Alcohols oxidation with Jones reagent

The synthetic sequence, which shows only the succesful solutions adopted in every step, is outlined in Scheme 13.1.11. Reaction of l Chloroadamantan-4-one (39) [15] with sodium-potassium alloy in ether gave a mixture of ketonic and hydroxylated material which upon oxidation with Jones reagent gave 7-methylenebicyclo[3.3.1]nonan-2-one (40) in 75% yield. Reduction of 40 with sodium borohydride gave the alcohol 41 which could be also obtained in better yields from l-chloroadamantan-4-one with a large excess of sodium-potassium... 

The acid 350 was demethylated with pyridine hydrochloride, then realkylated with benzyl bromide in aqueous potassium hydroxide to give 351. The latter was converted to the diazoketone 352 by the sequential treatment of 351 with oxalyl chloride and etheral diazomethane. Reaction of 352 with concentrated hydrobromic acid gave the bromoketone 353. The latter was reduced with sodium borohydride at pH 8 -9 to yield a mixture of diastere-omeric bromohydrins 354. Protection of the free hydroxyl as a tetrahydro-pyranyl ether and hydrogenolysis of the benzyl residue afforded 355. The phenol 355 was heated under reflux with potassium m/V-butoxide in tert-butyl alcohol for 5 hr to give a 3 1 epimeric mixture of dienone ethers 356 and 357 in about 50% yield. Treatment of this mixture with dilute acid gave the epimeric alcohols 358 and 359. This mixture was oxidized with Jones reagent to afford the diketone 349. 

A special category of ethers are trimethylsilyl ethers. Trimethylsilyl ethers of primary alcohols, on treatment with Jones reagent, give acids [590]. On treatment with A-bromosuccinimide under irradiation, trimethylsilyl ethers yield esters [744]. Secondary alkyl trimethylsilyl ethers are converted into ketones by oxidation with both reagents [590, 744, 981]. Oxidation with Jones reagent is regiospecific the 2-ferf-butyldimethylsilyl 11-Krf-butyldiphenylsilyl ether of 2,11-dodecanediol is oxidized only in the sterically less hindered position [590]. Trimethylsilyl ethers of tertiary alcohols are degraded by periodic acid to carboxylic acids with shorter chains [755] (equations 336-339). 

The conversion of 187 into lycopodine was readily accomplished. Reduction of 187 with lithium aluminum hydride gave the mixture of epimeric alcohols 193 that was oxidized with Jones reagent to the ketone 192. Selenium dioxide gave the known diosphenol 194 which was converted into a separable mixture of lycopodine, anhydro-dihydrolycopodine (195), and dihydrodeoxylycopodine (196) by heating with hydrazine in diethylene glycol at 155°. 

Mild acid then cleaves off the silyl protecting group. The alcohol at position 17 is then oxidized with Jones reagent (chromium trioxide in acetone) to afford 14a-hydroxyestrone 3-methyl ether (32-5). 

Two series of reactions were carried out on this compound. In one of these, the tosyl amino alcohol 418 was reacted with /3-chloropropionyl chloride followed by oxidation with Jones reagent to give the tosyl keto amide 419. Elimination of HC1 with potassium carbonate in methylene chloride and cyclization of the acrylamide with Meerwein s reagent gave the N-tosyl keto lactam 420. This compound was also prepared by the previously discussed route (203). 

Baneijee and Vera [21] developed an alternative route for the synthesis of the diester (42) as depicted in "Fig (4)" whose conversion to warburganal (12) has already been reported [20], The starting material for the present synthesis was the ketone (1) which was converted to the alcohol (24) by procedure [12] as shown in "Fig (3)" and this on oxidation with Jones reagent afforded the ketone (6) whose alternative preparation has already been reported [10], The ketone (6) on treatment with... 

The keto ether (187) on treatment with diethyl carbonate in presence of sodium hydride in 1,2-dimethoxyethane afforded the keto ether (188), which was made to react with methyl-lithium in ether, to obtain the tertiary alcohol (189). This on being refluxed with methanolic hydrochloric acid yielded the phenol (190). It was methylated to yield(191) and heated with zinc, zinc iodide and acetic acid to produce pisiferol (192). Its methyl derivative (193) on oxidation with Jones reagent at room temperature, followed by esterification, furnished the keto ester (194). Reduction of (194) with metal hydride produced an alcohol whose tosyl derivative on heating with sodium iodide and zinc dust furnished the ester (195). Its identity was confirmed by comparing its spectral data and melting point with an authentic specimen [77]. The transformation of the ester (195) to pisiferic acid (196) was achieved by treatment with aluminium bromide and ethanethiol. The identity of the resulting pisiferic acid (196) was confirmed by comparison of its spectroscopic properties (IR and NMR) with an authentic specimen [77]. 

Fig. (17). The already described alcohol (15) prepared from the methyl analog of Wieland-Miescher ketone (2) is converted to olefinic compound (201) applying the standard organic reactions. Its transformation to the ketone (202) is subjected to hydroboration-oxidation with Jones reagent, metal hydride reduction respectively. Its conversion to pisiferic acid (196) was carried out by the procedures described in Fig. (16)" and thus requires no comments.

This is what you would expect, based on the information in (ii). So, what s coprostanol Because it gives J on oxidation with Jones reagent, it must be one of the two alcohols... 

Jones reagent. Oxidation of the alcohol (1) with Jones reagent does not give the expected ketone, but the 8-lactone (2). The -methaxy group was shown to be essential for this oxidation of a methyl group. The expected ketone is obtained under Oppenauer conditions. 

Then, commercially available o-xylose (471) was treated with cyclopentanone to protect two of the four alcohol groups as acetals. Subsequent tosylation of the primary alcohol function and reduction to a methyl group led to compound 472 in 65% over four steps. In the next step, the xylose derivative was coupled with olefin chloride 470, followed by desilylation and oxidation with Jones reagent to provide the xylose derivative 473. This was coupled with verrucarol (454) and then converted into phosphono ester compound 474 (Scheme 8.19 and 8.20). 

Finally, the remaining steps were accomplished by methylation of 26a with methyl fluorosulphonate in ether to give the methylammonium salt 25, reductive cleavage of the N-0 bond with LAH and oxidation of the resulting alcohol with Jones reagent. The yields of the last three steps are almost quantitative and the overall yield of the seven steps synthetic sequence leading to optically pure (+)-luciduline (1) is 33%. 

The mechanism of the oxidation of alcohols with Jones reagent is often depicted as given below.4... 

In fact, it has been reported34 that benzyl ethers can react with Jones reagent, resulting in the formation of ketones and benzoates. This happens under relatively harsh conditions, and nonnally no interference from benzyl ethers is observed during the oxidation of alcohols with Jones reagent. 

Nitrocompounds resist the action of PDC during the oxidation of alcohols.157 On rare occasions, PDC can promote the attack of nucleophiles on nitro groups, in a similar manner to the one observed with Jones reagent (see page 10). 

The oxidation of primary alcohols with K2Cr207 in aqueous solution to nothing but the aldehyde, (i.e., without further oxidation to the carboxylic acid) is possible only if a volatile aldehyde results and is distilled off as it is formed. This is the only way to prevent the further oxidation of the aldehyde in the (aqueous) reaction mixture. Selective oxidations of primary alcohols to aldehydes with the Jones reagent succeed only for allylic and benzylic alcohols. Otherwise, the Jones reagent directly converts alcohols into carboxylic acids (see above). 

Cyclization of enone (9) in hexane with boron trifluorideetherate in presence of 1,2-ethanedithiol, followed by hydrolysis with mercury (II) chloride in acetonitrile, yielded the cis-isomer (10) (16%) and transisomer (11) (28%). Reduction of (10) with lithium aluminium hydride in tetrahydrofuran followed by acetylation with acetic anhydride and pyridine gave two epimeric acetates (12) (32%) and (13) (52%) whose configuration was determined by NMR spectroscopy. Oxidation of (12) with Jones reagent afforded ketone (14) which was converted to the a, 3-unsaturated ketone (15) by bromination with pyridinium tribromide in dichloromethane followed by dehydrobromination with lithium carbonate and lithium bromide in dimethylformamide. Ketone (15), on catalytic hydrogenation with Pd-C in the presence of perchloric acid, produced compound (16) (72%) and (14) (17%). The compound (16) was converted to alcohol (17) by reduction with lithium aluminium hydride. 

Oxidation of anopterine with chromic acid-pyridine followed by hydrolysis afforded (85). Oxidation of anopterine with Jones reagent, followed by hydrolysis, was shown to yield a monoketone, which was assigned probable structure (86). Reduction of (86) with sodium borohydride gave a 4 1 mixture, with anopteryl alcohol as the major product. Jones oxidation of anopteryl alcohol gave a mixture of (87) and (88). On oxidation of (85) (from anopterine) with Jones reagent, the tetraketone (89) was obtained. 

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