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. 2012:8:829-40.
doi: 10.3762/bjoc.8.93. Epub 2012 Jun 6.

An intramolecular inverse electron demand Diels-Alder approach to annulated α-carbolines

Zhiyuan Ma  1 , Feng Ni, Grace H C Woo, Sie-Mun Lo, Philip M Roveto, Scott E Schaus, John K Snyder
Affiliations

An intramolecular inverse electron demand Diels-Alder approach to annulated α-carbolines

Zhiyuan Ma et al. Beilstein J Org Chem. 2012.

Abstract

Intramolecular inverse electron demand cycloadditions of isatin-derived 1,2,4-triazines with acetylenic dienophiles tethered by amidations or transesterifications proceed in excellent yields to produce lactam- or lactone-fused α-carbolines. Beginning with various isatins and alkynyl dienophiles, a pilot-scale library of eighty-eight α-carbolines was prepared by using this robust methodology for biological evaluation.

Keywords: 1,2,4-triazine; chemical diversity; inverse electron demand Diels–Alder; isatin; pyrido[2,3-b]indole; α-carboline.

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Figures

Figure 1
Figure 1
Natural products with α-carboline subunits.
Scheme 1
Scheme 1
Retrosynthetic inverse electron Diels–Alder approach to α-carbolines.
Scheme 2
Scheme 2
Condensation of isatins with ethyl oxaloamidrazonate to form triazines.
Scheme 3
Scheme 3
Amidation of triazine ester 8a.
Scheme 4
Scheme 4
Microwave-promoted IEDDA reaction of isatin derived triazines.
Scheme 5
Scheme 5
One-pot amidation/cycloaddition of triazine ester 8a.
Scheme 6
Scheme 6
Amidation/cycloaddition forming α-carbolines 14.
Scheme 7
Scheme 7
Intramolecular hydrogen bonding prevents IEDDA cycloaddition of 14b.
Scheme 8
Scheme 8
Preparation of unprotected triazine 15, and its lack of reactivity in cycloadditions.
Scheme 9
Scheme 9
Transesterification and subsequent cycloaddition of 17a.
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