Esters allyl, ozonolysis

The ozonolysis of substituted-allyl silyl ethers or allyl esters followed by treatment with bases or Ph3P give the corresponding a-silyloxy ketones or a-acyloxy ketones.116 The reaction is proposed to proceed via an ene-diol rearrangement of the corresponding a-silyloxyaldehyde or a-acyloxyaldehydes intermediates. 

The second synthetic approach to oidiolactone C (61) is summarized in Scheme 20. This route also commences with the ozonolysis of trans-communic acid 180. Now, when this compound was exposed to ozone in excess, keto aldehyde 187 was obtained in 76% yield. The key step in this approach was the y-lactone closure via chemoselective reduction of the lactone moiety on compound 189 through a SN2 mechanism. Compound 189 could be prepared by saponification of the corresponding methyl ester with sodium propanethiolate. Once the primary alcohol is oxidized, the completion of the synthesis of key lactone 103 only requires the allylic oxidation of the C-17 methyl with concomitant closure of the 8-lactone. This conversion was achieved with Se02 in refluxing acetic acid to give 103 in 51% yield. 

The reaction of methyl ester of D-alanine 185 with 4-methoxy-2-nitrobenzenesulfonyl chloride 186 in presence of ethyl diisopropylamine gave the sulfonamide 187, which was alkylated with allyl bromide 188 to afford 189 (Scheme 41). Ozonolysis of 189 resulted in the formation of aldehyde 190, and the subsequent reductive cyclization with zinc and AcOH led to the benzothiadiazepine 120 through intramolecular reductive alkylation. Using similar reaction sequence, the 1,2,5-thiadiazepines 191 and 192 were also synthesized <2003JME1811>. 

Le Carrer-Le Goff and co-workers have reported an expeditious synthetic route to a-substituted statines by the well-defined metal-mediated allylation of V-protected a-amino aldehydes followed by the ozonolysis of the double bond (Scheme 11.3).16 Ozonolysis of the double bond in 13, carried out in dichloromethane/methanol, at -78°C in the presence of sodium hydroxide permits the intermediate ozonide to be converted directly to the statine methyl ester 14.17... 

The alkaloids are chiral as a result of restricted rotation of the biaryl system as well as of the possession of asymmetric carbon atoms the methyl at C-3 is on the a-face in all alkaloids and that at C-1 on the B-face in most, but not all cases. The structure of ancistrocladine has been determined by oxidation to the acid (13) the methyl ester of which is prepared by two routes, and by Hofmann degradation of its 0,n-dimethyl-derivative successively to the methine base (14) and the nitrogen-free products (15) and (16), the second of which on ozonolysis gives an aldehyde which yields the lactone (17) on oxidation. The position of the phenolic hydroxyl group in the alkaloid has been confirmed by Claisen rearrangement of the allyl ether (T.R. Govindachari and P.C. Parthasarathy, Tetrahedron, 1971, 1013). 

Dimethylcyclohexenone was treated with vinyl magnesium bromide in the presence of cuprous bromide to afford a ketone 2. After protection of the carbonyl group with ethylene acetal, hydroboration, oxidation, and methylation with diazomethane yielded a methyl ester 6. The methyl ester 6 was treated with LDA/allyl bromide to give 7, followed by ozonolysis to afford an aldehyde 8. 

Allylic substitution. Di-Boc-allylamines are readily obtained from allyl acetates. The products are converted into protected glycine esters on ozonolysis. 

When simple aldehydes were converted to allylic alcohols, they could be transformed to the corresponding trichloroacetimidates and subjected to thermal rearrangement to provide aUyl amines. The aUyl amine functionality was also accessible from enantio-selective reduction of propargyl ketones followed by conversion to the phthalamide derivative and reduction of the triple bond. Ozonolysis of these substrates provided the corresponding a-amino methyl esters in good yield (eq 48). As with the allyl alcohols, optically active substrates were treated with ozone without loss of enantiopurity of the chiral center. 

Synthesis of the /3-amino methyl esters was accomplished by Grignard addition to aldehydes or epoxides to deliver the ho-moallylic alcohols. After conversion to the homoamino derivative as prescribed in the allylic alcohol to allylic amine conversion, ozonolysis delivered the targets in good yield, without loss of optical activity or nitrogen protection (eq 49). Numerous additional examples as well as synthetic possibilities exist for the synthesis of natural product fragments utilizing this methodology. 

Analogues 249 (X = H, OH) of UDP-GlcNAc have been prepared as potential inhibitors of chitin synthetases. The synthetic route involved a C-allyl derivative of GlcNAc, which was elaborated by ozonolysis, Wittig reaction and coupling with the nucleoside, followed by hydrogenation or hydroxylation as appropriate. The corresponding amides were also prepared from 5 -amino-5 -deoxyuridine. Lipophilic amino acid methyl esters and methylamides have been coupled to 0-5 of AZT by carbamate links. The products showed anti-HIV activity, but this was not due to carbamate hydrolysis or to direct inhibition of reverse transcriptase, and the mechanism of action may be one not previously observed with nucleoside antivirals. ... 

The aldehyde 218 possessing 2,6-frans-tetrahydropyran, was synthesized as shown in Scheme 48. /3-Keto ester 220 was reduced by Noyori hydrogenation [97] to give 6-hydroxy ester 221 in 94% ee, which was converted into iodide 222. Asymmetric alkylation using Myers chiral auxiliary [98] with 222, followed by acid treatment, furnished 5-lactone 223 with high stereoselectivity. Reductive acetylation, axial allylation by the Hosomi-Sakurai reaction, and ozonolysis completed the synthesis of 218. 

Lithiated allyl sulfide 256-Li reacted with m-xylylene dibromide 257 to afford the bis-sulfide 258. A double Mislow-Evans rearrangement of 258 and subsequent reductive trapping of the sulfenate ester provided the symmetric trans-diol 255. Monoprotection, Sharpless asymmetric epoxidation, and reductive ring-opening of the epoxide gave 1,3-diol 259 in 97% ee. After several functionalizations, the arene was subjected to Birch reduction to provide 1,4-cyclohexadiene 254. Ozonolysis of the diene, followed by reductive workup and treatment of the resulting 1,3-diketone with acid furnished pyra-... 

The synthesis of 252 began with Brown s asymmetric crotylation to aldehyde 261. The resulting homoallyl alcohol was converted benzyl ester 262, which was reduced to give lactol acetate 263. Axial allylation to 263 formed 2,6-trans-tetrahydropyran 264, which was subjected to ozonolysis to give an aldehyde. Addition of alkenylzinc, prepared by hydrozircona-tion of an alkyne 265, to the aldehyde mediated by chiral ligand 266 yielded allyl alcohol 267 with a 5.1 1 diastereoselectivity [110]. The stereochemistry of the major isomer was found, unexpectedly, to be the S-form at Cl7, which rendered the macrolactonization to adopt the Mitsunobu reaction. The iodide 252, prepared from 267 in three steps, reacted with... 

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