Chapter 11 Lecture PowerPoint Electrophilic Addition to Nonpolar π Bonds 1

General Electrophilic Addition Mechanism HCl serves as the strong Brønsted acid in this electrophilic addition. Step 1 shows a pair of electrons from the electron-rich π bond that forms a bond to the acid’s electron-poor H atom. Step 2 is a coordination step, whereby Cl⁻ forms a bond to the carbocation.

Rate Determining Step

Benzene Rings and Electrophilic Addition of Brønsted Acids The π electrons that would be used to form the new bond to H are too heavily stabilized.

The Stability of Benzene The source of this stability is a phenomenon called aromaticity. If HA were to add across one of the C=C double bonds then the delocalization of the π electrons would cease to exist, and the resulting stabilization would be destroyed.

Regiochemistry In the addition of a Brønsted acid across a double bond, the hydrogen atom can bond to one of two possible carbon atoms. With an asymmetric alkene, two constitutional isomers can be produced.

Markovnikov’s rule This type of regioselectivity is called Markovnikov addition. Electrophilic addition with the opposite regioselectivity is called anti-Markovnikov addition.

Mechanistic Explanation of Markovnikov’s Rule The addition of the proton in the first step favors the production of the more stable carbocation intermediate. This can happen when the proton adds to the less-substituted carbon of the alkene.

Mechanistic Explanation of Markovnikov’s Rule continued…

Carbocation Rearrangements 2-Chloro-3-methylbutane is the product of a normal Markovnikov addition of HCl across the C=C double bond. Electrophilic addition of a Brønsted acid across a C=C double bond is susceptible to carbocation rearrangements.

Carbocation Rearrangement Mechanism A 1,2-hydride shift can account for the formation of 2-chloro-2-methylbutane.

Stereochemistry Depending upon the symmetry of the product, stereochemistry may or may not be an issue. In the above reaction a single tetrahedral stereocenter is formed, and the products are indeed chiral.

Producing Two Tetrahedral Stereocenters When DBr (whose reactivity is nearly identical to that of HBr) reacts with an achiral alkene such as cyclohexene, the product molecules are chiral. These product molecules contain two stereocenters, so there are 4 stereoisomers that exist. In this case, all four stereoisomers are produced.

DBr Mechanism

Addition of a Weak Acid: Acid Catalysis Effectively no reaction occurs if an alkene is treated with water—a weak acid—under neutral conditions.

Acid-Catalyzed Hydration Reaction

Acid-Catalyzed Hydration Mechanism If an alcohol was added, then it would be called an acid-catalyzed alkoxylation reaction. Such an alkoxylation reaction produces an ether.

Electrophilic Addition of a Strong Brønsted Acid to an Alkyne The triple bond of an alkyne is relatively electron rich and the π electrons are relatively easily accessible.

Mechanism for the Electrophilic Addition to an Alkyne A hydrogen halide adds to an alkyne in a Markovnikov fashion, proceeding through the more stable of two possible carbocation intermediates.

Low Yields and Electrophilic Addition to an Alkyne The yield is poor because the positive charge in the carbocation intermediate is on a vinylic C. The positive charge is rather poorly stabilized, which makes the reaction proceed slowly.

High Yields and Electrophilic Addition to an Alkyne A second addition of a strong Brønsted acid to an alkyne is synthetically useful.

Mechanism for the Addition of Two Equivalents of HBr to an Alkyne

Acid-Catalyzed Hydration of an Alkyne: Synthesis of a Ketone

Mechanism for the Acid-Catalyzed Hydration of an Alkyne

Increasing the Yield of Acid-Catalyzed Hydration The yield of an acid catalyzed hydration can be increased by using a Brønsted acid catalyst stronger than sulfuric acid, or by using a mercury(II) catalyst.

