Lithiated dihydrofuran

The western part 97 of tylosin aglycon (96), a 16-membered macrolide, has also been synthesized using this Kocienski metalate rearrangement [66]. Treatment of the lithiated dihydrofuran 99 with the stannyl cuprate [67] obtained from Bu3SnLi and CuCN, followed by Mel alkylation, exclusively gave the E vinyl stan-nane 100, in 80% yield. In the last stage, stannyl cupration [68] of the deprotected enyne diol 101 afforded the desired ( , E) stannyl diene 97 in 85% yield. 

The addition of active methylene compounds to 2,3-dihydrofuran was promoted by catalytic amounts of AuCl3-AgOTf, providing 2-substituted THF derivatives, as depicted in the scheme below <05OL673>. 2-Lithiated dihydrofurans were shown to lead to heterospiro cycloalkanones <05H(66)57>. 

The first cyclization of a-hydroxyalkoxyallenes goes back to the pioneering experiments of Brandsma, Hoff and Arens, who found that dihydrofuran derivatives 102 are formed by treatment of 101 with KOtBu in DMSO (Scheme 8.26) [12c], This reaction protocol was successfully applied by others [61, 63, 64, 80-83], for example in the preparation of spiro compound 104 (Eq. 8.19) [83] and in the cyclization of 64 leading to a-amino acid-derived dihydrofurans 105 (Scheme 8.27) [61, 63], Acidic hydrolysis of dihydrofurans furnished 3(2H)-dihydrofuranones, which could be used again as carbonyl components in the repetitive addition of lithiated methoxyal-lene 42. This concept was employed in syntheses of racemic [82] and enantiomeri-cally pure [64] primary helical spirocycles. 

The effect of lithiating various unsaturated ethers, including 2,3-dihydrofuran, has been examined by means of 13C NMR spectroscopy and from the results (Table 24) the degree of s character in the unsaturated carbon atoms has been estimated. It differs but little amongst vinyl ethers and is somewhat more than the 33.3% of a formal sp2 hybrid (80JOC4959). 

Carbon-13 shift of common non-aromatic heterocycles with endo- and exocyclic double bonds are reviewed in Table 4.66 [416-432], - Deshieldings of / -carbons induced by carbonyl groups in heterocyclic a, /1-enones due to (—)-M electron withdrawal (e.g. 2-pyrones, coumarins) and shieldings of [ carbons in cyclic enol ethers arising from (+ )-M electron release (e.g. 2,3-dihydrofuran and oxepine derivatives in Table 4.66) fully correspond to the effects described for the open-chain analogs. Outstandingly large shift values are observed for the lithiated carbon in cyclic a-lithium enol ethers (Table 4.66). In terms of its a and / carbon-13 shifts, 2,7-dimethyloxepine is also a typical enol ether [420], Further, 2,6-dimethyl-4-pyrone [421] and flavone [422] display similiar shift values for the a, /1-enone substructure. 

Lithiation of 2,3-dihydrofurans (54) followed by elimination of a 1-alkene provides dUithium ynolate (55) (equation 22) . The properties and synthetic utility of 55 have not yet been studied. 

Another reaction of the lithiated l,3-dithiole-2-thione 103 with aryl carboxaldehydes, followed by acidic quenching of the resulting oxyanions, afforded bisalcohol products 109. In the presence of perchloric acid, a 1,4-aryl shift was observed to furnish new formylated derivatives 112 and 113. Phenyl and 2-methoxyphenyl diols gave dihydrofurans 110 and 111, respectively (Scheme 7) <2001CC369>. 

One of the first uses of directed metalation as a route to heterocycles was the synthesis of phthalans (2,3-benzo-l,4-dihydrofurans) by the thermally induced cyclization of the methiodides of ortho-substituted di-methylbenzylamines (Reaction 37) (45). The amine was lithiated in the ortho position by n-butyllithium and condensed with benzaldehyde and benzophenone. The corresponding alcohols obtained upon aqueous work-up were converted to their respective methiodides. Heating the methiodides to 200°C for one hour under nitrogen gave the phthalans... 

