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. 2020 Feb 21;85(4):2846-2853.
doi: 10.1021/acs.joc.9b03402. Epub 2020 Jan 10.

Tricyclic Imidazolidin-4-ones by Witkop Oxidation of Tetrahydro-β-carbolines

Derek A Leas, Yuxiang Dong, Jered C Garrison, Xiaofang Wang, Edward L Ezell, Douglas E Stack  1 , Jonathan L Vennerstrom
Affiliations

Tricyclic Imidazolidin-4-ones by Witkop Oxidation of Tetrahydro-β-carbolines

Derek A Leas et al. J Org Chem. .

Abstract

1-Substituted and 1,1-disubstituted tetrahydro-β-carbolines undergo sodium periodate oxidative ring expansion in the presence of formaldehyde and other aldehydes to form 5,6-dihydro-7H-1,4-methanobenzo[e][1,4]diazonine-2,7(3H)-diones in 30-81% yield. In most cases, the reaction to form this new 6/8/5-tricyclic ring system proceeds with high diastereoselectivity. These benzannulated medium-ring keto imidazolidin-4-ones expand the menu of tetrahydro-β-carboline oxidation products.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1.
Figure 1.
Modeled PES (M062x/aug-cc-pvtz/M062x/cc-pvdz) for the iminol mechanism in the conversion of 2b to 3b.
Scheme 1.
Scheme 1.
Conversion of Tetrahydro-β-carboline 1a to Tricyclic Imidazolidin-4-one 3a via Intramolcular Ring Closure
Scheme 2.
Scheme 2.
Synthesis of Tricyclic Imidazolidin-4-one 3b from Tetrahydro-β-carboline 1b and 1,4-Diazonin-2,7-dione 2b
Scheme 3.
Scheme 3.
Conversion of 2b to Tricyclic Imidazolidin-4-one Oxime Ether 6 via 7-Methoxyimino-1,4-diazonin-2-one 5
Scheme 4.
Scheme 4.
Tetrahydro-β-carboline Substrate Scope
Scheme 5.
Scheme 5.
Further Reaction Scope; Thermal Ellipsoid Plot of 3p
Scheme 6.
Scheme 6.
Aldehyde Scope; Thermal Ellipsoid Plot of 3q
Scheme 7.
Scheme 7.
Reactions of Imidazolidin-4-ones 3a and 3m; Key 13C–1H HMBC (Black Arrow), 15N–1H HMBC (Blue Arrows), and ROESY (Red Arrows) Correlations of 7; Thermal Ellipsoid Plot of 8
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References

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