Chapter 5: Stereochemistry at Tetrahedral Centers
Chirality occurs when a carbon has four different groups
Chirality is a geometric property: an object is chiral when it cannot be superimposed on its mirror image. Hands are the everyday illustration, and the term derives from the Greek for hand. In molecules built on tetrahedral carbon, the ordinary origin of chirality is a stereocenter, an sp3 carbon bonded to four different groups. Because the four bonds point to the corners of a tetrahedron, exchanging any two of the groups produces an arrangement that is a mirror image of the original and cannot be rotated back into it. The two arrangements are enantiomers. Both terms sit inside a wider one:…
Enantiomers rotate plane-polarized light in equal and opposite senses
Chirality has a directly measurable physical consequence. (This section refers to the R and S configuration labels in passing; they are defined in the next section, and nothing here assumes you already know how to assign them.) When plane-polarized light passes through a solution of a single enantiomer, the plane of polarization emerges rotated; the compound is said to be optically active. The instrument that measures the angle of rotation is a polarimeter. The observed angle grows with the number of chiral molecules in the light path, so it depends on both the concentration of the solution…
The CIP rules translate a three-dimensional arrangement into R or S
Configuration at a tetrahedral stereocenter is specified unambiguously by the Cahn-Ingold-Prelog rules, which convert the three-dimensional arrangement into the single letter R or S. The procedure has two stages: rank the groups, then read the geometry. Ranking is by atomic number. The four atoms bonded directly to the stereocenter are compared, and the one of highest atomic number receives priority 1. If two or more of those first atoms are the same, the tie is broken by moving outward to the next atoms and comparing the highest at the first point of difference. Atoms held by a double or…
The priority-rotation arrow: reading R and S at a glance
A tetrahedral stereocenter carries a rotation that the priority ranking makes visible. After the four attached groups are ordered by the sequence rules, a curved arrow drawn from priority 1 through priority 2 to priority 3 traces a sense of rotation, and that sense names the configuration. The rule holds only from a defined viewpoint: the lowest-priority group, usually a hydrogen, must point directly away from the viewer, into the page. From that vantage a clockwise arrow denotes R and a counterclockwise arrow denotes S. The two figures make the contrast concrete. Both depict 2-bromobutane…
Several stereocenters can result in diastereomers, and symmetry can give meso compounds
A single stereocenter produces two stereoisomers. Additional stereocenters multiply the possibilities, and the upper bound is compact: a molecule with n stereocenters has at most 2 raised to the power n stereoisomers, since each center is independently R or S. Classifying the relationships among those isomers is the central skill. Two stereoisomers that are non-superimposable mirror images are enantiomers; two stereoisomers that are not mirror images are diastereomers. 3-Bromobutan-2-ol, with two different stereocenters, realizes the full four stereoisomers, arranged as two pairs of…
Enantiomers are separated by converting them temporarily into diastereomers
The equal physical properties of enantiomers, so convenient when they let a single specific rotation characterize both, become an obstacle when the two must be separated. A racemate is a single-phase mixture in which the components share melting point, boiling point, and solubility in ordinary solvents, so distillation, recrystallization from achiral solvents, and achiral chromatography all fail to enrich one over the other. Resolution circumvents the problem by temporarily creating diastereomers, which are separable. A chiral reagent supplied as a single enantiomer, the resolving agent,…
Chiral environments distinguish enantiomers, and prochirality selects between paired groups
The molecules of life are homochiral: proteins are assembled almost exclusively from L-amino acids and nucleic acids from D-sugars. A consequence is that the binding sites of enzymes and receptors are chiral cavities, and such a cavity discriminates between the two enantiomers of any chiral guest much as a right glove distinguishes the two hands. Two enantiomers of a drug can accordingly show markedly different biological activity: one may be therapeutic while its mirror image is inactive or harmful. This is the practical reason that stereochemical control, and often single-enantiomer…
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