Acid-promoted cyclization reactions of tetrahydroindolinones. Model studies for possible application in a synthesis of selaginoidine

Article abstract of DOI:10.1021/jo0619783

The synthesis of various substituted bicyclic lactams by an acid-induced Pictet-Spengler reaction of tetrahydroindolinones bearing tethered heteroaromatic rings is presented. The outcome of the cyclization depends on the position of the furan tether, tether length, nature of the tethered heteroaromatic ring, and the substituent group present on the 5-position of the tethered heteroaryl group. A one-pot procedure was developed to efficiently prepare tetrahydroindolinones containing tethered furan rings. In a typical example, the reaction of furanyl azide 26 with n-Bu₃P delivered iminophosphorane 27, which was allowed to react with a 1-alkyl-(2-oxocyclohexyl) acetic acid to provide the desired furanyl-substituted tetrahydroindolinone system 29. Treatment of 29 with trifluoroacetic acid afforded the tetracyclic lactam skeleton 30 found in the alkaloid (±)-selaginoidine.

Full text of DOI:10.1021/jo0619783

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Supporting Information
Acid-Promoted Cyclization Reactions of Tetrahydroindolinones. Model
Studies for Possible Application in a Synthesis of Selaginaidine
Mickea Rose, Michael P. Cassidy, Paitoon Rashatasakhon and Albert Padwa*
Department of Chemistry, Emory University, Atlanta, GA 30322
chemap@emory.edu
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13
Supporting Information Available: H and C-NMR spectra for new compounds
lacking elemental analyses. This material is available free of charge via the Internet at
http://pubs.acs.org.
General Experimental Section Paragraph: Melting points are uncorrected. Mass
spectra were determined at an ionizing voltage of 70eV. Unless otherwise noted, all
reactions were performed in flame dried glassware under an atmosphere of dry
nitrogen. Solutions were evaporated under reduced pressure with a rotary evaporator
and the residue was chromatographed on a silica gel column using an ethyl acetate-
hexane mixture as the eluent unless specified otherwise. A CEM Discover Focused™
Microwave system was used and the reaction mixture temperature was measured using
an internal fiber-optic probe.
Table of Contents for Supporting Information:
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S5
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H-NMR spectrum of compound 16
H-NMR spectrum of compound 18
H-NMR spectrum of compound 20
H-NMR spectrum of compound 21
H-NMR spectrum of compound 24
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C-NMR spectrum of compound 25
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H-NMR spectrum of compound 26
H-NMR spectrum of compound 29
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H-NMR spectrum of compound 30
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C-NMR spectrum of compound 31
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H-NMR spectrum of compound 32
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C-NMR spectrum of compound 33
C-NMR spectrum of compound 35
C-NMR spectrum of compound 36
C-NMR spectrum of compound 42
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H-NMR spectrum of oxidized compound 42
H-NMR spectrum of compound 44
H-NMR spectrum of compound 45
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C-NMR spectrum of compound 46
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H-NMR spectrum of compound 47
H-NMR spectrum of compound 48
H-NMR spectrum of compound 49
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C-NMR spectrum of precursor to compound 50
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H-NMR spectrum of compound 50
H-NMR spectrum of compound 51
H-NMR spectrum of precursor to compound 53
H-NMR spectrum of compound 53
H-NMR spectrum of compound 56
H-NMR spectrum of compound 57
H-NMR spectrum of compound 58
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C-NMR spectrum of compound 60
C-NMR spectrum of compound 61
C-NMR spectrum of compound 64
C-NMR spectrum of compound 65
C-NMR spectrum of ketal of compound 65

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