication History

Received 24 December 2003
Publication Date:
06 February 2004 (online)

Abstract
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Abstract

The Pd(0)-catalyzed ring-expansion reactions of hydroxy methoxyallenyl-4,4-dialkylisochroman derivatives in the presence of P(o-tolyl)₃ proceeded smoothly via hydropalladation to give 3-benzoxepan-1-one derivatives in high yields. Treatment of isochroman-1-one derivatives with lithio methoxyallene followed by quenching the reaction with water furnished 3-benzoxocan-6-one derivatives in good yields.

Key words

allenes - cyclic ether - palladium - hydropalladation - ring expansion

References

1a Katrizky AR. Ress CW. Scriven EFV. In Comprehensive Heterocyclic Chemistry II Pergamon Press; Oxford UK: 1996.

Google Scholar
1b Lecount DJ. Progress in Heterocyclic Chemistry 1998, 10: 320

Google Scholar
2a Shimizu Y. Chou HN. Bando H. Van Duyne G. Clardy JC. J. Am. Chem. Soc. 1986, 108: 514

Crossref Google Scholar
2b Pawlak M. Tempesta MS. Golik J. Zagorski MG. Lee MS. Nakanishi K. Iwashita T. Gross ML. Tomer KB. J. Am. Chem. Soc. 1987, 109: 1144

Crossref Google Scholar
3 Murata M. Legrand AM. Ishibashi Y. Yasumoto T. J. Am. Chem. Soc. 1989, 111: 8929

Crossref Google Scholar
4a Nicolaou KC. Hwang CK. Duggan ME. Bal Reddy K. Tetrahedron Lett. 1987, 28: 1501

Crossref Google Scholar
4b Paquette LA. Sweeney TJ. Tetrahedron 1990, 46: 4487

Crossref Google Scholar
4c Clark DL. Chou W.-N. White JB. J. Org. Chem. 1990, 55: 3975

Crossref Google Scholar
4d Clark JS. Krowiak SA. Street LJ. Tetrahedron Lett. 1993, 34: 4385

Crossref Google Scholar
4e Robinson RA. Clark JS. Holmes AB. J. Am. Chem. Soc. 1993, 115: 10400

Crossref Google Scholar
4f Clark JS. Whitlock GA. Tetrahedron Lett. 1994, 35: 6381

Crossref Google Scholar
4g Clark JS. Dossetter AG. Whittingham WG. Tetrahedron Lett. 1996, 37: 5605

Crossref Google Scholar
4h Clark JS. Fretwell M. Whitlock GA. Burns CJ. Fox DNA. Tetrahedron Lett. 1998, 39: 97

Crossref Google Scholar
4i Bueno AB. Moser WH. Hegedus LS. J. Org. Chem. 1998, 63: 1462

Crossref Google Scholar
4j Xie RL. Hauske JR. Tetrahedron Lett. 2000, 41: 10167

Crossref Google Scholar
4k Wang EC. Hsu MK. Huang KS. Heterocycles 2002, 57: 1997

Crossref Google Scholar
4l Peczuh MW. Snyder NL. Tetrahedron Lett. 2003, 44: 4057

Crossref Google Scholar
4m Kulesza A. Ebetino FH. Mazur AW. Tetrahedron Lett. 2003, 44: 5511

Crossref Google Scholar
5a Jeong I.-Y. Nagao Y. Tetrahedron Lett. 1998, 39: 8677

Google Scholar
5b Jeong I.-Y. Lee WS. Goto S. Sano S. Shiro M. Nagao Y. Tetrahedron 1998, 54: 14437

Google Scholar
5c Jeong I.-Y. Nagao Y. Synlett 1999, 576

Google Scholar
5d Jeong I.-Y. Shiro M. Nagao Y. Heterocycles 2000, 52: 85

Google Scholar
5e Nagao Y. Tanaka S. Ueki A. Jeong I.-Y. Sano S. Shiro M. Synlett 2002, 480:

