Barton esters reactions

DBU IS most widely employed as the base m the Barton-Zard reaction Stronger nonionic bases such as PrMeNCH-,CH-j,N and the phosphazene base Csiipplied by Flukai are more effective to induce pyrrole formadon in the reaction of nitroalkenes v/ith isocyano esters than DBU Sterically hindered nitroalkenes are converted into the corresponding pyrroles using these bases, as shovm in Eq 10 35, but DBU is not effective in this transformation... 

Pyrroles prepared by the Barton-Zard reaction are very important as precursors of porphyrins and also of conducting polymers. The ester group at the 2-position is readily removed on heating with KOH in ethylene glycol at 170 °C to give a-free pyrroles, which are useful for preparing porphyrins (Eq. 10.42)47 or polypyrroles (Eq. 10.43).38a,4S... 

Note 2), and 40 mL of methylene chloride (Note 3). The resulting homogeneous solution is cooled to 0°C and 4.99 g (27.1 mmol) of 10-undecenoic acid (1) is added dropwise (Note 4). Following the addition of the undecenoic acid, the ice bath is removed and the reaction mixture is allowed to warm to room temperature and stirred for a further 8 hr. The bright yellow suspension that results is filtered through a bed of silica gel (Note 5). The solvent is removed under reduced pressure to give 8.06 g of the crude Barton ester (3) (Notes 6 and 7). 

Thioethers have also been prepared on cross-linked polystyrene by radical addition of thiols to support-bound alkenes and by reaction of support-bound carbon radicals (generated by addition of carbon radicals to resin-bound acrylates) with esters of l-hydroxy-l,2-dihydro-2-pyridinethione ( Barton esters Entry 6, Table 8.5). Additional methods include the reaction of metallated supports with symmetric disulfides (Entries 7-9, Table 8.5) and the alkylation of polystyrene-bound, a-lithiated thioani-sole [65],... 

J. Nicholas Kirwan, B. P. Roberts, and C. R. Willis, Deoxygenation of alcohols by the reactions of their xanthate esters with triethylsilane An alternative to tributyltin hydride in the Barton-McCombie reaction, Tetrahedron Lett., 31 (1990) 5093-5096. 

A variety of different sources of radicals have been used in several heteroaromatic substitution reactions [2] these include acyl peroxides, oxaziridines, thiohydroxa-mic Barton esters, the Gif reaction, alkyl xanthates, and ketones/H202 (Scheme 8). 

Further acid-catalyzed reactions include the use of />-toluene sulfonic acid-DMF in a cyclization of the protected amino acid 17 (DMF = dimethylformamide Scheme 15) <20040L4941>. This was the key step in the stereoselective synthesis of 5-hydroxypipecolic acid. A similar acid-catalyzed ring closure of a hemiacetal yielded the fused piperidine 18 <2004JOC1872> (Equation 32). The indolizidine alkaloid can be accessed by a Barton-Ester method utilizing a polyphosphoric acid (PPA) cyclization (Scheme 16) <1994T19157>. 

Reaction of the Barton ester (124) with vinyl sulfone can be carried out under irradiation with a tungsten lamp (eq. 4.43) [123]. 

One great advantage of the Barton-McCombie reaction is that acetal, ketone, ester, hydroxy, and amino groups are not affected during the reaction [6-18]. Polystyrene-supported di-/i-butylstannane can reduce a thiocarbonyl derivative under the same... 

Since Barton decarboxylation can be performed under mild conditions, thermal or photolytic treatment of the Barton ester (13) of propionic acid with TV-hydroxy-2-thiopyridone in the presence of chiral menthyl acrylates generates addition products (14). However, diastereoselectivity is rather poor, since the chiral menthyl center is too far away from the C-C bond-forming position, as shown in eq. 10.7. When the chiral center is adjacent to the reaction position, stereocontrol is significantly affected, as shown in eq. 10.8 [9-12]. 

