Brief Communication | Published:

Domino access to highly substituted chromans and isochromans from carbohydrates

Nature Chemical Biology volume 6, pages 199201 (2010) | Download Citation

Abstract

Herein we describe the synthesis of highly substituted chromans and isochromans using carbohydrates as starting materials. Our approach makes use of a Pd-catalyzed domino reaction consisting of oxidative addition, followed by two carbopalladation steps and completed by a cyclization to annelate the benzene moiety. The versatility of this route has been demonstrated by a small library of highly substituted chromans and isochromans.

  • Compound C17H20O4

    (7aR,11aS,11bR)-10,10-Dimethyl-2,3,4,5,7a,8,11a,11b-octahydrocyclopenta[g][1,3]dioxino[5,4-b]furo[2,3,4-de]chromene

  • Compound C23H24O4

    (7aR,11aS,11bR)-10,10-Dimethyl-6-phenyl-2,3,4,5,7a,8,11a,11b-octahydrocyclopenta[g][1,3]dioxino[5,4-b]furo[2,3,4-de]chromene

  • Compound C18H22O4

    (7aR,11aS,11bR)-6,10,10-Trimethyl-2,3,4,5,7a,8,11a,11b-octahydrocyclopenta[g][1,3]dioxino[5,4-b]furo[2,3,4-de]chromene

  • Compound C18H19D3O4

    (7aR,11aS,11bR)-6-Trideuteromethyl-10,10-dimethyl-2,3,4,5,7a,8,11a,11b-octahydrocyclopenta[g][1,3]dioxino[5,4-b]furo[2,3,4-de]chromene

  • Compound C27H28O8

    (7aR,11aS,11bR)-Dimethyl 10,10-dimethyl-6-phenyl-3,5,7a,8,11a,11b-hexahydrocyclopenta[g][1,3]dioxino[5,4-b]furo[2,3,4-de]chromene-4,4(2H)-dicarboxylate

  • Compound C16H18O5

    (7aR,11aS,11bR)-10,10-Dimethyl-3,5,7a,8,11a,11b-hexahydro-2H-[1,3]dioxino[5,4-b]difuro[2,3,4-de:3',4'-g]chromene

  • Compound C20H28O4Si

    ((7aR,11aS,11bR)-10,10-Dimethyl-2,3,4,5,7a,8,11a,11b-octahydrocyclopenta[g][1,3]dioxino[5,4-b]furo[2,3,4-de]chromen-6-yl)trimethylsilane

  • Compound C20H20O4

    (2aS,3S,4S)-3-(Benzyloxy)-4-methyl-1,2a,3,4,7,9-hexahydrodifuro[2,3,4-de:3',4'-g]chromene

  • Compound C27H26O3

    (2aS,3S,4S)-3-(Benzyloxy)-4-methyl-6-phenyl-2a,3,4,7,8,9-hexahydro-1H-cyclopenta[g]furo[2,3,4-de]chromene

  • Compound C31H30O7

    (2aS,3S,4S)-Dimethyl 3-(benzyloxy)-4-methyl-6-phenyl-3,4,7,9-tetrahydro-1H-cyclopenta[g]furo[2,3,4-de]chromene-8,8(2aH)-dicarboxylate

  • Compound C21H20O4

    (7aR,11aR,11bR)-10-Phenyl-2,3,4,5,7a,8,11a,11b-octahydrocyclopenta[g][1,3]dioxino[5,4-b]furo[2,3,4-de]chromene

  • Compound C27H24O4

    (7aR,11aR,11bR)-6,10-Diphenyl-2,3,4,5,7a,8,11a,11b-octahydrocyclopenta[g][1,3]dioxino[5,4-b]furo[2,3,4-de]chromene

  • Compound C13H14O3

    (2aS,3R)-2a,3,4,7,8,9-Hexahydro-1H-cyclopenta[g]furo[2,3,4-de]chromen-3-ol

  • Compound C26H24O3

    (2aS,3R)-3-(Benzyloxy)-6-phenyl-2a,3,4,7,8,9-hexahydro-1H-cyclopenta[g]furo[2,3,4-de]chromene

  • Compound C17H21BrO4

    2-Bromo-4,6-O-isopropylidene-3-(1',6'-octadiyne-8'-yl)-D-glucal

  • Compound C23H25BrO4

    2-Bromo-4,6-O-isopropylidene-3-(1'-phenyl-1',6'-octadiyne-8'-yl)-D-glucal

  • Compound C18H23BrO4

    2-Bromo-4,6-O-isopropylidene-3-(2',7'-nonadiyne-1'-yl)-D-glucal

  • Compound C18H20D3BrO4

    2-Bromo-4,6-O-isopropylidene-3-(9',9',9'-trideutero-2',7'-nonadiyne-1'-yl)-D-glucal

