2- Alkenyl-2,5-dihydrofurans

Optimum yields of (3-vinyl-y-butyrolactols from the Pd(II) promoted reaction of vinyl triflates with Z-but-2-en-l,4-diol (Scheme 6.33) are attained when tetra-n-butylammonium chloride is added (47]. The lactol is conveniently oxidized to the lactone with celite-supported silver carbonate. The corresponding arylbutyrolactols are obtained in high yield (70-80%) from an analogous reaction of iodoarenes with the enediol. The yields of 2-alkenyl-2,5-dihydrofurans, resulting from the Pd(0) catalysed reaction of cyclic alkynylcarbonates with acrylic esters via tandem C-C and C-0 bond forming reactions, are enhanced by the presence of tetra-n-butyl-ammonium fluoride (e.g. Scheme 6.33) (48]. 

Shibasaki and coworkers [15] also demonstrated that the reaction can be performed using hypervalent aikene iodinium salts 10 instead of alkenyl triflates, although yields are lower (22%). hi this case the 2-alkenyl-2,5-dihydrofuran product 11 is obtained (Scheme 11.8). 

Scheme 7.2 Heck reactions of dihydrofuran with aryl or alkenyl triflates with R)-BITIANP.

The preparation of 2,3,5-trisubstituted 4,5-dihydrofurans 81 with complete regio-control can be realized by an one-pot transformation involving epoxidation of 2-alkenyl-1,3-dicarbonyls by in situ generated dimethyldioxirane, and is followed by a S-exo-ieX intramolecular nucleophilic cyclization under the same basic condition <00TL10127>. 

Intramolecular process with rhodium catalyst has been described for the syntheses of indane, dihydroindoles, dihydrofurans, tetralins, and other polycyclic compounds. Wilkinson catalyst is efficient for the cyclization of aromatic ketimines and aldimines containing alkenyl groups tethered to the K z-position of the imine-directing group. 

Regio- and enantioselective Heck reactions of 2 3-dihydrofuran with aryl and alkenyl triflates in the presence of the chiral ligand (R)-BITIANP provides 2-substituted 23-dihydro-furans with complete regioselectivity, high enantioselectivity (86-96% ee) and good yields (76-93%) <99CC1811>. A catalytic oxyselenylation-deselenylation reaction of alkenes offers a stereoselective one-pot conversion of alkenes into 2 -dihydrofurans <99EF0797>. 

Dihydrofurans can be prepared efficiently by a Michael addition of (3-ketoesters to alkenyl sulfoxides followed by a Pummerer rearrangement (Scheme 36) (92JCS(Pi)945). 

BINAP-Ru complexes can catalyze the enantioselective hydrogenation of alkenyl ethers as shown in Scheme 1.15 [93], 2-Methyltetrahydrofuran with 91% ee and 87% ee can be synthesized by BINAP-Ru-catalyzed hydrogenation of 2-methylenetetrahydrofuran and the endo-type substrate, 2-methyl-3,4-dihydrofuran, in CH2C12 under 100 atm of hydrogen, respectively. With the same Ru complex, phenyl 1-phenylethyl ether, an acyclic alkenyl ether, is reduced in a moderate optical yield. 

The palladium-catalyzed cyclizative coupling reaction of a-allenols 41 with alkenyl halides was also explored. The transformation of allenols 41 into spirocyclic disubstituted dihydrofuran (3-lactams 43 was readily achieved in high yields, by treatment with allyl bromide or 2,3-dibromopropene in the presence of palladium (II) chloride (5 mol%) (Scheme 14) [60]. 

Alkylidene-4,5-dihydrofurans.1 Reaction of 2-alkenyl 1,3-dicarbonyl compounds (1) with I2 effects cyclization to iodoalkyldihydrofurans (2). Dehydroiodin-ation (DBU) of 2 results in 5-alkylidene-4,5-dihydrofurans (3), which undergo acid-catalyzed isomerization to furans (4). 