A mixture of 2-t-butylfuran and 2,5-di-t-butylfuran is obtained by the action of t-butyl chloride on furan in the presence of mesitylene nolybdenum tricarbonyl." The intermediate in the nitration of furan-2-aldehyde in acetic anhydride has been identified as compound (26). Treatment of 5-bromo-2-furoic acid with sulphur tetrafluoride in hydrogen fluoride yields the dihydrofuran (27). Bromo-furans are converted into aryl-furans by crosscoupling with aryl Grignard reagents in the presence of nickel(II)-phosphine complexes. 2-Furoic acid is lithiated at position 5, 3-furoic acid at C-2. 2-Methylfuran yields the 5-methylthio-derivative by lithiation and subsequent treatment with dimethyl disulphide. The corresponding phenylthio-compound (28) has been converted into a series of 4-substituted 2-methyl-furans (29 R = alkyl, MeaSi, CO2H, or RCHOH) by the sequence bromi-nation, lithiation, treatment with the appropriate electrophile, and, finally, desulphurization with Raney nickel. 2-Lithiofuran reacts with copper(II)... 

Methoxy- and 2-acetoxyfurans are available from 2,5-dimethoxy- and 2,5-diacetoxy-2,5-dihydrofurans (section 15.1.4) via acid-catalysed elimination. They undergo Diels-Alder cycloadditions the adducts can be further transformed into benzenoid compounds by acid-catalysed opening. 3,4-Dihydroxyfuran is undetectable in tautomeric equilibria between mono-enol and dicarbonyl forms the dimethyl ether behaves as a normal furan, undergoing easy a-electrophilic substitution, mono-or dilithiation at the o-position(s), and Diels-Alder cycloadditions.2,5-Bis(trimethylsilyloxy)furan is synthesised from succinic anhydride it too undergoes Diels Alder additions readily.Both 2- and 3-thiols can be obtained by reaction of lithiated furans with sulfur in each case the predominant tautomer is the thiol form. ... 

Various 3-ribofuranosyl-indoles, -pyrroles and -pyrazoles have been made by reaction of V-blocked heterocycles with 2,3,5-tri-C -benzyl-3-D-ribofuranosyl fluoride.Lithiation of 2,6-dichloroimida2o[l,2-a]pyridine occurs predominantly at C-5, and reaction with a ribono-y-lactone derivative and anomeric deoxygenation gives the 5-ribofuranosyl system 151 with good P-selectivity. The alternative 3-glycosylation pattern 152 could be obtained by palladium-catalysed coupling of 2,6-dichloro-3-iodoimidazo[l,2-a]pyridine with 2,3-dihydrofuran, followed by hydroxylation. Various pyrazolo[4,3-c]pyridine C-nucleosides such as 153 have been made using an effective tetrazole-to-pyrazole transformation carried out on a C-ribofuranosyltetrazole. A paper on the conformational properties of some purine-like C-nucleosides is mentioned in Chapter 21. 

Cyclic a-lithiated vinyl ethers can be smoothly generated by deprotonation of the kineticaUy acidic vinyl a-hydrogen of the parent compounds using an alkyUithium base, and their typical use in organic synthesis is as acyl anion equivalents (2005T3139). 2,3-Dihydrofuran, in particular, can be efficiently a-Hthiated with t-BuLi in THF to give anion 57, which can be subsequently alkylated by reaction with functionalized primary alkyl iodide 58 to furnish the substituted 2-alkyl-2,3-dihydrofuran 59. The latter can... 

Cydic akenyl ethers of general structure IV (X = O), like dihydrofuran and dihydropyran 50 (n = 1,2) are deprotonated by means of either f-BuLi in a mixture of pentane and THF or with -BuLi and TMEDA in hexane or pentane at 0 °C [41]. These compounds reacted with a great variety of electrophiles, their reaction with carbonyl compounds, followed by add treatment, giving spirocyclic ketones after suffering pinacol rearrangement [46]. Enantiomerically emidied spirocyclic compounds were obtained from the intermediate 51 (prepared from tin-lithium exchange) [47], or a-lithiated glucals 52 and 53 (prepared by direct deprotonation with t-BuLi) [48]. 

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