Google Scholar
5f Nagao Y. Ueki A. Asano K. Tanaka S. Sano S. Shiro M. Org. Lett. 2002, 4: 455

Google Scholar
5g Nagao Y. Sano S. J. Synth. Org. Chem., Jpn. 2003, 61: 1088

Google Scholar
6 Bell VL. Giddings PJ. Holmes AB. Mock GA. Raphael RA. J. Chem. Soc., Perkin Trans. 1 1986, 1515

Crossref Google Scholar
7a Mohler DL. Thompson DW. Tetrahedron Lett. 1987, 28: 2567

Crossref Google Scholar
7b Schultz AG. Kirincich SJ. J. Org. Chem. 1996, 61: 5631

Crossref Google Scholar
7c Kinder MA. Kopf J. Margaretha P. Tetrahedron 2000, 56: 6763

Crossref Google Scholar
8 Noureldin NA. Zhao D. Lee DG. J. Org. Chem. 1997, 62: 8767

Google Scholar
9a Weiberth FJ. Hall SS. J. Org. Chem. 1997, 62: 6450

Article in Thieme Connect Google Scholar
9b Zimmer R. Synthesis 1993, 165

Article in Thieme Connect Google Scholar
9c Pulz R. Synlett 2000, 1697

Article in Thieme Connect Google Scholar
13a Bhide BH. Shah KK. Indian J. Chem., Sect. B 1980, 19: 9

Crossref Google Scholar
13b Lamaty G. Moreau C. Mouloungui Z. Can. J. Chem. 1983, 61: 2643

Crossref Google Scholar
13c Isobe K. Takeda N. Mohri K. Tsuda Y. Chem. Pharm. Bull. 1989, 37: 3390

Crossref Google Scholar

10

Typical Experimental Procedure for the Synthesis of Hydroxy Methoxyallenyl-4,4-dialkylisochromans 7a-c: A solution of methoxyallene (280.4 mg, 4.0 mmol) in dry THF (4.0 mL) was treated with 1.58 M n-BuLi in n-hexane (1.52 mL, 2.4 mmol) under an argon atmosphere at -30 °C. The solution was stirred for 30 min, and then the solution was added to a THF (2.0 mL) solution of 4,4-dimethyl-isochroman-1-one (6a; 352.4 mg, 2.0 mmol) at -30 °C. After being stirred at -30 °C for 1 h, the reaction mixture was quenched with H₂O and extracted with Et₂O. The organic layer was washed with brine, dried over MgSO₄, and filtered. The filtrate was evaporated in vacuo to afford a crude product, which was purified by column chromato-graphy on silica gel with n-hexane-EtOAc (3:1) to give 1-hydroxy-1-methoxyallenyl-4,4-dimethylisochroman (7a; 483.2 mg, 98%) as a pale yellow oil.
