A Synthetic Pathway to the 1,4-Dihydro-2H-3-benzoxocine System from Morita–Baylis–Hillman Cinnamyl Alcohols with 2,5-Dimethoxy-2,5-dihydrofuran via the Heck Reaction

Abstract

A new synthetic method for methyl 2-methoxy-1-(meth­oxycarbonylmethyl)-1,4-dihydro-2H-3-benzoxocine-5-carboxylates was developed using the Heck reaction between 2,5-dimethoxy-2,5-dihydrofuran and methyl 2-(hydroxymethyl)-3-(2-iodophenyl)propenoates as a key step. The latter were readily obtained from the Morita–Baylis–Hillman reaction of iodobenzaldehydes with methyl acrylate through acetylation, rearrangement, and hydrolysis. The methyl 2-methoxy-1-(methoxycarbonylmethyl)-1,4-dihydro-2H-3-benzoxocine-5-carboxylates were converted into methyl 2-oxo-1,2,5,11b-tetrahydro-3aH-furo[3,2-a][3]benzoxocine-6-carboxylates on exposure to excess trifluoroacetic acid.

Key words

Morita–Baylis–Hillman - Heck reaction - 1,4-dihydro-2H-3-benzoxocines - iodobenzaldehydes - 2,5-dimethoxy-2,5-dihydrofuran

• References


For reviews of medium-ring cyclic ethers, see:
• 1a Elliott MC. Contemp. Org. Synth. 1994; 1: 457
• 1b Moody CJ, Davies MJ In Studies in Natural Products Chemistry . Vol. 10. Atta-Ur-Rahman, Ed.; Elsevier; New York: 1992: 201
• 2a Ohno H, Hamaguchi H, Ohata M, Kosaka S, Tanaka T. Heterocycles 2003; 61: 65
• 2b Ohno H, Hamaguchi H, Ohata M, Kosaka S, Tanaka T. J. Am. Chem. Soc. 2004; 126: 8744
• 3 Kurita J, Aruga T, Tsuchiya T. Heterocycles 1990; 31: 1769
• 4 Chaudhuri R, Das A, Liao H.-Y, Liu R.-S. Chem. Commun. 2010; 46: 4601
• 5 Samizu K, Ogasawara K. Heterocycles 1994; 38: 1745
• 6a Samizu K, Ogasawara K. Synlett 1994; 499
• 6b Sakagami H, Ogasawara K. Heterocycles 1999; 51: 1131

For reviews of the Morita–Baylis–Hillman reaction, see:
• 7a Drewes SE, Roos GH. P. Tetrahedron 1988; 44: 4653
• 7b Basavaiah D, Rao PD, Hyma RS. Tetrahedron 1996; 52: 8001
• 7c Ciganek E. Org. React. 1997; 51: 201
• 7d Langer P. Angew. Chem. Int. Ed. 2000; 39: 3049
• 7e Basavaiah D, Rao AJ, Satyanarayana T. Chem. Rev. 2003; 103: 811
• 7f Kataoka T, Kinoshita H. Eur. J. Org. Chem. 2005; 45
• 7g Basavaiah D, Rao KV, Reddy RJ. Chem. Soc. Rev. 2007; 36: 1581
• 7h Singh V, Batra S. Tetrahedron 2008; 64: 4511
• 7i Declerck V, Martinez J, Lamaty F. Chem. Rev. 2009; 109: 1
• 7j Gowrisankar S, Lee HS, Kim SH, Lee KY, Kim JN. Tetrahedron 2009; 65: 8769
• 7k Ma G.-N, Jiang J.-J, Shi M, Wei Y. Chem. Commun. 2009; 5496
• 7l Basavaiah D, Reddy BS, Badsara SS. Chem. Rev. 2010; 110: 5447
• 7m Zhong W, Liu Y, Wang G, Hong L, Chen Y, Chen X, Zheng Y, Zhang W, Ma Y, Shen Y, Yao Y. Org. Prep. Proced. Int. 2011; 43: 1

For our recent examples, see:
• 8a Hong WP, Lim HN, Park HW, Lee K.-J. Bull. Korean Chem. Soc. 2005; 26: 655
• 8b Hong WP, Lee K.-J. Synthesis 2005; 33
• 8c Hong WP, Lee K.-J. Synthesis 2006; 963
• 8d Song YS, Lee K.-J. J. Heterocycl. Chem. 2006; 43: 1721
• 8e Ji S.-H, Hong WP, Ko SH, Lee K.-J. J. Heterocycl. Chem. 2006; 43: 799
• 8f Lim HN, Ji S.-H, Lee K.-J. Synthesis 2007; 2454
• 8g Song YS, Lee K.-J. Synthesis 2007; 3037
• 8h Lim HN, Song YS, Lee K.-J. Synthesis 2007; 3376
• 8i Jeon KJ, Lee K.-J. J. Heterocycl. Chem. 2008; 45: 615
• 8j Park SP, Song YS, Lee K.-J. Tetrahedron 2009; 65: 4703
• 8k Han E.-G, Kim HJ, Lee K.-J. Tetrahedron 2009; 65: 9616
• 8l Park SP, Ahn S.-H, Lee K.-J. Tetrahedron 2010; 66: 3490
• 8m Ahn S.-H, Jang SS, Han E.-G, Lee K.-J. Synthesis 2011; 377
• 9a Park JB, Ko SH, Hong WP, Lee K.-J. Bull. Korean Chem. Soc. 2004; 25: 927
• 9b Park JB, Ko SH, Kim BG, Hong WP, Lee K.-J. Bull. Korean Chem. Soc. 2004; 25: 27
• 10 Mason PH, Emslie ND. Tetrahedron 1994; 50: 12001
• 11 Lee KY, Gowrisankar S, Kim JN. Bull. Korean Chem. Soc. 2004; 25: 413
• 12 Palladium is very sensitive to steric effects and generally forms less hindered complexes where possible. Thus, coordination of the palladium(II) intermediate occurs at the face of the dimethoxydihydrofuran anti to the methoxy group.
• 13 The NMR numbering systems used for compounds 10 and 14 are shown in Schemes 2 and 3.

Hartree–Fock 3-21G calculation data using Spartan are as follows:
• 14a cis-10a: dihedral angle = 76.80°, J _1,2 = 2.34 Hz; trans-10a: dihedral angle = 50.21°, J _1,2 = 6.84 Hz; cis-14a: dihedral angle = 38.19°, J _1,2 = 8.70 Hz; trans-14a: dihedral angle = 154.14°, J _1,2 = 7.26 Hz.
• 14b Observed J values: 10a: J _1,2 = 9.4 Hz; 14a: J _1,2 = 7.4 Hz.
• 15a Zhou N, Wang L, Thompson DW, Zhao Y. Org. Lett. 2008; 10: 3001
• 15b Akgün E, Glinski MB, Dhawan KL, Durst T. J. Org. Chem. 1981; 46: 2730
• 15c Dong L.-C, Crowe M, West J, Ammann JR. Tetrahedron Lett. 2004; 45: 2731