Ozonolysis synthesis applications

Ozonolysis has both synthetic and analytical applications m organic chemistry In synthesis ozonolysis of alkenes provides a method for the preparation of aldehydes and ketones... 

In 1991, Whitesides etal. reported the first application of aqueous medium Barbier-Grignard reaction to carbohydrate synthesis through the use of tin in an aqueous/organic solvent mixture (Eq. 8.48).106 These adducts were converted to higher carbon aldoses by ozonolysis of the deprotected polyols followed by suitable derivatization. The reaction showed a higher diastereoselectivity when there was a hydroxyl group present at C-2. However, no reaction was observed under the reaction conditions when there was an /V-acctyl group present at the C-2 position. 

This imide system can also be used for the asymmetric synthesis of optically pure a,a-disubstituted amino aldehydes, which can be used in many synthetic applications.31 These optically active a-amino aldehydes were originally obtained from naturally occurring amino acids, which limited their availability. Thus, Wenglowsky and Hegedus32 reported a more practical route to a-amino aldehydes via an oxazolidinone method. As shown in Scheme 2 20, chiral diphenyl oxazolidinone 26 is first converted to allylic oxazolidinone 27 subsequent ozonolysis and imine formation lead to compound 28, which is ready for the a-alkylation using the oxazolidinone method. The results are shown in Table 2-6. 

New and improved routes for the industrial synthesis of dinitrogen pentoxide mean that its use is increasing and for many applications it may replace the use of mixed acid in the near future. Dinitrogen pentoxide can be prepared by (1) ozonolysis of dinitrogen tetroxide, (2) electrolysis of nitric acid-dinitrogen tetroxide solutions, and (3) dehydration of nitric acid. ... 

A widely applied strategy for the synthesis of various difunctionalized organic molecules, e.g. diols, dialdehydes, etc., relies on the oxidative cleavage of olelinic double bonds. Besides transition metal catalysis for asymmetric synthesis, periodate oxidation and ozonolysis are the standard tools for oxidative bond cleaving reactions. For economic and safety reasons, technically applicable alternatives to osmium-based chemistry and ozonolysis are of great interest. 

Few synthetically useful examples of the oxidation of ethers by oxygen or ozcne have been publish-ed. In 1978, Ourisson and coworkers reported that ozonization of the natural product cedrane oxide (43) on silica gel at -78 °C led to the formation of the corresponding lactone 44) in 30% yield (equation 32). A small amount of the tertiary alcohol (45) was also produced. Later, in the course of a chiral total synthesis of compactin, Hirama examined the ozonolysis of the alkene (46 equation 33). Under carefully controlled conditions, selective ozonolysis of the double bond could be achieved in 88% yield. However, when excess ozone was employed, significant amounts of the benzoate (47) were obtained, even at -78 C. In subsequent studies, benzyl ethers of primary and secondary alcohols, and carbohydrates were oxidized to the corresponding benzoates in excellent yields. Surprisingly, no further synthetic applications of this reaction have been reported. 

The diene arises through the diazo compound 4 via a retro-[3 -f 2] reaction and diazo compounds of this type have been detected or isolated in several photolyses of 2,3-di-azabicyclo[3.1.0]hex-2-enes. The workup procedure for this particular reaction involves selective removal of the diene by ozonolysis, a chemical method of separating the products which may have applications in related systems since chromatography often proves difficult. In some cases, the intermediate diazabicyclohexenes also prove very sensitive and difficult to handle, rearranging to pyridazines under the influence of acid, base " or light and sometimes, as in the synthesis of methyl 4,4-dimethyl-l,3-diphenylbicyclo[1.1.0]butane-2-carboxyl-... 

The applicability of this method was further demonstrated in the stereoselective synthesis ofdiol 111, which is the key intermediate in the synthesis of (+)-frontalin (112) [53]. Ozonolysis of 111, obtained from solid phase chemistry, furnished frontalin 112 with 86% ee (Scheme 12.39). 

A typical example of an application of ozonolysis in synthesis is the cleavage of the alkene unit in 351 to give aldehyde 352, with loss of formaldehyde, a part of Smith s synthesis of (+)-thiazinotrienomycin In this case, the reductive workup used triphenylphosphine. Ozonolysis of 353 gave aldehyde 354, an intermediate in Corey s synthesis of the Cecropia Moth Juvenile hormone, via a reductive workup with DMS. Note that the electron rich vinyl ether moiety reacted in preference to the simple alkene moiety. The ozonolysis product of the methyl vinyl ether was a methyl ester. This method is particularly useful for the preparation of protected acids. In general, electron rich alkenes are oxidized faster than electron-poor alkenes. 

The reaction of olefins with ozone constitutes an important method of cleavage of carbon-carbon double bonds. This reaction has been a degradative tool for several decades and finds occasional use in synthesis. Recent years have seen the application of low-temperature and spectroscopic techniques to the study of the rather unstable species that are intermediates in the ozonolysis process. These studies have put early mechanistic ideas on a firmer basis and have elaborated many additional details of the reaction mechanism. 

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