Tetrahydrofuran coupling reactions

The lrialkyl(trifluorovmyl)slannanes were used in the Pd(0)-catalyzed coupling reaction of aryl halides [77] (equation 12). The product yield increased with the solvent type in the order hexamethylphosphorus triamide (HMPT) DMF > dimethyl sulfoxide (DMSO) > tetrahydrofuran (THF) > CgHg > C2H4CI2. 

Intermediate 8, the projected electrophile in a coupling reaction with intermediate 7, could conceivably be derived from iodolactone 16. In the synthetic direction, cleavage of the acetonide protecting group in 16 with concomitant intramolecular etherification could result in the formation of the functionalized tetrahydrofuran ring of... 

In several separate small scale experiments, It was noted that the coupling reaction was not impeded by adding pyridine, triethylamine, t-butyl alcohol, chlorotrimethylsilane, or diisopropylamine to the reaction mixture before adding the nickel catalyst. These results suggest that a variety of functional groups can be present in the enone partner of the coupling reaction. In addition toluene can be used instead of tetrahydrofuran as the solvent. 

The ratio of trimethylvinyltin to tetrahydrofuran is determined by NMR. The trimethylvinyltin/THF solution may be used in palladium-catalyzed coupling reactions without further purification. 

A kinetically controlled Negishi palladium-catalyzed coupling reaction was used in a highly stereospecific synthesis of (E)- or (Z)-a-fluoro-a,/(-unsaturated ketone (29), an intermediate to the above described depsipeptides [54], Reaction of E/Z gem-bromofluoroolefin (30) and alkoxyvinylzinc species (31) yielded (Z)-29 in 70-99% yields. When the unreacted (Z) bromo, fluoroolefin was allowed to react in tetrahydrofuran (THF) under reflux, (E)-29 was formed in up to 98% yield (Scheme 9). 

It was reported that Pd(0)-catalyzed coupling reactions of allenic alcohols, amines and acids with hypervalent iodonium salts afforded cyclized heterocyclic tetrahydrofurans, tetrahydropyrans, pyrrolidines, piperidines, or lactones under mild conditions <99SL324>. Intramolecular 1,5-hydrogen atom transfer radical cyclization reaction of pyrrolidine derivatives was examined. Reaction of 3,4-dialiyloxy-JV-(0-bromobenzyl)pyrtolidine gave hexahydro-... 

Among the solvents suggested for azo coupling reactions, aside from aqueous and specialized nonaqueous systems as mentioned above, are mixtures of water with water-soluble alcohols (e.g., methanol, ethanol, propanol), other water-soluble solvents such as tetrahydrofuran, N, A-dimethylacetamide, iV,iV-dimethylformamide, and organic acids such as formic, acetic, and propionic acids [11 ]. 

It has been reported that a tetrahydrofuran solution of the disodium salt of the tetramer of a-methyl styrene reacts with iodine to form coupled products with molecular weights of up to 3 x 103 331). Although it would be expected that iodine would favor the coupling reaction, the lack of specific product and yield information precludes further discussion of this result. 

Marko et al. initially employed allylsilane 171 during their study on the scope and limitations of the IMSC methodology in 1993 [65] and expected to obtain the exo-methylene tetrahydrofurans 175 (Scheme 13.60). However, none of the desired furan derivatives 175 was obtained when a mixture of 171 and aldehydes 174 was treated with a range of Lewis acids. Rather, the diastereomerically pure exo-methylene tetrahydropyrans 173 were isolated, albeit in modest yields (Scheme 13.61). In 1995, Oriyama et al. [79] published the IMSC reaction of acetals with allylsilane 171, yielding the desired tetrahydrofurans 175 in the presence of the SnC /AcCl system (See Chapter 13.4.2). Interestingly, product 173 was not formed when the corresponding acetals were used instead of the aldehydes in this coupling reaction and vice-versa [49, 65]. 

Thus, for our present purposes a similar approach was followed using Suzuki cross-coupling reactions as the key steps in the synthesis of our target compounds. Symmetrically substituted compounds were synthesized in a twofold Suzuki crosscoupling reaction from commercially available p-substituted phenylboronic acids or esters and 4,4 -dibromobiphenyl or 4,4 -biphenyl-bis-boronic acid ester and a p-substituted arylhalide, respectively, using tetrakis (triphenylphosphino) palladium as catalyst together with cesium fluoride as base in dry tetrahydrofurane as shown in Scheme 8.1. The desired products were obtained in respectable yields after heating at reflux for 50 h. 

A tetrahydrofuran fused with a seven-membered ring was obtained from an enyne through a [5+2] cycloaddition reaction catalyzed by [(C10H8)Rh(COD)]+ SbF6 complex <02AG(E)4550>. Rhodium-catalyzed carbonylative alkene-alkyne coupling reactions... 

A related one-pot three component coupling reaction leading to allyli-dene tetrahydrofuran derivatives 80 and which combines a conjugate addition of a propargyl alcohol with an activated olefin and an in situ palladium-catalyzed carbopalladation-cyclization in the presence of a large excess of allyl chloride has been recently developed by Lu and Iiu (Scheme 31) [77]. The cyclization process is here initiated by addition of a catalytic amount of Pd(OAc)2 and in marked contrast with the above-discussed reactions, a catalytic cycle involving divalent palladium proceeds in the reaction. In this process, the ester enolate formed in the Michael addition undergoes... 

When propargyl allyl ethers are subjected to transition metal-catalyzed enyne cyclization reactions, 3-alkylidene-substituted tetrahydrofurans are usually formed. A useful variation of this scheme is the Pd(0)-catalyzed tandem enyne cyclization/Suzuki coupling reaction with various arylboronic acids (Equation 90) <2005JOC1712>. The stereoselectivity of this reaction is explained by invoking a chairlike transition state. 

A Ni-catalyzed cyclization cross-coupling reaction of iodoalkenes with alkyl zinc halides has been employed for the synthesis of various tetrahydrofuran derivatives <2007AGE-ASAP>. The TiCU-catalyzed anti-Markovnikov hydration of alkynes has been applied to the synthesis of various benzo[3]furans <2007JOC6149>. 

While alkylation of sulfonyl-stabilized oxiranyllithiums with primary alkyl triflates proceeds in high yield, the reaction towards epoxides is relatively slow ( 2 h) and the decomposition of oxiranyllithium is marked, such that it decreases the yield, especially in the case of a Z-isomer (eq 7 and 8). Addition of boron trifluoride diethyl etherate promotes this epoxide-epoxide coupling reaction. One of the diastereoisomers of eq 8 has been elaborated via 5-endo cyclization into a marine tetrahydrofuran isolated from a brown alga. ... 

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