Intramolecular Diels–Alder Cycloaddition of Furans (IMDAF) for Natural Product Synthesis

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

“…The subsequent reaction of furfurylamines 4 with maleic anhydride easily provides the corresponding isoindolocarboxylic acids 5, which were isolated in good overall yields. The IMDAF reaction is highly stereoselective [33,34]; in the course of the tandem N-acylation/[4+2] cycloaddition sequence, only exo-adducts form as a mixture of two diastereomers (trans-5A and cis-5B) based on the orientation of the 3-allyl (or 3-methallyl) substituent relative to the 3a,6-epoxy-bridge (Figure 2). According to the statements above and with the knowledge that there are no reports on the efficient synthetic methods for diversely polyfunctionalized cyclopenta[b]furo [2,3-c]pyrroles using easily available 3-allyl-3a,6-epoxyisoindoles derived from 1-(furan-2-yl)-N-arylmethanimines through the intramolecular Diels-Alder furan (IMDAF) reaction, our research was focused on: (i) Establishing the optimal conditions for the diastereoselective preparation of 3-allyl-3a,6-epoxyisoindoles, according to the variables: solvent, acid catalysts, reaction time and temperature; (ii) With the determined conditions in hand, preparing diverse 3a,6-epoxyisondol-7-carboxylic acids and their methyl esters; (iii) Corroborating the spatial structure of isomeric acids and their esters; (iv) Studying the catalytic activity of ruthenium catalysts 1 and 2 in the RRM of 3a,6-epoxyisoindole-7-carboxylates in comparison with HG-II catalyst; and (v) With the established conditions in hand, preparing the desired cyclopenta[b]furo [2,3-c]pyrroles.…”

“…The subsequent reaction of furfurylamines 4 with maleic anhydride easily provides the corresponding isoindolocarboxylic acids 5, which were isolated in good overall yields. The IMDAF reaction is highly stereoselective [33,34]; in the course of the tandem N-acylation/[4+2] cycloaddition sequence, only exo-adducts form as a mixture of two diastereomers (trans-5A and cis-5B) based on the orientation of the 3-allyl (or 3-methallyl) substituent relative to the 3a,6-epoxy-bridge (Figure 2). Considering the fact that reversible Diels-Alder reactions are most influenced by the reaction temperature and the polarity of the solvent [35][36][37][38], we compared the isomeric composition of the most diverse acids 5a,b,g,i,m formed under the conditions indicated in Table 1.…”

Unusual Structure-Energy Correlations in Intramolecular Diels–Alder Reaction Transition States

“…The Diels–Alder reaction of furan has been widely used in the synthesis of complex targets and as a probe for the investigation of substituent effects [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18]. We recently reported a comprehensive, computational and experimental study of halogenation effects in intramolecular Diels–Alder reactions [19].…”

The Trapping of Phenyldiazenes in Cycloaddition Reactions

“…Only low to moderate yields of pyridazinium salts 16 and 17 were obtained in the experiments with unsubstituted furan (group 1), [26] thereby indicating a strong preference for an electron-withdrawing substituent on the aromatic core of the azocarboxylate. The product yields significantly increased when 2-methylfuran was used as diene and only one regioisomer was found for the pyridazinium salts 18-21 (group 2).…”