Ozonolysis formylation

Ozonization of A -steroids usually gives complex mixtures (however, see ref. 48). Ozonolysis became a practical step in the general synthesis of B-norsteroids with the discovery that added methanol" (or formaldehyde ) improves yields significantly. Thus, Tanabe and Morisawa prepared 5/ -hydroxy-6/ -formyl-B-norsteroids (74) from cholesterol acetate, dehydroepiandrosterone acetate and pregnenolone acetate in overall yields of 64-74% by the reaction sequence represented below. 

Ozonuies (1,2,4-trioxolanes) are generally obtained by the reaction of fluoroalkenes with ozone Thus, vmyl fluonde is oxidized to monofluoroozomde and formyl fluonde [23] (equation 15) The same ozomde is formed by ozonolysis of a mixture of cis 1,2-difluoroethylene with ethylene [24]... 

The (Z)- and ( )-styrylpyrazine structures 20j and 20k were assigned on the base of the mass, NMR, and UV spectral data. The mass spectrum of Z isomer (20j) shows a base peak (the molecular ion) at m/z 210 with a peak at m/z 133 formed by the loss of a phenyl group firom 20j. The H-NMR spectrum shows the presence of five aromatic and two olefinic protons in addition to one heteroaromatic proton and two methyl groups attached to the heteroaromatic nucleus. Ozonolysis of the Z isomer (20j) yields 3-formyl-2,5-dimethylpyrazine (487) and benzaldehyde, confirming the styryl moiety in 20j. The ( )-styryl derivative (20k) is readily isomerized to the Z isomer (20j) on exposure to sunlight (Scheme 60). Extraction of the pyrazines from I. humillis in the dark indicates that E isomer 20k is the naturally occurring product 144,145). 

Ozonolysis and subsequent reduction open the way to formyl and hydroxymethyl branched-chain derivatives [18]. High stereoselectivities are generally observed on Grignard addition on conformationally biased ketosugars such as 3 (Scheme 6), equatorial attack being strongly favored, giving the axial alcohol 4 as the major product. 

An attempted synthesis of 9-methylnaphtho[crf]oxepine-2-one 494 by heterocyclization of 8-acetyl-1-naphthoic acid 491 (R = Me, R = H) has failed. In acidic medium or on heating acid 491 to 150°C, as well as under formation conditions for the acid chloride or ester from acid 491, 2-acetylacenaphthene-l-one 495 is obtained (79ZOR1562). A synthesis of tribenzo[c]oxepine derivatives 499 and 501 has been described as resulting from heterocyclization of the products of reduction (498) or oxidation (500) of 4-formyl-5-carboxyphenanthrene 497. The latter compound was obtained on ozonolysis of pyrene 496 [71JCS(C)729]. 

Ozonolysis of tri-O-acetyl-D-glucal (22) followed by work-up with Et3N-Ac20, led to the O-formylated derivative 23 of methyl-D-arabinonate in 77% yield.48... 

Ozonolysis of the cyclic vinyl ethers 71 (n = 2, 3 or 4) in the presence of M-benzylidene-benzylamine affords the dioxazoles 73 by dipolar cycloaddition to transient carbonyl oxides 72. The dioxazoles fragment to mixtures of phenylcycloalkenes, benzaldehyde and N-formyl-benzylamine by the action of silica gel (94JCS2449). Carbonyl oxides 75 (E = C02Me), generated by thermolysis of the peroxides 74, add to phenyl isocyanate to yield 1,2,4-dioxa-zolidin-3-ones 76 (94JCS3295). 

One method for the synthesis of hydroxyalkyl-substituted P-lactams is by the Staudinger reaction, the most frequently used method for the synthesis of P-lactams.86 This method for the preparation of 4-acetoxy- and 4-formyl-substituted P-lactams involves the use of diazoketones prepared from amino acids. These diazoketones are precursors for ketenes, in a diastereoselective, photochemically induced reaction to produce exclusively tram-substituted P-lactams. The use of cinnamaldimines 96, considered as vinylogous benzaldimines, resulted in the formation of styryl-substituted P-lactams. Ozonolysis, followed by reductive workup with dimethyl sulfide, led to the formation of the aldehyde 97, whereas addition of trimethyl orthoformate permitted the production of the dimethyl acetal 98 (Scheme 11.26). 

According to the Criegee mechanism, formyl and acetyl zwitterions, HC HOO and CHaC HOO, are reactive intermediates in the ozonolysis of propylene. Among several thermochemically feasible reactions of the zwitterions, the following scheme provides a chain oxidation mechanism which is consistent with the observed data. 

Aminopenicillanic acid (8) was converted to 6(5)-bromopenicillanic acid by trapping of the diazo-intermediate with hydrogen bromide. Esterification of the dicyclohexylamine salt (93) with p-methoxybenzyl bromide, followed by oxidation, afforded the sulphoxide (94) in 60% yield from 6-APA. Elaboration of this sulphoxide to the disulphide (96) was effected by the procedure established by Kamiya et al. [98] the sulphenic acid (95), formed by heating the sulphoxide to reflux in toluene, was intercepted by reaction with 2-mercaptobenzothiazole to yield the disulphide (96). The latter was transformed by base-catalysed double bond isomerization to the conjugated ester disulphide (97) [95% yield from (94)]. Reductive formylation of disulphide (97) then provided the formylthio-derivative (98). Cyclization of the oxalimide (99), obtained by ozonolysis of... 

In this synthesis, the C4-formyl monosaccharide 155 was prepared from the benzoylated thionocarbamate 153 using a stereoselective radical based allylation. The exclusive equatorial selectivity observed in the manno series is remarkable and can probably be explained by the unfavorable axial approach of the incoming allyl group due to steric interactions with the axially oriented C2-substituent. Exchange of the protecting groups, rhodium-catalyzed double bond migration and reductive ozonolysis then produced the aldehyde 155. 

Michaelis-Arbnzov Reactions Phosphonomethylation Michael Addition Anionic Formylation Oxidation Ozonolysis Rednction... 

Ozonolysis of compound (36) gave a strongly reducing methyl 2-formyl-/S-L-pentopyranoside which showed no carbonyl absorption in the infrared. This compound, obtained crystalhne in 54% yield, underwent mutarota-tion and afforded a crystalline W-phenylglycosylamine and a mono-0-methyl derivative (with methanolic hydrogen chloride). It was considered to have structure (37). Reduction (Pt/H2) of (37) gave a crystalline methyl 2- (hydroxymethyl)- -L-pentopyranoade. 

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