Furan, photocycloaddition

A recent synthesis of 3-substituted furan derivatives illustrates an important application of the furan-carbonyl photocycloaddition. Zamojski has reported the rearomatization of oxetane (115) in the presence of p-toluenesulfonic acid to 3-furylmethanol derivative (116). Synthesis of (117), itself a substrate for the intramolecular photocycloaddition reaction (Section 2.4.6), involved a similar rearomatization process (PPTS/CHjClj) and capitalized upon the chemoselectivity observed in the ketone-furan photocycloaddition. Similarly, a synthesis of perillaketone (118) by Kawanisi involved irradiation of a carbonyl compound and furan. A complication in the rearomatization is that acid also catalyzes the reversion of the photoadduct to starting materials to circumvent this problem the photoreaction was run in the presence of acid, so that rearomatization would occur in situ and the products of competitive reversion would promptly recombine. 

The thermo- and photocycloaddition of alkenes will be discussed in Chapter 12, on pericyclic reactions. On the other hand, transition-metals have effectively catalyzed some synthetically useful cycloaddition reactions in water. For example, Lubineau and co-worker reported a [4 + 3] cycloaddition by reacting a,a-dibromo ketones with furan or cyclopen-tadiene mediated by iron or copper, or a-chloro ketones in the presence of triethylamine (Eq. 3.48).185... 

The Paterno-Buchi photocycloaddition between carbonyl compounds and furans was first described in 1965 (equation 6)80. This report noted that only the head-to-head product 171 was formed, and that high exo face selectivity was exhibited. Subsequent to this and other early reports, this reaction has been systematically explored by several groups, owing largely to the various ways in which the 2,7-dioxabicyclo[3.2.0]hept-3-ene ring system can be exploited730,81. 

These cycloadducts, at their most elementary level, are excellent intermediates for the synthesis of 3-substituted furan derivatives. For example, Kawanisi and coworkers reported a synthesis of perillaketone 174 in which the critical step was a Paterno-BUchi photocycloaddition between furan and 4-methylpentanal in the presence of methanesul-fonic acid (Scheme 39)82. This reaction furnished two initial photoadducts, 172 and 173. The unexpected product 173 presumably arises from a Norrish Type II cleavage of 4-methylpentanal to give acetaldehyde, and subsequent cycloaddition with furan. The desired cycloadduct 172 was then converted uneventfully to 174 via acid-catalyzed aromatization and oxidation. 

Hoveyda has also studied the intramolecular variant of the furan-carbonyl photocycloaddition87. Several examples of this reaction, each of which proceeds in modest yield, are shown in Scheme 44. However, given the ease of synthesis of the starting materials and the complexity of the adducts produced in these photocycloadditions, these... 

Zamojski and coworkers have explored the use of the furan-carbonyl photocycloaddition in asymmetric synthesis, with somewhat limited success88. Irradiation of chiral glyoxylate derivative 196 [R = (R)(—)-menthyl and (R)(—)-8-phenylmenthyl] afforded... 

The literature of mechanistic aromatic photochemistry has produced a number of examples of [4 + 4]-photocycloadditions. The photodimerization of anthracene and its derivatives is one of the earliest known photochemical reactions of any type97. More recently, naphthalenes98, 2-pyridones" and 2-aminopyridinium salts100 have all been shown to undergo analogous head-to-tail [4 + 4]-photodimerization. Moreover, crossed [4+4]-photocycloaddition products can be obtained in some cases101. Acyclic 1,3-dienes, cyclohexadienes and furan can form [4 + 4]-cycloadducts 211-214 with a variety of aromatic partners (Scheme 48). 

Molecular mechanics-valence bond dynamics have been used to study the model 4 + 4-photocycloadditions of butadiene with butadiene. The photoirradiation of t-butyl 9-anthroate and furan produces a mixture of 4 + 4-cycloadduct and 4 - - 4-cyclodimers. 

Heteroaromatic compounds do not undergo the same variety of photocycloadditions with alkenes as do their carbocyclic counterparts. There are very few reports of this type of reaction for six-membered ring compounds such as pyridines, but five-membered ring systems such as furans do give 1,2-cycloadducts with a range of alkenes (e.g. 357). 

Furans are able to undergo photocycloaddition of the [W2S+ 2S] and the [W4S+ 4S] type to suitable substrates. With benzene (80JCS(P1)2174) five 1 1 products are obtained. The relative proportions of these products are highly variable and depend on the relative concentration of the reactants, the irradiation time, the light intensity and the temperature of the solution. For the shortest irradiation time with a low-pressure mercury lamp at 15 °C, the relative proportions are 1 1 10 40 2. The major product is the 2,5 l, 4 -adduct (301) and the next most prolific is the 2,3 l, 2 -adduct (302). Adduct (301) is unreactive to dienophiles but gives adduct (302) by Cope reaction at 60-70 °C. This reaction can also be achieved by irradiation of a cyclohexane solution of (301). Adduct (302) reacts readily with dienophiles in ethereal solution to form Diels-Alder adducts. The minor adducts possess structures (303), (304) and (305). The reaction is thought to involve the first excited triplet of benzene or an excited state complex. A [ .4s+ .4g] photoadduct (306) is formed... 

