2.5- Dimethylfuran synthesis

Hexanedione [110-13-4] (acetonylacetone) is one of the most widely used 1,4-diketones. It is a colorless high boiling Hquid prepared by the hydrolysis of 2,5-dimethylfuran (332,333), by oxidation of 2,5-hexanediol (334) or 5-hexen-l-one (335), and from allylacetone (336). Its main use is in solvent systems and as a raw material for chemical synthesis. It is reportedly not highly toxic (336). 

Efficient synthesis of the mycotoxin asteltoxin 189 was accomplished beginning with the cycloaddition between 3,4-dimethylfuran and 3-benzyloxypropanal, which furnished pho-toaldol 183 in 63% yield (Scheme 42)84. Epoxidation from the convex face of this adduct, with subsequent epoxide opening, afforded 184, which was then elaborated through a series of steps to 185. The side chain was introduced via lithiosulfoxide 186 to furnish, after double sigmatropic rearrangement, 187. Hydrolysis of this afforded 188, which was oxidized and elaborated to 189 in two steps. 

Ruthenium(n) systems containing imidazol-2-ylidene or imidazolidin-2-ylidene have been used to catalyze the synthesis of 2,3-dimethylfuran starting at (Z)-3-methylpent-2-en-4-yn-l-ol [Eq. (54)]. The activity of the catalyst strongly depends on the nature of the NHC ligand. Benzimidazolin-2-ylidenes give the best results for this transformation. Similar systems have also been used for olefin metathesis reactions. ... 

Males from Galerucella calmariensis and Galerucellapusilla (Coleoptera Chrysomelidae) emit an aggregation pheromone while feeding on host foliage. The compound was identified by spectrometric and other microchemical tests as the novel dimethylfuran lactone, 12,13-dimethyl-5,l4-dioxabicyclo[9.2.1]-tetradeca-l(13),ll-dien-4-one. The structure was confirmed by synthesis and the synthetic compound attracted both males and females in field tests. 

PREPARATION OF tert-BUTYL ACETOTHIOACETATE AND USE IN THE SYNTHESIS OF 3-ACETYL-4-HYDROXY-5.5-DIMETHYLFURAN-2(5H)-ONE (Acetoacetic acid, 1-thio-, S-tert-butyl ester)... 

Carboxy-4-methyl-5-pentyl-2-furanpropanoic acid (273), isolated from blood and urine, is a hitherto unknown class of metabolic compound. The structure of (273) has recently been confirmed by synthesis (80CB699). 2,4,5-Trialkyl substituted furan-3-carboxylic acids have been synthesized from acyloin and /3-ketoesters by treatment with zinc chloride. By analogy with this synthetic route, the reaction of acetoin with 3-oxoadipic acid dimethyl ester was found to yield the 2,3-dimethylfuran (274). The dimethyl ester (275) was prepared by condensation of 3-chloro-2-octanone with 3-oxoadipic acid dimethyl ester and was shown to be identical with the dimethyl ester of the natural product. 

Diels-Alder reaction.1 The first step in a synthesis of citreoviral (5), a metabolite of Penicillium citreoviride, from 2,4-dimethylfuran (2) is a Diels-Alder reaction with 1, to give a 7 5 mixture of endo- and exo-adducts (3). Both are converted in 3 steps to the diol (4), a precursor to 5. 

The exo-selective formation of bicyclic oxetanes of furan derivatives is reported as being successful when applied to the synthesis of natural products (Scheme 7.19) [15e,37]. For example, the total synthesis of asteltoxin and avenaciolide was achieved from 3,4-dimethylfuran and furan, with the PB reaction being used as an initial step of the synthesis. 

The facial diastereoselectivity derived from-the ratio (3 + 4)/(5 + 6) was 50%, while the exo/endo selectivity derived from the product ratio (3 + 5)/(4 4- 6) was 40%. Oxetanes 9a,b were obtained with a low diastereoselectivity from the reaction of (R)-isopropylideneglyceraldehyde 7 with 3,4-dimethylfuran 8 [6]. Oxetanes 9a,b have been used for the synthesis of asteltoxin. Enantiopure acyl cyanides were used in the same way as chiral carbonyl reaction partners [7] and camphor for the addition with electron-poor alkenes like dicyanoethylene [8]. In the latter case the reaction occurs in the S i state of the carbonyl compound. 