  • Compound C27H29BrO8

    2-Bromo-4,6-O-isopropylidene-3-(4',4'-di(methoxycarbonyl)-1'-phenyl-1',6'-octadiyne-8'-yl)-D-glucal

  • Compound C16H19BrO5

    2-Bromo-4,6-O-isopropylidene-3-(4'-oxa-1',6'-octadiyne-8'-yl)-D-glucal

  • Compound C16H20BrNO4

    2-Bromo-4,6-O-isopropylidene-3-(6'-cyano-2'-hexyne-1'-yl)-D-glucal

  • Compound C20H29BrO4Si

    2-Bromo-4,6-O-isopropylidene-3-(1'-trimethylsilyl-1',6'-hexadiyne-8'-yl)-D-glucal

  • Compound C20H21BrO4

    2-Bromo-4-O-benzyl-3-(5'-oxa-2',7'-octadiyne-yl)-L-rhamnal

  • Compound C27H27BrO3

    2-Bromo-4-O-benzyl-3-(1'-phenyl-1',6'-octadiyne-8'-yl)-L-rhamnal

  • Compound C31H31BrO7

    2-Bromo-4-O-benzyl-3-(4',4'-di(methoxycarbonyl)-1'-phenyl-1',6'-octadiyne-8'-yl)-L-rhamnal

  • Compound C21H21BrO4

    2-Bromo-4,6-O-benzylidene-3-(1',6'-octadiyne-8'-yl)-D-galactal

  • Compound C27H25BrO4

    2-Bromo-4,6-O-benzylidene-3-(1'-phenyl-1',6'-octadiyne-8'-yl)-D-galactal

  • Compound C13H15BrO3

    2-Bromo-3-(2',7'-octadiyne)-D-arabinal

  • Compound C26H25BrO3

    4-O-Benzyl-2-bromo-3-(8'-phenyl-2',7'-octadiyne)-D-arabinal

  • Compound C18H20O6

    ((2aS,4R,5R)-5-Acetoxy-2a,4,5,7,8,9-hexahydro-1H-cyclopenta[g]furo[4,3,2-ij]isochromen-4-yl)methyl acetate

  • Compound C24H24O6

    ((2aS,4R,5R)-5-Acetoxy-6-phenyl-2a,4,5,7,8,9-hexahydro-1H-cyclopenta[g]furo[4,3,2-ij]isochromen-4-yl)methyl acetate

  • Compound C24H24O6

    ((2aS,4R,5S)-5-Acetoxy-6-phenyl-2a,4,5,7,8,9-hexahydro-1H-cyclopenta[g]furo[4,3,2-ij]isochromen-4-yl)methyl acetate

  • Compound C18H21BrO6

    4,6-Di-O-acetyl-2-bromo-1-(S)-(1',6'-octadiyne-8'-yl)-D-galactal

  • Compound C24H25BrO6

    4,6-Di-O-acetyl-2-bromo-1-(S)-(1'-phenyl-1',6'-octadiyne-8'-yl)-D-galactal

  • Compound C24H25BrO6

    4,6-Di-O-acetyl-2-bromo-1-(S)-(1'-phenyl-1',6'-octadiyne-8'-yl)-D-glucal

  • Compound C14H16O4

    (2aR,3S,4R)-4-(Hydroxymethyl)-2a,3,4,7,8,9-hexahydro-1H-cyclopenta[g]furo[2,3,4-de]chromen-3-ol

  • Compound C20H20O4

    (2aR,3S,4R)-4-(Hydroxymethyl)-6-phenyl-2a,3,4,7,8,9-hexahydro-1H-cyclopenta[g]furo[2,3,4-de]chromen-3-ol

  • Compound C15H18O4

    (2aR,3S,4R)-4-(Hydroxymethyl)-6-methyl-2a,3,4,7,8,9-hexahydro-1H-cyclopenta[g]furo[2,3,4-de]chromen-3-ol

  • Compound C24H24O8

    (2aR,3S,4R)-Dimethyl 3-hydroxy-4-(hydroxymethyl)-6-phenyl-3,4,7,9-tetrahydro-1H-cyclopenta[g]furo[2,3,4-de]chromene-8,8(2aH)-dicarboxylate

  • Compound C13H14O5

    (2aR,3S,4R)-4-(Hydroxymethyl)-1,2a,3,4,7,9-hexahydrodifuro[2,3,4-de:3',4'-g]chromen-3-ol

  • Compound C20H20O3

    (2aS,3S,4S)-4-Methyl-6-phenyl-2a,3,4,7,8,9-hexahydro-1H-cyclopenta[g]furo[2,3,4-de]chromen-3-ol

  • Compound C24H24O7

    (2aS,3S,4S)-Dimethyl 3-hydroxy-4-methyl-6-phenyl-3,4,7,9-tetrahydro-1H-cyclopenta[g]furo[2,3,4-de]chromene-8,8(2aH)-dicarboxylate

