Furans, silylated

Fig (19) Octalin ketal (163) is converted to kete dithioacetal (164) by the cleavage of ketal function and condensation with carbon disulfide and methyl iodide. Subjection of (164) to the action of dimethylsulfonium niethylide and acid hydrolysis leads to the formation of unsaturated lactone (165).lts furan silyl ether derivative is caused to undergo Diets-Atder reaction with methyl acrylate to obtain salicyctic ester (166) which is converted by standard organic reactions toabietane ether (167). It is converted to aiiylic alcohol (168) by epoxidation and elimination. Alcohol (169) obtained from (168) yields orthoamide which undergoes transformation to amide (170). Its conversion to the previously reported intermediate has been achieved by epoxidation, elimination and hydrolysis. 

Potential 2,5-dihydroxy compounds (185) exist in the dicarbonyl forms (186). Succinic anhydride (186 Z = O) on silylation is converted into 2,5-bis(trimethylsilyloxy)furan (187) the latter compound readily participates in Diels-Alder addition reactions (80TL3423). Reaction of thiosuccinic anhydride (186 Z = S) with the triphenylphosphorane Et02CH=PPh3 gives a product which exists in the aromatic form (188) (75LA1967). 

Synthesis of multisubstituted furan rings using silyl protection 99CSR209. Synthetic applications of furan Diels-Alder chemistry 97T14179. Transformation of furans to N-heterocycles by aza-Achmatovicz reaction 98SL105. 

The O-silylated acyloins such as 1920 c and 1927 are useful synthons for preparation of five-membered aromatic heterocycles such as the substituted imidazole 1925, pyrrole 1926, and furan 1928 [119] (Scheme 12.35). 

When furans were tethered to silyl enol ethers at the 2-position, spiroannulation also occurred at the 2-position under electrochemical conditions <06CC194>, as exemplified below. The formation of the kinetic products is the result of the higher nucleophilicity of the furan C2-position. 

Deprotection of 2,2-disubstituted-l,3-dithiolanes to give carbonyl compounds can be achieved using Oxone with KBr in aq. MeCN <06TL8559> and a review of silylated heterocycles as formyl anion equivalents includes reference to 64 <06CC4881>. A method for transformation of propargylic dithiolanes 43 into tetrasubstituted furans has been reported <06SL1209> and Michael addition of enolates to the chiral dithiolane dioxide 65 takes place... 

Benzo[c]furans (isobenzofurans) are reactive molecules usually employed as reactive dienes in the synthesis of more complex molecules. In the synthesis of spiro compounds related to fredericamycin A, Kumar generated the trimethylsiloxytrimethylsilylbenzo[c]furan 125 from phthalide via two consecutive deprotonations and silylations of the resulting anions. Diels-Alder reaction of the isobenzofuran as shown below with a spiroenedione leads to the formation of an endo-exo mixtures that can be smoothly converted to the dihydroxydione <00IJC(B)738>. 

The generation and trapping of 5,6-bis(trimethylsilyl)benzo[c]furan 126 was reported by Wong utilizing Warrener s s-tetrazine methodology. The trapping of the silylated isobenzofuran with A-phenylmaleimide is illustrated below. A number of other dienophiles such as dimethyl acetylenedicarboxylate, benzoquinone, naphthoquinone and anthra-l,4-quinone have also been used <00TL5957>. 

Nucleophilic addition of furan to nitrone occurs upon treatment with trimethyl-silyl triflate (TMSOTf) (586, 587). Catalyzed TMSOTf stereoselective addition of 2-[(trimethylsilyl)oxy]furan to chiral nitrones was carried out in a short synthesis of [IS (la, 2[), 7f>, 8a, 8aa)]-l,2-di(t-butyldiphenylsilyloxy)-indolizidine-7,8-diol (588). Addition to N -gulosyl-C-alkoxymethyl nitrones led to the synthesis of the core intermediate of polyoxin C (218). 