Both Bu3SnH and (Me3Si)3SiH are able to reduce alkyl iodides or bromides but not alcohols. However, in the Barton-McCombie reaction, they reduce certain alcohol derivatives, namely, ones that contain a C=S double bond (e. g., thiocarboxylic esters or thiocarbonic esters). Figure 1.39 shows how the OH group of cholesterol can he removed by means of a Barton-McCombie reaction. The C=S-containing alcohol derivative used there is a xanthate. 

The best-known reactions belonging to this class are based either on the photo-NOCAS process [32] or on the photochemistry of Barton esters [69]. In the first case, a three-component reaction involving a cyanoarene, an olefin, and a nucleophile (usually the solvent) occurs. The reaction is generally initiated by a PET process between the aromatic and the olefin. The examples presented below are chosen from among the most representative and most recent. A typical reaction is illustrated in Scheme 3.26, where an enolized P-dicarbonyl compound acts as an added nucleophile. 

Musso has reported the synthesis of diasterane (tricyclo-[3.1.1.I2 4]octane) 15. For this first member of the series of asteranes, the decarboxylation of 16b -> 16c was best achieved via the photolysis of the Barton ester of 16a in the presence of BuSH, as shown in Scheme 5.14 Fukumoto has accomplished asymmetric total synthesis of atisine 17, where the bridged pentacyclic intermediate 18, a precursor for atisine, was synthesized via an intramolecular double Michael reaction starting with 19, Scheme 6.15 Barton protocol was favored during the late stages of the synthesis and the presence of various functionalities was easily accommodated. 

Vogel and coworkers have described the synthesis of anti-1,6 7,12-/ wmethano[ 14]annulene 44 for studies of its -electron structure.32 Incorporation of AIBN into decarboxylative bromination of vinylogous carboxylic acid 45 via Barton esters increased the efficiency of this reaction, Scheme 16b. Harvey... 

All these reactions discussed thus far have called upon thermal or photoinitiation techniques for the generation of radicals from Barton esters. An altogether new approach was developed by Dauben and coworkers where the "CC13 radical generated by ultrasound propagates the chain sequence outlined in Scheme 51.82... 

Piperidine 141 was synthesized from the Barton-McCombie reaction <75JCSP11574> of 142 which gave the expected amido-ester (96 %) as a 3 2-mixture of diastereomers. The mixture was hydrolyzed to the corresponding carboxylic acid which, upon thermal decarboxylation, gave the desired /V-bcnzyl lactam (85% overall yield) as a single diastereomer whose structure was unequivocally established by a single-crystal X-ray analysis. Reduction of the lactam with LiAlH4 (81%) followed by debenzylation via... 

An icc-cooled mixture of Barton ester 19(R = CHjBn 1.036 g, 4.00 mmol). l,l-dichloro-2,2-difluoroethene (5 mL. ca. 53 mmol), and MeCN (5 mL) in a reaction flask equipped with a reflux condenser, in which 30 C coolant (EtOH/H O) was circulated, was irradiated with a 500-W tungsten lamp until the yellow color disappeared (in this case. 7h). After recovery of unreacted l.l-dichloro-2.2-difluoroethene by distillation at 30 C. the solvent was removed under reduced pressure. The residue was chromatographed (silica gel. hexane/EtOAc) to give pure products phenethyl 2-pyridyl sulfide (21. R = CHjBn) yield 291 mg (36%) and l.l-dichloro-2.2-difluoro-4-phenylbutyl 2-pvridyl sulfide (20. R = CH,Bn) yield 552mg (40%). 

Taddei [7] has studied the use of the Barton decarboxylation reaction in solid-phase chemistry. FeasibiUty studies began with the preparation of simple immobihzed Barton ester 37 from Wang resin-derived acid 36 (Scheme 8). Irradiation of 37 followed by acid cleavage gave 38 in good overall yield. Attempts to prepare bromide 39 by interception of the intermediate radical... 

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