Organic Chemistry Exam 2

Mechanism: Addition of Hydrogen Halides to Alkenes

1) Electron pair in the pi bond of an alkene is donated to the hydrogen of the hydrogen halide. As a result, the carbon-carbon double bond is protonated on the carbon atom with smaller number of alkyl substituents. The other carbon (the one with the greater number of alkyl substituents) becomes positively charged and electron-deficient (called a carbocation). Lewis acid. 2) Halide ion, which is a Lewis base, or nucleophile, reacts with the carbocation at it electron-deifient carbon atom.

Mechanism: Bromine (Br2) Addition (Analogous to Chlorine and Iodine Additions)

1) Formation of bromonium ion (a species that contains a bromine bonded to two carbon atoms; the bromine has an octet of electrons and a positive charge). Occurs in a single mechanistic step involving three curved arrows —Once carbon of the double bond acts as a nucleophile toward Br using the pi electrons to form one C-Br bond —The other bromine acts as a leaving group to form bromide ion —The electrophilic bromine also acts as a nucleophile toward the other carbon of the double bond to form the other C-Br bond 2) Bromide ion donates an electron pair to either one of the ring carbons of the bromonium ion *Carbocations do not form because bromonium ions are more stable (more covalent bonds, and every atom has an octet)

Mechanism: Ozonolysis

1) Formation of ring at double bond in alkene (three oxygens of the ozone remain intact at this point). Concerted mechanism 2) The initial cycloaddition product is unstable and spontaneously forms the ozonide. In this reaction, the remaining carbon-carbon bond of the alkene is broken. This process occurs, first, by a cyclic electron flow to form an aldehyde and an aldehyde oxide. An O-O bond (very weak) is broken in the process. The aldehyde flips over, and a second cycloaddition, completes the formation of the ozonide 3) When the ozonide is treated with dimethyl sulfide (CH3)2S the ozonide is split

The Peroxide Effect

In the presence of peroxides, the addition of HBr to alkenes occurs such that the hydrogen is bound to the carbon of the double bond bearing the greater number of alkyl substituents *Regioselectivity of HI or HCl additions is NOT affected by the presence of peroxides

Catalyst

Increases the reaction rate by lowering the standard free energy of activation Not consumed (may be consumed in one step, but if so, it is regenerated in a subsequent step) Does not affect the energies of reactants and products (or equilibrium constant) Accelerates both the forward and the reverse of a reaction by the same factor

Hydroboration-Oxidation

One of the most important reactions of organoboranes is their conversion into alcohols with hydrogen peroxide (H2O2) and aqueous NaOH Boron is replaced by an —OH in each alkyl group Net result of hydroboration-oxidation is addition of the elements of water (H and OH) to the double bond of an alkene so that the —OH ends up at the carbon of the double bond with the smaller number of alkyl substituents

Hyperconjugation

Overlap of bonding electrons from the adjacent sigma bonds with the unoccupied 2p orbital of the carbocation. Causes stability of carbocations with greater number of alkyl substituents (Energetic advantage of hyperconjugation is that it involves additional bonding. That is, the electrons in the C-H bonds participate in bonding not only with the C and H, but also with the electron-deficient carbon)

R,S Nomenclature

1) Identify an asymmetric carbon and the four different groups bonded to it 2) Assign priorities to the four different groups according to the rules given in Sec. 4.2B. (The convention we use is that the highest priority=1 and the lowest priority=4) 3) View the molecule along the bond formed from the asymmetric carbon to the group of lowest priority — that is, with the asymmetric carbon nearer and the lowest-priority group farther away. This is essentially a Newman projection about this bond 4) Consider the clockwise or counterclockwise order of the remaining group priorities. If the priorities of these groups decrease in the clockwise direction, the asymmetric carbon is said to have the R configuration. If the priorities decrease in the counterclockwise direction, the asymmetric carbon is said to have the S configuration. *A stereoisomer is named by indicating the configuration of each asymmetric carbon before the systematic name of the compound

