Intramolecular Diels-Alder reactions furan IMDAF

Intramolecular Diels-Alder reactions of the furan diene (IMDAF) rapid construction of highly functionalized isoquinoline skeletons [65i]... 

The intramolecular Diels-Alder reaction of furans, often designated as IMDAF,15 helps to overcome the sluggishness of this heteroaromatic ring system toward [4+21-cycloaddition. Not only do IMDAF reactions allow for the preparation of complex oxygenated polycyclic compounds, but they also often proceed at lower temperatures than their intermolecular counterparts.9 Even more significantly, unactivated rc-bonds are often suitable dienophiles for the internal cycloaddition. Indeed, the submitters discovered that the IMDAF reaction of a series of furanamide derivatives occurred... 

In 2011, Wipf and Petronijevic reported their synthesis route to ( )-cycloclavine (169) (Scheme 4.4), in which the total synthesis proceeded in 14 steps with 1.25% overall yield (148). One key feature of their approach included the formation of the indole moieties through an allylic alcohol-IMDAF (intramolecular Diels-Alder cycli-zation of furan) reaction (212 to 213) (149,150). Another pivotal step of this route is the synthesis of the cycloclavine indoline core through a stereoselective intramolecular Diels-Alder reaction of a methylenecyclopropane building block (208 to 209). 

Intramolecular Diels-Alder reactions involving furan (IMDAF) are useful synthetic tool for the formation of two or more rings with stereo- and regiocontrol in a single reaction step [14], The literature examples of... 

The IMDAF (intramolecular Diels-Alder furan) precursors 492 were prepared via Michael addition of nucleophiles possessing an unsaturated tether 491 to furoyl nitroalkene 490. Furyl nitroalkene 490 was prepaperd via the nitroaldol (Flenry) reaction. Compound 492 was heated in appropriate solvent such as toluene, xylene, etc., to provide the IMDAF cycloadducts 65 and 66 (Table 16) <2005JOC2235>. 

Padwa and co-workers have shown that the amides 55 can be conveniently prepared in high yield by [4 + 2]-cycloaddition of an acetylenic dienophile to the corresponding 2-amino oxazole derivative 54 (Eq. (6)). The reaction was extended to intramolecular reactions (e.g. 56 - 57, Eq. (7)), giving convenient 2-aminofuran precursors for further intramolecular Diels Alder furan (IMDAF) reactions (see Section Il.C.l.e) (99JOC3595, 99TL1645). 

HIMDA intramolecular hetero Diels-Alder reaction IMDAF intramolecular furan Diels-Alder reactions i-Pr isopropyl Me methyl Ms mesityl neoPn neopentyl P pressure Ph phenyl... 

Furans are also useful 4ti components for tandem Ugi condensation/intramolecular Diels-Alder cascade reactions. For example, stirring a methanolic mixture of compounds 131-133 and benzylamine at room temperature gave the Ugi condensation product 134 that underwent a subsequent intramolecular Diels-Alder furan cycloaddition (IMDAF) to furnish 135 in 70-90% yield (Scheme 13.35) [69,70]. This methodology also allowed for a solid-phase synthesis by using an ArgoGel-Rink resin as the amine component, thereby providing cycloadducts 135 (after cleavage from the resin) in 90-95% yields. 

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