Keto tosylate

The key step in a reported laboratory synthesis of sativene, a hydrocarbon isolated from the mold Helminthosporiuni sativum, involves the following base treatment of a keto tosylate. What kind of reaction is occurring How would you complete the synthesis ... 

Treatment of 21 with p-TsCl in pyridine, followed by acid hydrolysis of the acetal-tosylate 22 (HCl in acetone) afforded the keto tosylate 23 in 89% yield (Scheme 13.2.6). Although the introduction of the e /o-A-methylamino group into the acetal-tosylate 22 by an Sf 2 substitution is apparently an almost trivial... 

With the appropriate precursor rac-35 in hand, the rearrangement key step was examined. As expected, basic treatment of y-keto-tosylate rac-35 resulted in the formation of a 56/44 mixture of the formal substitution product rac-43 and rac-44 as the product of homoallylic rearrangement (Scheme 12), in a combined yield of 95%. 

Ganter has developed three different approaches to tricyclo[5.2.1.0 ]decane (403), yet another of the nineteen isomeric hydrocarbons of adamantaneland As seen in Scheme XXXIII, the routes involve intramolecular cyclization of keto tosylate 399 followed by Wolff-Kishner reduction of the resulting ketone, thermo-cyclization of 400 and subsequent dechlorination, hydrogenation, and photocycli-zation of aldehydes 401. Majerski s approach involved hypoiodite cleavage of alcohol 402... 

Treatment of the other product, the keto-tosylate, with base leads to an intramolecular enolate alkylation—a cyclization on the inside of the folded molecule that actually closes a four-membered ring. The reaction is easily seen in conformational terms and the product cannot readily be drawn in conventional diagrams. 

The synthesis of the tricyclic enone (237) has been reported (Scheme 35). The carbonyl group has previously been removed from this ketone to produce isolongifolene. The key step in this synthesis is the facile intramolecular y-alkylation of the keto-tosylate (236). 

The key step in the stereocontrolled total synthesis of the tricyclic (+)-kelsoene by M. Koreeda et al. was a base-catalyzed homo-Favorskii rearrangement of a y-keto tosylate to elaborate the 4-5 fused ring portion of the target molecule. The bicyclic 5-6 fused y-keto tosylate was treated with excess potassium fert-butoxide, which effected the desired rearrangement in less than 2 minutes at room temperature. The nucleophilic solvent was too bulky to effect the opening of the cyclobutanone intermediates, making their isolation possible. The mixture of isomeric cyclobutanones was converted to a separable 1 1 mixture of cyclobutanones with p-TsOH, and the ketone functionality was then removed via the corresponding tosylhydrazone. 

Intramolecular alkylation of a ketone. The key step in Whitlock s synthesis of twistane " was cyclization of the keto-tosylate with solid NaH in dimethylformamide. 

S—C Bond heterolysis dominates the photochemical reactivity of the keto tosylate 263247. Irradiation in benzene gives p-toluenesulphonic acid in 74% yield. The other products formed from this reaction are the ketones 264 and 265. The reaction is presumed to proceed via the intermediate carbocation 266 formed by S—C bond fission. The tosylate 267 is more able to undergo intramolecular addition due to the electron-donating methoxy group and gives 268 and 269 in 24% and 23% yields. An analogous mechanism is involved in the conversion of the sulphonate 270 on irradiation in benzene into the two products 271 and 272 in a ratio of 4 1249. The formation of the major product 271 presumably involves the heterolytic fission of an O—C bond to afford a cation which... 

Acetoacetates Exhibiting Fragmentation. The first class of add amplifiers consists of a-methylated acetoacetate derivatives having an add-labile ester unit (2). This type of compounds is transformed by the add-catalyzed deprotection into p-keto-acetic acid which is readily decarboxylated by heating into the corresponding keto-tosylate (3). 3 undergoes smoothly e p-elimination to afford an unsaturated ketone... 

Ketal Tosylates. The second candidate for the acid proliferation is ketal derivatives having a tosylated residue (5). These were synthesized by the ketalization of benzoylacetate, followed by LAH reduction and tosylation (5). Compound 5 (mp 48-50 C) had to be stored in a refrigerator since crystals of 5 were converted into black materials gradually at an ambient temperature upon prolonged storage. The ketal compound (5) was readily converted in the present of an addic spedes into p-keto-tosylate (6) which is subjected to the -elimination to give TsOH in a non-linear maimer (Scheme 2(b)). NMR spectra of a solution of 5 in the presence of TsCH at 100 revealed that e p-keto-tosylate (6) as an intermediate was formed during the reaction (6). 

The bicyclic keto-tosylate (103 X — OTs) and triflate (103 X = OTf) fragment on treatment with nucleophiles to give derivatives of 5-methylenecyclo-octene carboxy-late. Base-catalysed decomposition of iV-nitroso-compounds (104) proceeds by intramolecular diazoalkane-carbonyl addition hence (104 n = 1, m = 3) gave diethyl cycloheptane-1,4-dicarboxylate when treated with sodium ethoxideA [3,2,l]Propellane reacts with dimethyl acetylenedicarboxylate to give methylene-cycloheptane (105) amongst other products. 

Bicyclic compounds have apparently never been detected in the products resulting from the carbonium ion reactions of either acyclic precursors [e.g., (33-X) or (34-X)], or monocyclic menthane reactants [e.g., (35-X)] under quite a variety of conditions (77, 84, 86, 87), It appears to be necessary to provide additional driving force as in the acid-catalyzed cyclization of carvone enol acetate (44) 87) or the intramolecular enolate alkylation of keto tosylate (45) 88, 89) in order to overcome the strain energy of the bicyclo[2.2.1]heptane and bicyclo-[3.1.1]heptane rings. An additional factor in the latter case is, of course, increased electrophilic demand at a primary, as opposed to a tertiary, center. 

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