Retroaldol reactions

There are at least two routes currently being used to produce natural benzaldehyde. Principal flavor houses are reported to market a product which is derived from cassia oil. The chief constituent of cassia oil is cinnamic aldehyde which is hydrolyzed into its benzaldehyde and acetaldehyde constituents. This is a fermentative retroaldol reaction. Whether this hydrolysis allows the final benzaldehyde product to be considered natural is of great concern. The FDA has reportedly issued an opinion letter that benzaldehyde produced from cassia oil is not natural (15). 

Scheme 8.51 Construction of the tricyclic core of phomactin A through a retroaldol reaction.

C. Schwarzinger, On the mechanism of thermally assisted hydrolysis and methylation of carbohydrates the contribution of aldol and retroaldol reactions, J. Anal. Appl. Pyrol., 68 69, 137 149 (2003). 

It has been demonstrated that beta-hydroxynitrosamines such as NDE1A may undergo retroaldol-type reactions in strongly alkaline medium to form nitrosamlnes of lower molecular weight (19, 20). In some cases the nitrosamlnes formed from the retroaldol reaction are more potent animal carcinogens than is NDE1A. 

A Hammett correlation has been reported for the retroaldol reaction of a series of /jflra-substituted benzylidenemalonitriles, XC6H4CH=C(CN)2, catalysed by hydroxide in aqueous methanol." ... 

Vicinally donor-acceptor-substituted cyclopropanol carboxylic esters have been proven to be versatile synthetic building blocks in organic synthesis [11]. They readily undergo a retroaldol reaction, thus creating a stable enolate that at the same time can be considered as a homoenolate in relation to the newly formed carbonyl function. Shimada et al. applied this strategy to the preparation of y-substituted lactones starting from cyclopropane 21 (Scheme 3) [12]. 

Diastereomer ratios were determined by gas chromatography. Since the aldol adduct undergoes retroaldol reaction on the column, it must be silylated prior to injection. Approximately 5 mg of the crude adduct is filtered through a short plug of silica gel to remove any trace metals. The material is taken up into 1-2 mL of dichloromethane in a 2-raL flask or small test tube. To this solution are added 4-5 drops of N,N-diethyl-1,1,1-trimethylsilylamine and a small crystal of 4-(N,N-dimethylamino)pyridine (Note 11), The solution is stirred for 2 hr and injected directly onto the column. (Column conditions 30 m x 0.32 mm fused silica column coated with OB 5, 14 psi hydrogen carrier gas, oven temperature 235°C). 

Sudha Sawargara M, Adinarayana M (2003) Kinetics and mechanism of protection of thymine from sulphate radical anion under anoxic conditions. Proc Indian Acad Sci (Chem Sci) 115 123-128 Sugiyama H.Tsutsumi Y, Fujimoto K, Saito I (1993) Photoinduced deoxyribose C2 oxidation in DNA. Alkali-dependent cleavage of erythrose-containing sites via a retroaldol reaction. J Am Chem Soc 115 4443-4448... 

Upon attack at C(2 ) and in the presence of 02, the sugar moiety is mainly modified into an erythrose unit (Sugiyama et al. 1993) which is an alkali-labile site and undergoes a retroaldol reaction after deprotonation of H4 [reaction (45)], but a Z-form type structure favors C(2 )-hydroxylation. 

Knowledge of the Maillard reaction is being extended very actively in many different ways. The participation of free radicals has already been dealt with in Chapter 2 and work on colour and flavour aspects is being deferred to Chapters 4 and 5, respectively. This chapter deals with a number of relatively disparate topics, namely, the effects of pH, high pressure, 7g, and the use as reactants of amines other than amino acids, of lipids, and of oligo- and polysaccharides, as well as the determination of a-dicarbonyl intermediates, control of aldol/retroaldol reactions, fluorescence, kinetic aspects, and sites of protein glycation. 

The bicyclic isoxazolines 59 underwent molybdenum-mediated tandem reductive N-O bond cleavage-retroaldol reactions to provide the compounds 60 or 61 as mixtures of stereoisomers <020L4101>. 

All the chemical work (80, 81) on macusine A is in accord with the given structure. Pyrolysis of macusine A chloride did not yield the expected nor-base but rather the ester (LII) formed by loss of formaldehyde in a retroaldol reaction. This was established by reducing the base from the pyrolysis with lithium aluminum hydride to afford normacusine B (L). With the absolute configuration of normacusine B firmly established, it follows that the absolute configuration shown in formula LIII correctly represents macusine A. 

Scheme 5.62. Ab72D4 catalyzes the 4/( -selective p-elimination reaction and the 45-selective retroaldol reaction.

In a follow-up study, Baker utilized the theozyme of Scheme 9.4d but without the tyrosine residue. The modeling of the potential proteins to host this theozyme allowed for finer grained side-chain rotamer examination than in the previous study. This led to 42 designs, all of which were expressed in E. coli and all were soluble. Of these, 33 had activities of 10 times or more than the rate of the uncatalyzed retroaldol reaction. The higher success rate here was attributed to a design that better accommodated the TS and a polar environment to host the later steps in the reaction sequence. 

Photochemical cyclobutane annealings are much more promising and find their way into synthesis to a greater extent. Photochemical cycloaddition reactions to enolized 1,3-diketones and consecutive ring openings via retroaldol reactions have been applied in ring expansion reactions numerous times. 

The desired cyclization leading to the six-membered ring was achieved by intramolecular photocycloaddition of dioxolenone 107 as shown in Scheme 26. Consecutive cleavage of the ketal followed by retroaldol reaction augmented the initial ring system by a C2 unit to trans-bicycle 108 (90). Attempts to apply this reaction principle to a trans-decalin system in order to reach a taxane skeleton failed (97). 

There are also some special syntheses. For example, in an attempted acid-catalyzed hydrolysis of a benzobis(oxazole) into a diaminobenzoquinoline-quinone, 240 was obtained instead. This compound has two more carbon atoms than expected. In addition, in the presence of acetaldehyde, the yield of 240 increased whereas addition of propionaldehyde generated compound 241. During these transformation, 2 equivalents of the aldehyde are incorporated in what is explained as a retroaldol reaction of benzobis(oxazole) during deprotection (85JOC4276). 

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