2 -Furanones, cycloaddition

A versatile synthetic route to enantiomeric ally pure Diels-Alder adducts was deduced and found dependent on the application of enantiomerically pure 5-methoxy-174a (R=Me) and 5-(l-menthyloxy)-2(5//)-furanones 174b (R = menthyl), which were expected to undergo tt-face-selective cycloaddition with dienes. The reaction was effected by heating no Lewis acid catalysts were required (Scheme 55) (88JOC1127). 

Thermal cycloadditions of butadiene to 3-bromo- 133 and 3-methoxy-5-methylene-2(5//)-furanones 220 were studied (95TL749). These systems contain substituents at C3 capable of stabilizing also a possible radical intermediate, influencing hereby the rate and/or the course of the reaction. Thus, the reaction of 133 and 220, respectively, with butadiene at 155°C afforded mixtures of the expected 1,4-cycloadducts 221 and 222, respectively, and of the cyclobutane derivatives... 

The use of chiral dipolarophiles, such as the nitrile oxide additions to chiral furanones, have received much interest. The cycloaddition of various 1,3-dipolar reagents to the enantiomeric ally pure furanones 170 and 227 showed excellent diastereofacial control by the menthyloxy substituent, especially in nitrone and nitrile oxide additions (cf. Table II) (88TL5317). 

Furanones are a class of chiral dienophiles very reactive in thermal cycloadditions. For example, (5R)-5-(/-menthyloxy)-2-(5H)-furanone (28) underwent Diels Alder reaction with cyclopentadiene (21) with complete re-face-selectivity (Equation 2.10), affording a cycloadduct which was used as a key intermediate in the synthesis of dehydro aspidospermidine [27]. 

Very high levels of diastereomeric and enantiomeric excess have been observed in the cycloadditions of (5R) and (5S)-5-menthyloxy-2(5H)-furanones 28 and 29 (Figure 2.2), readily available from furfural and d- and /-menthol [28]. 

The isoquinolinium ylide 241 reacts with allyl alcohol in a [3+2] cycloaddition to give the tetracyclic product 242 (Equation 32) the primary cycloaddition product spontaneously undergoes an intramolecular transesterification to give the isolated furanone. Similarly, reaction of such ylides with vinylene carbonate gives the tetracycles 243 (Equation 33) <1988BCJ2513>. 

Reaction of the aldehyde-tethered furanone 244 with pipecolinic acid results in the formation of the oxazolopyr-idine derivative 245, which undergoes spontaneous decarboxylation to give the ylide 246. This in turn undergoes an intramolecular cycloaddition with the tethered exomethylene group to give 247, or with the endocyclic alkene to give the furoindolizine 248 <1997T10633> (Scheme 66). 

H)-furanones undergo efficient cycloadditions as oxa-enones 450). The cycloadducts have been successfully utilized as synthetic precursors for 8-valerolactones 473) (4.62) or for 2-cyclohexenones (4.63)474>. 

A very remote secondary H/D isotope effect has been measured for the 2 + 2-cycloaddition of TCNE to 2,7-dimethylocta-2,fran -4,6-triene. The reaction of nitric oxide with iV-benzylidene-4-methoxyaniline to produce 4-methoxybenzenediazonium nitrate and benzaldehyde is thought to proceed via a 2 + 2-cycloaddition between nitric oxide and the imine double bond. A novel mechanism for the stepwise dimerization of the parent silaethylene to 1,3-disilacyclobutane involves a low-barrier [1,2]-sigmatropic shift. Density functional, correlated ab initio calculations, and frontier MO analysis support a concerted 2 + 2-pathway for the addition of SO3 to alkenes. " The enone cycloaddition reactions of dienones and quinones have been reviewed. The 2 + 2-photocycloadditions of homochiral 2(5H)-furanones to vinylene carbonate are highly diastereoisomeric. ... 

During the initial model study, it was found that intramolecular 1,4-transfer of a hydrogen atom was more facile than any inter- or intramolecular cycloaddition process. Although the synthetic scheme shown was not the anticipated path, furanone (207) provided the basis for a possible two step path via acylation of 207 to form an amidofuran, followed by Diels-Alder cycloaddition to provide 211 (Scheme 4.54). 

With an ot, y-ketodiol, cyclization to produce a 3-furanone derivative is feasible, as is shown for the synthesis of ascofuranone (71) and geiparvarin (72) (Scheme 6.57) (286). The precursor for 71 was prepared by the cycloaddition of diene 66 to nitroalcohol 67. In this case, regioselective attack occurred only on the terminal double bond. Reductive cleavage-hydrolysis of the isoxazoline adduct 68 with Mo(CO)6 followed by acid-induced cyclization led to the furanone intermediate (286). A similar strategy was used for the synthesis of geiparvarin (72) (Scheme 6.58) (286). 

Other novel diazo compounds that have been subjected to 1,3-dipolar cycloaddition with activated alkenes, and that give unusually functionalized pyrazolines (Scheme 8.7), include l-diazo-3-trimethylsilylpropan-2-one (20) (49), 2-diazo-methyl-4(57/)-furanones (21) (50), methyl 2-diazo-5-methylanilino-5-oxopentano-ate (22) (51), 2-(acylamino)-2-diazoacetates (23) (51), ethyl 2-diazo-4,4,4-trichloro-3-(ethoxycarbonylamino)butyrate (24) (52), and diazopropyne (53). 

Chiral furanones (butanolides) such as 191 have been used as dipolarophUes in various 1,3-dipolar cycloadditions. The chiral 4-substituted butanolide 190 was prepared from 191 and the chiral auxiliary menthol (Scheme 12.55) (310,311). The single diastereomer 191 is obtained by crystallization and epimerization of the other diastereomer, as the amount of 191 in solution decreases. 1,3-Dipolar... 

Dipolar cycloaddition of />-methoxyphenyl azide with furanones 160a-c conducted at 60 °C in an autoclave, in the absence of solvent, yielded the corresponding triazolines 161a-c. The results and experimental conditions are given in Table 4. Only in the case of 160a (R = OMe) were two isomeric triazolines formed (Scheme 17). The reactions... 

Table 4 1,3-Dipolar cycloaddition of furanones 160a-c with p-methoxyphenyl azide...

The homochiral 2(57/)-furanone 141 undergoes photochemical cycloaddition to vinylene carbonate <1996T1267, 1998TL6961> to generate cycloadducts derived from an r-vo-approach (Equation 45). 

CYCLOADDITION Alumina chloride. l,2-Bis(trimethylsilyloxy)cyclo-butene. 2,2-Dimcthyl-3(2//)-furanone. Lthylaluminum dichloridc. Kctcnc diethyl acetal.. Methyl cyclobutene-carboxylate. Trimethyl-1,3-dioxolen-one. Zinc chloride. 

The predominant orientation (A) was found to be in accord with the re-giochemistry reported for the cycloaddition of dipole 28 to other 2(5 H)-furanones (70S365 87CCC1315 88TL5317) and a, /3-unsaturated lactones [99JCS(CC)440]. 

At room temperature in water cycloaddition of (S)-a-acetylvinyl sulfoxide (35) to furanone 36 leads to the formation of the chiral adduct 37 (Scheme 10) (94SC447). 

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