Chapter 10: addition and/or elimination reactions

ADDITION REACTIONS
Electrophilic additions Nucleophilic additions
Carbonyls: hydration Carbonyls: cyanohydrin
Alkenes and alkynes: hydration Grignard
HX addition LAH reduction
halogen addition Alkenes: conjugate addition
hydroboration
epoxidation

Radical additions Carbene additions (and insertions)

1
Electrophilic hydration of alkenes

mechanism similar to carbonyl hydration, but intermediate now of higher energy

requires extremely strong acids

rate determining proton transfer  general acid catalysed

2
Regiochemistry

Markovnikov addition: nucleophilic addition to the most substituted carbon

most crowded product, so a kinetic and not thermodynamic product

Substituent effects

faster when carbocation is stabilised; i.e. with electron donating subsituents

 vinyl ethers and enamines hydrolyse readily (and further…)

3
Electrophilic hydration of alkynes

Mechanism similar to alkenes:

- general acid catalysis
- irreversible proton transfer
- Markovnikov addition

4
Electrophilic addition of hydrogen halides to alkenes
general mechanism:

side reactions inform on detailed mechanism:

HCl

AcOH

5
Electrophilic addition of hydrogen halides to alkynes

Vinyl carbenium cations (sp) are more unstable than regular (sp2) carbenium ions
why?

Consequence….

6
Electrophilic addition of halogens to alkenes

Intermediate?

Why?

Consequence: anti addition

Other evidence for halonium ion:

- kinetics: first order in Br2 and alkene (low [Br2] or very polar solvent)
- substituent effects

hydration  < 

bromination < < <

7
Other evidence for halonium ion (cntd):

- large secondary isotope effect

H(D)
Br2

H(D)

kH/kD = 0.53 (normally 0.8)

- isolated:
Br

8
Other evidence for halonium ion (cntd):

Hans Wijnberg

Chem. Commun. 1969, 908 9

Addition of halogens to alkynes

alkyne derived bromonium ions less stable than alkene derived ones
why?

substituent effects:
Br2

10
Hydroboration of alkenes
Synthetically much more useful than hydration

BH3 has Lewis-acidic character (= electron pair acceptor)

Mechanism

Regiochemistry: anti-Markovnikov
(different from hydration and hydrohalogenation)

Why: boron ends up at least hindered carbon

nucleophilic hydrogen attacks most electropositive carbon
Note the difference in polarisation of B-H vs X-H bond

11
 Epoxidation of alkenes
peracids allow nucleophilic attack on oxygen!!
Cl
Why?
oxygen flanked by another oxygen so less electronegative than usual
O carboxylic acid is good leaving group
H O
O
MCPBA

One-step mechanism supported by:

- rate law: first order in peracid and alkene
- small solvent dependence
- Hammett  for XArCH=CH2 = 1.2 (using +)
- primary kie for RO3H(D) = 1.1 - 1.2
- secondary kie on (hydrogen on alkene carbons) inverse
- cis or trans stereochemistry of double bond fully retained in epoxide
12
 Chapter 10: addition and/or elimination reactions

ADDITION REACTIONS
Electrophilic additions Nucleophilic additions
Carbonyls: hydration Carbonyls: cyanohydrin
Alkenes and alkynes: hydration Grignard
HX addition LAH reduction
halogen addition Alkenes: conjugate addition
hydroboration
epoxidation

Radical additions Carbene additions (and insertions)

13
 Nucleophilic addition to carbonyls

Hydration requires activation of the carbonyl by an electrophilic reagent (i.e.

an acid) prior to nucleophilic attack
Better nucleophile can react without prior activation

Cyanohydrin formation

Addition of Grignard reagents

14
Alternative mechanisms for Grignard reactions

electron transfer mechanism

which side reactions can you expect?

Other complications
RMgX is in equilibrium with R2Mg and MgX2
Reactions often higher order in RMgX

15
LAH reductions
taught as:

Observation: no reaction upon addition of cryptand

O O O

N N
O

activity restored upon addition of Li salt

Explanation: the Li+ counterion acts as a Lewis acid

16
Orbital considerations

Carbonyl is a polarised bond

- bonding orbital has more character on the more electronegative atom (O)
- antibonding orbital has more character on the more electropositive atom (C)
orbital that accepts nucleophilic attack is the antibonding *

Nucleophile approaches carbonyl at Bürgi-Dunitz angle (105º; appr. sp3)

Nu
evidence: X-ray crystal structures
computational studies

C O

*
Similar angle for addition reactions to alkene (because of similar orientation of *)

17
Alkenes vs. carbonyls: HOMO-LUMO considerations

18
Stereochemistry

How does the stereochemistry on the carbon adjacent to the carbonyl

influence the new stereocentre?

1 - Start by ranking the three substituent on the  carbon by size: S, M, L

2 - Draw specific Newman projection
3 - Decide on side of nucleophilic attack

19
Cram model
- Newman projection: carbonyl gauche to S and M
- Nu attacks from diastereotopic face that has the S group

Nu

C O

Other models:
Karabatsos model
Felkin-Ahn model

20