Compound 7a: pale yellow oil. IR (neat): 3428, 1956 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.26 (s, 3 H), 1.33 (s, 3 H), 3.42 (s, 1 H), 3.47 (s, 3 H), 3.61 (d, J = 11.0 Hz, 1 H), 4.04 (d, J = 11.0 Hz, 1 H), 5.60 (d, J = 8.3 Hz, 1 H), 5.66 (d, J = 8.3 Hz, 1 H), 7.17-7.36 (m, 4 H). ¹³C NMR (75 MHz, CDCl₃): δ = 24.5, 28.2, 33.4, 56.8, 70.8, 94.3, 96.1, 124.4, 125.7, 127.4, 128.5, 133.7, 137.2, 144.1, 197.1. HRMS-EI calcd for C₁₅H₁₈O₃: MW 246.1256. Found: m/z = 246.1254 (M⁺). Compound 7b: pale yellow oil. IR (neat): 3470, 1956 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 0.77 (t, J = 7.7 Hz, 3 H), 0.81 (t, J = 7.7 Hz, 3 H), 1.62-1.82 (m, 4 H), 3.48 (s, 3 H), 3.50 (s, 1 H), 3.76 (d, J = 11.2 Hz, 1 H), 4.11 (d, J = 11.2 Hz, 1 H), 5.52 (d, J = 8.3 Hz, 1 H), 5.55 (d, J = 8.3 Hz, 1 H), 7.16-7.31 (m, 3 H), 7.36-7.39 (m, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 8.6, 8.7, 28.5, 31.3, 39.4, 56.9, 66.5, 94.0, 96.3, 125.5, 125.6, 127.6, 128.0, 135.2, 136.7, 141.2, 197.4. HRMS-EI calcd for C₁₇H₂₂O₃: MW 274.1569. Found: m/z = 274.1569 (M⁺). Compound 7c: white powder. IR (KBr): 3420, 1957 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 0.83 (t, J = 7.3 Hz, 3 H), 0.86 (t, J = 7.3 Hz, 3 H), 1.06-1.29 (m, 4 H), 1.59-1.73 (m, 4 H), 3.48 (s, 3 H), 3.49 (s, 1 H), 3.76 (d, J = 11.5 Hz, 1 H), 4.10 (d, J = 11.5 Hz, 1 H), 5.52 (d, J = 8.3 Hz, 1 H), 5.55 (d, J = 8.3 Hz, 1 H), 7.15-7.30 (m, 3 H), 7.35-7.37 (m, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 14.9, 15.0, 17.3, 17.4, 39.2, 39.4, 41.7, 57.0, 67.4, 94.1, 96.3, 125.4, 125.5, 127.6, 128.0, 134.7, 136.6, 141.9, 197.3. HRMS-EI calcd for C₁₉H₂₆O₃: MW 302.1882. Found: m/z = 302.1888 (M⁺).