Mechanism: Free-Radical Addition of HBr to an Alkene

1) Initiation: —The first initiation step in free-radical addition of HBr to an alkene is the homolysis of the peroxide —The second initiation step is the removal of a hydrogen atom from HBr by the free radical that was formed in the first initiation step (process called radical abstraction) 2) Propagation: —The first propagation step of free-radical addition of HBr to an alkene is the reaction of the bromine atom (generated in initiation step two) with the pi bond —The second propagation step is another atom abstraction reaction: removal of a hydrogen atom from HBr by the free-radical product of propagation step one to give the addition product and a new bromine atom. The bromine atom, in turn, can react with another molecule of alkene, and the cycle continues until the reactants are consumed 3) Termination: radicals react to give small amounts of nonradical by-products

Stability of Carbocations

Carbocations are classified by the degree of alkyl substitution at their electron-deficient carbon atoms. Alkyl substituents at the electron-deficient carbon strongly stabilize carbocations. Therefore, tertiary>secondary>primary

If a molecule contains n asymmetric carbons, how many stereoisomers does it have?

2^n (Unless there are meso compounds. If there are meso compounds, then there are fewer than 2^n stereoisomers)

What physical property can be used to distinguish enantiomers?

A compound and its enantiomer can be distinguished by their effects on polarized light (The melting points, boiling points, densities, indices of refraction, heats of formation, standard free energies, etc. of enantiomers are identical)

Free Radical Chain Reactions

A free-radical chain reaction involves free-radical intermediates and consists of the following three fundamental reaction steps: —Initiation: the free radicals that take part in subsequent steps of the reaction are formed from a free-radical initiator (a molecule that undergoes homolysis with particular ease). The initiator is the source of free radicals. Peroxides (with the exception of H2O2) are frequently used as free-radical initiators. (Azoisobutyronitrile, AIBN, is also widely used because the very stable molecule dinitrogen is liberated as a result of homolytic cleavage) (sometimes heat or light can also initiate a free-radical reaction) —Propagation: Radicals react with non-radical starting materials to give other radicals; starting materials are consumed and products are formed. Propagation steps occur repeatedly. When the propagation steps are considered together, there is no net formation or destruction of any of the radical species involved (meaning that if a radical is formed, it must be consumed in a subsequent propagation step and another radical must be formed to take its place) —Termination: Two radicals react to give nonracial products. Typically, termination involves a radical recombination reaction, in which two radicals come together to form a covalent bond (reverse of homolysis). These products are present in very small amounts because they are formed only from free radicals, which are also present in small amounts. Very exothermic, but does not occur often due to low concentration of radicals.

Products: Hydration of Alkenes

A hydrogen of the water molecule adds to the carbon of the double bond with the smaller number of alkyl substituents while the OH group adds to the carbon of the double bond with the greater number of alkyl substituents

Meso Compounds

A meso compound is an achiral (and therefore optically inactive) compound that has chiral diastereomers. In virtually all of the examples we will cover, a meso compound is an achiral compound that has at least two asymmetric centers. Note: cis- and trans-2-butene are stereoisomers, and they are achiral, but they are not meso compounds because neither has any asymmetric carbons. The existence of meso compounds shows that some achiral compounds have asymmetric carbons.

Suppose that we have a structure that contains two or more asymmetric carbons. How can we tell whether it can exist as a meso stereoisomer?

A meso compound is possible only when a molecule with two or more asymmetric atoms can be divided into halves that have the same connectivity.

Writing Organic Reactions

Catalysts are sometimes written over the arrow Solvent is often written under the arrow However, in many cases, organic chemists abbreviate reactions by showing only the organic starting materias and the major organic product(s). The other reactants and condition are written over the arrow.

Racemates

A mixture containing equal amounts of two enantiomers is known as a racemate (or racemic mixture) Racemates typically have physical properties that are different from those of the pure enantiomers. The optical rotation of any racemate is zero (because a racemate contains equal amounts of two enantiomers whose optical rotations of equal magnitude and opposite sign exactly cancel each other). In a racemate, the EE is also 0.

