Molecules with Multiple Stereogenic Centers

Many naturally occurring compounds contain several stereogenic centers. By an analysis similar to that described for the case of two stereogenic centers, it can be shown that the maximum number of stereoisomers for a particular constitution is 2 , where n is equal to the number of stereogenic centers. 

When two or more of a molecule s stereogenic centers are equivalently substituted, meso forms are possible, and the number of stereoisomers is then less than 2 . Thus, 2 represents the maximum number of stereoisomers for a molecule containing n stereogenic centers. 

The best examples of substances with multiple stereogenic centers are the carbohydrates (Chapter 25). One class of carbohydrates, called hexoses, has the constitution 

Since there are four stereogenic centers and no possibility of meso forms, there are 2 , or 16, stereoisomeric hexoses. All 16 are known, having been isolated either as natural products or as the products of chemical synthesis. 

PROBLEM 7.16 A second category of six-carbon carbohydrates, called 2-hexu-loses, has the constitution shown. How many stereoisomeric 2-hexuloses are possible  

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Efficient and elegant syntheses of complex organic molecules with multiple stereogenic centers continue to be important in both academic and industrial laboratories (Nicolaou et al. 2003, 2006). In particular, catalytic asymmetric multicomponent domino reactions, used in the course total syntheses of natural products and synthetic building blocks, are highly desirable (Nicolaou et al. 2003, 2006 Tietze and Beifuss 1993 Tietze 1996 Tietze and Haunert 2000 Wasilke et al. 2005 Ramon and Yus 2005 Guo and Ma 2006 Pellissier 2006 Pellisier 2006 Tietze... 

Desymmetrization is the modification of a symmetric object that results in the loss of symmetry elements. When coupled with the catalytic asymmetric process, it provides an efficient method for enantioselective synthesis of chiral molecules with multiple stereogenic centers [116]. 

Diastereomers (Nonoptical Stereomers) Diaster-eomers—stereoisomers that are not enantiomers (mirror image isomers) and are usually encountered in molecules with multiple stereogenic centers. Unlike enantiomers, each diastereomer has a unique set of physical and chemical properties (Table 1.2). However, because they have the... 

In order to distinguish enantiomorphic structures, molecular chirality has conventionally been expressed in terms of center-, axis-, and plane-chirality. In the case of compounds involving several stereogenic centers, however, these terms seem to be insufficient to express their whole molecular chirality or anisotropy, although their local chirality is well confirmed in the conventional manner. Indeed, the steroidal molecules (Figure 26.13a), which have asymmetric, amphiphilic, facial structures with multiple stereogenic carbon atoms, are saddled with such a structural complexity. In order to solve this problem, we introduced a simple but unique concept, three-axial chirality , as shown in Figure 26.13b. Such three-axial chirality is based on the orthorhombic three axes applied in a molecular structure and is expressed by... 

The development of new methods to synthesize molecules with multiple stereo-genic centers in one flask is very important in organic synthesis [13]. Ftmctionalized allenes are of great interest since they serve as versatile synthetic intermediates in many asymmetric syntheses. Under mild conditions, stereoselective synthesis of p-hydroxyallenes was obtained via aldehyde addition to a-alkenyl-substimted zirconacyclopentenes (Scheme 2). The product 5 has two contiguous stereogenic centers and an adjacent axial chirality. 

Hey-Hawkins reported that the asymmetric Diels-Alder reactions of 2H-phospholes with the dienophile (5/ )-(l-menthyloxy)-(5//)-furanone allowed the generation of multiple stereogenic centers in 1-phosphanorbomadienes 256. The cycloaddition products were converted to their air-stable sulfur derivatives, which were isolated and the endo- and exo-isomers were separated by column chromatography (Scheme 81). In this case, the principle of face differentiation for a P=C bond is a synthetic tool for highly selective and efficient synthesis of P-chiral phosphanes from readily available starting materials. The observed selectivity was explained by the transition states of the two main isomers exo-A and endo-B (Scheme 82). The two molecules approach mainly in an endo fashion, which in consequence leads to the main diastereomer. Because of the favorable secondary orbital interactions between the C=0 functionality and the diene system, the endo product is kinetically favored, as is known for such systems with normal electron demand [170]. 

A Ci-symmetric cis-1 bis-adduct with an additional bridge between the addends was obtained in the reaction between two molecules of ethyl propio-late and C6o in the presence of triphenylphosphane.318 Its structure (( )-162, Figure 1.37) was established with the help of the HMBC- (heteronuclear multiple bond correlation) NMR technique and includes stereogenic centers in the addend moiety as well as a noninherently chiral addition pattern. The latter can be related to the head-to-tail connectivity of the two propiolate units. 

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