11

Typical Procedure for the Ring-Expansion Reaction of Hydroxy Methoxyallenyl-4,4-dialkylisochromans 7a-c: A mixture of 1-hydroxy-1-methoxyallenyl-4,4-dimethyl-isochroman (7a; 173.1 mg, 0.703 mmol), Pd(PPh₃)₄ (40.6 mg, 5.0 mol%), P(o-tolyl)₃ (21.4 mg, 10.0 mol%) in THF (7.0 mL) was refluxed under an argon atmosphere for 3 h. The reaction mixture was evaporated in vacuo to afford a solid residue, which was purified by column chromato-graphy on silica gel with n-hexane-EtOAc (3:1) to give 5,5-dimethyl-2-methoxy-2-vinyl-3-benzoxepan-1-one (8a; 137.4 mg, 79%) as colorless prisms.
Compound 8a: colorless prisms; mp 78.5-79.5 °C (n-hexane-EtOAc). IR (KBr): 1711 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.14 (s, 3 H), 1.60 (s, 3 H), 3.36 (s, 3 H), 3.69 (d, J = 13.2 Hz, 1 H), 4.03 (d, J = 13.2 Hz, 1 H), 5.37 (dd, J = 1.6, 10.3 Hz, 1 H), 5.53 (dd, J = 1.6, 17.3 Hz, 1 H), 5.65 (dd, J = 10.3, 17.3 Hz, 1 H), 7.21-7.25 (m, 1 H), 7.41-7.50 (m, 3 H). HRMS-EI calcd for C₁₅H₁₈O₃: MW 246.1256. Found: m/z = 246.1258 (M⁺). Anal. Calcd for C₁₅H₁₈O₃: C, 73.15; H, 7.37. Found: C, 73.03; H, 7.38. Compound 8b: colorless oil. IR (neat): 1700 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 0.46 (t, J = 7.5 Hz, 3 H), 1.07 (t, J = 7.5 Hz, 3 H) 1.44-1.58 (m, 2 H), 1.76-1.89 (m, 1 H), 2.13-2.23 (m, 1 H), 3.35 (s, 3 H), 3.86 (d, J = 13.7 Hz, 1 H), 4.10 (d, J = 13.7 Hz, 1 H), 5.35 (dd, J = 1.5, 10.5 Hz, 1 H), 5.48 (dd, J = 1.5, 17.3 Hz, 1 H), 5.62 (dd, J = 10.5, 17.3 Hz, 1 H), 7.22-7.26 (m, 1 H), 7.24 (d, J = 7.8 Hz, 1 H), 7.42 (dd, J = 1.5, 7.7 Hz, 1 H), 7.46-7.50 (m, 1 H). HRMS-EI calcd for C₁₇H₂₂O₃: MW 274.1569. Found: m/z = 274.1558 (M⁺). Anal. Calcd for C₁₇H₂₂O₃: C, 74.42; H, 8.08. Found: C, 74.17; H, 8.08. Compound 8c: colorless oil. IR (neat): 1701 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 0.54-0.73 (m, 4 H), 0.92-1.04 (m, 4 H), 1.33-1.50 (m, 3 H), 1.63-1.78 (m, 3 H), 3.34 (s, 3 H), 3.87 (d, J = 13.7 Hz, 1 H), 4.11 (d, J = 13.7 Hz, 1 H), 5.35 (dd, J = 1.5, 10.5 Hz, 1 H), 5.48 (dd, J = 1.5, 17.3 Hz, 1 H), 5.61 (dd, J = 10.5, 17.3 Hz, 1 H), 7.21-7.24 (m, 1 H), 7.36 (d, J = 7.8 Hz, 1 H), 7.40 (dd, J = 1.5, 7.8 Hz, 1 H), 7.46-7.50 (m, 1 H). HRMS-EI calcd for C₁₉H₂₆O₃: MW 302.1882. Found: m/z = 302.1888 (M⁺). Anal. Calcd for C₁₉H₂₆O₃: C, 75.46; H, 8.67. Found: C, 75.21; H, 8.71.

12

X-ray data for 8a: C₁₅H₁₈O₃, MW = 246.31, colorless block, orthorhombic, space group Aba2 (#41), a = 22.4114 Å, b = 7.929(2) Å, c = 14.737 (4) Å, V = 2618 (1) Å³, Z = 8, R = 0.181, Rw = 0.181. The structure factors are available from the author upon request.

