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An efficient and expeditious synthesis of novel 2,2-dialkyl-2,3-dihydrobenzofurans from phenols and 2,2-dialkylacetaldehydes

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Abstract

Reactions of 2,2-dialkylaldehydes with electron-rich 2-naphthols and para-substituted phenols in presence of catalytic amount of \(p\)-TSA under closed vessel solvent-free microwave irradiation conditions resulted in formation of corresponding 2,2-dialkyl-1,2-dihydronaphtho[2,1-\(b\)]furans and 2,2-dialkyl-2,3-dihydrobenzofurans, respectively, in good to excellent yields. The effect of stoichiometry, temperature, and catalyst in reaction progress was systematically investigated. 14-Alkyl-\(14H\)-dibenzo[\(a,j\)]xanthenes was obtained as minor products when 2-naphthol and 6-bromo-2-naphthols were used as starting phenols. Simple phenols gave a lower yield of the 2,2-dialkyl-2,3-dihydrobenzofurans products than their electron-rich naphthalene counterparts. Also, xanthene-type products were not detected in case of simple phenols by GC–MS or column chromatography.

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References

  1. Varanda EA, Raddi MSG, Dias FLP, Araujo MCS, Gibran SCA, Takahashi CS, Vilegas W (1997) Mutagenic and cytotoxic activity of an isocoumarin (paepalantine) isolated from Paepalanthus vellozioide. Teratogen Carcinog Mutagen 17:85–95. doi: 10.1002/(SICI)1520-6866(1997)17:2<85:AID-TCM4>3.0.CO;2-A

  2. Apers S, Vlietinck A, Pieters L (2003) Lignans and neolignans as lead compounds. Phytochem Rev 2:201–217. doi:10.1023/B:PHYT.0000045497.90158.d2

    Article  CAS  Google Scholar 

  3. Hussein AA, Barberena I, Capson TL, Kursar TA, Coley PD, Solis PN, Gupta MP (2004) New cytotoxic naphthopyrane derivatives from Adenaria floribunda. J Nat Prod 67:451–453. doi:10.1021/np030223d

    Article  PubMed  CAS  Google Scholar 

  4. Gravot A, Larbat R, Hehn A, Lievre K, Gontier E, Goergen J, Bourgaud F (2004) Cinnamic acid 4-hydroxylase mechanism-based inactivation by psoralen derivatives: cloning and characterization of a C4H from a psoralen producing plant—Ruta graveolens —exhibiting low sensitivity to psoralen inactivation. Arch Biochem Biophys 422:71–80. doi:10.1016/j.abb.2003.12.013

    Google Scholar 

  5. Marumoto S, Miyazawa M (2011) Microbial reduction of coumarin, psoralen, and xanthyletin by Glomerella cingulata. Tetrahedron 67:495–500. doi:10.1016/j.tet.2010.10.089

    Article  CAS  Google Scholar 

  6. Martini JC, Franke NW, Singerman GM (1970) New preparation of coumarins. J Org Chem 35:2904–2907. doi:10.1021/jo00834a011

    Article  CAS  Google Scholar 

  7. Casnati G, Pochini A, Terenghi MG, Ungaro R (1983) O-Quinonemethide intermediates and their role in coordinated reactions of magnesium phenoxides with \(\alpha \)-branched aliphatic aldehydes. J Org Chem 48:3783–3787. doi:10.1021/jo00169a036

    Google Scholar 

  8. Bartz QR, Miller RF, Adams R (1935) The introduction of isobutyl groups into phenols, cresols and homologous compounds. J Am Chem Soc 57:371–376. doi:10.1021/ja01305a044

    Article  CAS  Google Scholar 

  9. Bagnell L, Cablewski T, Strauss CR, Trainor RW (1996) Reactions of allyl phenyl ether in high-temperature water with conventional and microwave heating. J Org Chem 61:7355–7359. doi:10.1021/jo961095j

    Article  PubMed  CAS  Google Scholar 

  10. Grant VH, Liu B (2005) Iridium(III)-catalyzed tandem Claisen rearrangement-intramolecular hydroaryloxylation of aryl allyl ethers to form dihydrobenzofurans. Tetrahedron Lett 46:1237–1239. doi:10.1016/j.tetlet.2005.01.006

    Article  CAS  Google Scholar 

  11. Arduini A, Pochini A, Ungaro R (1984) Selective synthesis of 2-alkenylphenols and 2,2-dialkyl-2,3-dihydrobenzofurans from 2-hydroxybenzyl alcohols. Synthesis 1984:950–953. doi:10.1055/s-1984-31033

    Article  Google Scholar 

  12. Choudhury PK, Almena J, Foubelo F, Yus M (1997) New homologation of 2-hydroxy and 2-mercapto benzylic alcohols. Tetrahedron 53:17373–17382. doi:10.1016/S0040-4020(97)10161-2

    Article  CAS  Google Scholar 

  13. Dohi T, Hu Y, Kamitanaka T, Washimi N, Kita Y (2011) [3+2] Coupling of quinone monoacetals by combined acid-hydrogen bond donor. Org Lett 13:4814–4817. doi:10.1021/ol201886r

    Article  PubMed  CAS  Google Scholar 

  14. Dohi T, Hu Y, Kamitanaka T, Kita Y (2012) Controlled coupling of quinone monoacetals using reusable polystyrene-anchored specific proton catalyst. Tetrahedron 68:8424–8530. doi:10.1016/j.tet.2012.07.089

    Article  CAS  Google Scholar 

  15. Palucki M, Wolfe JP, Buchwald SL (1996) Synthesis of oxygen heterocycles via a palladium-catalyzed C–O bond-forming reaction. J Am Chem Soc 118:10333–10334. doi:10.1021/ja962408v

