Furan-2-acetic esters

Intramolecular alkoxycarbonylation of alkynols is parallel to what has been described for alkenols except that functionalization of the triplebond produces a double bond. No lactone formation is observed in the Pd(II)-catalyzed oxidative cyclization-carbonylation of alkynes. Instead [(methoxycarbonyl)methylene]tetrahydrofurans are selectively formed [134, 135]. Moreover, starting from an enynol, furan-2-acetic ester is obtained resulting from a final aromatization step [136]. 

Z)-Enynols can also be employed as substrates when ruthenium or iridium catalysts are used <2006ASC1671>. Furan-2-acetic esters are obtained by a Pd(n)-catalyzed oxidative cyclization-alkoxycarbonylation of (Z)-enynols <1999JOC7693>. In analogy, 2-furan-2-ylacetamides are obtained in an aminocarbonylation with secondary amines (Equation 22) <2006S4247>. 

Intramolecular path b-type reaction of (Z)-alk-2-en-4-yn-l-ols 322, catalyzed by Pdl2 and KI, produced the furan-2-acetic ester 325 by efficient oxidative carbony-lation. The reaction is explained by intramolecular oxypalladation of the triple bond to generate 323, followed by CO insertion to give 324 and double bond isomerization [129]. 

Gabriele and coworkers [36] showed that, besides lactones, furans could also be prepared by a similar process starting from different substrates. Here, a variety of (Z)-2-en-4-yn-l-ols have been carbonylated under oxidative conditions to give substituted furan-2-acetic esters in good yields (Scheme 1.15a). The cycliza-tion/alkoxycarbonylation sequence was carried out in alcoholic media at 50-70 °C under 100 bar pressure of a 9 1 mixture of CO and air. As catalyst system, Pdl2 in combination with KI was used. The proposed reaction pathway involves the in situ isomerization of the initially formed ( )-2-[(alkoxycarbonyl)methylene]-2,5-dihydrofuran species, which in some cases have been isolated and proved to be the intermediates. Under similar reaction conditions, 3-yne-l,2-diols were transformed into the corresponding furan-3-carboxylic esters in good yield (Scheme 1.15b). 

Chiusoli and co-workers succeeded in preparing furan-2-acetic esters by Pd-catalyzed intramolecular alkoxycarbonylation of (Z)-2-en-4-yn-l-ols under oxidative conditions (Scheme However, a high carbon monoxide pressure (up to 100 atm) and an ex-... 

Costa, M. and Chiusoli, G.P. (1999) An effident and general synthesis of furan-2-acetic esters by palladiumoxidative carbonylation of (Z)-2-en-4-yn-l-ols. The Journal of Organic Chemistry, 64, 7693-7699. 

The synthesis of the target compound by this reaction involves the introduction of an acetic ester residue at C-3 without any apparent activation of the furan nucleus other than the somehow invigorating effect of the C-OH bond rupture, a group that is in fact absent in II. That is, the oxidation level of the carbinol carbon must be used up in some way to make the new C-C bond at C-3. 

The rhodium- or copper-catalyzed cyclopropanation of furan and its derivatives with diazo-acetic esters,300-302 or ethyl 2-diazopropanoate300 usually leads to a mixture of the 2-oxa-bicyclo[3.1.0]hex-3-ene-e co-6-carboxylate, ring-opened (4Z)-6-oxohexa-2,4-dienoates, and ring-substituted furans. Only with electron-deficient furans methyl furan-2-carboxylates, 2-[( )-2-methoxycarbonylvinyl]furan300 and with benzofuran,301,303 was the cyclopropane product obtained exclusively. Examples 37-40 are representative.300... 

Acetic esters, alcohols, alkyl halides, bzn., carbon disulfide, furan derivatives, ketones, nilromethane... 

The oxidation of the cyclic enol ether 93 in MeOH affords the methyl ester 95 by hydrolysis of the ketene acetal 94 formed initially by regioselective attack of the methoxy group at the anomeric carbon, rather than the a-alkoxy ketone[35]. Similarly, the double bond of the furan part in khellin (96) is converted ino the ester 98 via the ketene acetal 97[l23],... 

Esters of diphenylacetic acids with derivatives of ethanol-amine show mainly the antispasmodic component of the atropine complex of biologic activities. As such they find use in treatment of the resolution of various spastic conditions such as, for example, gastrointestinal spasms. The prototype in this series, adiphenine (47), is obtained by treatment of diphenyl acetyl chloride with diethylaminoethanol. A somewhat more complex basic side chain is accessible by an interesting rearrangement. Reductive amination of furfural (42) results in reduction of the heterocyclic ring as well and formation of the aminomethyltetrahydro-furan (43). Treatment of this ether with hydrogen bromide in acetic acid leads to the hydroxypiperidine (45), possibly by the intermediacy of a carbonium ion such as 44. Acylation of the alcohol with diphenylacetyl chloride gives piperidolate (46). ... 