Mechanism: Catalytic Hydrogenation of Alkenes

A number of noble metals, such as platinum, palladium, and nickel, are useful as hydrogenation catalysts. They are often used in conjunction with solid support materials such as alumina (Al2O3), barium sulfate (BaSO4), or activated carbon. Because hydrogenation catalysts are insoluble in the reaction solution , they are examples of heterogeneous catalysts. Both the hydrogen and the alkene must be adsorbed on the surface of the catalyst for a reaction to occur. The catalyst forms reactive metal-carbon and metal-hydrogen bonds that ultimately are broken to form the products and to regenerate the catalyst sites. (This is not a reaction for which a simple curved-arrow mechanism can be written)

Stereocenters

A stereocenter is an atom at which the interchange of two groups gives a stereoisomer. Not all carbon stereocenters are asymmetric carbons (Recall that the carbons involved in the double bonds of E and Z homers are also stereocenters) All asymmetric atoms are stereo centers, but not all stereo centers are asymmetric atoms

Free Radicals

Any species with at least one unpaired electron is called a free radical. Formed by homolysis (bond-breaking process that occurs with electrons moving in an unpaired fashion) — contrast with typical, heterolytic process of electrons pairs moving together *Use fishhook notation to show when electrons move individually Most free-radicals are very unstable and behave as reactive intermediates, meaning that they react before they can accumulate in significant amounts

Products: Catalytic Hydrogenation of Alkenes

Addition of hydrogen to an alkene in the presence of a catalyst (one of the best ways to convert alkenes to alkanes).

Electrophilic Addition

An addition reaction is en electrophilic addition when it begins with the donation of an electron pair from a pi bond to an electrophilic atom.

Asymmetric Carbon

An asymmetric carbon atom is a carbon to which four different groups are bonded. A molecule that contains ONLY one asymmetric carbon is chiral (However, no generalization can be made for molecules with two or more, and an asymmetric carbon is not a necessary condition for chirality) Although carbon is the most common, other atoms can be asymmetric as well. These are generally referred to as asymmetric centers

Mechanism: Conversion of Alkenes into Organoboranes

Because boron has three B-H bonds, one borane molecule can add to three alkene molecules. The addition of BH3 is called hydroboration. The hydroboration product of an alkene is a trialkylborane. Hydroboration is believed to occur in a single mechanistic step (concerted mechanism)

Products: Conversion of Alkenes into Organoboranes

Borane adds regioselectively to alkenes so that the boron becomes bonded to the carbon of the double bond with fewer alkyl substituents, and the hydrogen becomes bonded to the carbon with more alkyl substituents (because hydrogen is more electronegative than boron)

Symmetry Elements

Chiral molecules lack certain types of symmetry Symmetry elements are lines, points, or planes that relate equivalent parts of an object. A very important symmetry element is a plane of symmetry (sometimes called an internal mirror plane) which divides an object into halves that are exact mirror images. A molecules or other object that has a plane of symmetry is achiral Another important symmetry element is the center of symmetry (sometimes called a point of symmetry). This is a point through which any line contacts exactly equivalent parts of the object at the same distance in both directions.

Diastereomeric Salt Formation

Diastereomeric salt formation is a method used for the enantiomeric resolution of acidic or basic compounds. Amines are derivatives of ammonia in which one or more hydrogen atoms have been replaced by organic groups. Diastereomeric salt formation involving amines takes advantage of the fact that amines, like ammonia, are bases; so, they react rapidly and quantitatively with carboxylic acids to form salts. These salts are diastereomers because they differ in configuration at only one of their asymmetric carbons. Since these salts are diastereomers, they have different physical properties.

