2-substituted dihydrofurans

Substituted dihydrofuran system Substituted furan system... 

Mild Ni(0)-catalysed rearrangements of l-acyl-2-vinylcyclopropanes to substituted dihydrofurans have been developed.86 The room temperature isomerizations afford dihydrofuran products in high yield. A highly substituted, stereochemically defined cyclopropane has been employed in the rearrangement to evaluate the reaction mechanism. The Cu(II)-catalysed cycloisomerization of tertiary 5-en-l-yn-3-ols with a 1,2-alkyl shift affords stereoselectively tri- and tetra-cyclic compounds of high molecular complexity (Scheme 29).87 A proposed mechanism has been outlined in which... 

However, hydroxy-directed diastereoselectivity was not generalized to face-selectivity in the PB reaction of hydroxy-substituted dihydrofuran and furan derivatives (Scheme 7.28) [46],... 

Scheme 7.28 Face selectivity in the PB reactions of hydroxy-substituted dihydrofurans and furan derivatives.

A recent report detailed the synthesis and applications of a series of dicyanomethylene-substituted dihydrofurans 58 <2005USP2005009109>. All the fluorophoric compounds contained a 2-dicyanomethylen-3-cyano-2,3-dihydro-furan moiety and at least one donor group conjugated to the dihydrofuran ring. The donor group most often contained an aryl spacer with a substituted donor atom, such as N, O, S, or P, in the /> ra-position of the aryl substituent. These... 

The procedure described here involves the metallation of dihydrofuran and subsequent alkylation with an alkyl iodide (bromides are much less reactive).5 The resulting substituted dihydrofuran, the intermediate postulated in the Larson procedure, is then treated with chromic acid to hydrolyze the enol ether and oxidize the resulting primary alcohol to the corresponding carboxylic acid as in the Larson procedure. The isolated oxidation product is of suitable purity for subsequent reactions, but if necessary, recrystallization from hexanes is readily accomplished. ... 

Dihydrofiirans have seen considerable use as substrates in the Pauson-Khand reaction. The parent compound reacts in excellent yield with acetylene, terminal and internal alkynes. Yields in this system respond very well to the use of catalytic reaction conditions (equation 4). Another unusual experimental modification has also been found by Pauson to be useful in this system addition of tri-n-butylphosphine oxide nearly doubles the product yield in certain cases (equation 37). The role of the added substance is unclear. Addition of phosphine oxide does not always improve reaction efficiency at this time there are no guidelines to indicate when its use might be beneficial. Substituted dihydrofurans give somewhat lower but still acceptable yields the poor regioselectivity in unsymmetrical cases is the more significant difficulty with these substrates (equation 38). 

A brand-new methodology for synthesizing glycals from noncarbohydrate precursors, one based on cyclization of acetylenic alcohols, has emerged from the field of metalorganics. Molybdenum pentacarbonyl-trialkylamine complexes have been found to efficiently catalyze cyclization of l-alkyn-4-ols to substituted dihydrofurans [233,234]. This same transformation has been successfully carried out on asymmetrically substituted alcohols the furanoid glycals 132, 134, and 135 (O Scheme 45) so obtained have in turn been used as intermediates in the synthesis of nucleosides [235]. 

A variety of aldehydes can function as heteroallenophiles in this [3 + 2] annelation (Figure 13 and Table 9). Reactions of the C(3)-substituted allenylsilanes (66) gave predominantly the ds-substituted dihydrofurans (71). The cis stereochemistry was anticipated, based on the well-documented stereochemical course of Lewis acid catalyzed additions of 3-substituted allylsilanes to aldehydes. ... 

Research in the laboratory of R.L. Danheiser has shown that allenylsilanes can be reacted with electrophiles other than enones, such as aldehydes and A/-acyl iminium ions to generate oxygen and nitrogen heterocycles." Aldehydes can function as heteroallenophiles and the reaction of C3 substituted allenylsilane with the achiral cyclohexane carbaldehyde afforded predominantly c/s-substituted dihydrofurans. 

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. 

Alkyl-substituted methyl 2-(trimethylsiloxy)cyclopropanecarboxylates 24 undergo the same type of reaction when reacted with aldehydes or ketones in the presence of titanium(IV) chloride.The homoaldol adducts 25 were formed with high stereoselectivity and could subsequently be transformed to the highly substituted dihydrofuran derivatives 27 by treatment with boron trifluoride and/or by pyrolysis. 

Synthesis of furans has been carried out via three-component reactions involving intermolecular carbonyl ylide formation. Johnson and co-workers have revealed [65] the consequence of intermolecular carbonyl ylide generation followed by trapping with a selective dipolarophile to obtain furan ring systems. On the basis of this approach, the diazosulfone 8 underwent intermolecular reaction with aldehydes in the presence of Rh2 (oct)4 to form carbonyl ylide intermediates, which could be trapped by alkynes in an inter-or intramolecular manner to yield substituted dihydrofurans 9 or 11, which were later converted to furans 10 and 12, respectively (Scheme 2). 

