Asymmetric Synthesis of Functionalized Chromans via a One-Pot Organocatalytic Domino Michael-Hemiacetalization or -Lactonization and Dehydration Sequence

Abstract

Starting from 2-(nitrovinyl)phenols and various cyclic dicarbonyl nucleophiles, a one-pot thiourea-catalyzed diastereo- and enantioselective synthesis of polyfunctionalized chroman derivatives via a domino Michael-hemiacetalization and dehydration sequence as well as via a domino Michael-lactonization reaction is reported. Cyclopenta[b]chromenes, tricyclic spirochromans, and tetrahydro-1H-xanthenes bearing a variety of functional groups can be synthesized in this way in good to excellent yields (56-91%) and with very good diastereo- (88-99% de) and enantioselectivities (83-99% ee).

Key words

organocatalysis - domino reaction - thiourea - one-pot reaction - chromans

References

• For reviews on organocatalytic domino reactions, see:
• 1a Grossmann A. Enders D. Angew. Chem. Int. Ed.  2012,  51:  314 
• 1b Pellissier H. Adv. Synth. Catal.  2012,  354:  in press 
• 1c Enders D. Jeanty M. Grondal C. Nat. Chem.  2010,  2:  167 
• 1d Alba A.-N. Companyo X. Viciano M. Rios R. Curr. Org. Chem.  2009,  13:  1432 
• 1e Yu X. Wang W. Org. Biomol. Chem.  2008,  6:  2037 
• 1f Enders D. Grondal C. Hüttl MRM. Angew. Chem. Int. Ed.  2007,  46:  1570 
• For recent examples of organocatalytic asymmetric syntheses of chromans, see:
• 2a Enders D. Yang X. Wang C. Raabe G. Runsink J. Chem. Asian J.  2011,  6:  2255 
• 2b Enders D. Urbanietz G. Raabe G. Synthesis  2011,  1905 
• 2c Hong BC. Kotame P. Liao J.-H. Org. Biomol. Chem.  2011,  9:  382 
• 2d Ren Q. Siau W.-Y. Du Z. Zhang K. Wang J. Chem. Eur. J.  2011,  17:  778 
• 2e Hong BC. Kotame P. Lee G.-H. Org. Lett.  2011,  13:  5758 
• 2f Lee Y. Seo SW. Kim S.-G. Adv. Synth. Catal.  2011,  353:  2671 
• 2g Zhang X. Zhang S. Wang W. Angew. Chem. Int. Ed.  2010,  49:  1481 
• 2h Alemán J. Nuńez A. Marzo L. Marcos V. Alvarado C. Ruano JLG. Eur. J. Org. Chem.  2010,  16:  9453 
• 2i Lu D. Li Y. Gong Y. J. Org. Chem.  2010,  75:  6900 
• 2j Ramachary DB. Sakthidevi R. Org. Biomol. Chem.  2010,  8:  4259 
• 2k Manzano R. Andrés JM. Muruzábal MD. Pedrosa R. Adv. Synth. Catal.  2010,  352:  3364 
• 2l Enders D. Wang C. Yang X. Raabe G. Adv. Synth. Catal.  2010,  352:  2869 
• 3a Shen HC. Tetrahedron  2009,  65:  3931 
• 3b Ferreira SB. da Silva Fde C. Pinto AC. Gonzaga DTG. Ferreira VF. J. Heterocycl. Chem.  2009,  46:  1080 
• 3c Deiters A. Martin SF. Chem. Rev.  2004,  104:  2199 
• 3d Nicolaou KC. Pfefferkorn JA. Roecker AJ. Cao G.-Q. Barluenga S. Mitchell HJ. J. Am. Chem. Soc.  2000,  122:  9939 
• 3e Keay BA. In Comprehensive Heterocyclic Chemistry II   Vol. 2:  Pergamon; Oxford: 1996. 
• 3f Schweizer EE. Meeder-Nycz O. In Chromenes, Chromans, Chromones   Ellis GP. Wiley-Interscience; New York: 1977. 
• For examples of organocatalytic asymmetric Michael-hemiacetalization reactions, see:
• 4a Wang Y. Zhu S. Ma D. Org. Lett.  2011,  13:  1602 
• 4b Ishikawa H. Sawano S. Yasui Y. Shibata Y. Hayashi Y. Angew. Chem. Int. Ed.  2011,  50:  3774 
• 4c Belot S. Quintard A. Alexakis A. Krause N. Adv. Synth. Catal.  2010,  352:  667 
• 4d Maltsev OV. Kucherenko AS. Zlotin SG. Chimishkyan AL. Tetrahedron: Asymmetry  2010,  21:  2659 
• 4e Yao W. Wu Y. Wang G. Zhang Y. Cheng M. Angew. Chem. Int. Ed.  2009,  48:  9713 
• 4f Chandrasekhar S. Mallikarjun K. Pavankumarreddy G. Rao KV. Jagadeesh B. Chem. Commun.  2009,  4985 
• 4g Wang J. Yu F. Zhang X. Ma D. Org. Lett.  2008,  10:  2561 
• 4h Xie JW. Uang X. Fan LP. Xu DC. Li XS. Su H. Wen YH. Adv. Synth. Catal.  2008,  350:  1474 
• 5 The (E)-2-(2-nitrovinyl)phenols were prepared from the corresponding substituted salicylaldehydes and nitromethane in AcOH/NH₄OAc according to the literature procedure: Zhang B.-L. Wang F.-D. Yue J.-M. Synlett  2006,  567 
• 6 Okino T. Yasutaka Hoashi Y. Takemoto Y. J. Am. Chem. Soc.  2003,  125:  12672 
• 7 Vakulya B. Varga S. Csampai A. Soos T. Org. Lett.  2005,  7:  1967 

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CCDC 859260 contains the supplementary crystallographic data of 5d for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.