Stereogenic Centers and Planning of Syntheses

Forty years ago, stereogenic centers in a target structure were cause for serious headaches in synthesis planning. Since then, the methodology of stereoselective synthesis has been advanced to the point that aspects of stereogenic centers, while still important, are no longer the major hurdle in planning syntheses. For this reason, the relevant discussion was placed last (but not least) in this treatise. 

In due course, syntheses of sulcatol have been reported that were based on glutamic acid [7] or on 2-deoxy-ribose [8]. They required, though, that five of the seven steps before the concluding Wittig-reaction be refunctionalizations. By today s standard this is unacceptable for the introduction of just 

As a consequence, once a racemate is readily available, a resolution approach to obtain enantiomerically pure material is as valid today as in earlier times. In a multistep synthesis of targets having several stereogenic centers, a resolution approach should be limited to those cases where it can be applied early on in the synthesis, i.e., to obtain the first stereogenic center. 

COOH building block oriented from tartaric acid 

Takano, M. Yanase, M. Takahashi, K. Ogasawara, Chem. Lett. 1987, 16, 2017-2020. 

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The stereochemical outcome of the reaction is determined by the geometry of the transition state for the Claisen rearrangement a chairlike conformation is preferred,and it proceeds strictly by an intramolecular pathway. It is therefore possible to predict the stereochemical course of the reaction, and thus the configuration of the stereogenic centers to be generated. This potential can be used for the planning of stereoselective syntheses e.g the synthesis of natural products. 

New alkaloids lycoposerramines-X (74) and -Z (75) are phlegmarine-type alkaloids consisting of a piperidine ring with a novel nitrone residue and a decahydroquino-line ring with four stereogenic centers [43] (Fig. 6). From spectroscopic analyses, 74 and 75 were found to be diastereomers at the C-13 position, but their absolute configuration could not established. Then we planned the asymmetric total syntheses of 74 and 75 to confirm their structures, including the absolute stereochemistry. 

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