CYCLIC MOLECULES WITH STEREOGENIC CENTERS

Many cyclic compounds have stereogenic centers. We assign their configurations in the same manner we described previously for acyclic compounds. 

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Apart from cyclic or acyclic transition state geometry further distinctions of diastereoselec-tion have to be made with respect to the way in which the chiral center is attached to the reactive site. The term auxiliary control is used if a chiral subunit, e.g., an alcohol or an amine, is fixed covalently to the unsaturated substrate and then removed by bond cleavage after the addition. In contrast, if the stereogenic center remains part of the molecule after the addition, the term substrate control is applied (these definitions are given in Section A. 1.). 

An alternative concept is asymmetric desymmetrization of a prochiral molecule of type 83. The starting materials 83 have three keto groups and one carbon atom bearing at least three substituents. A prerequisite is the presence of a prochiral carbon atom with two identical substituents bearing a keto functionality (Scheme 6.39, Eq. (2)). This type of asymmetric intramolecular aldol reaction proceeds with formation of cyclic ketols of type 84 with two stereogenic centers. Dehydration can subsequently be performed, leading to optically active enones of type 85. The two types of intramolecular aldol reaction are shown conceptually in Scheme 6.39. 

The cinchona alkaloids have opened up the field of asymmetric oxidations of alkenes without the need for a functional group within the substrate to form a complex with the metal. Current methodology is limited to osmium-based oxidations. The power of the asymmetric dihydroxylation reaction is exemplified by the thousands (literally) of examples for the use of this reaction to establish stereogenic centers in target molecule synthesis. The usefulness of the AD reaction is augmented by the bountiful chemistry of cyclic sulfates and sulfites derived from the resultant 1,2-diols. 

As mentioned previously, reactions of cyclic molecules that involve formation of stereogenic centers are similar to those of acyclic systems in that they can proceed with clean retention or inversion of configuration, or a mixture of the two. Reaction of sodium azide (NaN3) and cis-4-rert-butyl-l-bromocyclohexane gives... 

The diastereoselectivity obtained for reactions on a ring makes it possible to use a cyclic molecule to fix a stereocenter in an acyclic target, as seen in the formation of 154 from 152. Diol 152 had been prepared by a multistep sequence, with control of the stereocenters. When this diol was subjected to oxidation with MCPBA lactone 153 was formed. Subsequent ring opening with methanolic potassium carbonate led to the acyclic fragment 154, with six contiguous stereogenic centers whose stereochemistry had been fixed in the cyclic... 

Cyclic molecules may have stereogenic centers and it is possible to generate enantiomers and/or diastereomers. Problems of identifying the stereogenic center and the number of stereoisomers arise with some cyclic molecules that do not as acute in acyclic molecules. This section will focus on these problems. 

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