2.6- Disubstituted-3 furanones

Face-selective [2 + 2] photocycloaddition reactions for a series of racemic 2,2-disubstituted furanones 25 were examined83. Irradiation of 25 in the presence of excess cyclopentene led to the formation of the diastereomeric adducts 26 and 27. The ratio of photoproducts (26/27) ranged from modest (42 58) to significant (4 96) as the steric bulk of the substituent R was increased from ethyl to rm-butyl. 

Scheme 37 Benzyl ketoesters as substrates for the synthesis of a,a-disubstituted furanones by copper-phosphine-catalysed ECA of triethylaluminium by Endo [68]...

In 1991, El-Ali and Alper reported the cyclocarbonylation reaction of terminal propargyl alcohols with formation of 5,5-disubstituted 2(5//)-furanones using Pd(dba)2 and l,4-bis(diphenylphosphino)butane (dppb) (91JOC4099). However, this reaction was not applicable to internal alkynols. 

McKervey and Ye have developed chiral sulfur-containing dirhodium car-boxylates that have been subsequently employed as catalysts for asymmetric intramolecular C-H insertion reactions of y-alkoxy-ot-diazo-p-keto esters. These reactions produced the corresponding ci -2,5-disubstituted-3(2H)-furanones with diastereoselectivities of up to 47% de. Moreover, when a chiral y-alkoxy-a-diazo-p-keto ester containing the menthyl group as a chiral auxiliary was combined with rhodium(II) benzenesulfoneprolinate catalyst, a considerable diastereoselectivity enhancement was achieved with the de value being more than 60% (Scheme 10.74). 

Biihler, H., Bayer, A. and Effenberger, F. (2000) Enzyme-catalyzed reactions, part 39. A convenient synthesis of optically active 5,5-disubstituted 4-amino- and 4-hydroxy-2(5f/)-furanones from (5)-ketone cyanohydrins. Chemistry - A European Journal, 6, 2564—2571. 

A palladium catalyst is used in the transformation of a siloxyfuran to a phenyl substituted furanone <00JCS(P1)3350>. Similar products, furan-2(5//)-one derivatives, are afforded through the reaction of tetra-n-butylammonium fluoride with the corresponding substituted 2-siloxyfuran <00S1878>, as well as the oxidation of 3,4-disubstituted furans by singlet oxygen . 

The application of immobilized heterobimetallic cobalt-rhodium in nanoparticles has also been reported. In the presence of water, CO, and amine, internal acetylenes 119 were converted to 3,4-disubstituted furan-2(5H)-ones 120 and 121 in high yields, in which an amine was necessary for the formation of furanone and a higher CO pressure was required for good yield (Equation (8)). It is important to notice that the catalyst has been easily recovered without loss of activity or formation of hydrogenated side-products. The reaction proceeded in good yield for the symmetric substrates (entries 1 and 2) while it always gave two regioisomers for asymmetric alkyne substrates (entries 3-8). The isomer ratio was dependent on the steric and electronic nature of the substituents. 

Several preparative methods exist for the synthesis of 3(2//)-dihydrofuranones. 2,5-Disubstituted or 2,2,5,5-tetrasubstituted 3(2i/)-dihydrofuranones are usually prepared by reaction of sodium or lithium acetylide with a ketone to yield an alkynic alcohol which is then treated with a carbonyl compound in the presence of base to afford alkynic diols. Mercury catalyzed hydration of the resultant diols in the presence of acid affords the furanones in good yields (76JMC709). 

Disubstituted 3(2H)-furanones.3 a-Alkoxy diazoketones undergo insertion into an adjacent ether C-H bond in the presence of Rh2(OAc)4 to form 3(2//)-furanones. This reaction was used for a synthesis of optically active ( + )-musearine (2) from D-alanine via (R)-2-bromopropionic acid (1). 

