Acid-Catalyzed Hydration of Alkenes 19

Acid-Catalyzed Hydration of Alkenes OH C H + H—OH reaction is acid catalyzed; typical hydration medium is 50% H2SO4-50% H2O Follows Markovnikov's Rule 2

Hydration – Thermodynamics Hydrohalogenation & hydration reactions are at equilibrium.

Hydration – Thermodynamics How could Le Châtelier’s principle be used to shift the equilibrium to the right or left? SEE: CONCEPTUAL CHECKPOINT 9.11.

Hydration – Thermodynamics Similar to hydrohalogenation, the stereochemistry of hydration reactions is controlled by the geometry of the carbocation. Draw the complete mechanism for the reaction above to show WHY a racemic mixture is formed. SEE: SKILLBUILDER 9.3.

Markovnikov's Rule H3C H 50% H2SO4 CH3 CH2CH3 C C 50% H2O CH3 OH (90%)

Follows Markovnikov's Rule OH CH3 50% H2SO4 50% H2O CH2 (80%) 4

involves a carbocation intermediate Mechanism involves a carbocation intermediate is the reverse of acid-catalyzed dehydration of alcohols to alkenes OH C CH3 H3C C CH2 H+ + H2O 5

Addition of Water to Alkene (alcohols)

Addition of Water to Alkenes (alcohols)

Question Which alkene will undergo acid-catalyzed hydrolysis at the fastest rate? A) B) C) D)

Principle of Microscopic Reversibility OH C CH3 H3C C CH2 H+ + H2O In an equilibrium process, the same intermediates and transition states are encountered in the forward direction and the reverse, but in the opposite order. 11

H2O addition: Markovnikov's Rule 3

Question The product isolated from the acid-catalyzed hydration of (Z)-3-methyl-2-pentene is: A) 2-ethyl-2-butanol B) 2-ethyl-1-butanol C) 3-methyl-2-pentanol D) 3-methyl-3-pentanol

Question The product isolated from the acid-catalyzed hydration of (E)-3-methyl-2-pentene is: A) chiral B) achiral

Oxymercuration-Demercuration Because rearrangements often produce a mixture of products, the synthetic utility of Markovnikov hydration reactions is somewhat limited. OXYMERCURATION-DEMERCURATION is an alternative process that can yield Markovnikov products avoiding rearrangements

Oxymercuration-Demercuration OXYMERCURATION begins with mercuric acetate. How would you classify the mercuric cation? As a nucleophile or an electrophile? As a Lewis acid or Lewis base?

Oxymercuration-Demercuration Similar to how we saw the alkene attack a proton previously, it can also attack the mercuric cation. Resonance stabilizes the mercurinium ion. Can you draw a reasonable resonance hybrid?

Oxymercuration-Demercuration The mercurinium ion is also a good electrophile, and it can easily be attacked by a nucleophile, even a weak nucleophile such as water. NaBH4 is generally used to replace the –HgOAc group with a –H group via a free radical mechanism.

Addition of Alcohol to Alkenes (ethers)

Stereochemistry of Addition to Alkenes + E—Y E Y Regiochemistry withstanding, in order to understand the stereochemistry of the product, you must consider two things: (1) Stereochemistry of the starting alkene (cis or trans; Z or E) (2) Stereochemistry of the addition (syn or anti) 2

Stereochemistry of Addition to Alkenes + E—Y E Y Optically inactive reactants produce optically inactive products. (Racemic mixtures are optically inactive) The correlary is that an optically active starting material MAY produce an optically active product depending on the mechanism. 2

Question The product isolated from the acid-catalyzed hydration of (E)- or (Z)-3-methyl-2-pentene is: A) optically active B) an optically inactive racemic mixture C) an optically inactive enantiomer

Hydroboration-Oxidation of Alkenes 19

Hydroboration-Oxidation To achieve anti-Markovnikov hydration, hydroboration-oxidation is often used. Note that the process occurs in two steps.

