Aldehydes formation from ozonolysis

Examples are given of common operations such as absorption of ammonia to make fertihzers and of carbon dioxide to make soda ash. Also of recoveiy of phosphine from offgases of phosphorous plants recoveiy of HE oxidation, halogenation, and hydrogenation of various organics hydration of olefins to alcohols oxo reaction for higher aldehydes and alcohols ozonolysis of oleic acid absorption of carbon monoxide to make sodium formate alkylation of acetic acid with isobutylene to make teti-h ty acetate, absorption of olefins to make various products HCl and HBr plus higher alcohols to make alkyl hahdes and so on. 

The ozonolysis was therefore repeated under a variety of conditions and new curves were constructed for each. The results were best at low temperature (—78° C. was better than —53° C.), at a high olefin concentration (as high as the solubility limitations would permit), in nonpolar solvents, and with a small amount of pyridine present in the solvent. The dramatic effect of the inclusion of approximately 1% pyridine is shown in Figure 3. The selectivity was greatly improved, the nuclear double bond remaining intact until the side-cham double bond had almost completely reacted. The aldehyde formation curve indicates that approximately two molecules of aldehyde were formed from the cleavage of each double bond. These curves represent optimal conditions and were selected from runs at various pyridine concentrations. 

An excellent synthetic method for asymmetric C—C-bond formation which gives consistently high enantioselectivity has been developed using azaenolates based on chiral hydrazones. (S)-or (/ )-2-(methoxymethyl)-1 -pyrrolidinamine (SAMP or RAMP) are chiral hydrazines, easily prepared from proline, which on reaction with various aldehydes and ketones yield optically active hydrazones. After the asymmetric 1,4-addition to a Michael acceptor, the chiral auxiliary is removed by ozonolysis to restore the ketone or aldehyde functionality. The enolates are normally prepared by deprotonation with lithium diisopropylamide. 

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). 

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. 

This aldol reaction was employed for an asymmetric synthesis of the azetidinone 9 from the adduct (5) of acetaldehyde and l.5 Azetidinone 9 is a versatile precursor to the antibiotic thienamycin 10. The configurationally stable aldehyde 6, obtained by ozonolysis of the silyl ether of 5, undergoes addition with allylzinc chloride to afford 7, which on transamination is converted to the N-methoxy amide 8. This product is converted in several steps to the desired 9 in 34% overall yield. An interesting feature of this synthesis is the early incorporation of the hydroxyethyl side chain at C6, a step that is difficult to effect after formation of the (3-lactam ring. 

The reaction takes place in the medium of acetic acid and yields are generally good. This is why the route to obtain aldehydes or ketones from alkenes via glycol formation is preferred over that of ozonolysis. Other compounds which are readily cleaved include those with the groups ... 

The formation of 1,2,3-trioxolanes from an alkene and ozone is the first step in the ozonolysis reaction, which is widely used in synthesis to convert alkenes to aldehydes or carboxylic acids. No instances of double bond migration during ozonolysis are known (since the first step is a cyclo-... 

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). 

With the exception of the diol 9, that was obtained from the corresponding aldehyde in up to 35% yield, most of the chiral diols mentioned above were isolated in yields of only 20-25%. The formation of the acyloin-type condensation products is in competition with the much more efficient reduction of the carbonyl carbon and saturation of the double bond of the unsaturated aldehydes that were used as substrates. We became interested in the mode of reduction of particular aldehydes such as 54-56 (Scheme 8) in a study of the total synthesis of natural a-tocopherol (vitamin E) (23). We expected to obtain chiral alcohols that would be useful for conversion into natural isoprenoids from the reduction of the a-double bond of the above aldehydes. Indeed, 54-56 afforded up to 75% yield of the saturated carbinols 57-59 by treatment with yeast. Whereas the ee of 57 and 58 was ca 85%-90%, that of 59 is 99%, as shown by NMR experiments on the (-)-MTPA derivative (24). The synthetic significance of carbinol 59 was based on the structural unit present in natural isoprenoids (see brackets in structural formulas). This protected synthon can be unmasked by ozonolysis, as indicated by the high yield conversion of 59 into (S)-(-) -3-methyl-y-butyrolactone 60 (Scheme 9). Product 59 is a bifunctional chiral intermediate which does not need protective manipulation in that... 

The same year Grieco s group published a synthesis of seco acid 58 by a route reminicent of the Masamune and Yamaguchi approaches.The C-8 to C-11 fragment was constructed from 2-methylcyclohexenone (69) as shown in Scheme 2.9. Osmylation and protection as the acetonide afforded a 65% yield of 70. This intermediate was then converted into ester aldehyde 71 (66%) via enol acetate formation, ozonolysis, and esterification with diazomethane. 

Masamune has also completed a synthesis of tylonide hemiacetal (291) based on the creative use of enantioselective aldol condensations, as shown in Scheme 2.26. The aldol condensation of 328, derived from (/f)-hexahydromandelic acid and prop anal, was found to be >100 1 diastereoselective, affording the 2,3 syn compound 329 in 97% yield. Transformation to the p,7-unsaturated ester 330 occurred via selenoxide elimination and periodate cleavage followed by esterification. Formation of the silyl ether, reduction, and protection of the ester followed by ozonolysis of the terminal olefin gave the diol-protected aldehyde 331. The C-11 to C-15 segment 332 was then completed via chain elongation and a subsequent reduction-oxidation sequence in 34% overall yield from 330. 

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