Application of New Efficient Hoveyda-Grubbs Catalysts Comprising an N→Ru Coordinate Bond in a Six-Membered Ring for the Synthesis of Natural Product-Like Cyclopenta[b]furo[2,3-c]pyrroles.

Alexandra S Antonova,Anna A Sinelshchikova,Marina A Vinokurova,Fedor I Zubkov,Mikhail S Grigoriev,Vladimir V Kouznetsov,Pavel A Kumandin,Kirill B Polyanskii,Roman A Novikov,Natalia L Merkulova

doi:10.3390/molecules25225379

Abstract

The ring rearrangement metathesis (RRM) of a trans-cis diastereomer mixture of methyl 3-allyl-3a,6-epoxyisoindole-7-carboxylates derived from cheap, accessible and renewable furan-based precursors in the presence of a new class of Hoveyda–Grubbs-type catalysts, comprising an N→Ru coordinate bond in a six-membered ring, results in the difficult-to-obtain natural product-like cyclopenta[b]furo[2,3-c]pyrroles. In this process, only one diastereomer with a trans-arrangement of the 3-allyl fragment relative to the 3a,6-epoxy bridge enters into the rearrangement, while the cis-isomers polymerize almost completely under the same conditions. The tested catalysts are active in the temperature range from 60 to 120 °C at a concentration of 0.5 mol % and provide better yields of the target tricycles compared to the most popular commercially available second-generation Hoveyda–Grubbs catalyst. The diastereoselectivity of the intramolecular Diels–Alder reaction furan (IMDAF) reaction between starting 1-(furan-2-yl)but-3-en-1-amines and maleic anhydride, leading to 3a,6-epoxyisoindole-7-carboxylates, was studied as well.

Highlights

The discovery of metathesis reactions has allowed the noticeable expansion of possibilities for the transformation of different unsaturated substrates, including those aimed at obtaining complex naturally occurring compounds and pharmacologically meaningful molecules, which is reflected in a number of recent reviews [1,2,3,4,5,6,7,8]
The ring-rearrangement metathesis (RRM) of biand polycyclic alkenes has made it possible to obtain systems that are practically inaccessible by Molecules 2020, 25, 5379; doi:10.3390/molecules25225379
Our systematic studies on furan chemistry and metathesis reactions resulted in the development of general, effective method for the synthesis of natural product-like cyclopenta[b]furo[2,3-c]pyrroles from available, renewable furan-based precursors

Summary

Introduction

The discovery of metathesis reactions has allowed the noticeable expansion of possibilities for the transformation of different unsaturated substrates, including those aimed at obtaining complex naturally occurring compounds and pharmacologically meaningful molecules, which is reflected in a number of recent reviews [1,2,3,4,5,6,7,8]. The ring-rearrangement metathesis (RRM) of biand polycyclic alkenes has made it possible to obtain systems that are practically inaccessible by Molecules 2020, 25, 5379; doi:10.3390/molecules25225379 www.mdpi.com/journal/molecules. The ring-rearrangement metathesis (RRM) of bi- and a number of recent reviews [1,2,3,4,5,6,7,8]. The ring-rearrangement metathesis (RRM) of bi- and polycyclic alkenes has made it possible to obtain systems that are practically inaccessible by means polycyclic alkenes has made it possible to obtain systems that are practically inaccessible byalkenes, means means of synthetic other synthetic pathways for the rearrangement of bridged of other pathways [9,10,11,12,13,14,15,16,17,18].[9,10,11,12,13,14,15,16,17,18].

Methods

Discussion

Conclusion