Substituting the benzene ring with a double bond, Pd-catalyzed intramolecular alkoxylation of alkyne 122 also proceeded via an alkenyl palladium complex to form furan 123 instead of a benzofurans [99, 100]. In addition, 3-hydroxyalkylbenzo[fc]furans was prepared by Bishop et al via a Pd-catalyzed heteroannulation of silyl-protected alkynols with 2-iodophenol in a fashion akin to the Larock indole synthesis, [101]. 

The reaction is applicable to acyclic and cyclic enol ethers and to various (3-dicarbonyl compounds, but fails with silyl enol ethers and simple 1,2-disubstituted alkenes. When applicable, this route to furans is useful because the yields and regioselectivity are consistently satisfactory. The paper includes a preparation of the reagent by reaction of Mn(NO,)3 with Ac20 at 100° to give Mn,0(0Ac)7 H0Ac in 60% yield. 

The reaction of acylsilanes with acid chlorides in the presence of A1C13 leads to furans (Table 9.41) [45]. In these reactions an acyl cation initiates the addition with ensuing silyl migration yielding an intermediate vinyl cation. Attack of the carbonyl oxygen followed by proton loss affords the observed products (Scheme 9.16). An analogous reaction with nitrosyl fluoroborate provides a route to oxazoles (Table 9.42) [65]. The nitrosyl cation serves as the electrophile in this application. 

The silylation of heteroarenes was also reported [96]. Silylation of thiophene or furan with 11 occurs selectively at the ot-position in the presence of [Ir(COD) (OMe)]2/2-ferf-butyl-l,10-phenanthroline (tbphen, 17). Silylation of pyrrole or indole under the same conditions was unsuccessful presumably due to the presence of the acidic N-H bond. Accordingly, N-substituted pyrrole and indole undergo silylation with 11, to selectively give 3-substituted products (Scheme 7). 

Falck has recently reported dehydrogenative silylation of heteroarenes with triethylsilane (18) [97]. Coupling with the Si-H bond of triethylsilane, rather than the disilane Si-Si bond, in conjunction with the use of norbomene that presumably acts as a hydrogen acceptor, gives good yields with indoles, thiophenes, and furans, under relatively mild condition (80°C). Unlike the reaction shown in Scheme 7, silylation of indole did not require protection of the N-H group. 

The addition of silyl radicals to double bonds in benzene or substituted benzenes (Reaction 5.2) is the key step in the mechanism of homolytic aromatic substitution with silanes [8,9]. The intermediate cyclohexadienyl radical 2 has been detected by both EPR and optical techniques [21,22]. Similar cyclohex-adienyl-type intermediates have also been detected with heteroaromatics like furan and thiophene [23]. 

The aromatic silylation of five-membered heteroarenes under the same conditions (catalyst, temperature, solvent) also proceeded in regioselective fashion. Both, thiophene and furane derivatives are exclusively silylated at the a-position, but 1-triisopropylsily 1-pyrrole and -indole each produce selectively ]3-silyl products (Equations 14.9 and 14.10). 

Oxidation of silyl enol ethers leading to carbon-carbon bond formation [85JCS(CC)420 87JCS(P1)559] finds an interesting application in the synthesis of furans. For example, l,4-di(3-thienyl)-l,4-butanedione (65), which... 

The class of 3-silyl-substituted reagents provides, upon addition with aldehydes, allylic silanes that offer many options for further derivatization. Oxidative processes are described in previous sections (see the sections on Preparation of 1,2-Diols and 1,4-Diols). If the appropriate silicon substituents are chosen, formal [3+2] cycloadditions with aldehydes can be promoted under Lewis acid catalysis. For example, the mismatched addition of the Z-3-propyl-3-benzhydryldimethyl allylsilane 183 to an a-benzyloxy aldehyde proceeds with low diastereofacial selectivity in favor of product 184 however, after protection of the secondary alcohol, an efficient [3+2] annulation provides the polysubsubstituted furan 185 in good yield and acceptable stereoselectivity (Scheme 24). ° The latter is brought forward to a tricyclic unit found in the antitumor natural product angelmicin B. 

---