Furan derivatives functionalized

If on the other hand the polymerization of a furan derivative takes place through a substituent containing an adequate functionality, such as C=C or C=0, the furan ring should in principle conserve its structure and the polymers obtained will bear it as a side group. It has been found, however, that in some of these systems the normal propagation is accompanied by other reactions which involve participation of the ring and which therefore alter the normal structure of the macromolecule. The second section of this chapter deals with monomers, such as 2-vinylfuran and 2-furaldehyde, which exhibit this general behaviour. 

The synthesis of benzo[Z>]furan derivatives has become a very active field because these molecules have been recently identified as having a variety of biological activities. For example, they can function as inhibitors of protein tyrosine phosphatase IB with antihyperglycemic properties <00JMC1293>, as well as potent and short-acting p-blockers in the treatment of various cardiovascular diseases . An inexpensive, reusable clay has been utilized to catalyze a facile cyclodehydration under microwave without solvent to form 3-substituted benzo[2>]furans from substituted a-phenoxy acetophenones 104. One of the important features of this procedure is that all the selected cyclodehydration reactions are complete in less than 10 minutes <00SL1273>. 

On the other hand, we also planned alternative completely new approach (Route B) to Nakadomarin A, which involves the spirolactam followed by coupling reaction with furan derivative and subsequent intramolecular electrophilic substitution reaction of an iminium cation generated from an aminal to give highly functionalized tetracyclic core system (Scheme 10.3). 

The propensity of the C5 site towards electrophilic substitution has been exploited to prepare functionalized oligomers by cationic polymerization. Thus monomers like isobutene, s ene, the vinyl ethers, etc. polymerize in the presence of simple furan derivatives such as 2-methyl furan to give essentially short chains (DP between 2 and 100 depending on the specific experimental conditions) with a terminal furan ring as a result of predominant transfer onto the C5 position of the added furan compound (20). 

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. 

Very useful building blocks have been generated by silylation of succinic anhydrides to afford 2,5-bis(trimethylsiloxy)furans (80TL3423). These compounds react with various dienophiles to give p-quinones and hydroquinones. The bis(silyloxy)furan thus functions as an equivalent of the inaccessible diketene (38). With an unsymmetrical dienophile, the regioisomer derived from para orientation predominates (Scheme 8). 

Notably, this reaction shows a high tolerance towards a wide variety of functional groups, such as CHO, C02R, I, Br, Cl, F, OH and OMe, and also thiophene and furan derivatives, which is a rare feature in Friedel-Crafts-type chemistry. In the reaction with o-xylene, various alcohols were successfully used as benzylation agents, forming the corresponding products in high yield and selectivity (Table 6.1). 

Furan derivatives with several functional groups have increased odor intensity as compared with lower homologues. 

G. Reese and W. Baltes, Ztschr. Lebensm. Unters. Forsch., in press). This reaction requires a carbonyl function in the position 2 of the furan derivative. By ring enlargement the carbonyl group is converted to a hydroxyl group in the (5-position, whereas the aliphatic residue (from a ketone ) remains in the cC-position of the pyridine ring. 

On the basis of this palladium-mediated Michael addition cyclization process, a novel two-step synthetic entry into functionalized furan derivatives 67 has also been devised (Scheme 28). Substitution of benzylidene (or alkyli-dene) malonates for their ethoxymethylene analog (65) as activating olefins gave rise to the formation of the corresponding 2-ethoxy-4-arylidene tetrahy-drofurans 66. An in situ addition of potassium ferf-buloxidc induced a decar-boxylative elimination reaction which was followed by an isomerization of the exocyclic double bond. The entire process successively involved a conjugate addition, a palladium-catalyzed cyclization-coupling reaction, a base-induced eliminative decarboxylation, and finally, a double bond isomerization [73]. 

The malic acid derivative 12 reacted with benzaldehyde to yield the oxetanes 13a,b with a diastereomeric excess of 80% (Scheme 4) [10]. It should also be mentioned that the regioselectivity and the exo/endo selectivity are complete. The favored formation of 13a is explained by the dominant conformation depicted in A, B. The syn approach of benzaldehyde excited in the 3n,7r state with respect to the alkoxy substituent (transition state A) is hindered by electrostatic repulsion between the substituent and the carbonyl group having a reversed polarity in the excited state. The addition of benzophenone to the furan derivative 14 was stereospecific [11]. In this case, however, the attack of the 3n,TT excited ketone occurred in a syn manner with respect to the hydroxy function to yield 15. The conformation indicated in the transition state C was supported by calculations. 

The copolymerization of furan and 2-methylfuran with dienophiles such as maleic anhydride leads to polymer structures with furan pendent functionality. Furan, 2-methylfuran, and 2,5-dimethylfuran have been copolymerized with acrylic monomers (51,52) and acrylonitrile (52,53). The furan ring of furan, 2-methylfuran, and 2,5-dimethylfuran participates as a diene in a free radical copolymerization with acrylonitrile. The initial step for furan and for 2,5-dimethylfuran is the attachment of an acrylonitrile radical at the 2-position, but for 2-methylfuran, the attack is at the-5-position. Propagation proceeds by the attack of the furan radical on an acrylonitrile molecule, to leave one olefinic bond in the structure derived from the furan ring. If this bond is in the 4,5- or 2,3-position, it may be involved in a second additional reaction by the return of the propagating chain. 

