189  

8.14 Substitution vs. Elimination: Predicting the Products SN2 – nucleophile replaces the LG with inversion (backside

attack) of stererochemistry (stereospecific).

SN1 – nucleophile replaces the LG, unless the intermediate carbocation undergoes rearrangement. The SN1 reaction is not stereospecific.

E2 – The more substituted alkene is usually favored (Zaitsev rule), unless bulky bases (e.g., t-butoxide) are used. The alkene geometry (E vs Z) is determined by the anti- periplanar conformation. In the case of a disubstituted alkene product, the trans geometry is favored.

E1 – The more thermodynamically favored alkene is favored.

This will be the more substituted alkene product (Zaitsev rule), with the most sterically demanding groups trans.

190  

Chapter 9. Addition Reactions of Alkenes 9.1 Introduction to Addition Reactions

Substitution Reactions: two reactants exchange parts to give new products (Chapter 7)

H3C H2C OH + H–Br H3C H2C Br + H–OH

Elimination Reaction: a single reactant is split into two (or more) products. Opposite of an addition reaction (Chapter 8)

C CBr H

H HH H

C CH

H H

H+ H-OH + Na-Br

NaOH

Addition Reaction: two reactants add to form a product with no (or few) atoms left over (Chapter 9).

C CH

H H

H+ H-Br C C

Br H

H HH H

95

Hydrohalogenation (Ch. 9.3)

Hydration (Ch. 9.4–9.6)

Hydrogenation (Ch. 9.7)

Halogenation (Ch. 9.8)

Halohydrin formation (Ch. 9.8)

Dihydroxylation (Ch. 9.9, 9.10)

C C

H–XX = Cl, Br, I

XH

H–OHOHH

H–HHH

X–OHOHX

HO–OH OHHO

XXX–X

X = Cl, Br

191  

YXC C X–Y+

addition

elimination

9.2: Addition vs. Elimination: A Thermodynamic Perspective

Addition reactions are usually enthalpically favorable, but entropically disfavored.

9.3. Hydrohalogenation

ΔG = ΔH – TΔS

low temperature

high temperature

Reactivity of HX correlates with acidity:

slowest HF << HCl < HBr < HI fastest

XHH–XX = Cl, Br, I

C C

192  

96

C CR

H H

H

H–Br C CR

Br

H

HH

H+ C CR

H

H

HH

Br

C CR"

R H

H

H–Br C CR

Br

H

HR"

H+ C CR

H

H

HR"

Br

C CR"

R R'

H

H–Br C CR

Br

R'

HR"

H+ C CR

H

R'

HR"

Br

C CR

H R'

H

H–Br C CR

Br

R'

HH

H+ C CR

H

R'

HH

Br

Regiochemistry

193  

Mechanism for hydrohalogenation

194  

97

Stereochemistry of hydrohalogenation – hydrohalogenation proceeds through a carbocation intermediate. No stereochemical preference.

H–X X X+

Carbocation rearrangements H–Cl

Cl

+Cl

(40%)expectedproduct

(60%)unexpectedproduct

195  

Cationic polymerization

H–A

styrene

polystyrene

9.4 Acid-Catalyzed Hydration – Alkenes - addition of water (H-OH) across the π-bond of an alkene to give an alcohol; opposite of dehydration

C CH2

H3C

H3C

H2SO4, H2O

H3C

OHC

H3C

H3C

196  

98

This addition reaction follows Markovnikov’s rule The more highly substituted alcohol is the product and is derived from the most stable carbocation intermediate. Reactions works best for the preparation of 3° alcohols, but poorly for 1°alcohols.

Mechanism of the acid-catalyzed hydration

197  

9.5 Oxymercuration-Demercuration – The acid-catalyzed hydration is not a general method for the hydration of an alkene.

Oxymercuration – Demercuration: a general (2-step) method for the Markovnokov hydration of alkenes.

H3C OC

OAc= acetate =

NaBH4 reduces the C-Hg bond to a C-H bond

C4H9 CC 1) Hg(OAc)2, H2O

C4H9 CC

H

Hg(OAc)

H

OHHH

H

H 2) NaBH4

C4H9 CC

H

H

H

OHH

198  

99

9.6 Hydroboration-Oxidation - Anti-Markovnikov addition of H-OH; syn addition of H-OH

CH31) B2H6, THF2) H2O2, NaOH, H2O CH3

H

HHO

Diborane 2 BH3

HB

HB

H

HH

H

O OBH

HH

Mechanism of hydroboration

199  

200  

Hydration of alkenes summary: addition of water (H–OH) across the π-bond of an alkene to give an alcohol.

1.  Acid catalyzed hydration- Markovnikov addition of H–OH Not a good method for hydration of an alkene

2.  Oxymercuration- Markovnikov addition H–OH

3. Hydroboration- Anti-Markovnikov addition of H–OH,

Syn addition of H–OH

CH3 1) Hg(OAc)2, H2O2) NaBH4

CH3HO

HH

CH31) B2H6, THF2) H2O2, NaOH, H2O CH3

H

HHO

100

9.7 Catalytic Hydrogenation – Addition of H2 across the π-bond of an alkene to give an alkane. This is a reduction.

201  

R RH2, Pd

The catalysts (Pd, Pt, Rh, Ni) is not soluble in the reaction media; thus, this process is referred to as a heterogenous catalysis.

