Tebbe methylenation

PCC in the presence of 4 A MS to afford the corresponding keto sugars (175, 176), which after Tebbe methylenation led to the corresponding exoglycals, valuable intermediates for the synthesis of C-disaccharides. Dondoni el al.159 made use of PCC in the presence of powdered 4 A MS to introduce suitable formyl groups in the carbohydrate, and allowing the synthesis of >6)-linked oligosaccharides,... 

Tebbe methylenation < 1978JA3611 > of a-bromoacetophenone resulted in the formation of allylic bromide 165, which upon reaction with benzenesulfonamide gave the 1,6-diene 166 (Scheme 35). The acyclic diene 166 underwent photooxidative cyclization to form 1,2,5-dioxazepine 167 <1996TL815>. 

The opening move was the transformation of the known glucopyranoside 355 into exomethylene vinylpyranose 356. TIBAL-promoted Claisen rearrangement of 356 provided the cyclooctene derivative 357 almost quantitatively, which was then transformed to protected cyclooctanose 358 by methylation followed by hydroboration-oxidation. Installation of the hydroxymethyl function at C5 required three further operations oxidation of the Cs-hydroxyl, Tebbe methylenation, and hydroboration-oxidation. In the event, a mixture of epimeric... 

A Esterification B Tebbe methylenation C Oxocarbenium ion cyclization D Hydroboration... 

The synthesis of 4 and 5 provided an opportunity to evaluate the scope of a new C-glycosidation methodology that was used for 3 (28-34). Accordingly, esterification (step A) of the glycone component, l-thio-l,2-0-isopropylidene acetal (TIA) 16 and one or the other aglycone segments, C-branched saccharide acids 14 or 15, furnishes ester 12 or 13, respectively (Scheme 1). Tebbe methylenation (step B) of the latter provides enol ethers 10 or 11. Thiol... 

Lu X, Arthur G, Bittman R. Synthesis of a novel ceramide 91. analogue via Tebbe methylenation and evaluation of its antiproliferative activity. Org. Lett. 2005 7 1645-1648. 

The asymmetric total synthesis of the putative structure of the cytotoxic diterpenoid (-)-sclerophytin A was realized via a Tebbe-Claisen rearrangement of a tricyclic lactone precursor in the laboratory of L.A. Paquette/ The tricyclic lactone was subjected to the Tebbe methylenation protocol to provide the allyl vinyl ether that was then heated to 130-140 °C in p-cymene to undergo the Claisen rearrangement in good yield. 

Chlorodimethylaluminum (generated from the methylenation reagent) is presumed to be the catalyst in the one-pot Tebbe methylenation -Claisen rearrangement procedure. This process proceeds with 98% E selectivity17s. 

Quite recently, a new access to KDO from 1-thio-l, 2-O-isopropylidene acetal 196 has been reported [122]. Its condensation with 2-furoic acid, followed by the Tebbe methylenation afforded 198 (Scheme 42). Cyclization process was mediated by methyl triflate. Thus obtained 1-furano glycal derivative 199 was converted into KDO derivative 66 and its 2-deoxy-a-analog 200 in a reaction sequence shown in Scheme 43 [122]. 

The use of an acetal to tether the diene and dienophile has been investigated by Craig and co-workers [15], Preparation of the unsymmetrical acetal precursor was best achieved via the corresponding enol ether. For example, the isopropylidene-linked triene 28 was synthesized in two steps from acetate 29. Tebbe methylenation of 29 afforded enol ether 30, which was used directly in a Pd -catalyzed addition of the dienophile 3 to form 28 (acid-catalyzed addition with pTSA proved inferior). Thermolysis of 28 in toluene at 165°C allowed a remarkably facile and completely regiospecific cyclization to take place. Acidic methanolysis of the Diels-Alder adducts resulted in cleavage of the tether and isolation of a 2.7 1 mixture of lactones 31 and 32 in 72% yield (Scheme 10-9). 

The same group used a ketal tether as an alternative connecting group in the synthesis of the 1,4-linked C-disaccharide 236 [85 b]. Tebbe methylenation of acetate 237 provided the corresponding enol ether 238, which upon treatment with alcohol 235 in the presence of CSA at -40°C in acetonitrile, furnished linked disaccharide 239 in 81% yield. Subsequent radical cyclization, acidic hydrolysis of the tether and peracetylation provided the D-mannose-containing C-disaccharide 236 as the major product in 35% yield from 239 (Scheme 10-75). Cyclization was not completely stereoselective and a small amount of the )8-C-manno isomer was also isolated (a/)3 10 1). This result is in contrast to similar studies on tether-directed /J-C-mannoside syntheses (vide infra) where a much shorter tether attached to the axial 2-hydroxyl group forces obtention of the desired P-configuration. 

Hetero-fused 1,2-dioxanes result from the photo-oxygenation of 1,6-dienes obtained using Tebbe methylenation methodology (Scheme 16) <97T37>. 

Before tethering can be attempted, the 2-0-allyl group must first be iso-merised to a vinyl ether. Isomerisation was accomplished by treating glycosyl fluoride 74 with Wilkinson s catalyst and n-butyl lithium, which afforded vinyl ether 75 in an excellent yield of 96%. It is important to note that the Wilkinson s catalyst mediated isomersiation is very efiicient when compared to the previously used and capricious Tebbe methylenation methodology. Subsequent NIS-mediated tethering of secondary acceptor 76 to vinyl ether 75... 

Using double Tebbe methylenation (77 to 78) followed by a Claisen rearrangement, Paquette and co-workers developed a concise, reliable, and efficient scheme for 4-cyclooctenones. Using this methodology, Paquette reported an alternate enantioselective route to a key bicyclic intermediate,... 

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