Ozonolysis derivatives

Versatile [3 + 2]-cydoaddition pathways to five-membered carbocydes involve the trimethylenemethane (= 2-methylene-propanediyl) synthon (B.M. Trost, 1986). Palladium(0)-induced 1,3-elimination at suitable reagents generates a reactive n -2-methylene-l,3-propa-nediyl complex which reacts highly diastereoselectively with electron-deficient olefins. The resulting methylenecyclopentanes are easily modified, e. g., by ozonolysis, hydroboration etc., and thus a large variety of interesting cyclopcntane derivatives is accessible. 

As mentioned previously, aldehydes can be prepared by Stephen s method of reduction of nitriles by stannous chloride (37, 91). Polaro-graphic reduction of thiazolecarboxylic acids and their derivatives gives lower yields of aldehydes (58). Ozonolysis of styrylthiazoles, for example, 2-styryl-4-methylthiazole, followed by catalytic reduction gives aldehyde with 47% yield of crude product (30). 

Rhodium catalyst is used to convert linear alpha-olefins to heptanoic and pelargonic acids (see Carboxylic acids, manufacture). These acids can also be made from the ozonolysis of oleic acid, as done by the Henkel Corp. Emery Group, or by steam cracking methyl ricinoleate, a by-product of the manufacture of nylon-11, an Atochem process in France (4). Neoacids are derived from isobutylene and nonene (4) (see Carboxylic acids, trialkylacetic acids). 

In an unusual application of the Wittig reaction, treatment of clavulanic acid derivatives and esters of penicillin V with methoxycarbonylmethylenetriphenylphosphorane afforded the corresponding exo-alkylideneazetidines. Thus penicillin V benzyl ester (104) gave (lOS) as a mixture of E and Z isomers. The /3-lactam could be regenerated by low-temperature ozonolysis (81CC929). 

Ozonolysis, then reduction with Na2S204 at 50°, 57% yield.The 3,4-dimethoxyphenyl derivative was cleaved in 71% yield using these conditions. Ceric ammonium nitrate was reported not to work in this example. 

Tomoi and coworkers adopted a somewhat more direct approach in their synthesis of 16-crown-5 derivatives bearing a single alkenyl residue. They hoped to obtain precursors to polymers which could be used as phase transfer catalysts. In this approach I,I-bis-chloromethylethylene (a-chloromethallyl chloride) was allowed to react with the dianion of tetraethylene glycol (NaH/THF). By this method, methylene-16-crown-5 could be isolated in 66% yield after vacuum distillation. Ozonolysis led, in almost quantitative yield, to the formation of oxo-16-crown-5 as shown in Eq. (3.38). These authors prepared a number of other, closely related species by similar methods. 

The degradation of a 20-ketopregnane to a l7-ketoandrostane by ozonolysis first requires conversion of the 20-ketone to a A -oIefinic derivative. This can be accomplished by ... 

By converting the A" -3-ketone into its 2-hydroxymethylene derivative, selective ozonolysis to the 2,3-seco-2,3-dicarboxylic acid can be carried out in the presence of the A -double bond. Weisenborn has thus prepared A-nortesto-sterone and A-norprogesterone. In the latter case, selective formyla-tion at C-2 was achieved by first reducing the 20-ketone to the 20-ol (4). 

Butylethylidene and 1-phenylethylidene ketals were prepared selectively from the C4-C6, 1,3-diol in glucose by an acid-catalyzed transketalization reaction [e.g., Me3CC(OMe)2CH3, TsOH/DMF, 24 h, 79% yield PhC(OMe)2Me, TsOH, DMF, 24 h, 90% yield, respectively]. They are cleaved by acidic hydrolysis AcOH, 20°, 90 min, 100% yield, and AcOH, 20°, 3 days, 100% yield, respectively. Ozonolysis of the /-butylmethylidene ketal affords hydroxy ester, albeit with poor regiocontrol, but a more sterically differentiated derivative may give better selectivity, as was observed with the ethylidene ketal. ... 

The 2,2 -bis(phenylthiomethyl) dispiroketal (dispoke) derivative is cleaved by oxidation to the sulfone, followed by treatment with LiN(TMS)2. The related bromo and iodo derivatives are cleaved reductively with LDBB (lithium 4,4 -di- -butylbiphenylide) or by elimination with the P4- -butylphosphazene base and acid hydrolysis of the enol ether. The 2,2-diphenyl dispiroketal is cleaved with FeCl3 (CH2CI2, rt, overnight)." The dimethyl dispiroketal is cleaved with TFA, and the allyl derivative is cleaved by ozonolysis followed by elimination. ... 

Alicyclic hydroxamic acids undergo several specific oxidative cleavage reactions which may be of diagnostic or preparative value. In the pyrrolidine series compounds of type 66 have been oxidized with sodium hypobromite or with periodates to give y-nitroso acids (113). Ozonolysis gives the corresponding y-nitro acids. The related cyclic aldonitrone.s are also oxidized by periodate to nitroso acids, presumably via the hydroxamic acids.This periodate fission was used in the complex degradation of J -nitrones derived from aconitine. 