Suppose you wanted to prepare 1-decanol from 1-decene? Synthesis Suppose you wanted to prepare 1-decanol from 1-decene? OH Needed: a method for hydration of alkenes with a regioselectivity opposite to Markovnikov's rule. 13

Synthesis Two-step reaction sequence called hydroboration- oxidation converts alkenes to alcohols with a regiochemistry opposite to Markovnikov's rule. 1. hydroboration 2. oxidation OH 13

Hydroboration Step C H BH2 C + H—BH2 Hydroboration can be viewed as the addition of borane (BH3) to the double bond. But BH3 is not the reagent actually used. 14

Hydroboration reagents: Hydroboration Step C H BH2 C + H—BH2 Hydroboration reagents: H Diborane (B2H6) normally used in an ether-like solvent called "diglyme" H2B BH2 H 14

Hydroboration reagents: Hydroboration Step C H BH2 C + H—BH2 Hydroboration reagents: + O BH3 – •• Borane-tetrahydrofuran complex (H3B-THF) 14

Oxidation Step H2O2, HO– H BH2 C H OH C Organoborane formed in the hydroboration step is oxidized with hydrogen peroxide. 17

Example 1. B2H6, diglyme 2. H2O2, HO– OH (93%) 13

Example H C CH3 OH H3C CH3 1. H3B-THF 2. H2O2, HO– C H3C H (98%) 13

Features of Hydroboration-Oxidation hydration of alkenes regioselectivity opposite to Markovnikov's rule no rearrangement stereospecific syn addition 18

Example OH 1. B2H6, diglyme 2. H2O2, HO– (82%) 13

Stereochemistry of Hydroboration-Oxidation 19

Features of Hydroboration-Oxidation hydration of alkenes regioselectivity opposite to Markovnikov's rule no rearrangement stereospecific syn addition 18

only product is trans-2-methylcyclopentanol (86%) yield syn Addition H and OH become attached to same face of double bond H CH3 HO CH3 H 1. B2H6 2. H2O2, NaOH only product is trans-2-methylcyclopentanol (86%) yield 20

Question Hydroboration-oxidation of which one of the following yields a primary alcohol as the major product? A) B) C) D)

The product is optically active The product is a racemic mixture Question H C CH3 OH H3C CH3 1. H3B-THF 2. H2O2, HO– C H3C H The product is achiral The product is optically active The product is a racemic mixture The product is a single enantiomer 13

Conversion of Alkenes to Vicinal Halohydrins 20

in the Presence of Water Addition of Halogens in the Presence of Water (halohydrins)

alkenes react with X2 to form vicinal dihalides

alkenes react with X2 to form vicinal dihalides alkenes react with X2 in water to give vicinal halohydrins C C + X2 + H2O X OH + H—X 2

anti addition: only product Examples H2O H2C CH2 + Br2 BrCH2CH2OH (70%) OH Cl H Cl2 H H2O anti addition: only product 6

anti addition: only product Examples H2O H2C CH2 + Br2 BrCH2CH2OH (70%) OH Cl H Cl2 H H2O anti addition: only product 6

Figure Number: 05-02-46UN Title: 3-Bromo-2-butanol Isomers Caption: Named perspective formulas and Fischer projections of the isomers of 3-bromo-2-butanol. Notes: The first two structures on the left are enantiomers of each other. The last two structures on the right are also enantiomers. Each of the structures in the left pair is a diastereomer of each of the structures in the right pair.

Figure Number: 05-02-07UN-A Title: Erythro and Threo Diastereomers Caption: Erythro enantiomers are diastereomers of threo enantiomers. Notes: Diastereomers are stereoisomers which are not mirror images of one another. Erythro enantiomers are stereoisomers with two adjacent chirality centers, which have two similar groups on the same side of the carbon chain, and threo enantiomers have the two similar groups on opposite sides of the carbon chain.

Perspective formula Fischer projection

Regioselectivity CH3 OH C CH2Br H3C C CH2 Br2 H2O (77%) Markovnikov's rule applied to halohydrin formation: the halogen adds to the carbon having the greater number of hydrogens. 32

Explanation H O .. H O .. H3C H3C H3C H3C C CH2 CH2 C : Br : : Br :  transition state for attack of water on bromonium ion has carbocation character; more stable transition state (left) has positive charge on more highly substituted carbon 34

Question What is the product (in addition to its enantiomer) of the following reaction?

Conversion of Alkenes to Vicinal Diols 20

Syn Dihydroxylation SYN dihydroxylation adds across the C=C double bond in ONE step.

SEE: CONCEPTUAL CHECKPOINT 9.33. Syn Dihydroxylation MnO41- is similar to OsO4 but more reactive. SYN dihydroxylation occurs with KMnO4 only under mild conditions (cold temperatures). Diols are commonly further oxidized by MnO41-, and in addition MnO41- is reactive toward many other functional groups as well. It is very useful in qualitative analysis due to a pronounced color change. SEE: CONCEPTUAL CHECKPOINT 9.33.