Dihydrofuran natural products

A variety of natural products and pharmaceutical agents contain a tetrahydroquinoline moiety [31]. Recently, a simple and general access to these heterocycles by a so-far unknown domino reaction of aromatic nitro compounds 7-65 and 2,3-dihydrofuran mediated by indium in water has been described by Li and coworkers (Scheme 7.19) [32]. It is assumed that the process is initiated by reduction of the nitro group in 7-65 to give the aniline 7-66 on treatment with indium in... 

A further example of the reductive allene formation in the synthesis of a non-alle-nic natural product was reported recently by VanBrunt and Standaert (Scheme 2.47) [81]. Treatment of the propargylic silyl ether 147 with LiAlH4 led to the syn-stereose-lective formation of the hydroxyallene 148, albeit with unsatisfactory chemical yield (25-50%). The latter was then transformed into the antibiotic amino acid furanomy-cin (150) by silver-mediated cycloisomerization to dihydrofuran 149 and elaboration of the side-chain. 

In particular the synthetic approach to dihydrofurans (first equation in Figure 4.23) represents a useful alternative to other syntheses of these valuable intermediates, and has been used for the preparation of substituted pyrroles [1417], aflatoxin derivatives [1418], and other natural products [1419]. The reaction of vinylcarbene complexes with dienes can lead to the formation of cycloheptadienes by a formal [3 + 4] cycloaddition [1367] (Entries 9-12, Table 4.25). High asymmetric induction (up to 98% ee [1420]) can be attained using enantiomerically pure rhodium(II) carboxylates as catalysts. This observation suggests the reaction to proceed via divinylcyclopropanes, which undergo (concerted) Cope rearrangement to yield cycloheptadienes. 

Other examples of the iodonium ylide-based syntheses of furan derivatives involve cycloaddition reactions with alkenes or alkynes. Although the majority of these syntheses involve stable iodonium ylides (86JOC3453 94T11541) (e.g., Eqs. 16 and 17), in some cases the ylides are unstable and are generated in situ (92JOC2135) (e.g., Eq. 18). In the case of alkenes, dihydrofuran derivatives are obtained (Eqs. 16-18). This synthetic route is especially useful for the synthesis of dihydrobenzofuran derivatives that are related to the neolignan family of natural products (Eq. 18). 

When the chiral catalyst tetrakis(binaphtholphosphate)dirhodium was used, moderate enantiomeric excess (50%) was obtained in cycloaddition reactions with furans and dihydrofurans (359). This method has been applied to the synthesis of several natural products that contain fused furan rings, e.g., the human platelet... 

Highly substituted 2,3-dihydrofurans 44 (Scheme 1.3.18) would make particularly interesting starting materials for the asymmetric synthesis of tetrahydrofu-rans, structural motifs which can be found in many important natural products, including polyether antibiotics, lignans, and nucleosides [30]. Not only the activated double bond but also the vinylic silyl group of 44 should allow useful synthetic transformations. 

When a high-yield synthesis of the enantio- and diastereomerically pure mono-cyclic 2,3-dihydrofurans 44 from the vinyl sulfoximines 39 had been developed, the synthesis ofbicyclic 2,3-dihydrofurans of type 50 (Scheme 1.3.19) was investigated. Since a number of tetrahydrofuranoid natural products contain a fused bicyclic ring skeleton, the attainment ofbicyclic 2,3-dihydrofurans of the 50 type would also be desirable. 

For 2,3-dihydrofuran itself no molecular dimensions have been recorded as yet, though a few natural products containing the system have been studied by X-ray diffraction. These include prerotundifolin (73CL1035) and also nepetaefolin (75JA6236), some relevant dimensions of which are shown (68). A c/s-fused furofuran system is characteristic of several... 

A palladium-mediated annulation of Y-( o-bromoary l)pyrroles across strained alkenes led to the formation of pyrrolo[l,2-a]quinolines <07OL1761>. An intramolecular Heck reaction involving tethered iodoarenes produced an entry to pyrrolo[2,3-t/][2]benzazepin-7-ones, analogues of the pyrrole natural product latonduines <07T867>. A Heck reaction of a 3-iodopyrrole with a 2,3-dihydrofuran provided pyrrole deoxyribonucleosides <07T12747>. 

Enyne metathesis reactions in the context of natural product synthesis have been reviewed recently by Mori <2007ASC121>. Using the same ruthenium catalyst, a novel tandem diyne cycloisomerization-CM process has been devised to furnish 3,4-divinyl-2,5-dihydrofurans (Equation 57) <1999CC237>. 

The first total synthesis of the cytotoxic agent (+)-euplotin A was completed by the research team of R.L. Funk. The key step of the synthetic effort was the intramolecular hetero DIels-Alder cycloadditlon of a 3-acyl oxadiene (generated from 5-acyl-4H-1,3-dioxins via thermal retrocycloaddition) with a substituted dihydrofuran to afford the tricyclic skeleton of the natural product. The correct relative stereochemistry of the required dihydrofuran substrate was established using the Paterno-Buchi reaction between ethyl glyoxylate and furan. Subsequently, the oxetane ring was opened stereoselectively under Lewis acid catalysis. 

In theory, a prototropic shift in 2-methylfuran should be difficult because the product, 2-methylene-2,3-dihydrofuran, must lack aromaticity. And indeed no shift of this kind is known. Recently, it has become clear that the converse is not true 2-methylene-2,3-dihydrofurans do not easily revert to aromatic furans, as was once commonly assumed, but are often stable. They have become the subjects of legitimate study. Indeed, there are even some natural products in this class. 

The rearrangements of these compounds to functionalized dihydrofurans under thermolytic and low-temperature conditions have also been exploited in the synthesis of furanoid natural products (Tables 4 and 5). ... 

In contrast, tautens and coworkers recently focused on asymmetric hydroalumination using Ni-BINAP as catalyst [177]. The reaction involves ring-opening desymmetrization of several 1,4-dihydrofuran derivatives that produce important chiral building blocks for natural product synthesis high ee is usually obtained (Scheme 6.138) [178]. 

Functionalized substituted cyclopentanes and spirocyclopentanes were easily accessed by intramolecular photocycloaddition of dihydrofuran based dienes catalyzed by Cu(i) salts. Thus, tricyclic compound 39 was synthesized in 60% yield starting from 38 (Scheme 2.22). Notably, 39 can be easily transformed upon treatment with triflic acid into substituted cyclopentanones, which are important building blocks in the total synthesis of natural products. ... 

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