Indium-Catalyzed Cycloisomerization of 1,6-Cyclohexenylalkynes

Vincent Davenel,Jean-Marie Fourquez,Christian Nisole,Fabien Fontaine-Vive,Véronique Michelet,Chloé Puteaux

doi:10.3390/catal11050546

Vincent Davenel, Jean-Marie Fourquez + Show 4 more

Open Access

https://doi.org/10.3390/catal11050546

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Abstract

Efficient four- and five-step routes to access functionalized bicyclo[3.2.1]oct-2-ene and bicyclo[3.3.1]nonadiene via indium-mediated cycloisomerization of 1,6-enynes has been developed. This atom-economical catalytic process was optimized and relied on the efficiency of InCl3 leading to the preparation of functionalized bicyclic adducts in up to 99% isolated yield. The cyclization occurred on two different processes (5-exo versus 6-endo pathway) and were influenced by the substitution of the alkynyl moiety. The exo process was favored for non-substituted alkynes whereas the endo pathway was generally observed for substituted alkynes. Then, the presence of electron-withdrawing groups on the aryl substituted alkyne increased the ratio of the exo isomer. DFT calculations were performed on stability of intermediates and corroborated the intervention of InCl3.

Highlights

Indium was discovered in 1863 by Reich and Richter of the Freiberg School of Mines in Germany [1]
Used from the 1950s in the preparation of semiconductors, it is used in the form of indium phosphite in the development of light-emitting diodes (LEDs)
The first examples of indium-catalyzed intramolecular hydroarylation reactions of alkynes were reported by Fürstner’s group from o-alkyne biaryl derivatives leading to halophenanthrene derivatives in yields ranging from 59% to 95% (Scheme 1, (1)) [7]

Summary

Introduction

Indium was discovered in 1863 by Reich and Richter of the Freiberg School of Mines in Germany [1]. Chatani’s group studied in 2006 the rearrangement of 1,6-enynes in the presence of indium trichloride as catalyst leading to the formation of 1-vinylcyclo-alkene derivatives (1,3-diene) or 1-allylcyclo-alkene derivatives (diene-1,4) depending on the substitution of the alkyne (Scheme 1, (2)) [8]. These pioneered works were followed by other studies such as the one from Gandon’s team on the intramolecular hydroarylation cyclization reactions of ω-alkynyl-arenes derivatives [9]. These bicyclic derivatives key building blocks cycloisomerization processes on cyclohexenylalkynes [22]are in the presence of indium salts.and These bicyclic derivatives are key building blocks and represent privileged scaffolds represent privileged scaffolds for biologically active molecules and natural productsfor[23–.

Results

IPrAuNTf

Mechanistic

The effective-core potential of Hay and Wadt with a double-ξ valence b