An intramolecular cascade reaction initiated by the addition of an alkenyl radical to a furan was used to synthesize an indene <1998SL1215>. As illustrated in Scheme 31, radical fragmentation in the spiro-dihydrofuran radical 52 provided the intermediate triene 53, which underwent Cope-type rearrangement to form the product. A related reaction with 1-bromocyclohexene that led to unsaturated ketone product was also developed <2003EJ01729>. 

Functionalized 2-hydroxy-3-allenoates can be converted into 2,5-dihydrofurans by using 5-10 mol% of gold(lll) chloride as catalyst. This mild and efficient cyclization method can be applied to alkyl- and alkenyl-substituted allenes at room temperature, furnishing tri- and tetrasubstituted dihydrofurans in good to excellent yields and with complete axis-to-center chirality transfer (Equation 50) <20010L2537>. 

A BINAP-Pd complex catalyzes a highly enantioselective C-C bond formation between an aryl triflate and 2,3-dihydrofuran (eq 22). The intramolecular version of the reaction using an alkenyl iodide in the presence of PdCl2[(/J)-BINAP] and Silver(I) Phosphate allows enantioselective formation of a bicyclic ring system (eq 23). ... 

Cycloadditions. In the presence of AgjCOj/celite 1,3-dicarbonyl compounds add to various electron-rich alkenes to form dihydrofuran derivatives. The alkenes include l-dialkylalkenes, alkenyl sulfides, and enol ethers. ... 

Exchange reaction of (Z)-alkenyl and aryl iodides attached to Wang resin by an ether function then addition of aldehydes and subsequent cleavage with TFA provides 2,5-dihydrofurans and 1,3-dihydroisobenzofurans (Scheme 3.112) [139]. 

When acyclic and cyclicl-alkenyl aminosulfoxonium salts were allowed to react with a base, p-silyloxy alkylidene carbenes were generated, which underwent a l,5-0,Si-bond insertion and 1,2-silyl migration to form 2,3-dihydrofurans <04JA485ft>. As can be seen in the scheme below, 2,3-dihydrofurans could also be formed from various 2,2-dimethyl-5-methoxy-carbonyloxy-3-pentyn-l-ols in the presence of p-methoxyphenol via a palladium-catalyzed cyclization reaction <04TL1861>. 

This simple protocol for the preparation of carboxylic acids was also successfully applied to carbonylation of alkenyl and aryl bromides under the same reaction conditions [88]. The reaction of aryl halides (including heteroaromatics, e.g., halothiophenes) with methyl acrylate, phenyl vinyl sulfone, cy-clopentene, and dihydrofuran, proceeded smoothly in water using the same PS-PEG-supported catalyst to give the corresponding alkenylated aromatics in high yields [88,89]. 

Lautens et al. [344] reported the termination of a cascade of two intramolecular Heck 5-exo-trig carbopalladations by iodide leading from the o-bromobenzamide derivative 159 in the presence of potassium iodide to the heterotricycle 160 in 88% yield (Scheme 8.39). The same transformation was observed for the o-iodo analog of 159 and other o-iodophenyl derivatives with alkenyl side chains leading to various benzannelated dihydrofuran and dihydropyrrole derivatives. 

Difluoroallylic ketones readily underwent nucleophilic 5-endo-trig cyclization through the corresponding metal enolates to afford 5-fluorinated 2-alkylidene-2,3-dihydrofurans via intramolecular O-alkenylation... 

In the carbopalladation of alkenyl ethers it was found that stabilized carbanions added regioselectively to 2,3-dihydrofuran. When treated with PdCl2(MeCN)2 and 2 equiv of EtsN in 1 1 THF/DMF at room temperature (r.t.), addition at the oxygen-bearing carbon is observed along with migration of the double bond. This latter phenomenon appears to be the result of a series of elimination and readdition cycles by Pd—H (Scheme 4). 

The synthesis of functionalized 2,5-dihydrooxepines by [3,3]sigmatropic rearrangement of cyclopropane derivatives [1338] includes a Swern oxidation of 2-alkenyl substituted 2-siloxycyclopropyl alcohols 1831, which provides 2,5-dihy-drooxepine derivatives 1833 in 74-98% yield, while alcohols 1831 (R = H, Me R = R = H) bearing a 2-styryl substituent give dihydrofurans 1834. The forma-... 

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