Stereoselective U-4CRs and their Secondary Reactions

As a result of early pre-studies of the U-4CR, it was realized that the yield and stereoselectivity of this reaction depend greatly on the ratio of educts and on the reaction conditions [8, 93]. The individual goals of these syntheses can differ widely, especially if certain stereoisomers of products are formed preferentially [3, lib, 73]. Planning of syntheses by the U-4CR and related MCRs, and the suitable choice and availability of its educts, is even more important than in most other chemical reactions, particularly as these MCRs do not always function under optimal conditions, but may differ from case to case. 

The reaction mechanisms of the MCRs cannot be investigated with the usual methods. Some essential mechanistic information of a MCR can be obtained from a suitable combination of several methods, and not all of the usual detailed information can be expected. It is even more difficult to identify optimal reaction conditions to create certain isomers stereoselectively by U-4CRs. Nevertheless, studies of the reaction mechanism of the U-4CR can be accomplished more easily if a stereoselective U-4CR takes place, than without the stereochemical differences of its different products. Therefore, a particularly suitable model reaction of a stereoselective U-4CR was investigated. 

The number of essential steps was reduced by precondensing its aldehyde 1A and its amine component 2A into its Schiff base. Thus, the U-4CR can also proceed sufficiently well if somewhat low concentrations of educts are used. 

Between 1964 and 1967, many different ratios and concentrations of isobutyraldehyde-(S)-a-phenylethylamine, benzoic acid and tert-butylisocyanide in methanol at 0 °C were investigated [4,8,28]. In one series of experiments the dependence of the electrical conductivity of the Schiff base and its carboxylic acid was determined, while in a second series the relationship between educt concentration and the ratio of diastereoisomeric products was investigated by measurement of their optical rotation. 

In the early 1960s, in addition to the early finding of stereoselectively reacting amine components, several new types of achiral amines were also found whose U-4CR products could be cleaved selectively according to 18 - 28A [73]. However, even today, despite an ongoing search for optimal amine components, the simultaneous fulfillment of all conditions has not been accomplished. Indeed, it transpires that this problem remains one of the most difficult in preparative chemistry. 

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