3-Trimethylsilyl-2,5-dihydrofuranes

Furanes.3 Hydromagnesiation of 3-trimethylsilyl-2-propyne-l-ol (1) (11, 163) followed by reaction with an aldehyde or ketone provides E-3-trimethylsilyl-2-alkene-l,4-diols (2). These are converted into 3-trimethylsilyl-2,5-dihydrofuranes (3) on dehydration... 

This insertion reaction was also observed in the attempted cyclopropanation of 3-trimethylsilyl-2,5-dihydrofurane, which occurs in 32% yield irrespective of the activation method used (PTC or sonication). The insertion product, either on the 2 or 5 positions, is formed in 48-52% yield. ... 

Allenyltrimethylsilanes add to ethyl glyoxalate in the presence of a chiral pybox scandium triflate catalyst to afford highly enantioenriched homopropargylic alcohols or dihydrofurans, depending on the nature of the silyl substituent (Tables 9.39 and 9.40) [62]. The trimethylsilyl-substituted silanes give rise to the alcohol products whereas the bulkier t-butyldiphenylsilyl (DPS)-substituted silanes yield only the [3 + 2] cycloadducts. A bidentate complex of the glyoxalate with the scandium metal center in which the aldehyde carbonyl adopts an axial orientation accounts for the observed facial preference ofboth additions. 

The pyrimidine 5-fluorouracil (64) is used extensively in the clinic as an antimetabolite antitumor agent. As a consequence of poor absorption by the oral route, the drug is usually administered by the intravenous route. A rather simple latent ated derivative, tegafur (66), has overcome this limitation by providing good oral absorption. Reaction of 5-fluorouracil with trimethylsilyl chloride in the presence of base gives the disilylated derivative (65). Reaction of this with dihydrofuran (obtained by dehydro-... 

Dimethylene-2,3-dihydrofuran derivatives, which are produced by fluoride-induced 1,4-conjugative elimination of trimethylsilyl acetate from the [(trimethylsilyl)methyl]-3-furan precursor 207, undergo subsequent [4-1-4] dimerization reactions to produce cycloocta[l,2-3 6,5-. ]difuran derivatives as a mixture of isomers (Equation 137) <1995JA841 >. A methyl substituent at the 3-methylene position was found to retard the rate of dimerization, an observation which is consistent with the proposed two-step mechanism involving the initial formation of a diradical intermediate in the rate-determining step (Table 16). 

One process from US Patent 4,107,162 27.4 g of 2,4-bis(trimethylsilyl)-5-fluorouracil and 7.7 g of 2,3-dihydrofuran are dissolved in 70 ml of acetonitrile, and 30 ml of an acetonitrile solution containing 1.3 g of anhydrous stannic chloride are added thereinto with cooling and stirring. 50 ml of acetonitrile containing 1.3 ml of water dissolved therein are then dropwise added over 15 minutes. After return to room temperature, the reaction is further effected with stirring at 40°C for 5 hours. The reaction mixture is neutralized by adding 1 N aqueous ammonia with cooling and... 

The presence of five-membered rings such as cyclopentanes, cyclopentenes, and dihydrofurans in a wide range of target molecules has led to a variety of methods for their preparation. One of the most successful of these is the use of trimethylenemethane [3 + 2] cycloaddition, catalysed by pal-ladium(O) complexes. The trimethylenemethane unit in these reactions is derived from 2-[ (trimethylsilyl)methyl]-2-propen- 1-yl acetate which is at the same time an allyl silane and an allylic acetate. This makes it a weak nucleophile and an electrophile in the presence of palladium(0). Formation of the palladium 7t-allyl complex is followed by removal of the trimethylsilyl group by nucleophilic attack of the resulting acetate ion, thus producing a zwitterionic palladium complex that can undergo cycloaddition reactions. 

The reaction of trimethylsilyl cyanide with the cis ene diones 12, produced photo-chemically from furans, provides 2-cyano-5-hydroxy-2,5-dihydrofurans, which can be oxidized to 4-cyanobutenolides33 (equation 25). 

Heterocycles. Both the formation of 5-trimethylsilyl-2,3-dihydrofurans from i siloxy ketones and of cycloheptapyrrolones from (V-methylanilides of a-keto acids . olve condensation with the ketone group and subsequent Sn2 reaction or carbene nsertion. 

Raw Materials 2,4 -Bis(trimethylsilyl)-5-f luorouracil Ammonia 2,3 -Dihydrofuran 5-Fluorouracilmercury ... 

Metallation of 2,3,4,5-tetrahydrooxepin with Bu"Li or Bu Li leads to 7-lithio-2,3,4,5-tetra-hydrooxepin, i.e. vinylic deprotonation occurs <82JOC3094>. It is of interest that 2,3-dihydrooxepin, like 2,5-dihydrofuran, undergoes allylic deprotonation. The readily available trimethylsilyl ketene acetal of e-caprolactone is a convenient intermediate for the synthesis of 3-RO-substituted e-caprolactones (R is acyl or tosyl) using, as other reagents, lead(IV) carboxylates <83JOC4940> or [hydroxy(tosyloxy)iodo]benzene <89JOC1101>, respectively. 

The intermediate carbenes generated from ketones and TMSC-(Li)N2 have also been shown to undergo 1,5 0-Si and N-H insertion to produce 5-trimethylsilyl-2,3-dihydrofurans and 2-pyrrolines or 3-substituted indoles, respectively (eqs 61 and 62). Azulene 1-carboxylic esters may be generated in moderate yield by the reaction of TMSC(Li)N2 with alkyl 4-aryl-2-oxobutanoates, followed by oxidation with manganese dioxide. ... 

Trimethylsilyl homopropargylic alcohols, when treated with PdClN02(MeCN)2 catalyst and 1 A HCl in MeCN solvent or with wet DMF, give various y-butyrolactones (Scheme 44).[5 l The y-butyrolactone is thought to be formed by the Wacker reaction of 4-silylated 2,3-dihydrofurans formed in situ. Silyl-substituted bis(homo)propargylic... 

Reddy et al. [54] developed a method involving in situ-generated aza-diene, from A -[methyl-A -(trimethylsilyl)methyl]aniline using catalytic amount of molecular iodine which undergoes smooth [4+2] cycloaddition with electron-rich enol ethers, such as 3,4-dihydro-2/f-pyran and 2,3-dihydrofuran to afford the corresponding hexahydropyrano 26 and furo[3,2-c]quinoline derivatives 27, respectively, in good yields (Scheme 10.20). 

Furan and Dihydrofuran Synthesis. Trapping the 3-lithio derivative of (1) with decanal leads to the allenic alcohol (eq 2). Aqueous acid under carefully controlled conditions produces 2-trimethylsilyl-5-nonylfuran. The addition product of the 3-lithio... 

Isoretronecanol (112) has also been synthesized by a nitrone cycloaddition involving (108) and dihydrofuran. Reduction of the adduct (109) followed by silylation led to (110), which was shown to react with trimethylsilyl iodide selectively to give the iodide (111). Fluoride ion then caused deprotection and cycliza-... 

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