3-Tetrahydrofuran-3-carbaldehydes

Although aldehydes obtained through the hydroformylation of dihydrofurans are interesting building blocks for organic synthesis, few studies have been reported on the subject. In 1998, previous work on the control of the regio-selectivity in the hydroformylation of dihydrofurans has been reported with rhodium systems modified with different ligands [77,78]. In the hydroformylation of 2,5-dihydrofuran 46 the expected product is the tetrahydrofuran 3-carbaldehyde 49 (Scheme 7). 

In agreement with this mechanism, it was found that the epoxide (4RS)-4,4-(epoxy-methano)tricyclo[5.1.0.02,5]octane-e c/o-8-carbaldehyde 2,2-dimethylpropaneT,3-diyl acetal (1) gave 4-oxotricyclo[6.1.0.02,6]nonane- ,/ttreatment with lithium iodide in tetrahydrofuran.71 Several examples employing this oxaspirohexane to cyclopentanone isomerization method are shown (see Table 7).69-80 Lithium bromide in the presence of hexamethylphosphoric triamide was also effective in these transformations.70,74,76 79,80... 

Rearrangement of 4-alkyloxy- 48 and 4-acyloxy-l,3-dioxepanes 21 in the presence of an acid depends on the solvent. The rearrangement in DCM gave 2-substituted l,3-dioxane-4-carbaldehydes whereas reaction in aqueous solution afforded tetrahydrofuran derivatives 93. Crossover experiments indicated that the rearrangement in aqueous solution probably proceeds via 3-deoxyglycerotetrose, which immediately reacts with the carbonyl compound to give 93b and 93d (Scheme 18) <2001AGE177>. 

Dihydroxy-l,3-dioxepins readily undergo vinylacetal rearrangement in the presence of a Lewis acid to give tetrahydrofuran-3-carbaldehydes (CHEC-II(1996)). This methodology was applied in a tandem Heck reaction -rearrangement process for the synthesis of a variety of 2,4-substituted tetrahydrofuran-3-carbaldehydes (Scheme 19) <2006CC3119>. 

These reductions can be combined with other transformations as exemplified by cyclopropane 120, which has been converted to the nitrile 122, the spiro lactone 123, and the functionalized spiro tetrahydrofuran 121 61). All products are eventually derived from cyclohexane carbaldehyde. 

Further work on the acid-catalysed rearrangement of 4,5-dihydro-l,3-dioxepins (157) to tetrahydrofuran-3-carbaldehydes (158) and (159) has shown that the reaction is stereoselective and favours the (Z)-isomer (158) under kinetically controlled conditions (cfl 8 1 at — 78°C, for the example shown). At higher temperatures, these isomerize to the more stable (E)-... 

Thus, the rearrangement of cyclic vinyl acetals of type 1 yields tetrahydrofuran-3-carbaldehydes 2, 3), which are useful precursors in the synthesis of polyether antibiotics. The rearrangement of acyclic vinyl acetals (4) produces the aldol ethers Sand 6 stereoselectively. E. g., star-tingwiththe 1,3-dioxolanyl vinyl acetal7or the 1,3-dioxanyl vinyl acetalft the aldehydes 12are obtained, which contain the 1,2- and the 1,3-diol structural subunit... 

Rh4(CO)i2 in the hydroformylation of 2,3-dihydrofuran produced mainly tetrahydrofuran-2-carbaldehyde (Scheme 4.24) [18]. Also, modification of the metal by monodentate phosphites or phosphoramidites and bidentate phosphites favors a-regioselective hydroformylation as well as higher temperatures, low syngas pressure, and low P/Rh ratios [17, 19, 20]. PPhj or mixed bidentate phosphine phosphites and phosphine phosphonites stimulate isomerization and hence the formation of the fi-isomeric aldehyde [19, 21, 22]. There was no clear... 

As mentioned above, in comparison to dihydrofurans, dihydropyrans require more severe conditions than those used for the five-membered congener [17]. Moreover, cychc allyl ethers easily undergo isomerization to produce the corresponding thermodynamically more stable vinyl ethers (Scheme 4.36). Nevertheless, 2,5-dihydrofuran could be converted with PPhj as a hgand with an almost quantitative yield into 3-formyl tetrahydrofuran (a, n = 1). With 3,4-dihydro-2//-pyran as a substrate, at elevated syngas pressure and temperature mainly tetrahydropyran-2-carbaldehyde (b, = 2) was formed. Almost the same regiochemical outcome was stated with the isomeric substrate 3,6-dihydro-2//-pyran. This effect can best be explained by the prior isomerization of the latter into the more stable 3,4-dihydro-2H-pyran. In this case, the corresponding P Carbaldehyde (a, n = 2) was formed only in minor quantities and the 4-formyl isomer c was not observed at all. 

Ligand 18a was also successfully applied in the Rh-catalyzed asymmetric hydroformylation of 2,5-dihydrofuran and 2,3-dihydrofuran. Good enantioselectivities (up to 75% ee) and excellent regioselectivities (up to 99%) were achieved. Note that both enantiomers of tetrahydrofuran-3-carbaldehyde can be obtained using this ligand by simple substrate change from 2,5-dihydrofuran to 2,3-dihydrofuran [21]. 

A solution of sodium dicarbonyl(cyclopentadienyl)ferrate prepared from the dicarbonyl(T] -cyclopentadienyl)iron dimer [Cp(CO)2pe]2 (4.11 g, 11.6 mmol) and sodium amalgam (2%, 35.3 g) in tetrahydrofuran (80 mL) is added slowly at -78 °C to a solution of 4-bromo-2//-chromene-3-carbaldehyde (5.5 g, 23 mmol) in tetrahydrohiran (70 mL). The mixture is stirred at -78 °C for 1 h and then allowed to warm to room temperature over a period of 1 h. The solvent is evaporated in vacuo, and the residue is dissolved in diethyl ether/acetone (1 1) and subsequently purified by column chromatography on silica gel. With petroleum ether/diethyl ether (2 1) tetracarbonyl(dicyclopentadienyl)diiron is separated, whereas with diethyl ether/acetone (1 1) the alkenyl-Fp complex is obtained. The solvent is evaporated and the yellow-brown solid is dissolved in dichloromethane (200 mL), dried (magnesium sulfate), and the solution concentrated in vacuo to yield the q -alkenyl-Fp complex as a yellow-brown, amorphous solid 6.9 g (89%). ... 

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