There are several reports scattered in the literature of the retarding effect of simple furan derivatives in the polymerization of a specific monomer. Hardy69, U6 found that furan, 2-furoic acid and its esters, and 5-substituted-2-furoie acids were strong retarders in the radical polymerization of vinyl acetate, but did not act likewise with styrene. He proposed that as a result of the reactions of the free radicals with the furan derivatives, dihydro- and tetrahydrofurans would form, but he did not produce any evidence to support these speculations. Clarke, Howard and Stock-... 

Benzo[c]furans (isobenzofurans) are very reactive but generally unstable dienes which are prepared in situ and trapped. The in ihu-generated isobenzo-furan 33 was trapped by cycloaddition reaction with bis(methyl (S)-lactyl) ester 34 to afford [32] optically active naphthols (Equation 2.12). The cycloaddition was carried out in the presence of a catalytic amount of glacial acetic acid and represents a facile one-pot procedure to synthesize substituted naphthols. 

The relative reactivities of several of these 2-hetero substituted 2-cyclopropylideneacetates 4 and 53-55 as well as of the parent 2-cyclopropylidene-acetate 52 and acrylates 56a-d towards 6,6-dimethylfulvene (57) and furan (7) were determined by competition experiments [17,19] (Table 5). The endo/exo selectivity is low, but usually still higher than for simple acrylic esters. 

Unexpectedly, some diazoesters seem to react by way of carbene intermediates even in highly ionic media at room temperature.276 With acetic acid alone 2-furyldiazoacetic ester supplies two products retaining the furan ring. But if the acetic acid is mixed with ether or dichloromethane then a Z-alkenyne (Scheme 53) appears just as if a carbene had been formed. The... 

Of particular interest was the carbonylation of (Z)-2-en-4-yn-l-ols and (Z)-(2-en-4-ynyl)amines, which afforded furan-2-acetic [104,105] and pyrrole-2-acetic [116] esters, respectively, in good yields, through spontaneous or acid-promoted aromatization of the initially formed ( )-2-(alkoxycarbonyl)-methylene-2,5-dihydro-furans or -pyrroles (Scheme 31). 

Ethyl trifluoroacetate Acetic acid, trifluoro-, ethyl ester (383-63-1), 75, 154 Furan (110-00-9), 75, 201... 

Hydrolysis of 20 with the aid of butanol followed by syn-selective reduction of jS-keto ester 21 and protection as the isopropylidene acetal was accomplished in 87% yield. L1A1H4 reduction and TBS protection of the primary alcohol gave 22 in very good yields. In this strategy, the furan residue serves as an aldehyde synthon and ozonolysis followed by esterification gave the corresponding methyl ester. Reduction and consecutive oxidation established aldehyde 23 in 71% yield. 

Anodic oxidation of fiirans in acetic acid leads to the 2,5-diacetoxy-2,5-dihydro-furan 58 [185, 186]which is readily converted to 2-acetoxyfiiran, This has proved a valuable intermediate for the synthesis of butenolides [187]. Reactions in moist acetonitrile yield the 2,5-dihydro-2,5-dihydroxyfurans which can be oxidised to the maleic anhydride 59 [188], Oxidation of furan-2-carboxylic acid in methanol and sulphuric acid is a route to the ester of a-ketoglutaric acid [189]. 

One of the earliest uses for rhodium(II)-catalyzed dipoles was demonstrated in Davies furan synthesis [22]. Isomiinchnones were also shown to produce substituted furans [115]. Additional furan syntheses have been described using silylacetates [116], unsaturated esters [117], and fluoroalkyl diazo acetates [118]. The synthesis of furofuranones and indenofuranones 35 from a-diazo ketones having pendant alkynes has also been reported (Eq. 6) [119]. Other fused heterocyclic systems include furo[3,4-c]furans [120, 121] furo[2,3-b]furans [122] as well as thiobenzofurans [123], and benzoxazoles[124] have also been synthesized with this methodology. 

The isomerization of terminal epoxyalkynes into furans catalyzed by RuCl(Tp)(PPh3) (MeCN) inthe presence of Et3N as abase at 80 °C in 1,2-dichloroethaneis explained by a related intramolecular nucleophilic addition of the oxygen atom of the epoxide to the a-carbon atom of a ruthenium vinylidene intermediate, as shovm by deuteration in the 3-position of the furan (Scheme 10.10) [45]. This reaction is specific for terminal alkynes and tolerates a variety of functional groups (ether, ester, acetal, tosylamide, nitrile). 

Wenkert and Khatuya (51) examined the competition between direct insertion of a carbene into furan (via cyclopropanation) and ylide formation with reactive side-chain functionality such as esters, aldehydes, and acetals. They demonstrated the ease of formation of aldehyde derived carbonyl ylides (Scheme 4.30) as opposed to reaction with the electron-rich olefin of the furan. Treatment of 3-furfural (136) with ethyl diazoacetate (EDA) and rhodium acetate led to formation of ylide 137, followed by trapping with a second molecule of furfural to give the acetal 138 as an equal mixture of isomers at the acetal hydrogen position. 

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