Bond Dissociation Energy

Energy required to break a bond homolytically. Measures intrinsic strength of a chemical bond. To calculate enthalpy of a reaction, subtract the bond dissociation energies of the bonds formed from the bond dissociation energies of the bonds broken

Diastereromers

For a pair of chiral molecules with more than one asymmetric carbon to be enantiomers, they must have opposite configurations at every asymmetric carbon. Stereoisomers that are not enantiomers are called diastereoisomers (or more simply, diastereomers). Diastereomers are not mirror images. Diastereomers differ in all of their physical properties (i.e. melting point, boiling point, heat of formation, standard free energy, etc.) and can therefore be separated by conventional means. Diastereomers may or may not be chiral. If diastereomers happen to be chiral, they can be expected to be optically active, but their specific rotations will have no relationship.

Hammond's Postulate

For a reaction in which an intermediate of relatively high energy is either formed from reactants of much lower energy or converted into products of much lower energy, the structure and energy of the transition state can be approximated by the structure and energy of the intermediate itself

Explanation of Peroxide Effect

Free radicals, like carbocations, can be classified as primary, secondary, and tertiary. Relative stability: tertiary. > secondary > primary Therefore, when a bromine atom reacts with the pi bond of an alkene, it adds to the carbon of the alkene with fewer alkyl substituents because this places the unpaired electron on the carbon with more alkyl substituents. In other words, the more stable free radical is formed.

Principle of Microscopic Reversibility

If a reaction occurs by a certain mechanism, the reverse reaction under the same conditions occurs by the exact reverse of that mechanism (Another consequence is that the rate-limiting transition states of a reaction and its reverse are the same)

Optical Activity

If plane-polarized light is passed through one enantiomer of a chiral substance (either the pure enantiomer or a solution of it), the plane of polarization of the emergent light is rotated. A substance that rotates the plane of polarized light is said to be optically active. Individual enantiomers of chiral substances are optically active. Enantiomers are distinguished by their optical activities because they rotate the plane of polarized light by equal amounts in opposite direction. There is no general correspondence between the sign of the optical rotation and the R or S configuration of a compound

Polymers

In the presence of free-radicals initiators such as peroxides or AIBN, many alkenes react to form polymers, which are very large molecules composed of repeating units. In a polymerization reaction, small molecules known as monomers react to form a polymer. Can happen through use of free-radicals

Another way to identify a meso compound . . .

If you can find any conformation of a molecule with asymmetric carbons — even an eclipsed conformation — that is achiral, the molecule is meso. Planes of symmetry are particularly easy to spot in eclipsed conformations, and a molecule with a plane of symmetry is achiral. Therefore, finding an eclipsed conformation with a plane of symmetry is sufficient to show that a compound is meso, even though the compound does not exist at the eclipsed conformation.

Once you recognize the possibility of a meso compound, how do you know which stereoisomers are meso and which are chiral?

In a meso compound, the corresponding asymmetric atoms in each half of the molecule must have opposite stereochemical configurations.

Carbocation Rearrangement in Hydrogen Halide Addition

In a rearrangement, a group from the starting material has moved to a different position in the product. (Group must come from a carbon directly attached to the electron-deficient, positively charged carbon of the carbocation) Can take the form of an alkyl group moving (with its bonding pair of electrons) from one carbon to another. Could also be a hydride shift (migration of a hydrogen with its two bonding electrons) Essentially a Lewis acid-base reaction in which the electron-deficient carbon is the Lewis acid and the migrating group is the Lewis base In both cases, one carbocation is converted into a different, more stable carbocation (almost always occurs when possible). If choice between alkyl or hydride group moving, hydride migration typically occurs because it gives the more stable carbocation

Products: Oxymercuration

In oxymercuration, alkenes react with mercuric acetate, Hg(OAc)2, in aqueous solution to give addition products in which an —HgOAc group and an —OH group derived from water have added to the double bond. The —HgOAc group goes to the carbon of the double bond with fewer alkyl substituents and the —OH group to the carbon of the double bond with more alkyl substituents

Formation of Halohydrins

In the addition of bromine, the only nucleophile available to react with the bromonium ion is the bromide ion. When other nucleophile are present, they too can react with the bromonium ion to form products other than dibromides. Example is when water is solvent and reacts with bromonium ion (because it is present in much higher concentration than bromide ion). Bonds to higher substituted carbon Another water molecule then comes in and removes acidic proton to give H3O+ and bromohydrin (compound containing both an -OH group and a -Br group, most commonly occupying vicinal positions)