The reaction takes places on the surface of the catalyst. Thus, the rate of the reaction is proportional to the surface area of the catalyst.

Stereospecificity – The addition of H2 across the π-bond is syn, i.e., from the same face of the double bond.

CH3

CH3

H2, Pd CH3

CH3

H

Hsyn addition of H2

(+ enantiomer)

CH3

H

H

CH3anti addition of H2

(not observed)

202  

H2C CH2

H2C CH2H2

H HH2C CH2H H

H CCH

HH

HH

C CH

H

H

HH

H

Mechanism: The catalyst assists in breaking the π-bond of the alkene and the H-H σ-bond.

Carbon-carbon π-bond of alkenes and alkynes can be reduced to the corresponding saturated C-C bond. Other π-bond bond such as C=O (carbonyls) and C≡N (nitriles) are not easily reduced by catalytic hydrogenation. The C=C bonds of aromatic rings are not easily reduced.

101

203  

9.8 Halogenation and Hydrohydrin Formation Addition of X2 (Cl2 and Br2) to Alkenes

    C C C C

XX

1,2-dihalidealkene

X2(vicinal dihalide)

+ Br2

Br

Br

+Br

Br

not observed

Stereochemistry – anti addition of X2 across the π-bond

CH3 CH3Br

BrH

Br2

204  

Mechanism for halogenation

Bromonium ion intermediate explains the stereochemistry of Br2 addition.

102

205  

Halohydrin formation

C C C COHX

halohydrinalkene

"X-OH"

X

OH

antistereochemistry

X2, H2O+ HX

206  

Regiochemistry of halohydrin formation – For unsymetrical alkenes, halohydrin formation is Markovnikov-like in that the orientation of the addition of X–OH can be predicted by considering carbocation stability

CH3 CH3HO

BrH

Br2, H2O+ HBr

103

207  

Organic molecules are sparingly soluble in water as solvent. The reaction is often done in a mix of organic solvent and water using N-bromosuccinimide (NBS) as he electrophilic bromine source.

DMSO, H2ON

O

O

Br+Br

OH

N

O

O

H+

Note that the aryl ring does not react!!! 9.9 Anti Dihydroxylation formal addition of HO-OH across the π-bond of an alkene to give a vicinal-diol. This is an overall oxidation. Vicinal diols have hydroxyl groups on adjacent carbons (vic-diols, 1,2-diols, glycols)

C CH

H H

HHO

OH"HO–OH"

RCO3H OH3O+

hydrolysis

OH

OH

racemic

Epoxide (oxirane): three-membered ring, cyclic ethers.

208  

R OH

O

R O

O

OH

carboxylic acid peroxyacid

HO–OH

peroxide

Peroxyacids Epoxidation mechanism

Stereochemistry of the epoxidation of alkenes: syn addition of oxygen. The geometry of the alkene is preserved in the product

Groups that are trans on the alkene will end up trans on the epoxide product. Groups that are cis on the alkene will end up cis on the epoxide product.

104

209  

Epoxide hydrolysis to anti vicinal diols 9.10 Syn Dihydroxylation  

OsO4

OOs

O

O

O

osmate esterintermediate

NaHSO3, H2OOH

OH

210  

9.11 Oxidative Cleavage (ozonolysis) - oxidative cleavage of an alkene to carbonyl compounds (aldehydes and ketones). The π- and σ-bonds of the alkene are broken and replaced with C=O double bonds. 3 O2 2 O3

electrical discharge Ozone (O3): O O

O _+

1) O3

2) (H3C)2S or

Zn, H2O

1) O3

2) (H3C)2S or

Zn, H2O

1) O3

2) (H3C)2S or

Zn, H2O

O

O

O

O

H

+

O

H

O

R2

R1 R3

R4

O3, CH2Cl2-78 °C O

OO

R1R2 R4

R3 O

OOR1

R2 R4

R3

molozonide ozonide

R1

R2

OR4

R3O+

+ ZnO or (H3C)SO

Zn-or-

(H3C)2S

mechanism

105

211  

9.12 Predicting the Products of an Addition Reaction

1.  What atoms or groups are being added to the double bond. Account for these groups in the reagents.

2.  What is the regiochemistry: Markovnikov vs anti-Markovnikov

3. What is the stereochemistry: Syn vs Anti addition, or no stereochemical preference.

X

H–X

OH

H3O+

-or-1) Hg(OAc)2, H2O2) NaBH4

1) B2H6, THF, 2) HOOH, NaOH H2O

syn addition

H2, PdH3COH

syn addition

X

X

X2

OH

X

X2, H2O

anti addition anti addition

OH

OH

OH

OH

1) RCO3H2) H2O

1) OsO42) NaHSO3

anti addition syn addition

Markovnikov MarkovnikovOH

anti-Markovnikov Markovnikov-likeH H

H

H

H

212  

9.13 Synthesis Strategies – Construct larger, more complex molecules out of smaller ones using known and reliable reactions

One-step synthesis:

Substitution

Elimination

Addition Change the position of the leaving group (halide or alcohol)

Change the position of a π-bond Retrosynthetic analysis – working a synthesis problem backward from the desired product to the starting substrate.

106