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. 2011 Sep 2;13(17):4732-5.
doi: 10.1021/ol202024a. Epub 2011 Aug 9.

Multicomponent macrocyclization reactions (MCMRs) employing highly reactive acyl ketene and nitrile oxide intermediates

John M Knapp  1 , James C Fettinger, Mark J Kurth
Affiliations

Multicomponent macrocyclization reactions (MCMRs) employing highly reactive acyl ketene and nitrile oxide intermediates

John M Knapp et al. Org Lett. .

Abstract

An efficient synthesis of spiro-fused macrolactams by a multicomponent macrocyclization reaction (MCMR) is reported. The use of highly reactive, transient intermediates in this MCMR permits short reaction times, even at high dilution. The methods employed for this MCMR were first developed as a four-component strategy for the synthesis of β-ketoamide isoxazolines and a new macrocyclization reaction is reported.

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Figures

Figure 1
Figure 1
Crystal structures of (a) 3CR 20 and (b) MCMR 30.
Scheme 1
Scheme 1
Multicomponent macrocyclization plan
Scheme 2
Scheme 2
β-Ketoamide-based 4CRs
Scheme 3
Scheme 3
Beta-ketoamide 3CRs
Scheme 4
Scheme 4
Synthesis of macrocycle precursors 24a–c
Scheme 5
Scheme 5
12-Membered macrocycle-forming reactions
Scheme 6
Scheme 6
Four related MCMRs
Scheme 7
Scheme 7
Preposed MCMR sequence to a spiro-fused macrocycle.
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