Furan derivatives, additions

The addition of p-quinone to enamines normally produces furan derivatives, especially when the enamine possesses a 3 hydrogen (see Section III. A). 1,2 Cycloaddition is claimed to take place to give a cyclobutane derivative when p-quinone and an enamine with no jS hydrogens are allowed to react at low temperatures (51). However, little evidence is reported to verify this structural assignment, and the actual structure probably is a benzofuranol (52). Reaction of a dienamine (formed in situ) with p-quinone in the presence... 

Reduction of 3,5,5-tris-aryl-2(5// )-furanones 115 (R, R, R = aryl) with dimethyl sulfide-borane led to the formation of the 2,5-dihydrofurans 116 in high yields. However, in the case of 3,4-diaryl-2(5//)-furanones 115 (R, R = aryl R = H or r = H R, R = aryl), the reduction led to a complicated mixture of products of which only the diarylfurans 117 could be characterized (Scheme 36) (88S68). It was concluded that the smooth conversion of the tris-aryl-2(5//)-furanones to the corresponding furan derivatives with the dimethylsulfide-borane complex in high yields could be due to the presence of bulky aryl substituents which prevent addition reaction across the double bond (88S68). 

In the same area, a (5)-tryptophan-derived oxazaborolidine including a p-tolylsulfonylamide function has been used by Corey et al. to catalyse the enantioselective Diels-Alder reaction between 2-bromoacrolein and cyclo-pentadiene to form the corresponding chiral product with an unprecedented high (> 99% ee) enantioselectivity (Scheme 5.27)." This highly efficient methodology was extended to various 2-substituted acroleins and dienes such as isoprene and furan. In addition, it was applied to develop a highly efficient total synthesis of the potent antiulcer substance, cassiol, as depicted in Scheme 5.21... 

Yosikoshi reported the synthesis of furan derivatives by the reaction of 1,3-diketones with nitroalkenes, in which the Michael addition of the anions of 1,3-diketones and the subsequent intramolecular displacement of the nitro group by enolate oxygen are involved as key steps (Eq. 7.40).42... 

Monitored by ESR spectroscopy, the continuous radiolysis of furan derivatives in water leads, in effect, to the addition of the hydroxy group at the 2-position ring opening of the resultant radical is rapid.2Sla... 

Etherification using a metal vinylidene has also been combined with G-G bond formation through the reaction of an alkynyl tungsten complex with benzaldehyde (Scheme 14). The addition of an internal alcohol to the incipient /3,/Udialkylvinylidene that is generated leads to dehydration and the formation of a Fischer-type alkylidene complex. Further reactions of this carbene with a range of nucleophiles have provided access to various furan derivatives.374,375... 

In contrast to the rich chemistry of alkoxy- and aryloxyallenes, synthetic applications of nitrogen-substituted allenes are much less developed. Lithiation at the C-l position followed by addition of electrophiles can also be applied to nitrogen-containing allenes [10]. Some representative examples with dimethyl sulfide and carbonyl compounds are depicted in Scheme 8.73 [147, 157]. a-Hydroxy-substituted (benzotriazo-le) allenes 272 are accessible in a one-pot procedure described by Katritzky and Verin, who generated allenyl anion 271 and trapped it with carbonyl compounds to furnish products 272 [147]. The subsequent cyclization of 272 leading to dihydro-furan derivative 273 was achieved under similar conditions to those already mentioned for oxygen-substituted allenes. 

The synthesis of oxygen heterocycles in which cyclization onto a pendant alkyne is a key step has also been achieved. Reaction (7.36) shows an example of iodoacetal 29 cyclization at low temperature that afforded the expected furanic derivative in moderate Z selectivity [47]. A nice example of Lewis acid complexation which assists the radical cyclization is given by aluminium tris(2,6-diphenyl phenoxide) (ATPH) [48]. The (3-iodoether 30 can be com-plexed by 2 equiv of ATPH, which has a very important template effect, facilitating the subsequent radical intramolecular addition and orienting the (TMS)3SiH approach from one face. The result is the formation of cyclization products with Z selectivity and in quantitative yield (Reaction 7.37). 

Additionally, the acid-catalyzed decomposition of substituted tetrahydro-l,2-dioxin-3-ols yielded adequately the substituted furan derivatives <1994JHC1219, 1998S1457>. 

The sesquiterpene skeleton has also been assembled by the intramolecular nitrile oxide cycloaddition sequence. Oxime 238 (obtained from epoxy silyl ether 237), on treatment with sodium hypochlorite gave isoxazoline 239, which was sequentially hydrolyzed and then subjected to the reductive hydrolysis conditions-cyclization sequence to give the furan derivative 240 (330) (Scheme 6.93). In three additional steps, compound 240 was converted to 241. This structure contains the C11-C21 segment of the furanoterpene ent-242, that could be obtained after several more steps (330). 

The intramolecular addition of hydroxyl groups to triple bonds might be utilised in the formation of furane derivatives. Enynols, having the appropriate double bond geometry, underwent ring closure and subsequent double bond isomerisation in the presence of both palladium and ruthenium catalysts to give substituted furans (3.52.),66... 

Furans, thiophenes and pyrroles have all been obtained by addition of alkyne dienophiles to a variety of other five-membered heterocycles, as illustrated in Scheme 64 (see also Sections 3.4.1.9.1 and 4.2.3.3.4). As the alkyne moiety provides carbons 3 and 4 of the resulting heterocycle, this synthetic approach provides an attractive way of introducing carbonyl-containing substituents at these positions, especially as many of the heterocyclic substrates are readily available. Even furans can be converted into other furan derivatives by this method (Scheme 65) (85JHC1233,87BSF131). 

Preparation of addition polymers having the oxolene (dihydrofuran) functionality can be envisioned to occur in two possible ways (Scheme 13). Both, in fact, have been observed (77MI11102). Whereas furan (53) or its derivatives do not homopolymerize under free radical conditions, 1 1 alternating copolymers possessing the 1,4-structure are produced with maleic anhydride (50). Intermediate formation of a CT complex between monomers (50) and (53) is believed to be necessary before polymerization can occur. On the other hand, cationic polymerization is quite facile. The outcome is straightforward with benzo[f>]furan derivatives, producing 1,2-polymers. Optically active poly(benzofurans) are formed when the cationic polymerizations are conducted in the presence of a chiral anion. 

In this section we refer to types of addition to the carbonyl group, which by their very nature lead to C4-elongation. Examples are found in the addition of furan derivatives and [4+2] cycloaddition. We have recently described [39] the stereoselective addition of 2-furyl-lithium 26 to N,N-diprotected alaninals. For example, the reaction of 26 with alaninal 25 led to a mixture of diastereoisomers syn-21 and anti-28, with predominance of the latter isomer (Scheme 10). A similar method was used in the synthesis of methyl a-D-lincosaminide (see Sec. III.F). 

Furo[3,4-c]pyridin-4-one derivatives have been prepared from 3,4-disubstituted furans (Scheme 20). Thus Michael addition of acetoacetic esters to /rans-3-hexene-2,5-dione gives adducts with a cyclohemiacetal structure (90) which easily dehydrates to furan derivatives (91) by treatment with acid. These compounds are suitable intermediates for the preparation of furo[3,4-c]pyridin-4-ones and furo[3,4-c]pyranones (Section 3.17.2.2.1) (78JHC993). These latter compounds are far more stable than the previously described furo[3,4-c]-pyridine itself. 

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