Molecules with Multiple Chirality Centers

The synthesis of new chiral organic compounds and the improved synthesis of known substances will always be a major task for the professional chemist. When constructing target molecules with multiple chirality centers, a scientist must consider either total synthesis step by step or assembly from smaller chiral blocks as an alternative approach. 

The feature of 2-chlorobutane that makes it chiral is the presence of a carbon attached to four different groups. Such carbons are another type of stereocenter. The currently accepted term to describe such a carbon, or any other tetrahedral atom attached to four different groups, is chirality center. (Some older terms that you may encounter are chiral carbon atom or asymmetric carbon atom.) Any molecule with one chirality center as its only stereocenter is chiral. (As we shall see shortly, many, but not all, molecules with multiple chirality centers are also chiral.) So, another way to identify a chiral molecule is to look for a single chirality center, which requires some practice. It helps to remember that any carbon that is attached to two identical groups (this includes all doubly and triply bonded carbons) is not a chirality center. Consider these examples ... 

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. 

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]. 

Let us begin our study of molecules with multiple chiral centers by considering 2,3,4-trihydroxybutanal, a molecule with two chiral centers, shown here highlighted. 

Chemists use two-dimensional representations called Fischer projections to show the configuration of molecules with multiple chiral centers, especially carbohydrates. To write a Fischer projection, draw a three-dimensional representation of the molecule oriented so that the vertical bonds from the chiral center are directed away from you and the horizontal bonds from the chiral center are directed toward you. Then write the molecule as a two-dimensional figure with the chiral center indicated by the point at which the bonds cross. 

Multiple Chiral Centers. The number of stereoisomers increases rapidly with an increase in the number of chiral centers in a molecule. A molecule possessing two chiral atoms should have four optical isomers, that is, four structures consisting of two pairs of enantiomers. However, if a compound has two chiral centers but both centers have the same four substituents attached, the total number of isomers is three rather than four. One isomer of such a compound is not chiral because it is identical with its mirror image it has an internal mirror plane. This is an example of a diaster-eomer. The achiral structure is denoted as a meso compound. Diastereomers have different physical and chemical properties from the optically active enantiomers. Recognition of a plane of symmetry is usually the easiest way to detect a meso compound. The stereoisomers of tartaric acid are examples of compounds with multiple chiral centers (see Fig. 1.14), and one of its isomers is a meso compound. 

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