STEREOCHEMISTRY

STEREOCHEMISTRY

refer Jerry March

Circular polarization means that the plane of the oscillating electric field does not remain

steady, but instead twists to the right or the left, referred to as right or left circularly polarized light.

1. Homotopic groups cannot be differentiated by chiral reagents.

2. Enantiotopic groups can be differentiated by chiral reagents.

3. Diastereotopic groups are differentiated by achiral and chiral reagents.

Stereochemical Terminology

Stereochemistry has engendered a sometimes confusing terminology, with several terms that are frequently misused. Here we provide definitions of the most common terms.

Absolute configuration. A designation of the position or order of arrangement of the ligands of a stereogenic unit in reference to an agreed upon stereochemical standard.

Achiral. Not chiral. A necessary and sufficient criterion for achirality in a rigid molecule is the presence of any improper symmetry element (Sn, including _and i).

Achirotopic. The opposite of chirotopic. See ‘‘chirotopic’’ below.

Anomers. Diastereomers of glycosides or related cyclic forms of sugars that are specifically

epimers at the anomeric carbon (C1 of an aldose, or C2, C3, etc., of a ketose).

Anti. Modern usage is to describe relative configuration of two stereogenic centers along a chain. The chain is draw in zigzag form, and if two substituents are on opposite sides of the plane of the paper, they are designated anti. See also ‘‘syn’’, ‘‘antiperiplanar’, and ‘anticlinal’’.

Anticlinal. A term describing a conformation about a single bond. In A–B–C–D, A and are anticlinal if the torsion angle between them is between 90 and 150 or –90 and –150.

Antiperiplanar. A term describing a conformation about a single bond. In A–B–C–D,

A and D are antiperiplanar if the torsion angle between them is between_150_ to –150_.

Apical, axial, basal, and equatorial. Terms associated with the bonds and positions of

ligands in trigonal bipyramidal structures.

Asymmetric. Lacking all symmetry elements (point group C1). All asymmetric molecules

are chiral.

Asymmetric carbon atom. Traditional term used to describe a carbon with four different

ligands attached. Not recommended in modern usage.

Atactic. Aterm describing the relative configuration along a polymer backbone. In an

atactic polymer, the stereochemistry is random—no particular pattern or bias is seen.

Atropisomers. Stereoisomers (can be either enantiomers or diastereomers) that can be interconverted by rotation about single bonds and for which the barrier to rotation is large

enough that the stereoisomers can be separated and do not interconvert readily at room

temperature.

Chiral. Existing in two forms that are related as non-congruent mirror images. A necessary

and sufficient criterion for chirality in a rigid molecule is the absence of any improper

symmetry elements (Sn, including _ and i).

Chiral center. Older term for a tetracoordinate carbon or similar atom with four different substituents. More modern, and preferable, terminology is ‘‘stereogenic center’’ (or

‘‘stereocenter’’).

Chirotopic. The term used to denote that an atom, point, group, face, or line resides in a chiral environment.

Cis. Describing the stereochemical relationship between two ligands that are on the same side of a double bond or a ring system. For alkenes only, Z is preferred.

Configuration. The relative position or order of the arrangement of atoms in space that characterizes a particular stereoisomer.

Conformers or conformational isomers. Stereoisomers that are interconverted by rapid rotation about a single bond.

Constitutionally heterotopic. The same groups or atomswith different connectivities.

D and L. An older system for identifying enantiomers, relating all stereocenters to the

sense of chirality of d- or l-glyceraldehyde. See discussion in the text. Generally not used

anymore, except for biological structures such as amino acids and sugars.

Diastereomers. Stereoisomers that are not enantiomers.

Diastereomeric excess (de). In a reaction that produces two diastereomeric products in amountsAand B, de_100%(_A–B_)/(A_B).

Diastereotopic. The relationship between two regions of a molecule that have the same connectivity but are not related by any kind of symmetry operation.

Dissymmetric. Lacking improper symmetry operations.A synonym for ‘‘chiral’’, but not the same as ‘‘asymmetric’’.

Eclipsed. A term describing a conformation about a single bond. In A–B–C–D, A and D are eclipsed if the torsion angle between them is approximately 0_.

Enantiomers. Molecules that are related as non-congruent mirror images.

Enantiomeric excess (ee). In a reaction that produces two enantiomeric products in Amounts A and A, ee_100%(_A–A_)/(A_A).

Enantiotopic. The relationship between two regions of a molecule that are related only by an improper symmetry operation, typically a mirror plane. 

Endo. In a bicyclic system, a substituent that is on a bridge is endo if it points toward the larger of the two remaining bridges. See also ‘‘exo’’.

Epimerization. The interconversion of epimers.

Epimers. Diastereomers that have the opposite configuration at only one of two or more stereogenic centers.