Inversion at Other Atoms

Inversion processes can occur at other atoms. When the central atom comes from the second period of the periodic table, inversion is very rapid, as it is with amines. Therefore,if one of these atoms is the only asymmetric center in a compound, the compound cannot be resolved into enantiomers and cannot maintain optical activity. However, when the central atom comes from the third and greater periods of the periodic table, inversion is very slow. Reason for difference lies in the hybridization of the central atom. See section 6.9 for details.

Which is more stable: the equatorial or axial conformation of a substituted cyclohexane?

It is usually the case that the equatorial conformation of a substituted cyclohexane is more stable than the axial conformation. Examination of axial methylcyclohexane shows that van Der Waals repulsions occur between one of the methyl hydrogens and the two axial hydrogens on the same face of the ring. Such unfavorable interactions between axial groups are called 1,3-diaxial interactions. These van der Waals repulsions destabilize the axial conformation relative to the equatorial conformation, in which such van der Waals repulsions are absent.

Stereochemical Correlation

Knowing how to assign the R and S designation to compounds with asymmetric carbons is one thing, but you can't apply this system to a molecule until you know the actual three-dimensional arrangement of its atoms— that is, its absolute configuration (or absolute stereochemistry) The absolute configurations of most organic compounds are determined instead by using chemical reactions to correlate them with other compounds of known absolute configurations. This process is called stererochemical correlation. See section 6.5 for an in-depth example

Products: Addition of Hydrogen Halides to Alkenes

Produces alkyl halides, in which halogen is bonded to saturated carbon atom Main product is isomer in which the halogen is bonded to the carbon of the double bond with the greater number of alkyl substituents, and the hydrogen is bonded to the carbon with the smaller number of alkyl substituents Size of substituents does not matter

Oxymercuration-Reduction

Products of oxymercuration are easily converted into alcohols by treatment with the reducing agent sodium borohydride (NaBH4) in the presence of aqueous NaOH. We will not consider the mechanism of this reaction, but know that a carbon-mercury bond is replaced by a carbon-hydrogen bond. Together with oxymercuration, this process is referred to collectively as oxymercuration-reduction of an alkene. Overall result of oxymercuration-reduction is the net addition of the elements in water (H and OH) to an alkene double bond with —OH group being added to the more branched carbon *Gives same overall transformation as the hydration reaction but without use of carbocations. Therefore, no rearrangements are observed.

Products: Addition of Chlorine (Cl2) and Bromine (Br2)

Products of these reaction are vicinal dihalides (compounds with halogens on adjacent carbons)

Chair Conformation of Cyclohexane

See attached picture Two types of carbons: —Six C-H bonds are perpendicular to the plane of the table. These hydrogens, marked in red, are called axial hydrogens —The remaining C-H bonds point outward along the periphery of the ring. These hydrogens, marked in blue, are called equatorial hydrogens. Other groups can be substituted for the hydrogens, and these groups also can exist in either axial or equatorial arrangements. In a chair conformation, all bonds are staggered. Staggered bonds are energetically preferred over eclipsed bonds. The stability of cyclohexane is a consequence of the fact that all of its bonds can be staggered without compromising the tetrahedral carbon geometry.

Cyclic Meso Compounds

See picture. The internal plane of symmetry means that this compound is achiral. Because it has asymmetric carbons and chiral stereoisomers (the trans isomers), this is an example of a meso compound)

Selective Crystallization

Selective crystallization is another method of enantiomeric resolution in which a solution of a mixture of enantiomers is cooled to superstation and a seed crystal of the desired enantiomer is added. In this case, the seed crystal serves as the resolving agent and promotes crystallization of the desired enantiomer.

