3 -furanones, 5-alkoxy

The direct combination of selenium and acetylene provides the most convenient source of selenophene (76JHC1319). Lesser amounts of many other compounds are formed concurrently and include 2- and 3-alkylselenophenes, benzo[6]selenophene and isomeric selenoloselenophenes (76CS(10)159). The commercial availability of thiophene makes comparable reactions of little interest for the obtention of the parent heterocycle in the laboratory. However, the reaction of substituted acetylenes with morpholinyl disulfide is of some synthetic value. The process, which appears to entail the initial formation of thionitroxyl radicals, converts phenylacetylene into a 3 1 mixture of 2,4- and 2,5-diphenylthiophene, methyl propiolate into dimethyl thiophene-2,5-dicarboxylate, and ethyl phenylpropiolate into diethyl 3,4-diphenylthiophene-2,5-dicarboxylate (Scheme 83a) (77TL3413). Dimethyl thiophene-2,4-dicarboxylate is obtained from methyl propiolate by treatment with dimethyl sulfoxide and thionyl chloride (Scheme 83b) (66CB1558). The rhodium carbonyl catalyzed carbonylation of alkynes in alcohols provides 5-alkoxy-2(5//)-furanones (Scheme 83c) (81CL993). The inclusion of ethylene provides 5-ethyl-2(5//)-furanones instead (82NKK242). The nickel acetate catalyzed addition of r-butyl isocyanide to alkynes provides access to 2-aminopyrroles (Scheme 83d) (70S593). 

A possible mechanism for the formation of the furanones 6 and 7 is illustrated in Scheme 2. The initial alkoxy radical generated from the alcohol 5 and lead tetraacetate (LTA) undergoes /3-scission to produce the acyl radical intermediate 9. Subsequent cyclization to 10 proceeds through attack of the radical at the carbonyl oxygen. The resulting Pb(IV) intermediate 11 finally collapses via the reductive... 

Functionalized 5-alkoxymethyl- and 5-phenoxymethyl-2(5//)-furanones 44-46 were obtained starting from 3-alkoxy- and 3-phenoxy-2-hydroxy ketones 40 (98T1801). Condensation of the hydroxy ketones 40 with a slight excess of diethyl malonate 41 (Z = COOMe R = Me), ethyl cyanoacetate 42 (Z = CN R = Me),... 

It has been thought that when an oxygen atom is inserted between the phenyl group and the furanone moiety, the activity may be enhanced. A series of alkoxy-lactones 101 were synthesized according to the procedure described by Scheme 30 (99BMC2207). Alcohols are condensed with sodium chloracetate to provide the... 

Optically active dihydro-2-methylene-2(3//)-furanones fused to 5- and 6-membered carbocyclic rings were synthesized with 64-92% ee using the intramolecular reaction between chiral 2-alkoxy-carbonylallylsilanes and aldehydes80. 

In y-alkoxyfuranones the acetal functionality is ideally suited for the introduction of a chiral auxiliary simultaneously high 71-face selectivity may be obtained due to the relatively rigid structure that is present. With ( + )- or (—(-menthol as auxiliaries it is possible to obtain both (5S)- or (5/ )-y-menthyloxy-2(5//)-furanones in an enantiomerically pure form293. When the auxiliary acts as a bulky substituent, as in the case with the 1-menthyloxy group, the addition of enolates occurs trans to the y-alkoxy substituent. The chiral auxiliary is readily removed by hydrolysis and various optically active lactones, protected amino acids and hydroxy acids are accessible in this way294-29s-400. 

Various diastereoselective Michael reactions are based on y-bromo-, y-alkyl-, or y-alkoxy-2(5//)-furanones following the trans-face selectivity shown in Section 1.5.2.3.1.2. Thus the lithium enolates of esters such as ethyl propanoate, ethyl a-methoxyacetate and ethyl a-phenylacetate add to methoxy-2(5/f)-furanone with complete face selectivity269-273 (see Section 1.5.2.4.4.2.). 

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). 

The reaction of a-bromoacetals with trimethylsilylenolates catalyzed by titanium tetrachloride provides /3-alkoxy-y-bromoketones, which are useful furan precursors (Scheme 33) (75CL527). A new synthesis of acylfurans is exemplified by the formation of the 3-acetyl derivative (146) by heating the brdmoalkene (145) (78JOC4596). 2,2-Dimethyl-3(2//)-furanone (148) has been synthesized from 3-hydroxy-3-methylbutan-2-one treatment with sodium hydride and ethyl formate gave the hydroxymethylene derivative (147), which was cyclized and dehydrated to the furanone (148) with hydrochloric acid (Scheme 34) (71TL4891). O... 

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). 

Tandem radical addition/cydization reactions have been performed using unsaturated tertiary amines (Scheme 9.11) [14,15]. Radical attack is highly stereoselective anti with respect to the 5-alkoxy substituent of 2-(5f-J)-furanones, which act as the electron-deficient alkenes. However, the configuration of the a position of the nitrogen cannot be controlled. Likewise, tandem addition cyclization reactions occur with aromatic tertiary amines (Scheme 9.12) in this case, acetone (mild oxidant) must be added to prevent the partial reduction of the unsaturated ketone [14]. 

Excellent or complete diastereoselectivity was observed in cycloaddition of aryl azides with 5-alkoxy-2(5/f)-pyrrolones112. The dihydrotriazoles were obtained as a mixture of regioiso-mers 23-26 and converted photolytically to the aziridines in almost quantitative yields, although photolysis was performed only in an H-NMR tube. The thermal decomposition of the dihydrotriazoles in refluxing dimethylformamide gave a mixture of diastereomeric aziridines and enamines. Complete diastereoselectivity was provided by the cycloaddition of 4-methoxy-phenyl azide with 5-ethoxy-2(5//)-furanone to give 27 and 28112. 

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. 

Radical addition of triphenylgermane to vinyl oxiranes proceeded in the presence of triethylborane to yield 4-triphenylgermyl-2-buten-l-ol derivatives in good yield. Iodo acetals, prepared by iodoetherification of vinyl ethers with the allylic alcohol, underwent radical cychzation to give 2-alkoxy-4-vinyltetrahydrofurans which were converted into 4-vinyltetrahydro-2-furanones by Jones oxidation (Scheme 11.22) [38]. 

Similarly photocycloaddition of ethylene with chiral 5-alkoxyfuranones 181 proceeds with facial diastereoselection [153], Although selectivity remains low, the reaction has been used for the enantiospecihc synthesis of grandisol because it is easy to separate the initial diastereoisomers [154]. Selectivity is greatly influenced by temperature and by substituents on the ethylenic bond of the furanone ring. It was concluded that steric hindrance of the alkoxy group and stereoelectronic effects of substituents on the conjugated system are responsible for the selectivity observed. It was also proposed that the diastereoselection of the photocycloaddition of ethylene with 181 was dominated by the approach of ethylene to the vibrationally relaxed (71,71 ) excited furanone rather than by the selectivity of the reactions of biradicals. 

Hoffinann HMR, Schmidt B, Wolff S (1989) Preparation of 5-Bromotetronates [4-Alkoxy-5-bromo-2(5/7)-furanones] and a New Concept for the Synthesis of Aflatoxins and Related Structure Types. Tributyltin Hydride versus Palladium-Promoted Intramolecular Hydroarylation. 

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