Cycloadditions with furans

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. 

An electron-withdrawing group on the alkenyl double bond has been shown to greatly facilitate the Diels-Alder cycloaddition with furan as depicted below < 00TL9387>. 

Modes of cycloaddition of alkylideneallyl cation are also controlled by the reaction conditions. [4 + 3] Cycloaddition occurs in the reaction with furan. The [4 + 3] cycloaddition with furan was observed for the siloxy-substituted allyl cation 5S, but not for the methoxy-substituted allyl cation 5M. The lower electrophilicity of 5S may prefer the concerted pathway of [4 + 3] cycloaddition in competition with the stepwise pathway to yield a [3 + 2] cycloadduct and an electrophilic substitution product. 

A series of a,a-dimethoxysilyl enol ethers has been prepared and shown to undergo diastereoselective [4+3]-cycloaddition with furan and cyclopentadiene in the presence of catalytic amounts of trimethylsilyl triflate <99SL213>. Furo[3,4-d]oxazoles and furo[3,4-d]thiazo-les react with 13-dimethyloxyallyl to give [4+3]-cycloadducts. The ring opening reaction of these compounds with H2S04Mt20 yields armulated hydroxytropones <99H(51)1225>. 

Isoxazoline undergo [2 + 2] cycloaddition with furan or thiophene to yield the photocycloadducts (452) (83CL1357). 

The formation of (39) was further confirmed by its cycloadditions with furan and pyrrole to give the corresponding Diels-Alder adducts. When heated, (39) suffers valence isomerization, yielding the cyclopropenyl ketone (41), presumably via the vinylcarbene (40) (Scheme 4). 

Diphenylisobenzofuran also reacted with cyclopropa[a]naphthalene to give an adduct 9 of unknown stereochemistry in ca. 40% yield however, cycloadducts of cyclopropa[Z ]naph-thalene have not as yet been described. Cyclopropa[/]phenanthrene underwent cycloaddition with furan to give the endo-aAAuci 10 (28%) and its evo-isomer 11 (17%). ... 

Isoxazoline (145) underwent [2-1-2] cycloaddition with furan or thiophene (146) to yield the photocycloadduct (147) (Equation (28)) <83CL1357>. At this juncture it is worth mentioning that the same isoxazoline (145) with p-xylene (148) by hydrogen abstraction yielded the isoxazolidine (149) (Equation (29)) <83TL2299>. Conjugated isoxazoline C=N double bond as in (150) creates 1-aza-... 

Enantiomerically enriched products can also be obtained by employing a dienophile bearing a chiral controller group [13]. For example, the use of the camphanate ester derivative (S)-3b (also available in the (R) form) in the cycloaddition with furan gave a 29% yield of diastereomer 4 b after purification, along with other endo and exo isomers, Eq. 2. Saponification afforded the chiral ketone (+)-2. Reactions of 4b and 2 have been reported to occur with high regio-and stereocontrol (vide infra). 

Oxyallyl cations bearing oxygen substituents have been synthesized from 15 and catalytic TMSOTf (entry 2) [33], from 16andLiC104/Et3N (entry 3) [34], and from the reaction of pyruvaldehyde directly with SnCl4 (entry 4) [35]. Oxyallyl cations from 17 undergo cycloaddition with furan to give nitrile-substituted oxabicyclic compounds (entry 5) [34b]. 

The 2-oxyallyl cation has found a number of applications in organic synthesis. These species can be produced from a,a -dibromoketones, from a-halo-trialkylsilyl enol ethers or from allyl sulfones and a Lewis acid. For example, the 2-oxyallyl cation 192 can be prepared from the dibromide 191 and its cycloaddition with furan gave the adduct 193, used in a synthesis of nonactic acid (3.127). These reactions may take a concerted or a stepwise course, depending on the nature of the diene and the allyl cation and the reaction conditions. 

The diacetylene 15 readily underwent Diels-Alder cycloaddition with furan to furnish the endoxide 16, which was hydrogenated catalytically to the tetrahydro compound 17. Dehydration of 77 with polyphosphoric acid gave 1 in 16% yield (Eq. 7) Alternatively, deoxy nation of 16 with low valent titanium generated by reducing titanium tetrachloride with lithium aluminium hydride also afforded 7 in 50% yield... 

Lubineau, A. Bouchain, G. (1997) Water-promoted reactivities generation of oxyallyl intermediates and their [4+3] cycloadditions with furan and cyclopentadiene. Facile access to bridged cycloheptenones. Tetrahedron Lett., in press. 

Allenic esters have also been shown to add to fiirans in a highly regio- and stereo-specific fashion [25]. Lewis acids such as Eu(fod)3 and Pr(fod)3 were found to catalyze these cycloadditions. Several mol% significandy enhanced the selectivities and yields of these reactions without adversely affecting fragile functionalities. Particularly reactive bis-ester allenes such as 1,3-dicarboethoxyallene underwent rapid smooth cycloaddition with furan and 2,5-dimethylfuran at... 

In a somewhat related manner, Dewar furan derivative 48 was generated from 47 and underwent [4 + 2] cycloaddition with furan to provide the expected cycloadduct 49 (Scheme 13.15) [40]. 

The experimental observations and outcomes of the cycloadditions of oxyallyl cations, which are the same except for the identity of M, are compared in Table 18.1. Over a series of cycloadditions with furan as the common diene, the lithium oxyallyl cation (5, M = Li), formed from chloroke-tone la under basic conditions, was not highly electrophilic. 

Hosomi used a-bromo enolsilane 4a as substrate, from which was generated the siloxyallyl cation 5 through debro-mination facilitated by ZnCl2 (Scheme 18.8) [9]. This species underwent cycloaddition with furan and cyclopentadiene to afford 6 and 8, respectively. The reactions proceeded at low temperatures and were complete in a short reaction time. 

Craft and Gung developed a paUadium-catalyzed transannular [4+3] cycloaddition route in which all of the rings of cortistatins are prepared in one step from a single macrocyclic precursor (Scheme 19.50) [114]. Exposure of macrocyclic allene 233 to a catalytic amount of palladium (II) acetate in the presence of excess lithium bromide resulted in the formation of 238 as a single isomer in 37% yield. This is the first report of a transannular [4+3] cycloaddition. The proposed mechanism is shown in Scheme 19.50. The formation of allene-palladium complex 234 affords a a-allylpalladium intermediate, which rapidly isomerizes to the 7i-allylpalladium intermediate 235. This can then undergo intramolecular cycloaddilion via an endo (compact) transition strucmre 236 to give bromonium ion 237. The loss of a proton results in the formation of the observed product 238. Cycloadduct 238 was readily converted into the tetracyclic core skeleton of cortistatins 239 by selective reduction of the olefin formed by cycloaddition with furan, followed by reductive debromination. 

When unsymmetrical carbonyls (R Rj) are used for the photochemical cycloaddition with furans, the inherent stereoselectivity should be considered, i.e., exo-oxetanes vs. endo-oxetanes (Scheme 9). Shima initially investigated the photocycloaddition reaction in 1965 and an NMR study by Whipple and Evanega later provided evidence for the preference of the exo-selective cycloaddition. The exo-selective formation of the bicyclic oxetanes and their chemical transformations are now accepted as powerful tools for preparing the synthetically and biologically important materials. " ... 

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