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. 2008 Jan 30;130(4):1440-52.
doi: 10.1021/ja0773507. Epub 2008 Jan 4.

Metal-catalyzed 1,2-shift of diverse migrating groups in allenyl systems as a new paradigm toward densely functionalized heterocycles

Alexander S Dudnik  1 , Anna W Sromek, Marina Rubina, Joseph T Kim, Alexander V Kel'in, Vladimir Gevorgyan
Affiliations

Metal-catalyzed 1,2-shift of diverse migrating groups in allenyl systems as a new paradigm toward densely functionalized heterocycles

Alexander S Dudnik et al. J Am Chem Soc. .

Abstract

A general, mild, and efficient 1,2-migration/cycloisomerization methodology toward multisubstituted 3-thio-, seleno-, halo-, aryl-, and alkyl-furans and pyrroles, as well as fused heterocycles, valuable building blocks for synthetic chemistry, has been developed. Moreover, regiodivergent conditions have been identified for C-4 bromo- and thio-substituted allenones and alkynones for the assembly of regioisomeric 2-hetero substituted furans selectively. It was demonstrated that, depending on reaction conditions, ambident substrates can be selectively transformed into furan products, as well as undergo selective 6-exo-dig or Nazarov cyclizations. Our mechanistic investigations have revealed that the transformation proceeds via allenylcarbonyl or allenylimine intermediates followed by 1,2-group migration to the allenyl sp carbon during cycloisomerization. It was found that 1,2-migration of chalcogens and halogens predominantly proceeds via formation of irenium intermediates. Analogous intermediate can also be proposed for 1,2-aryl shift. Furthermore, it was shown that the cycloisomerization cascade can be catalyzed by Brønsted acids, albeit less efficiently, and commonly observed reactivity of Lewis acid catalysts cannot be attributed to the eventual formation of proton. Undoubtedly, thermally induced or Lewis acid-catalyzed transformations proceed via intramolecular Michael addition or activation of the enone moiety pathways, whereas certain carbophilic metals trigger carbenoid/oxonium type pathway. However, a facile cycloisomerization in the presence of cationic complexes, as well as observed migratory aptitude in the cycloisomerization of unsymmetrically disubstituted aryl- and alkylallenes, strongly supports electrophilic nature for this transformation. Full mechanistic details, as well as the scope of this transformation, are discussed.

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Figures

Figure 1
Figure 1
Direct Cycloisomerization of Thioallenones 13 into Furans 14.
Scheme 1
Scheme 1
General Cu-Catalyzed Cycloisomerization of Alkynyl Ketones and Imines toward Furans and Pyrroles
Scheme 2
Scheme 2
Introduction of Different Migrating Groups toward Trisubstituted Heterocycles
Scheme 3
Scheme 3
1,2-H Vs 1,2-S Migration during Cycloisomerization
Scheme 4
Scheme 4
Selective 1,2-Sufur Migration during Cycloisomerization of 12a
Scheme 5
Scheme 5
Competitive 6-exo-dig Cyclization of 12g in the Absence of the Base
Scheme 6
Scheme 6
Nazarov Cyclization of Tetrasubstituted Phenyl-allenylketone 25d
Scheme 7
Scheme 7
Direct Observation of Selenoallenic Intermediate 19b
Scheme 8
Scheme 8
Proposed Irenium Intermediates in the 1,2-Chalcogen Migration/Cycloisomerization Cascade
Scheme 9
Scheme 9
Proposed Halirenium Intermediates in the 1,2-Halogen Migration/Cycloisomerization Cascade
Scheme 10
Scheme 10
Deuterium Labeling Study of Bromoallenone 4-d-20m
Scheme 11
Scheme 11
Proposed Cationic Intermediates in the 1,2-Alkyl/Aryl Migration/Cycloisomerization Cascade Triggered by Lewis Acid Catalysts
Scheme 12
Scheme 12
Proposed Intermediates in the Transition Metal-catalyzed 1,2-Alkyl/Aryl Migration/Cycloisomerization Cascade
Scheme 13
Scheme 13
Generalized Mechanism for the Metal-Catalyzed Synthesis of Furans via Allene Intermediate Involving 1,2-Migration of Different Migrating Groups
See this image and copyright information in PMC

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