Stereoisomers

Stereoisomers are compounds that have the same atomic connectivity but a different arrangement of atoms in space. (Recall that E and Z isomers of an alkene are stereoisomers)

Mechanism: Hydration of Alkenes

The alkene double bond undergoes reversible addition of water in the presence of moderately concentrated strong acids such as H2SO4, HClO4, and HNO3. Because the catalyzing acid is soluble in the reaction solution, it is a homogeneous catalyst. 1) Strong acid leads leads to formation of H3O+, which then protonates double bond to form more stable carbocation. 2) Water (nucleophile) combines with the carbocation. 3) Proton is lost to solvent to give the alcohol and regenerated H3O+ catalyzing acid.

Boat Conformation

The boat conformation is not a stable conformation of cyclohexane. Two sources of instability: —Certain hydrogens are eclipsed —The two hydrogens on the "bow" and "stern" of the boat, experience modest van der Waals repulsions.

Why is cyclohexane so stable?

The bonds in cyclohexane are essentially the same as the bond angles in an alkane — very close to the ideal 109.5 degree tetrahedral angle. If the bonds were significantly distorted from tetrahedral, we would expect to see a greater heat of formation.

Why is the peroxide effect not observed for HCl and HI?

The first propagation step (which is exothermic for HBr) is endothermic, and therefore energetically unfavorable, for HI and HCl. This can be seen through calculations involving bond dissociation energies. Propagation steps of any free-radical chain reaction are in competition with recombination steps that terminate free-radical reaction. These recombination steps are so exothermic that they occur on every encounter of two radicals. The energy required for an endothermic propagation step, in contrast, represents an energy barrier that reduced the rate of this step. In effect, only exothermic propagation steps compete successfully with recombination steps

Products: Ozonolysis

The net transformation is the replacement of a carbon-carbon double bond with two carbon-oxygen double bonds (now on separate molecules) If a carbon of the double bond in the starting alkene bears a hydrogen, then an aldehyde is formed. In contrast, if a carbon of the double bond bears no hydrogens, then a keytone is formed instead *If ozonide is simply treated with water, hydrogen peroxide is formed as a by product. Under these conditions (or if hydrogen peroxide is added specifically), aldehydes are converted into carboxylic acids, but keynotes are unaffected

Transition State

The rate of a chemical reaction can be defined for our purposes as the number of reactant molecules converted into product in a given time. The theory of reaction rates used by many organic chemists postulates that as the reactants change into products, they pass through an unstable state of maximum free energy, called the transition state. The transition state has a higher energy than either the reactants or products and therefore represents an energy barrier (called the standard free energy of activation) to their interconversion. The higher the barrier, the smaller the rate. A reaction and its reverse have the same transition state and, therefore, the same energy of activation. Each step of a multistep reaction has its own characteristic rate and therefore its own transition state. It often happens that one step of a multistep reaction is considerably slower than any of the others. This slowest step is called the rate-limiting step and it is the one with the transition state of highest free energy. In such cases, the rate of the overall reaction is equal to the rate of the rate-limiting step

Mechanism: Oxymercuration

The solvent is a mixture of water and THF, a widely used ether (important because it is able to dissolve both water and many water-insoluble organic compounds. Its role in oxymercuration is to dissolve both the alkene and the aqueous mercuric acetate solution. 1) Formation of a cyclic ion called a mercurinium ion (similar to bromonium ion) and acetate ion 2) Mercurinium ion reacts with the solvent water at the carbon with the greater number of alkyl substituents. (Another difference between oxymercuration and halohydrin formation: oxymercuration is highly regioselective even if carbon only has one alkyl substituent, but halohydrin formation is only highly regioselective if one of the alkene carbons has two alkyl branches) 3) Addition is completed by the transfer of a proton to the acetate ion formed in step one.