14

Typical Experimental Procedure for the Ring-Expansion Reaction of Isochroman-1-ones 9a-e: A solution of methoxyallene (140.2 mg, 2.0 mmol) in dry THF (2.0 mL) was treated with 1.58 M n-BuLi in n-hexane (0.76 mL, 1.2 mmol) under an argon atmosphere at -30 °C with stirring for 30 min. Then the solution was added to a THF (1.0 mL) solution of 7-methoxy-isochroman-1-one (9d; 178.2 mg, 1.0 mmol) at -30 °C. After being stirred at -30 °C for 1 h, the reaction mixture was quenched with H₂O and extracted with Et₂O. The organic layer was washed with brine, dried over MgSO₄, and filtered. The filtrate was evaporated in vacuo to afford a crude product, which was purified by column chromatography on silica gel with n-hexane-EtOAc (3:1) to give 5,8-dimethoxy-4-methyl-1,2-dihydro-3-benzoxocin-6-one (10d; 166.6 mg, 69%) as colorless plates.
Compound 10a: colorless oil. IR (neat): 1619, 1596 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 2.12 (s, 3 H), 2.98 (t, J = 5.7 Hz, 2 H), 3.73 (s, 3 H), 4.02 (t, J = 5.7 Hz, 2 H), 7.16 (d, J = 7.6 Hz, 1 H), 7.35 (t, J = 7.6 Hz, 1 H), 7.44 (d, J = 7.6 Hz, 1 H), 7.74 (d, J = 7.6 Hz, 1 H). HRMS-EI calcd for C₁₃H₁₄O₃: MW 218.0943. Found: m/z = 218.0957 (M⁺). Anal. Calcd for C₁₃H₁₄O₃: C, 71.54; H, 6.47. Found: C, 71.32; H, 6.43. Compound 10b: colorless needles; mp 72.5-73.5 °C (CHCl₃-n-hexane-Et₂O). IR (KBr): 1620, 1601
cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 2.11 (s, 3 H), 2.36 (s, 3 H), 2.94 (t, J = 5.9 Hz, 2 H), 3.72 (s, 3 H), 4.00 (t, J = 5.9 Hz, 2 H), 7.05 (d, J = 7.8 Hz, 1 H), 7.23-7.26 (m, 1 H), 7.56 (d, J = 0.7 Hz, 1 H). HRMS-EI calcd for C₁₄H₁₆O₃: MW 232.1100. Found: m/z = 232.1104 (M⁺). Anal. Calcd for C₁₄H₁₆O₃: C, 72.39; H, 6.94. Found: C, 72.13; H, 6.96. Compound 10c: colorless prisms; mp 56.0-56.5 °C (n-hexane-Et₂O). IR (KBr): 1617, 1608 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 2.11 (s, 3 H), 2.37 (s, 3 H), 2.95 (t, J = 5.7 Hz, 2 H), 3.72 (s, 3 H), 4.01 (t, J = 5.7 Hz, 2 H), 6.97 (s, 1 H), 7.15 (d, J = 8.1 Hz, 1 H), 7.69 (d, J = 8.1 Hz, 1 H); HRMS-EI calcd for C₁₄H₁₆O₃: MW 232.1100. Found: m/z = 232.1092 (M⁺). Anal. Calcd for C₁₄H₁₆O₃: C, 72.39; H, 6.94. Found: C, 72.17; H, 6.98. Compound 10d: colorless plates; mp 81.0 °C (n-hexane-EtOAc). IR (KBr): 1613, 1600 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 2.12 (s, 3 H), 2.92 (t, J = 5.6 Hz, 2 H), 3.72 (s, 3 H), 3.83 (s, 3 H), 3.99 (t, J = 5.6 Hz, 2 H), 7.00 (dd, J = 2.0, 8.3 Hz, 1 H), 7.07 (d, J = 8.3 Hz, 1 H), 7.30 (d, J = 2.0 Hz, 1 H). HRMS-EI calcd for C₁₄H₁₆O₄: MW 248.1049. Found: m/z = 248.1049 (M⁺). Anal. Calcd for C₁₄H₁₆O₄: C, 67.73; H, 6.50. Found: C, 67.76; H, 6.52. Compound 10e: colorless needless; mp 147.0-147.5 °C (n-hexane-EtOAc); IR (KBr) 1617, 1596 cm^-1; ¹H NMR (400 MHz, CDCl₃) d = 2.11 (s, 3 H), 2.97 (t, J = 5.7 Hz, 2 H), 3.72 (s, 3 H), 3.92 (s, 3 H), 3.94 (s, 3 H), 4.03 (t, J = 5.7 Hz, 2 H), 6.62 (s, 1 H), 7.44 (s, 1 H). HRMS-EI calcd for C₁₅H₁₈O₅ MW 278.1154, found m/z 278.1172 (M⁺). Anal. Calcd for C₁₅H₁₈O₅: C, 64.47; H, 6.52. Found: C, 64.74; H, 6.58.

15

X-ray data for 10b: C₁₄H₁₆O₃, MW = 232.28, colorless needle, monoclinic, space group P2₁/c (#14), a = 10.223(3) Å, b = 8.743(2) Å, c = 14.193(3) Å, V = 1237.9(5) Å³, β = 102.64(1)^o, Z = 4, R = 0.087, Rw = 0.131. The structure factors are available from the author upon request.