    Article  CAS  Google Scholar 

  16. Mann G, Incarvito C, Rheingold AL, Hartwig JF (1999) Palladium-catalyzed C–O coupling involving unactivated aryl halides. sterically induced reductive elimination to form the C–O bond in diaryl ethers. J Am Chem Soc 121:3224–3225. doi:10.1021/ja984321a

    Article  CAS  Google Scholar 

  17. Kataoka N, Shelby Q, Stambuli JP, Hartwig JF (2002) Air stable, sterically hindered ferrocenyl dialkylphosphines for palladium-catalyzed C–C, C–N, and C–O bond-forming cross-couplings. J Org Chem 67:5553–5566. doi:10.1021/jo025732j

    Google Scholar 

  18. Niu J, Guo P, Kang J, Li Z, Xu J, Hu S (2009) Copper(I)-catalyzed aryl bromides to form intermolecular and intramolecular carbon–oxygen bonds. J Org Chem 74:5075–5078. doi:10.1021/jo900600m

    Article  PubMed  CAS  Google Scholar 

  19. Wang X, Lu Y, Dai H-X, Yu J-Q (2010) Pd(II)-catalyzed hydroxyl-directed C–H activation/C–O cyclization: expedient construction of dihydrobenzofurans. J Am Chem Soc 132:12203–12205. doi:10.1021/ja105366u

    Article  PubMed  CAS  Google Scholar 

  20. Lafrance M, Gorelsky SI, Fagnou K (2007) High-yielding palladium-catalyzed intramolecular alkane arylation: reaction development and mechanistic studies. J Am Chem Soc 129:14570–14571. doi:10.1021/ja076588s

    Article  PubMed  CAS  Google Scholar 

  21. He Z, Yudin AK (2006) Palladium-catalyzed oxidative activation of arylcyclopropanes. Org Lett 8:5829–5832. doi:10.1021/ol062476e

    Article  PubMed  CAS  Google Scholar 

  22. Huang P-JJ, Stanley Cameron T (2009) Novel synthesis of 2,2-dialkyl-3-dialkylamino-2,3-dihydro-1H-naphtho[2,1-b] pyrans. Tetrahedron Lett 50:51–54. doi:10.1016/j.tetlet.2008.10.083

  23. Jha A, Paul NK, Trikha S, Cameron TS (2006) Novel synthesis of 2-naphthol Mannich bases and their NMR behaviour. Can J Chem 84:843–853. doi:10.1139/v06-081

    Article  CAS  Google Scholar 

  24. Paul NK, Dietrich L, Jha A (2007) Convenient synthesis of 1-arylmethyl-2-naphthols. Synth Commun 37:877–888. doi:10.1080/00397910601163547

    Article  CAS  Google Scholar 

  25. Huang P-JJ, Youssef D, Cameron TS, Jha A (2008) Microwave-assisted synthesis of novel 2-naphthol bis-Mannich bases. Arkivoc 16:165–177

    Article  Google Scholar 

  26. Mukherjee C, MacLean ED, Cameron TS, Jha A (2010) Enzyme-assisted kinetic resolution of novel 2-naphthol Mannich bases. J Mol Catal B Enzym 62:46–53. doi:10.1016/j.molcatb.2009.09.001

    Google Scholar 

  27. Vaughan D, Jha A (2009) Convenient synthesis of novel 2,2-dialkyl-1,2-dihydronaphtho[2,1-b]furans. Tetrahedron Lett 50:5709–5712. doi:10.1016/j.tetlet.2009.07.087

    Article  CAS  Google Scholar 

  28. Vaughan D, Naidu AB, Jha A (2012) One-pot annulation of 2-naphthol analogs to heterocycles. Curr Org Synth 9:613–649. doi:10.2174/157017912803251747

    Article  CAS  Google Scholar 

  29. Kumar R, Nandi GC, Verma RK, Singh MS (2010) A facile approach for the synthesis of 14-aryl- or alkyl-14H-dibenzo[a,j] xanthenes under solvent-free condition. Tetrahedron Lett 51:442–445. doi:10.1016/j.tetlet.2009.11.064

    Google Scholar 

  30. Urinda S, Kundu D, Majee A, Hajra A (2009) Indium triflate- catalyzed one-pot synthesis of 14-alkyl or aryl-14H-dibenzo[a,j] xanthenes in water. Heteroatom Chem 20:232–234. doi:10.1002/hc.20539

    Google Scholar 

  31. Kobayashi S, Sugiura M, Kitagawa H, Lam WWL (2002) Rare-earth metal triflates in organic synthesis. Chem Rev 102:2227–2302. doi:10.1021/cr010289i

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors sincerely thank Natural Sciences and Engineering Research Council of Canada (NSERC) and Acadia University for research funding and salary support. Dr. Matthew Lukeman is thanked for providing access to the GC/MS instrument in his laboratory.

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  1. Department of Chemistry, Acadia University, Wolfville, NS, B4P 2R6, Canada

    Amitabh Jha, Ting-Yi Chou & Doug Vaughan

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  1. Amitabh Jha
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  2. Ting-Yi Chou
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  3. Doug Vaughan
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Correspondence to Amitabh Jha.

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Dedicated to Professor Virinder Singh Parmar, Department of Chemistry, University of Delhi on his 65th birthday.

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Jha, A., Chou, TY. & Vaughan, D. An efficient and expeditious synthesis of novel 2,2-dialkyl-2,3-dihydrobenzofurans from phenols and 2,2-dialkylacetaldehydes. Mol Divers 17, 261–270 (2013). https://doi.org/10.1007/s11030-013-9429-y

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