Asymmetric Nitrogen: Amine Inversion

The two enantiomers of amines cannot be separated because they rapidly interconvert by a process called amine inversion. In this process, the larger lobe of the electron pair seems to push through the nucleus to emerge on the other side (molecule is turning itself inside out). Process occurs through a transition state in which the amine nitrogen becomes sp2-hybridized. Because this process is rapid at room temperature, it is impossible to separate the enantiomers. (Example of racemization)

Stereoisomers Interconverted by Internal Rotations

The two gauche conformations of butane are noncongruent mirror images, or enantiomers. Consequently gauche-butane is chiral. The chirality of gauche-butane shows that some chiral molecules do not contain asymmetric carbons. The two gauche conformations of butane are conformational enantiomers (enantiomers that are interconverted by a conformational change). The "conformational change" in this case is an internal rotation. The anti conformation of butane, in contrast, is achiral and is a diastereogmer of either one of the gauche conformations. Anti-butane and either one of the gauche-butanes are therefore conformational diastereomers (diastereomers that are interconverted by a conformational change) Despite the chirality of any one guache conformation of butane, the compound butane is not optically active because the two gauche conformations are present in equal amounts *A molecule is said to be achiral when it consists of rapidly equilibrating enantiomeric conformations that cannot be separated on any reasonable time scale. (In butane, the rapidly equilibrating conformations are the two gauche conformations). Like saying it is a "time-averaged conformation" that is achiral. **Therefore, if we know that the conformational equilibrium is rapid, then the molecule is achiral if we can find one achiral conformation (even an unstable conformation such as an eclipsed conformation)

Which is more stable: trans- or cis- isomer?

Trans- (In cis- molecule, larger substituents are forced to occupy the same plane, thereby decreasing stability)

Which is more stable: alkene with one alkyl substituent on the double bond or two?

Two (Alkenes are stabilized by alkyl substituents on the double bond. The alkene with the greatest number of substituents is most stable. Identity of substituents not as important as number of them-- i.e. alkene with two smaller alkyl substituents still more stable than alkene with one large alkyl substituent)

Enantiomers

Two molecules that are mirror images of each other but are not congruent (cannot be superimposed) are enantiomers. Molecules that can exist as enantiomers are said to be chiral. (Molecules that are not chiral are said to be achiral)

Steric Effect

When a chemical phenomena (such as a reaction) is affected by van der Waals repulsions, it is said to be influenced by a steric effect. Example: During radical addition of HBr to an alkene, when the rather large bromine atom reacts at the more-branched carbon of the double bond, it experiences van der Waals repulsions with the hydrogens in the branches. These repulsions increase the energy of the transition state. When the bromine atom reacts at the less-branched carbon of the double bond, these van der Waals repulsions are absent Example: Preference of butane for the anti rather than the gauche conformation Example: Greater stability of trans-2-butene relative to cis-2-butene

Cis-Trans Isomerism in Disubstituted Cyclohexanes

When both substituents have the same relative orientation—both up or both down—the substitution pattern is called cis When both substituents have different relative orientations—one up and the other down—the substitution pattern is called trans

Chair Interconversion

When one chair conformation is converted to another, the equatorial hydrogens become axial; the axial hydrogens become equatorial; up carbon become down carbons; and vise versa. Energy barrier for chair interconversion is low enough that it is very rapid (happens about 10^5 times per second at room temperature). Therefore, although the axial hydrogens are stereochemically different from the equatorial hydrogens in any one chair conformation, the chair interconversion causes these hydrogens to change positions rapidly. Hence, averaged over time, the axial and equatorial hydrogens of cyclohexane are equivalent and indistinguishable.

Enantiomeric Excess

When one enantiomer of a chiral compound is uncontaminated by the other enantiomer, it is said to be enantiomerically pure. However, mixtures of enantiomers occur commonly. The enantiomeric composition of a mixture of enantiomers is expressed as the enantiomeric excess, abbreviated EE, which is defined as the difference between the percentages of the two enantiomers in the mixture. If we know the optical activity of the pure major enantiomer, and if the two enantiomers are the only optically active substances present in a sample, then the enantiomeric excess in the sample can be determined from the specific rotation of the mixture.

"Modified Markovnikov's Rule"

When the two groups that add are different, the carbon of the double bond with fewer alkyl substituents becomes bonded to the less electronegative group, and the carbon of the double bond with more alkyl substituents becomes bonded to the more electronegative group