3- silyloxyfurans

An efficient two-step annelation of functionalized orthoesters with trimethyl-silyloxyfuran derivatives has been reported that produces bicyclo[3. .0]lactones. ° The reaction in Scheme 7 shows an example in which the initial condensation between silyl enol ether and orthoester is followed by the radical cyclization reaction under standard conditions. It is worth underlining the complete diastereocontrol in which three contiguous stereocenters are generated in one step with >95% stereoselectivity. 

As a furllier example of the addition of electron rich heteroaromatics to electron deficient alkenes, MacMillan has shown that y-butenolides can be prepared in one-step by the addition of silyloxyfurans (45) to a,p-unsaturated aldehydes (Scheme 19) [88]. Reactions were tolerant to substitution at the 4- and 5-positions of the furan... 

MacMillan reported a short and effective synthesis of spiculisporic acid which elegantly exemplified his Mukaiyama-Michael addition of silyloxyfurans to a,P-unsatu-rated aldehydes [88], Robichaud and Tremblay augmented this in a formal synthesis of compactin [224], Within this report it was shown that low enantioselectivities were obtained in the conjugate addition to aCTolein. Use of p-silyl acrolein 177 circumvented this and gave butenohde 178 in 95% yield and 82% ee. Conversion of adduct 178 to the decaUn (179) in eight steps resulted in a formal synthesis (Scheme 71). 

Bismuth-Catalyzed Mukaiyama Aldol Reaction of Silyloxyfurans. 102... 

Reactions. These silyloxyfuranes undergo Diels-Alder reactions much more readily than furane itself (6, 161). The reaction provides a route top-quinones and hydroquinoncs (equation I). 

In 2006, Hoveyda and coworkers developed an asymmetric Mannich reaction of silyloxyfurans and aldimines using a similar catalyst system (Scheme 9.18).28 The diastereo- and enantioselective reaction between silyloxyfurans and aldimines in the presence of catalyst gave y-butenolides, which are useful building blocks for organic synthesis. They also reported a mechanistic study of this reaction.2811... 

Scheme 9.18. Vinylogous Mannich reaction with silyloxyfurans.

The synthetic utility of vinylogous Mannich additions of 2-silyloxyfurans to cyclic iminum ions <2001T3221> that provided threo- mAucts predominantly was demonstrated by the assembly of the complete carbon framework during the total synthesis of the plant alkaloid, crommine, as shown in Scheme 11 <1996JA3299, 1999JA6990>. 

The convenient precursors of unsaturated sugars, dihydrop)Tan or dihydrofuran derivatives, can be also obtained from an appropriately functionalized furan molecule. Two main approaches are used. The first is based on the oxidative rearrangement of furfuryl alcohols (Achma-towicz reaction) [22], the second one involves an acid-catalyzed reaction of aldehydes with 2-trimethyl-silyloxyfuran (Casiraghi reaction) [23] (O Scheme 4). 

In the laboratory of S.F. Martin, the vinylogous Mannich reaction (VMR) of a 2-silyloxyfuran with a regioselectively generated iminium ion was utilized as the key step in the enantioselective construction of (+)-croomine. " The carboxylic acid moiety of the starting material was converted to the acid chloride which spontaneously underwent decarbonylation to give the corresponding iminium ion. Reaction of this iminium ion with the 2-silyloxyfuran afforded the desired threo butenolide isomer as the major product. 

The newest techniques employ silylation. Even the anions of saturated butenolides afford the enol ester on reaction with chlorotrimethylsilane91 applied to a butenolide the method readily supplies a 2-silyloxyfuran. Such ethers are even more easily procured by allowing a butenolide to react with chlorotrimethylsilane in the presence of triethylamine and zinc chloride but for reasons that remain unclear, acetonitrile is the only satisfactory solvent.92 A typical transformation of 2-trimethylsilyloxyfuran is shown in Scheme 19. 

Selenides of furan series, synthesis and reactivity 72KGS723. Silyloxyfurans as dienes in Diels-Alder reaction 84YGK860. 

Takei utilized a furan as the synthetic equivalent of a 1,4 dicarbonyl compound in his synthesis of pyrenophorin as described in Scheme 4.6. ° Thus butenolide 28, obtained by Michael addition of butenolide 27 to methyl vinyl ketone, was silylated to provide the silyloxyfuran. Treatment with lead tetraacetate followed by aqueous hydrolysis gave 29 in 55% yield. Protection of the ketones as dimethyl ketals followed by selective removal of the C-7 ketal and reduction gave seco acid 30. Dimerization and hydrolysis gave a mixture of 9 and 18 (17% from 29). 

Table5.2 Silver catalyzed vinylogous Mannich reaction of 2 silyloxyfuran 17awith aliphatic imines according to Hoveyda, Snapper and coworkers [8].

The less well-studied 3-silyloxyfuran was shown to react with aldehydes in an aldol addition manner under Lewis acidic conditions. High 5yn-diastereoselectivity was obtained with bulky aldehydes <05OL387>. 4-Alkoxy-3-lithio-2-silyloxyfurans reacted with a variety of electrophiles to form 3-substituted tetronates after acidic hydrolysis <05SL2735>. Furans and 2-trimethylsilyloxyfuran are effective nucleophiles in the organocatalytic tandem... 

Siphonodicidine, a natural sesquiterpene containing a 2,4-disubstituted furan as a substructure, was synthesized in a regioselectivity-controlled manner. The key intermediate was prepared by the coupling of a silyloxyfuran with a bromogeranyl acetate in the presence of silver trifluoroacetate followed by reduction and hydrolysis as depicted in the following scheme <04JNP1383>. 

Alternatively, the iminium-activation strategy has also been apphed to the Mukaiyama-Michael reaction, which involves the use of silyl enol ethers as nucleophiles. In this context, imidazolidinone 50a was identified as an excellent chiral catalyst for the enantioselective conjugate addition of silyloxyfuran to a,p-unsaturated aldehydes, providing a direct and efficient route to the y-butenolide architecture (Scheme 3.15). This is a clear example of the chemical complementarity between organocatalysis and transition-metal catalysis, with the latter usually furnishing the 1,2-addition product (Mukaiyama aldol) while the former proceeds via 1,4-addition when ambident electrophiles such as a,p-unsaturated aldehydes are employed. This reaction needed the incorporation of 2,4-dinitrobenzoic acid (DNBA) as a Bronsted acid co-catalyst assisting the formation of the intermediate iminium ion, and also two equivalents of water had to be included as additive for the reaction to proceed to completion, which... 

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