Erythro and threo. Descriptors used to distinguish between diastereomers of an acyclic structure having two stereogenic centers. When placed in a Fischer projection using the

convention proper for carbohydrates, erythro has the higher priority groups on the same

side of the Fischer projection, and threo has them on opposite sides.

Exo. In a bicyclic system, a substituent that is on a bridge is exo if it points toward the smaller of the two remaining bridges. See also ‘‘endo’’.

E, Z. Stereodescriptors for alkenes (see discussion in the text).

Gauche. A term describing a conformation about a single bond. In A–B–C–D, A and D are gauche if the torsion angle between them is approximately 60_ (or –60_).

Geminal. Attached to the same atoms. The two chlorines of 1,1-dichloro-2,2- difluoroethane are geminal. See also ‘‘vicinal’’.

Helicity. The sense of chirality of a helical or screw shaped entity; right (P) or left (M).

Heterochiral. Having an opposite sense of chirality. For example, d-alanine and l-leucine are heterochiral. See also ‘‘homochiral’’.

Heterotopic. The same groups or atoms in inequivalent constitutional or stereochemical

environments.

Homochiral. Having the same sense of chirality. For example, the 20 natural amino

acids are homochiral—they have the same arrangement of amino, carboxylate, and sidechain

groups. Has also been used as a synonym for ‘‘enantiomerically pure’’, but this is not

recommended, because homochiral already was a well-defined term before this alternative

usage became fashionable.

Homotopic. The relationship between two regions of a molecule that are related by a

proper symmetry operation.

Isotactic. A term describing the relative configuration along a polymer backbone. In

an isotactic polymer, all stereogenic centers of the polymer backbone have the same sense

of chirality.

Meso. A term describing an achiral member of a collection of diastereomers that also

includes at least one chiral member.

Optically active. Rotating plane polarized light. Formerly used as a synonym for

‘‘chiral’’, but this is not recommended.

Prochiral. Agroup is prochiral if it contains enantiotopic or diastereotopic ligands or

faces, such that replacement of one ligand or addition to one face produces a stereocenter.

R, S. The designations for absolute stereochemistry (see earlier discussion in the text).

Racemic mixture or racemate. Comprised of a 50:50 mixture of enantiomers.

Relative configuration. This refers to the configuration of any stereogenic center with

respect to another stereogenic center. If one center in a molecule is known as R, then other

centers can be compared to it using the descriptors R* or S*, indicating the same or opposite stereochemistry, respectively.

Resolution. The separation of a racemic mixture into its individual component enantiomers.

Scalemic. A synonym for ‘‘non-racemic’’ or ‘‘enantiomerically enriched’’. It has not

found general acceptance, but is used occasionally.

S-cis and s-trans. Descriptors for the conformation about a single bond, such as the

C2–C3 bond in 1,3–butadiene, or the C–N bond of an amide. If the substituents are synperiplanar, they are termed s-cis (‘‘s’’ for ‘‘single’’); if they are antiperiplanar, they are termed s-trans.

Stereocenter. See ‘‘stereogenic center’’.

Stereogenic center. An atom at which interchange of any two ligands produces a new

stereoisomer.Asynonym for ‘‘stereocenter’’.

Stereogenic unit. An atom or grouping of atoms at which interchange of any two ligands

produces a new stereoisomer.

Stereoisomers. Molecules that have the same connectivity, but a different arrangement

of atoms in space.

Stereoselective. A term describing the stereochemical consequences of certain types

of reactions. A stereoselective reaction is one for which reactant A can give two stereoisomeric products, B and B’, and one product is preferred. There can be degrees of stereoselectivity.

All stereospecific reactions are stereoselective, but the converse is not true.

Stereospecific. Aterm describing the stereochemical consequences of certain types of

reactions. A stereospecific reaction is one for which reactant A gives product B, and stereoisomeric reactantA gives stereoisomeric product B’. There can be degrees of stereospecificity. Stereospecific does not mean 100% stereoselective.

Syn. Modern usage is to describe the relative configuration of two stereogenic centers

along a chain. The chain is drawn in zigzag form, and if two substituents are on the same side of the plane of the paper, they are syn. See also ‘‘anti’’, ‘‘synperiplanar’’, and ‘‘synclinal’’.

Synclinal. Aterm describing a conformation about a single bond. In A–B–C–D,Aand

D are synclinal if the torsion angle between them is between 30_ and 90_ (or –30_ and –90_).

Syndiotactic. Aterm describing the relative configuration along a polymer backbone.

In a syndiotactic polymer, the relative configurations of backbone stereogenic centers alternate along the chain.

Synperiplanar. A term describing a conformation about a single bond. In A–B–C–D,

A and D are synperiplanar if the torsion angle between them is between _30_ and –30_.