A stereospecific total synthesis of polyoxin C and related nucleosides is reported, in which thereacdon of l-Cphenylthioi-l-nitroalkenes v/ith nucleophiles and siibseqiientozono lysis are key reacdons Addidonof potassium trimethylsilanoate to l-Cphenylthioi-nitroalkenes derived from D-ribose followed by ozonolysis gives the cr-hydroxy thioester, which is formed v/ith excellent diastereoselecdvity fScheme 4 5 This conformadon meets the stereo-electronic requirements for andperiplanar addition of the nucleophile with the result of high 5-fS stereochemical bias in the reacdons... 

Metalated SAMP- or RAMP-hydrazones derived from alkyl- or arylethyl ketones 3 add to arylaldehydes both diastereo- and enantioselectively. Substituted / -hydroxy ketones with relative syn configuration of the major diastereomer are obtained with de 51-80% and 70-80% ee. However, recrystallization of the aldol adducts, followed by ozonolysis, furnishes diastereo- and enantiomerically pure (lS, S )-. yn-a-mcthyl-/3-hydroxy ketones 5 in 36-51% overall yield. The absolute configuration of the aldol adducts was established by X-ray crystallographic analysis. Starting from the SAMP- or RAMP-hydrazone either enantiomer, (S,S) or (R,R), is available using this methodology16. 

Ebdon and coworkers22 "232 have reported telechelic synthesis by a process that involves copolymerizing butadiene or acetylene derivatives to form polymers with internal unsaturation. Ozonolysis of these polymers yields di-end functional polymers. The a,o>dicarboxy1ic acid telechelic was prepared from poly(S-s tot-B) (Scheme 7.19). Precautions were necessary to stop degradation of the PS chains during ozonolysis. 28 The presence of pendant carboxylic acid groups, formed by ozonolysis of 1,2-diene units, was not reported. 

The location of the position of double bonds in alkenes or similar compounds is a difficult process when only very small amounts of sample are available [712,713]. Hass spectrometry is often unsuited for this purpose unless the position of the double bond is fixed by derivatization. Oxidation of the double bond to either an ozonide or cis-diol, or formation of a methoxy or epoxide derivative, can be carried out on micrograms to nanograms of sample [713-716]. Single peaks can be trapped in a cooled section of a capillary tube and derivatized within the trap for reinjection. Ozonolysis is simple to carry out and occurs sufficiently rapidly that reaction temperatures of -70 C are common [436,705,707,713-717]. Several micro-ozonolysis. apparatuses are commercially available or can be readily assembled in the laboratory using standard equipment and a Tesla coil (vacuum tester) to generate the ozone. Reaction yields of ozonolysis products are typically 70 to 95t, although structures such as... 

Diastereoselective conjugate addition of oxygen and nitrogen- centered nucleophiles to nitroalke-nes derived from (+)-camphoisulfonic acid and ozonolysis give a-hydroxy and a-amino thiol acid derivatives (Eq. 4.39). In all cases, the (/ )-diasteromer is formed as the major component.49... 

The strategy employed in studies aiming at the synthesis of the spiro segment of halichlorine (see also Section 12.01.11.4) involved a ring expansion in indolizidine 264. The double bond of this compound was cleaved by ozonolysis yielding compound 265, which was cyclized to quinolizidine derivative 266 in the presence of base (Scheme 56) <2004TL2879>. 

Several lupin alkaloids have been derived from the unsaturated quinalozidine 433, that was obtained in the treatment of amine 431 with ortho-quinone 432. This quinone behaves as a model of topaquinone, the cofactor of copper-containing amine oxidases. The cyclization step involved a nucleophilic attack of the piperidine nitrogen of 431 onto a side-chain aldehyde function that is unmasked by the oxidative deamination. Quinolizine 433, when treated with dehydropiperidine, gave the oxime ether 434 that, on ozonolysis followed by reduction, afforded sparteine 10, presumably via the bis(iminium) system 435 (Scheme 102) <1996JOC5581>. 

Protected pyrazoline derivatives 429 can be transformed by conventional ozonolysis methodology to the corresponding aldehydes 430, then the Cbz protecting group is removed and the intramolecular reductive amination using... 

Iridium-catalyzed transfer hydrogenation of aldehyde 73 in the presence of 1,1-dimethylallene promotes tert-prenylation [64] to form the secondary neopentyl alcohol 74. In this process, isopropanol serves as the hydrogen donor, and the isolated iridium complex prepared from [Ir(cod)Cl]2, allyl acetate, m-nitrobenzoic acid, and (S)-SEGPHOS is used as catalyst. Complete levels of catalyst-directed diastereoselectivity are observed. Exposure of neopentyl alcohol 74 to acetic anhydride followed by ozonolysis provides p-acetoxy aldehyde 75. Reductive coupling of aldehyde 75 with allyl acetate under transfer hydrogenation conditions results in the formation of homoallylic alcohol 76. As the stereochemistry of this addition is irrelevant, an achiral iridium complex derived from [Ir(cod)Cl]2, allyl acetate, m-nitrobenzoic acid, and BIPHEP was employed as catalyst (Scheme 5.9). 

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