6.19 Epoxides – essential synthetic intermediates Crixivan® (Indinavir, Merck & Co.) – protease inhibitor used to treat HIV (excellent oral bioavailability)

Ch. 6 – Reactions of Alkenes: Addition Reactions 6.1 Hydrogenation of Alkenes Needs a precious metal catalyst such as Pt or Pd Not covering Mechanism 6.1

6.2 Heats of hydrogenation of isomeric C4H8 alkenes Figure 6.1

Table 6.1

6.3 Stereochemistry of Alkene Hydrogenation H atoms have added to the same face of the alkene - syn addition

6.3 Stereochemistry of Alkene Hydrogenation Figure 6.2

6.4 Electrophilic Addition of Hydrogen Halides to Alkenes Stronger acids react faster : H-I > H-Br > H-Cl >> H-F Electrophilic Addition mechanism

Mechanism 6.2 a

6.5 Regioselectivity in Electrophilic Addition Markovnikov’s Rule Since the reaction involves formation of cations, the major product arises from the most stable intermediate carbocation

6.6 Mechanistic Basis for Markovnikov's rule Figure 6.4

Figure 6.5

Examples of H-X Addition

6.7 Cation Rearrangements in H-X Addition to Alkenes 2o cation undergoes intramolecular rearrangement to more stable 3o cation

6.8 Free Radical Addition of H-Br to Alkenes Mechanism 6.3

6.9 Electrophilic Addition of Sulfuric Acid 6.10 Acid-catalyzed hydration of alkenes Note the Markovnikoff regioselectivity

Mechanism 6.5

6.10 Acid-catalyzed hydration of alkenes Table 6.2

6.11 Thermodynamics of addition-elimination How do you get one product over the other? In dehydration (elimination) – remove alkene In hydration (addition) – use excess water Both are using Le Châtelier’s principle

Reaction is regioselective and stereoselective 6.12 Hydroboration - Oxidation of Alkenes 1. Addition 2. Oxidation Reaction is regioselective and stereoselective

6.12 Hydroboration – Avoiding Steric Interactions

6.13 Stereochemistry of Hydroboration Addition of BH3 is a concerted syn addition Oxidation step retains the stereochemistry from first step

6.14 Mechanism of Hydroboration/Oxidation

6.14 Mechanism of Hydroboration/Oxidation Larger BR2 group adds to less substituted end of the alkene

6.14 Mechanism of Hydroboration/Oxidation The oxidation features a concerted alkyl migration so the syn stereochemistry is retained from the R2BH addition in the first step.

6.15-6.17 Addition of Halogens - Anti addition via cations No syn addition product formed Stepwise mechanism???:

6.18 Addition of “X-OH” - Halohydrin Formation Regioselectivity:

6.19 Epoxides from Alkenes Via bromohydrins: By direct epoxidation:

6.19 Epoxides – essential synthetic intermediates Crixivan® (Indinavir, Merck & Co.) – protease inhibitor used to treat HIV (excellent oral bioavailability)

6.20 Ozonolysis of Alkenes - cleavage of the double bond

6.21 Introduction to Organic Chemical Synthesis Chapters 2-6

6.22 Reactions of Alkenes with Alkenes - Polymerization

6.22 Radical Polymerization Mechanism 6.12