Tacticity. A generic term describing the stereochemistry along a polymer backbone.

See ‘‘atactic’’, ‘‘isotactic’’, and ‘‘syndiotactic’’.

Trans. Aterm describing the stereochemical relationship between two ligands that are

on opposite sides of a double bond or a ring system. For alkenes only, E is preferred.

Vicinal. Attached to adjacent atoms. In 1,1-dichloro-2,2-difluoroethane, the relationship

of either chlorine to either fluorine is vicinal. See also ‘‘geminal’’.

Although the ultimate criterion is, of course, nonsuperimposability on the mirror

image (chirality), other tests may be used that are simpler to apply but not always

accurate. One such test is the presence of a plane of symmetry. A plane of symmetry

 (also called a mirror plane) is a plane passing through an object such that

the part on one side of the plane is the exact reflection of the part on the other side

(the plane acting as a mirror). Compounds possessing such a plane are always optically

inactive, but there are a few cases known in which compounds lack a plane of

symmetry and are nevertheless inactive. Such compounds possess a center of symmetry,

such as in a-truxillic acid, or an alternating axis of symmetry. A

center of symmetry is a point within an object such that a straight line drawn

from any part or element of the object to the center and extended an equal distance

on the other side encounters an equal part or element. An alternating axis of symmetry

 of order n is an axis such that when an object containing such an axis is

rotated by 3600/n about the axis and then reflection is effected across a plane at

right angles to the axis, a new object is obtained that is indistinguishable from

the original one. Compounds that lack an alternating axis of symmetry are always

chiral.

When three, five, or any odd number of cumulative double bonds exist, orbital

overlap causes the four groups to occupy one plane and cis–trans isomerism is

observed. When four, six, or any even number of cumulative double bonds exist, the situation is analogous to that in the allenes and optical activity is

possible.

• If the reagents and reaction conditions are all symmetrical, the product must be a racemic mixture. No optically active material can be created if all starting materials and conditions are optically inactive.94 This statement also holds when one begins with a racemic mixture. Thus racemic 2-butanol, treated with HBr, must give racemic 2-bromobutane.

The Fischer Projection

they may not be rotated 900,although 1800 rotation is permissible:

It is also permissible to keep any one group fixed and to rotate the other three clockwise

or counterclockwise

If the lowest ranking group is either at the top or the bottom (because these are the two positions pointing away from the viewer), the (R) configuration is present if the other three groups in descending order are clockwise, for example,

• That molecules with the same (either D or L) configuration need not rotate the plane of polarized light in the same direction. This fact should not surprise us when we remember that the same compound can rotate the plane in opposite directions under different conditions.

For glyceraldehyde, the (+) enantiomer is (R)

• The Cahn–Ingold–Prelog system has also been extended to chiral compounds that do not contain stereogenic centers, but have a chiral axis. Compounds having a chiral axis include unsymmetrical allenes, biaryls that exhibit atropisomerism, and alkylidene cyclohexane derivatives, molecular propellers and gears, helicenes, cyclophanes, annulenes, trans-cycloalkenes, and metallocenes.

Optical rotator dispersion (ORD) is a measurement of specific rotation, [a], as a function of wavelength. The change of specific rotation [a] or molar rotation with wavelength is measured, and a plot of either versus wavelength is often related to the sense of chirality.

In general, the absolute value of the rotation increases as the wavelength decreases. The plot of circular dichroism (CD) is the differential absorption of left and right circularly polarized radiation by a nonracemic sample, taking place only in spectral regions in which absorption bands are found in the isotropic or visible electronic spectrum.

The primary application of both Optical rotatory Dispersion (ORD) and circular Dichroism (CD)  is for the assignment of configuration or conformation.

diastereomers have different specific rotations; indeed one diastereomer may be chiral and rotate the plane of polarized light while another may be achiral and not rotate at all (an example is presented below).

enantiomers react at different rates with other chiral molecules, but at the same rate with achiral molecules.

When the three groups on one chiral atom are the same as those on the other, one of the isomers (called a meso form) has a plane of symmetry, and hence is optically inactive, even though it has two chiral carbons.

The newer method, which can be applied to all cases, is based on the Cahn–Ingold–Prelog system The two groups at each carbon are ranked by the sequence rules. Then that isomer with the two higher ranking groups on the same side of the double bond is called (Z) (for the German word zusammen meaning together); the other is (E) (for entgegen meaning opposite)

If there is more than one double bond in a molecule and if W not equal to X and Y not equal to Z for each, the number of isomers in the most general case is 2n, although this number may be decreased if some of the substituents are the same, as in

When a molecule contains a double bond and an asymmetric carbon, there are four

isomers, a cis pair of enantiomers and a trans pair: