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. 2007 Jan 19;72(2):538-49.
doi: 10.1021/jo0619783.

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

Mickea D Rose  1 , Michael P Cassidy, Paitoon Rashatasakhon, Albert Padwa
Affiliations

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

Mickea D Rose et al. J Org Chem. .

Abstract

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.

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Figures

Figure 1
Figure 1
Representative Erythrinan and Homoerythrinan Alkaloids
Scheme 1
Scheme 1
Pictet-Spengler Cyclization
Scheme 2
Scheme 2
NBS Promoted Cyclization Reaction
Scheme 3
Scheme 3
Retrosynthetic Analysis Toward Selaginoidine (10)
Scheme 4
Scheme 4
Mechanism of the Acid Promoted Cyclization
Scheme 5
Scheme 5
Dimer Formation Using an Unsubstitued Furan
Scheme 6
Scheme 6
Seven-Membered Ring Skeleton
Scheme 7
Scheme 7
Use of Iminophosphoranes for the Synthesis of Tetrahydroindolinones
Scheme 8
Scheme 8
Acid-Promoted Cyclization of Various Heteroaromatic Systems
Scheme 9
Scheme 9
Cyclization of Indolyl Substituted Systems
Scheme 10
Scheme 10
Pummerer/Mannich Cyclizations
Scheme 11
Scheme 11
A Failed Pummerer/N-Acyliminium ion Cascade
Scheme 12
Scheme 12
Synthesis of a Bromo Substituted Tetrahydroindolinone
Scheme 13
Scheme 13
Tetrahydroindolinone Containing a 1,3-Dioxolanyl Group
Scheme 14
Scheme 14
Successful Cyclization Leading to the Homoerythrina Skeleton
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