In the case of methyl ethers of MBH adducts, the reaction proceeds through p-C-H activation to provide the substituted dihydrofurans 396, which have been subjected to in situ treatment with TMSOTf/EtaN, affording substituted furan rings 397 in moderate to good yields (Scheme 3.174). ... 

The acid-sensitive hydroxyl group was protected as an O-thiocarbamate, and treatment of the resulting vinyloxirane 49 with catalytic amounts of trifluoroacetic acid (TFA) afforded the substituted-dihydrofuran derivative 50 in high yield. Free-radical deoxygenation followed by the cleavage of the methyl ethers conpleted the synthesis. 

Liu, Y, Song, F., Song, Z., Liu, M. and Yan, B. 2005. Gold-catalyzed cyclization of (Z)-2-En-4-yn-l-ols Highly efficient synthesis of fuUy substituted dihydrofurans and furans. Org. 

Following the general strategy depicted in Scheme 5.4, Nair and coworkers have described an easy route for the synthesis of highly substituted dihydrofuran derivatives 2-5 by the one-pot reaction of dimethoxycarbene I, generated in situ from oxadia-zole 1, DMAD, and different carbonyl compounds, such as aldehydes (a) [5,6], ketones (b) [7], a,p-unsaturated ketones (c) [5, 8], or quinones (d) [5,6] (Scheme 5.5). hi the specific case of enones (c), the addition of the zwitterion II took place in the carbonyl group regioselectively. 

SCHEME 5.5 Synthesis of substituted dihydrofuran derivatives by MCR of dimethoxycarbene I. 

As seen in Section 5.2.1, the easy access to dimethoxycarbene I by simple thermolysis of oxadiazole 1 has been applied by Nair and coworkers in a multicomponent procedure for the synthesis of highly substituted dihydrofurans (Section 5.2.1, Scheme 5.5). This protocol offers great potential for the rapid access to a variety of important molecules. For... 

V. Nair, A. Deepthi, M. Poonoth, B. Santhamma, S. VeUalath, B. Pattoorpady, R. Mohan, E. Suresh, J. Org. Chem. 2006, 71, 2313-2319. Reaction of dhnethoxycarhene-DMAD zwitter-ions with 1,2-diones and anhydrides a novel synthesis of highly substituted dihydrofurans and spirodihydrofurans. 

In preliminary attempts, hydroformylation was carried out with an unmodified rhodium catalyst [72]. Later on, Rh complexes based on monodentate [73] or bidentate phosphorus ligands [74] became the catalysts of choice in order to produce the corresponding 4-hydroxy aldehydes, which are in equilibrium with cyclic hemi-acetals. This transformation can be used to synthesize substituted dihydrofurans by elimination of water in a final step [75]. 

In reactions of a C-3 substituted allenylsilane with achiral aldehydes, cis-substituted dihydrofurans are the predominant products (eq 11). ... 

A nickel catalyst allows reaction between (1) and an enol phosphate, silyl enol ether, or substituted dihydrofurans and dihydropyrans to afford allylsilanes. Additional functionality can be tolerated in the substrate. ... 

Wang Y, Zhu S (2(X)1) A simple synthesis of fluoroaJkyl substituted dihydrofurans by rhodium(II)-catalyzed 1,3-dipolar reactions. Tetrahedron 57 3383-3387... 

An isolated report suggests that 1,3-dicarbonyl compounds can be coupled to butadiene in the presence of manganese(iii) acetate to produce vinyl-substituted dihydrofurans this could be a potentially useful process. ... 

Nickel(0)-catalyzed ring-expanding rearrangement of l-acyl-2-vmylcyclo-propane 73 occurred at room temperature to afford substituted dihydrofuran 74 (Scheme 2.58) [80]. 

MCPs were found to serve as a one-carbon component In some nickel-catalyzed annulation reactions. Enone 115 underwent hetero [4-f-l] annulation with MCP 83 to give densely substituted dihydrofuran 116 (Scheme 2.74) [127]. 

The 7, i5-unsaturated alcohol 99 is cyclized to 2-vinyl-5-phenyltetrahydro-furan (100) by exo cyclization in aqueous alcohol[124]. On the other hand, the dihydropyran 101 is formed by endo cyclization from a 7, (5-unsaturated alcohol substituted by two methyl groups at the i5-position. The direction of elimination of /3-hydrogen to give either enol ethers or allylic ethers can be controlled by using DMSO as a solvent and utilized in the synthesis of the tetronomycin precursor 102[125], The oxidation of the optically active 3-alkene-l,2-diol 103 affords the 2,5-dihydrofuran 104 in high ee. It should be noted that /3-OH is eliminated rather than /3-H at the end of the reac-tion[126]. 

---