6.19 Epoxides – essential synthetic intermediates YSU Crixivan® (Indinavir, Merck & Co.) – protease inhibitor for HIV

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

YSU

6.2 Heats of hydrogenation of isomeric C4H8 alkenes Figure 6.1 YSU

Table 6.1

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

6.3 Stereochemistry of Alkene Hydrogenation YSU Figure 6.2

6.4 Electrophilic Addition of Hydrogen Halides to Alkenes YSU 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 YSU 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 YSU Figure 6.4

Figure 6.5

Examples of H-X Addition YSU

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

6.8 Free Radical Addition of H-Br to Alkenes YSU Peroxides = HOOH, ROOR (R = organic)

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

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

Mechanism 6.5

6.10 Acid-catalyzed hydration of alkenes YSU Table 6.2

6.11 Thermodynamics of addition-elimination YSU 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 YSU 1. Addition 2. Oxidation Reaction is regioselective and stereoselective

6.12 Hydroboration – Avoiding Steric Interactions YSU

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

6.14 Mechanism of Hydroboration/Oxidation YSU Mechanism 6.6

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

6.14 Mechanism of Hydroboration/Oxidation YSU 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 YSU No syn addition product formed Stepwise mechanism???:

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

6.19 Epoxides from Alkenes YSU Via bromohydrins: By direct epoxidation:

6.19 Epoxides – essential synthetic intermediates YSU Crixivan® (Indinavir, Merck & Co.) – protease inhibitor for HIV

6.20 Ozonolysis of Alkenes - cleavage of the double bond YSU

6.21 Introduction to Organic Chemical Synthesis YSU Chapters 2-6

6.22 Reactions of Alkenes with Alkenes - Polymerization YSU

6.22 Radical Polymerization YSU Mechanism 6.12