The 3(2H)-furanones are - as the other 4-hetero-2-cyclopentenones - normally 2,2-disubstituted to avoid enolization to the respective 3-hydroxyfuran. If one of the substituents is an alkenyl side chain, then intramolecular [2 + 2]-photocydoaddition reactions are possible with the regioselectivity being dependent on the chain length (Scheme 6.20). The allyl-substituted substrate SO (n— 1) gave predominantly the formal straight product SI [62], while the butenyl-substituted substrate 50 (n = 2) resulted in formation of the crossed product 52 [63]. 

Racamonde, M., Alibes, R., Figueredo, M., Font, J., and de March, P. (2008) Photochemical cycloaddition of mono-1,1-, and 1,2-disubstituted olefins to a chiral 2(5H)-furanone. Diastereoselective synthesis of (+ (-lineatin. Journal of Organic Chemistry, 73, 5944-5952. 

Furfural (18) was oxidized to give the butenolide 19, which on Michael condensation with diethyl ethylmalonate afforded lactone 20. Hydrolysis of 20 yielded the dilactone 21. This was treated with ethanol in the presence of sulfuric acid. The isomer mixture obtained was separated by preparative thin-layer chromatography, yielding 4-ethoxy-3-ethoxycarbonylmethyl-2-ethyl-4-butanolide (22). Elimination of ethanol, with the aid of p-amino-benzenesulfonic acid, gave 2-(3//)-furanone 23 the 2-(5//)-furanone isomer 24 was obtained with the aid of orthophosphoric acid. Both isomeric esters gave the acid 25 after hydrolysis, which on catalytic hydrogenation afforded m-3-carboxymethyl-2-ethyl-4-butanolide 26, identical to homopilopic acid. This synthesis of homopilopic acid differs from earlier syntheses because the less stable cw-2,3-disubstituted butanolide (26) is formed in the last step. 

A combination of radical and electron transfer steps mediated by manganese triacetate has been used in the synthesis of 5-acetoxyfuranones 21 through carbox-ymethyl radical addition to mono- and disubstituted alkynes 20, followed by oxidative cyclization of the resulting vinyl radicals 22 (Scheme 2.4). The cyclic intermediate 24 is transformed into the furanone 21 through stepwise one-electron oxidation and capture of the resulting aUyl cation 26 by acetate. 

Oxidative cydocarbonylation of 1,1-disubstituted allylic alcohols was accomplished with the RuCl2(PPh3)3 catalytic system to form 2(5H)-furanones (Eq. 11.26). 

Treatment of the alkoxy diazoketones 218 with rhodium(II) acetate affords 3(2//)-furanones in suitable yields (89TL1749). The carbenoid cycliza-tion reaction to form 2,5-disubstituted 3(2//)-furanones exhibits a stereoselection favoring the cis isomers. This phenomenon was exploited in an enantioselective synthesis of (-t-)-muscarine (89TL1753). The formation of furanone 219 illustrates the clear preference for the five-membered ring when two ether oxygens are present to activate the C—H bonds, leading to either the five- or six-membered rings. 

As shown in Scheme 36,2,2-disubstituted-5-alkyl-3(2//)-furanones also undergo -y-alkylation via their extended dienolate intermediates (75). Similarly, 4-isopropyl-6-methyl-(2H)-pyran-2-one, which may be regarded as a vinylogous S-alkyl-3(2//)-furanone, was deprotonated and alkylated at the methyl group. ... 

In 1995 we accomplished the total synthesis of (+)-eremantholide A (8). Our synthetic scheme was completely different from that of the Boeckman group. We selected our building block 2 as the starting material, and the retrosynthetic analysis is outlined in Scheme 6. At first, disconnection of two carbon-carbon bonds in 8 as depicted leads to two fragments, an A/B ring equivalent 55 and known disubstituted 3(2if)-furanone derivative 56. We planned the direct connection of intact 3(2if)-furanone 56 to 55 at a... 

---