Asymmetric synthesis substrate controlled, examples

The latter work is a rare example in which a high stereoselectivity was reported for a substrate-controlled Ugi synthesis. In asymmetric Ugi reactions carried out with removable chiral auxiliaries, however, high diastei eoselections were achieved (see Section 1.4.4.3.1.). 

Internal diastereomers of the kind depicted in Figure 3 have two kinds of interaction between the chiral centers the total interaction and that part of the total interaction which is discriminatory. The latter we call the diastereotopic interaction, and it is only this part of the interaction that causes either Kx in Figure 3 to be displaced from unity or the activation energies of the diastereomeric transition states to be different. It follows that the object in asymmetric synthesis is to maximize the diastereotopic interaction. In the absence of a clear lock-and-key compatibility for the inducing molecule and the substrate, the stereochemical criteria for maximizing the diastereotopic interaction are not always obvious. For example, it is a commonly held view that an increase in the relative steric bulk of certain groups will increase discrimination. This may only increase the nondiscriminatory interaction unless such elaboration is directed at features of the substrate which control the discrimination. 

We sought catalytic methods that would allow formation of chiral tethers that are asymmetric at the silicon center. Synthesis of the chiral tether by our method would be advantageous for the reasons we described in the Introduction. Chiral information could be transferred during an intramolecular reaction. This would be an example of substrate-controlled transformation. 

Asymmetric synthesis introduces one or more new features of chirality in a molecule. Several approaches are possible. In general, preferential formation of an enantiomer or diastereoisomer is achieved as a result of the influence of a chiral element present in the substrate, a reagent, catalyst or the environment. Chirality control is also possible in the electronically excited state,584 as demonstrated in the following examples. 

Substrate-controlled routes to optically enriched materials via diastereoselective oxidative dearomatizations constitute a second strategy for harnessing this process in asymmetric synthesis. Best results are obtained in intramolecular dearomatizations in which a preexisting stereogenic center is present on the side-chain nucleophile of a prochiral arene substrate [50]. For example, intramolecular oxidative dearomatization of 54 proceeds diastereoselectively as a consequence of conformational effects operative in the course of acetal formation (Scheme 15.20) [51]. 

Many other examples illustrate substrate control in asymmetric synthesis, wherein an existing stereogenic center in the ketone or aldehyde biases the attack of a nucleophile preferentially to one of the two diastereotopic faces. From the reduction of very simple chiral ketones such as 3 (Equation 2) [36] to the synthesis of highly complex molecules exemplified by Kishi s breathtaking synthesis of palytoxin (8, Scheme 2.1) [26, 38], the ability to conduct diastereoselective additions to carbonyl groups provides synthetic chemists with a powerful means to prepare chiral alcohols. 

Nogano and co-workers [3] reported similar examples of asymmetric induction for natural product synthesis using protected sugars and a variety of R MgX, where X = C1, Br, or 1. In Table 2, entries 3 and 4, the tetralose carbonyl can also contain in the Ri position an ether, ester, urethane, alkyl, or aryl group [13]. The authors reported the diastereometer ratio from the R substrate and the labeled carbon-2 varied from 80 20 to 10 90 (2S/2R). The variability was controlled by the nature of the nucleophile, the solvent, and the temperature. The authors rationalized the product distribution based on chelation of the metal and steric bulk of the reactants, favoring the R-isom.er. 

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