Page 304 - Academic Press Encyclopedia of Physical Science and Technology 3rd Organic Chemistry

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Encyclopedia of Physical Science and Technology EN016B-738 July 31, 2001 14:0

Stereochemistry 85

Asymmetric (or enantioselective) synthesis is a targeted
method for obtaining individual enantiomers from achiral
precursors. Ordinarily, the introduction of a chiral center
(or other chiral element) in the course of synthesis leads
to equal formation of the two enantiomers, i.e., to a race-
mate. Selectivity can, however, be achieved by using a
chiral (enantiomeric) reagent or catalyst, in which case FIGURE 5 Ordering substituents (A > B > C > D) according to
the transition states leading to the two enantiomeric prod- the Cahn–Ingold–Prelog chirality rule.
ucts are diastereomeric, or by attaching a chiral auxiliary
(see above) to the starting material so that the products are
diastereomers rather than enantiomers, in which case their in lactic acid]. This “factorization” allows us to specify
free energies and the activation energies for their forma- configuration by assigning a configurational “descriptor”
tion also differ and one isomer is formed in preference over to each chiral center or other chiral element.
the other. At the end of the reaction, the chiral auxiliary The configurational descriptors now universally used
is chemically removed. By way of example: Reduction of are “R” (for rectus, right, in Latin) and “S” (for sinister,
pyruvic acid, CH 3 COCO 2 H, to lactic acid with an achiral left) (Cahn et al., 1966); they are sometimes called “CIP
reagent such as sodium borohydride gives racemic lactic descriptors” after their proponents. To assign a descrip-
acid, CH 3 CHOHCO 2 H, since approach of hydride from tor to a chiral center, assume that its four ligands, a, b, c,
either face of the keto-carbonyl group is equally likely. and d, can be ordered by some convention: a > b > c > d.
But when reduction (by a reducing coenzyme) is carried The molecule is then viewed from the side away from the
out in the presence of the chiral enzyme lactic acid dehy- lowest ranked ligand (d) such that the other three ligands
drogenase, only (+)-lactic acid is formed. (a, b, c) lie in a plane (Fig. 5). If a–b–c then describe a
A distinct process, sometimes called “enantiospecific clockwise array, the descriptor is R; if the array is coun-
synthesis,” is one in which an enantiomerically pure start- terclockwise, the descriptor is S. To establish priorities in
ing material (natural or man-made) is converted by stan- a real molecule one orders the ligands by atomic number,
dard reactions into an enantiomerically pure product. thus in CHFClBr, Br > Cl > F > H. For lactic acid the pri-
Among other methods are diffusion through chiral ority is O > C > H, but no immediate decision is reached
membranes and partition methods involving chiral for CH 3 versus CO 2 H. Here one goes out to the next atom
solvents. away from the chiral center: O for CO 2 H and H for CH 3
and since O > H, CO 2 H has priority over CH 3 . Where
still no decision is reached, one goes out one tier more,
VIII. STRUCTURE, CONFIGURATION, thus –CH 2 CH 2 OH has priority over –CH 2 CH 2 CH 2 OH.
NOTATION Once a decision is reached, the process stops. In the out-
ward path, one always gives preference to the atom of
By “structure” of a molecule we understand the totality higher priority; thus –NHCl has priority over –N(CH 3 ) 2 :
of the nature and array of its atoms. This comprises the Cl > C overrides C > H. All ligands on the atom reached
identity and connectivity of these atoms (“constitution”) must be probed, thus –CO 2 H > –CHO (two O’s over one
and their arrangement in space (“configuration,”“con- O). When the lack of a decision is caused by a doubly
formation”; see below). Structure may be determined by bonded ligand (e.g., CH O vs. CH 2 OH as in glyceralde-
X-ray, electron, or neutron diffraction of a crystal of the hyde, HOCH 2 CHOHCH O) the double bond is replaced
substance in question. by two single bonds with the ligands “complemented” at
Constitution can usually be inferred from elemental either end; thus –CH O is considered as O–CH–(OC) and
analysis and chemical degradation or by various spectro- thus has priority over CH 2 OH. An absent ligand (as the
scopic methods, such as nuclear magnetic resonance. Con- lone pair in N: or :O:) is considered to have atomic num-
stitutional isomers, such as butane and 2-methylpropane, ber zero. When chirality is due merely to the presence
have the same elemental composition but differ in con- of an isotope, as in C 6 H 5 CHDOH, the ligand of higher
nectivity. In contrast, the two enantiomers of lactic acid, atomic weight is given priority: O > C > D > H. For more
CH 3 CHOHCO 2 H, identical in constitution, differ in the complicated cases, the reader is referred to standard texts.
spatial disposition of the ligands at C(2): They are said to There are two exceptions to the current use of CIP
differin “configuration” and maybecalledconfigurational descriptors, α-amino acids and sugars, where an older
isomers. While configuration is a property of the molecule nomenclature is often used. Before considering this point,
as a whole, it is convenient to “factorize” it into elements a discussion of projection formulas is required. Since
of chirality, notably the “center of chirality” [e.g., at C(2) molecules are three dimensional but paper is planar,