The periselectivity of the reaction of a given diene with tropone is critically dependent on temperature. The variable course of the cycloaddition of ( )-l-trimethylsilyloxybutadiene with tropone as a function of reaction temperature is a Carnatic illustration of this phenomenon. At 80 C the major adduct is bicy-clo[4.4.1]undecenone (10), whereas in refluxing xylene the [4 + 2] cycloadduct (11) prevails as a mixture of regioisomers. A further example of the dichotomy between [6 + 4] and [4 + 2] reaction pathways can be seen with (Z)-l-acetoxybutadiene, which provides some [6 + 4] cycloadduct along with larger quantities of various [4 -i- 2] pr ucts as depicted in equation (1). In contrast to these results, dienes such as ethyl 2,4-hexadienoate and furan do not yield any [6 + 4] or [4 2] products when heated with tropone. The latter result, in particular, may be reflective of the reversibility of the furan cycloadducts. Various furan derivatives do provide modest yields of mixtures of endo and exo [4 + 2] cycloadducts with tropone when reacted together at 3 kbar and 130 C. ... 

The ring-opened dipolar intermediate suggests reactivity towards nucleophiles and electrophiles. The latter occurs in the TiCl4 promoted addition of methyl 2-siloxycyclo-propanecarboxylates to carbonyl compounds and to an iminium salt (equation 99). The products of both processes are very versatile intermediates allowing synthesis of different furan derivatives and other compounds Concerning the liberated carbonyl function, both reactions can be classified as homoenolate additions, thus putting further emphasis on the cyclopropane homoalkene equivalence. 

As is the case for oxycyclopropanes extra activation and extended product functionality is achieved by using sulphur-substituted cyclopropanes with a vicinal acceptor group. According to equation 116 synthesis of a variety of y-oxothioesters and j -oxoketene dithioacetals is possible. A formylcyclopropane of this type has been converted to a furan derivative " . Transformation of the carbonyl to a hydroxymethyl group and acid treatment allows preparation of dienes " ... 

G. J. Burger, Functionalization of Furan Derivatives, Ph.D. Thesis, University of Port Elizabeth, South Africa, 1993. 

A furan-derived macrocycle ( calixfuran ), obtained by the condensation of furan with 2-hydroxymethylfuran, has been reported by Musau and Whiting (Figure 14) [25]. Higher oligomers (cyclic pentamer, hexamer and the octamer) were also isolated in small quantities. Functionalized calixfurans are likely to be of interest for further investigations. 

The same was observed for steroidal dicnamines having a carbonyl group at C-17 and for enamino esters which were reduced by LiAlH4 at the keto and ester functions, respectively, leading in the latter case to saturated pyran and furan derivatives (Scheme 111). 

In the presence of a Lewis acid, alkyl 2-silyloxycyclopropanecarboxylates (14) react with a wide range of carbonyl compounds to give a diester (15), which has b n converted to a variety of furan derivatives (Scheme 18). An interesting use of the oxyanionic tautomer of a homoenolate involves the reaction of a magnesium cyclopropanolate (12) with the lithium enolate of cyclohexanone, from which a tricyclic ring containing a functionalized cycloheptanone (13) is formed in a single step (Scheme 18). ... 

Radicaloid insertions of olefins into the Rh H bond of [Rh (TPP)(H)] has been used to obtain Rh —CH2—(alkyl)—Nu// species (NuH = OH, NH) using olefins functionalized with end-on —OH and —NH functionalities. Under basic conditions, intramolecular SN2-type attack of the Nu at the a-carbon atom of Rh —CH2—(alkyl)—Nu yields [Rh (TPP)] and cyclic organic products (—CH2—(alkyl)—Nu—) (see Fig. 47). Protonation of [Rh TPP)] then allows regeneration of [Rh° (TPP)(H)]. The combination of these reactions constitutes a new method for selective intramolecular anti-Markovnikov hydrofunctionalization of olefins with O—H and N—H functionalities (150). In this way, three-and five-membered ring compounds (epoxides, furan derivatives, pyrrolidine derivatives) were readily obtained. Formation of four- or six-membered rings... 

In the above condensation resist designs, the phenolic resin offers a reaction site as well as base solubility. Self-condensation of polymeric furan derivatives has been utilized as an alternative crosslinking mechanism for aqueous base development (Fig. 126) [375]. The copolymer resist is based on poly[4-hydroxy-styrene-co-4-(3-furyl-3-hydroxypropyl)styrene], which was prepared by radical copolymerization of the acetyl-protected furan monomer with BOCST followed by base hydrolysis. The furan methanol residue, highly reactive toward electrophiles due to a mesomeric electron release from oxygen that facilitates the attack on the ring carbons, readily yields a stable carbocation upon acid treatment. Thus, the pendant furfuryl groups serve as both the latent electrophile and the nucleophile. Model reactions indicated that the furfuryl carbocation reacts more preferentially with the furan nucleus than the phenolic functionality. 

Hetero-/-fused derivatives of indeno[/i]benzopyrans result from the chromenylation of fluoreno[3,4-()][l]benzofuranols and related S andNMe analogues. The furo- 25 and thieno-26 [2,3-7]benzopyrans show absorption bands between 450 - 530 nm and 550 - 640 nm according to the substituents on the gem diaryl function and generally appear as various shades of brown. The half-lives vary between 1 and 6 minutes, with the thiophene analogues exhibiting faster fade rates than the furan derivatives. The closed form of the sole pyrano-... 

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