  • Compound C14H16O4

    (2aR,3R,4R)-4-(Hydroxymethyl)-2a,3,4,7,8,9-hexahydro-1H-cyclopenta[g]furo[2,3,4-de]chromen-3-ol

  • Compound C20H20O4

    (2aR,3R,4R)-4-(Hydroxymethyl)-6-phenyl-2a,3,4,7,8,9-hexahydro-1H-cyclopenta[g]furo[2,3,4-de]chromen-3-ol

  • Compound C19H18O3

    (2aS,3R)-6-Phenyl-2a,3,4,7,8,9-hexahydro-1H-cyclopenta[g]furo[2,3,4-de]chromen-3-ol

  • Compound C9H13BrO4

    2-Bromo-4,6-O-isopropylidene-D-glucal

  • Compound C6H9BrO4

    2-Bromo-D-glucal

  • Compound C11H15BrO5

    2-Bromo-3-O-acetyl-4,6-O-isopropylidene-D-glucal

  • Compound C14H21BrO6

    2-Bromo-3-O-(tert-butoxycarbonyl)-4,6-O-isopropylidene-D-glucal

  • Compound C6H9BrO3

    2-Bromo-L-rhamnal

  • Compound C10H13BrO5

    2-Bromo-3,4-di-O-acetyl-L-rhamnal

  • Compound C13H15BrO3

    2-Bromo-4-O-benzyl-L-rhamnal

  • Compound C12H15BrO7

    2-Bromo-3,4,6-tri-O-acetyl-D-galactal

  • Compound C12H16O7

    3,4,6-Tri-O-acetyl-D-galactal

  • Compound C6H9BrO4

    2-Bromo-D-galactal

  • Compound C13H13BrO4

    2-Bromo-4,6-O-benzylidene-D-galactal

  • Compound C9H13BrO4

    2-Bromo-3,4-isopropylidene-D-galactal

  • Compound C9H11BrO5

    2-Bromo-3,4-di-O-acetyl-D-arabinal

  • Compound C9H12O5

    3,4-Di-O-acetyl-D-arabinal

  • Compound C5H7BrO3

    2-Bromo-D-arabinal

  • Compound C14H13I

    1-Iodo-8-phenyl-2,7-octadiyne

  • Compound C14H14O

    1-Hydroxy-8-phenyl-2,7-octadiyne

  • Compound C14H24OSi

    1-(tert-Butyldimethylsiloxy)-2,7-octadiyne

  • Compound C8H10O

    1-Hydroxy-2,7-octadiyne

  • Compound C15H26OSi

    1-(tert-Butyldimethylsiloxy)-2,7-nonadiyne

  • Compound C9H12O

    1-Hydroxy-2,7-nonadiyne

  • Compound C9H11I

    1-Iodo-2,7-nonadiyne

  • Compound C9H8D3I

    9,9,9-Trideutero-1-iodo-2,7-nonadiyne

  • Compound C18H17BrO4

    1-Bromo-4,4-di(methoxycarbonyl)-8-phenyl-2,7-octadiyne

  • Compound C14H14O4

    Dimethyl-2-(3-phenylprop-2-ynyl)-malonate

  • Compound C4H4Br2

    1,4-Dibromobutyne

  • Compound C7H8IN

    6-Cyano-1-iodo-2-hexyne

  • Compound C7H9NO

    6-Cyano-1-hydroxy-2-hexyne

  • Compound C8H9I

    1-Iodo-2,7-octadiyne

  • Compound C7H7IO

    1-Iodo-5-oxa-2,7-octadiyne

  • Compound C18H21BrO6

    4,6-Di-O-acetyl-2-bromo-1-(S)-(1',6'-octadiyne-8'-yl)-D-glucal

  • Compound C12H15BrO7

    3,4,6-Tri-O-acetyl-D-glucal

  • Compound C12H13BrO3

    2-Bromo-4-O-benzyl-D-arabinal

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Acknowledgements

We are grateful to the Deutsche Forschungsgemeinschaft and the Fonds der Chemischen Industrie for financial support (Emmy Noether Fellowship and Liebig Fellowship to D.B.W.). D.C.K. thanks the Studienstiftung des deutschen Volkes for his undergraduate fellowship and the Fonds der Chemischen Industrie for his PhD fellowship. S.C.S. acknowledges the Konrad-Adenauer-Stiftung for her undergraduate fellowship. We thank L.F. Tietze (University of Göttingen) for helpful discussions and generous support of our work.

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  1. Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Göttingen, Göttingen, Germany

    • Markus Leibeling
    • , Dennis C Koester
    • , Martin Pawliczek
    • , Svenia C Schild
    •  & Daniel B Werz

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Contributions

D.B.W. designed the project. M.L., D.C.K., M.P. and S.C.S. performed the experiments. The manuscript was written by D.B.W.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Daniel B Werz.

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DOI

https://doi.org/10.1038/nchembio.302

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