This reaction was recently used by F tizon and Baranger for the synthesis of tetramethylfuran.69 In a similar way 2,3,4-trimethylfuran is obtained,70 and 2,4-dimethylfuran is formed in 76% yield from mesityl oxide.71... 

A recent application of the furan-carbonyl photocycloaddition involved the synthesis of the mycotoxin asteltoxin (147)." Scheme 16 shows the synthetic procedure that began with the photoaddition of 3,4-dimethylfuran and p-benzyloxypropanal to furnish photoaldol (148), which was epoxidized with MCPBA to afford the functionalized product (149) in 50% overall yield. Hydrolysis (THF, 3N HCl) provided the monocyclic hemiacetal which was protected as its hydrazone (150). Chelation-controlled addition of ethylmagnesium bromide to the latent a-hydroxy aldehyde (150) and acetonide formation produced compound (151), which was transformed through routine operations to aldehyde (152). Chelation-controlled addition of the lithium salt of pentadienyl sulfoxide (153) followed by double 2,3-sigma-tropic rearrangement provided (154) as a 3 1 mixture of isomers (Scheme 17). Acid-catalyzed cyclization of (154) (CSA/CH2CI2) gave the bicyclic acetal (155), which was transformed in several steps to ( )-asteltoxin (147). ... 

The stereoselective synthesis of unsaturated oxetanes has recently been achieved by Feigenbaum and coworkers.Previous studies have indicated that photochemical cis-trans isomerization of enals is rapid and results in the formation of equivalent amounts of stereoisomeric alkene adducts. " For example, irradiation of rran.r-crotonaldehyde and 2,6-dimethylfuran produced a 1 1 mixture of alkenic isomers (174) and (175) in 64% yield. Irradiation of 4-trimethylsilylbutyn-2-one and furan provided with S 1 stereoselectivity the bicyclic oxetane (176) in which the methyl group occupies the exo position, presumably because of the small steric requirement of the triple bond. Desilyation of the protected al-kyne produced an alkynic oxetane which was hydrogenated under Lindlar conditions to bicyclic vinyl-oxetane (177) attempts to use the unprotected butyn-2-one gave low isolated yields of oxetane because of extensive polymerization. The stereochemical outcome thus broadens previous alkynyloxetane syn-theses and makes possible the preparation of new oxetane structures that may be synthetically useful. 

One of the key steps used in a new synthesis of the bis(tetrahydrofuran) moiety of Asteltoxin (94) is the photoaddition of the propanal (95) to 3,4-dimethylfuran, yielding the adduct (96). This cycloaddition is a common outcome of the irradiation of aldehydes or ketones with furans. An analogous adduct (97) results from the photoreaction of butyl glyoxalate with 2-methylfuran. Two other products [(98) and (99)] are also formed, the first of which is presumably the result of ring opening of the isomeric oxetane (100), while (99) is produced by a hydrogen abstraction radical coupling pathway. 

Periodate cleavage of an oxabicyclic diol was also a key step in the synthesis of citreoviral from the Diels-Alder adduct of 2,4-dimethylfuran and vinylene carbonate [136]. 

Hydrogenation of HMF leads to 2,5-dimethylfuran, an interesting compound for use as a booster due to its high research octane number. Kuster [20] has reviewed intensively the manufacture of HMF and a detailed review of the synthesis, chemistry, and applications of HMF has been published by Lewkowski [21]. 

Danishefsky and Harvey have reported the synthesis of an important subunit in the construction of tirandamycin (Scheme 51). Trimethylsilyl diene (14) reacts with 4,5-dimethylfuran-2-carbaldehyde (184) followed by a brief treatment with TFA to give exclusively the syn pyrone (185). Pyrone (185) is reduced using LAH and subjected to a Ferrier-like rearrangement using benzyl alcohol in the presence of... 

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