Electrophilic Addition of a Brønsted Acid to a Conjugated Diene Buta-1,3-diene has conjugated double bonds because the two double bonds are separated by another bond. A conjugated diene such as buta-1,3-diene is electron rich so it undergoes electrophilic addition with Brønsted acids.

1,2- and 1,4-Addition Reaction of the conjugated diene yields a mixture of isomeric products. The H and Cl atoms that added to the diene to produce 3-chlorobut-1-ene are separated by two C atoms, making it the product of 1,2-addition. 1-Chlorobut-2-ene is the product of 1,4-addition because the H and Cl atoms that added to the diene are separated by four C atoms.

Mechanism for 1,2- and 1,4-Addition Both products are produced from the same carbocation intermediate.

Kinetic versus Thermodynamic Control for a Conjugated Diene If the electrophilic addition of HCl to buta-1,3-diene is carried out at room temperature, then the 1,4-adduct is the major product

Kinetic versus Thermodynamic Control for a Conjugated Diene continued… If the electrophilic addition of HCl to buta-1,3-diene is carried out at cold temperatures, then the 1,2-adduct is the major product

Temperature and Reversibility The temperature at which the reaction is run governs whether the reaction is reversible or irreversible. At low temperatures, the product molecules do not possess enough energy to climb over the energy barrier in the reverse direction to reform reactants at a significant rate, effectively making electrophilic addition to the diene irreversible. At high temperatures the product molecules do possess enough energy to make the reaction reversible.

The 1,2 Adduct is the Kinetic Product The 1,2-adduct is the kinetic product as a result of the location of Br⁻ after completion of the first step of the mechanism. Upon addition of the H+ to the diene, Br⁻ is closer to C2 than it is to C4

Stability and the Thermodynamic Product The thermodynamic product is the most stable alkene product. In the addition of HCl to buta-1,3-diene, the 1,4-adduct is the thermodynamic product because it is disubstituted, whereas the alkene group in the 1,2-adduct is only monosubstituted.

Terpene Biosynthesis: Carbocation Chemistry in Nature Many natural products are terpenes or terpenoids, including essential oils from plants and steroids. A terpene or terpenoid consists of multiple isoprene units linked by their terminal carbons.

Isopentenyl pyrophosphate

Dimethylallyl Pyrophosphate The electrophilic addition step produces the more stable carbocation intermediate, thus adhering to Markovnikov’s rule.

Synthesis of Neryl Pyrophosphate Insert eq 11-35 61_p599_Karty1_CH11 Dimethylallyl pyrophosphate then loses its pyrophosphate group (a rather good leaving group) in a heterolysis step resulting in an allylic carbocation. Neryl pyrophosphate can eventually be converted to cholesterol and other steroid hormones.

Summary and Conclusions A strong Brønsted acid, such as HCl or HBr, has an electron-poor proton, thus making it an electrophile. An electrophilic addition reaction occurs when a Brønsted acid adds across a C=C double bond or C≡C triple bond. The rate-determining step in the addition of a Brønsted acid to an alkene or alkyne is the addition of the proton, which is Step 1 of the general mechanism. Benzene does not undergo electrophilic addition with Brønsted acids.

Summary and Conclusions continued… The regiochemistry of the addition of a Brønsted acid across a C=C double bond or C≡C triple bond is described by Markovnikov’s rule. Because the mechanism proceeds through a carbocation intermediate, these reactions are susceptible to carbocation rearrangements. When water adds, the reaction is called an acid-catalyzed hydration reaction. When an alkyne undergoes a single electrophilic addition of a Brønsted acid, a vinyl-substituted alkene is produced. The yield of these reactions is generally low.

Summary and Conclusions continued… The acid-catalyzed hydration of an alkyne produces an enol, which quickly tautomerizes to a ketone. A conjugated diene undergoes electrophilic addition via 1,2-addition and 1,4-addition, producing a mixture of products. Electrophilic addition to a conjugated diene takes place under kinetic control at cold temperatures, and under thermodynamic control at warm temperatures.