Photocycloaddition of oxygen heterocycles to alkynes has been of some use in the preparation of cyclobutene derivatives.279 Irradiation of tetrakis(trifluoromethyl)furan (336) and dimethylacetylene, for example, affords the adduct (337), which on further irradiation, is converted to the... 

In certain cases benzene will undergo photocycloaddition to oxygen and sulfur heterocycles. The two major photoproducts of irradiation of a mixture of furan and benzene are adducts 356 and 357, arising, respectively, by [ 2 + 2] and [ 4 + 4] cycloaddition processes.306 Irradiation of benzene and 2,2-dimethyl-l,3-dioxol (358) similarly affords adducts 359 and 360, together with dimer 361.307 Thiochromone 1,1-dioxide also undergoes photoaddition to benzene.308... 

This type of 2 + 2 photocycloaddition [49] is possible with ketosugars on one of the double bond of furan. The less crowded adducts 51 and 52 are formed with equatorial C-C bonds as shown in Scheme 24. 

Scheme 53 Ortho photocycloaddition of 2-fluorobenzonitrile with furan and further reactions of the adduct.

The photocycloaddition of cyclic and acyclic 1,3-alkadienes or furans to aromatic rings has been shown in some cases. Not only symmetrically allowed (4 + 4) photocycloaddition but also (4 + 2) photocycloaddition to benzene, naphthalene, and anthracene rings have been reported. These results are also shown in the following subsections. 

Gilbert also reported that the photocycloaddition of furan to benzonitrile gave only the 2,5-2, 6 (meta) adduct (9) as a sole product, although the donor-acceptor interaction between addends is relatively high [71,72] (Scheme 6). Unsubstituted benzene reacts with furan to give a mixture of (4 + 4), (4 + 3), (3 + 2), and (2 + 2) adducts by 254-nm irradiation [73,74],... 

Pentafluoropyridine is known to undergo photocycloaddition with ethylene [89,90] and cycloalkenes [91] at the 3,4-position of the pyridine ring. Recently, Sakamoto et al. reported that metacrylonitrile adds to the 2,3-position of 2-alkoxy-3-cyano-4,6-dimethylpyridines (24a,b) to give 7-azabicyclo[4.2.0]octa-2,7-di-enes (25a,b) [92] (Scheme 10). This work was developed to the photocycloaddition of furan to pyridine ring as a first example (Scheme 10) [93],... 

By the low-temperature irradiation experiments, Noh and Kim reinvestigated the photocycloaddition of furan to 1-cyanonaphthalene [139], which was first reported by Pacetal. [100,101], Irradiation of a mixture through Pyrex filter at 78°C yielded exclusively endo-(4 + 4) cycloadduct (endo-26) with a small amount of syn-(2 + 2) cycloadduct. Formation of 81 was proposed by Cope rearrangement of exo-(4 + 4) cycloadduct (exo-26)... 

The photocycloaddition of furan derivatives to 2-cyanonaphthalene (2-CN) affords caged products, which was first reported by Pac et al. [100-105], The product ratio in the photoreaction of 2-CN with 2-methylfuran is almost 1 1. 

No reaction is observed when 50 and 1,1-dimethoxyethene are allowed to stand in the dark for an equivalent period of time. Irradiation of 50 with 4 equiv. of cyclohexene in methylene chloride solvent gives a 51% isolated yield of the (2 + 2)-cyclo-adduct 52 assigned cis-anti-cis stereochemistry. These two cycloadditions were the first two well defined examples of the (2 + 2)-photocycloaddition reaction of an olefin to a carbon-nitrogen double bond. With furan the (2 + 2)-photocycloadduct 53 is formed, again regiospecifically. 

The lack of reactivity of the aryloxazolinones (65) in photocycloaddition to many of the olefins other than 1,1-dimethoxyethene and furan probably results from efficient decay of E2 or D. Exciplex E2 and diradical D are proposed as intermediates in these cases for several reasons. Exciplex formation is most likely dependent on olefin ionization potential, and the ionization potential of many of the un-reactive olefins are intermediate between the ionization potential of furan and 1,1-dimethoxyethene as determined from the maxima of tetracynoethylene olefin charge transfer bands60 66,67. Although ds-2-butene does not form a cycloadduct with 2-phenyl-2-oxazolin-4-one (65a), ds-2-butene is isomerized to rram-2-butene during the irradiation52. Cis-trans isomerization is expected from decay of a triplet diradical. Decay of the exciplex and diradical intermediates in competition with reaction presumably results from steric hindrance from the aryl substituent. The olefins which give cycloadducts, furan and 1,1-dimethoxyethene, are expected to produce low steric hindrance with the aryl substituent in an exciplex or diradical. 

An intramolecular [4+4] photocycloaddition of a 2-pyridone with a furan ring yields the complex 1,5-cyclooctadiene 231 <20060L3367>. The proposed transition state conformation leading to the realized (and desired) f vsy -product is shown (Equation 110). The isopropyl group on the cyclopentane of the pyridone demonstrated stereocontrol and the... 

The photocycloaddition of furan to 2,3-dihydro-2,2-dimethyl-477-thiopyran-4-one gives a mixture in which the major products are two trans-fused [4+2] adducts. Prolonged stirring with basic alumina results in initial conversion to the air-fused adducts and subsequently to 2,2-dimethylthiochroman-4-one (Scheme 228) <2005HCA1922>. 

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