Lecture 5:

ADDITION REACTIONS
Electrophilic additions Nucleophilic additions
To carbonyl compounds To carbonyl compounds
To alkenes and alkynes To alkenes and alkynes

Radical additions Carbene additions (and insertions)

ELIMINATION REACTIONS
Elimination to give - carbonyl compounds
- alkenes

1
 Nucleophilic addition to olefins
Seen before:

Only feasible when C=C LUMO is lowered  electron withdrawing substituents

examples: perhalogenated alkenes

coordination to Lewis-acid
phenyl substituted alkenes (rare)
alkene in conjugation with electron withdrawing group (conjugate add.)

2
 Conjugate additions = 1,4-addition = Michael addition
AdN2: Addition, nucleophilic, bimolecular
Electron pushing:

1,4 versus 1,2 addition

depends on: relative electrophilicity of carbonyl vs.  carbon
steric hindrance on carbonyl vs.  carbon
hardness/softness of nucleophile

soft Nu (thiolate, enolates, amines) give 1,4 addition

reason: largest orbital character of LUMO on  carbon

hard Nu (organolithium, Grignards) give 1,2 addition

additional reason: counterion (paired) coordinates carbonyl

3
 Intramolecular additions (incl sp2 centres)

Baldwin's rules for cyclisation reactions

apply to additions to carbonyls, alkenes and alkynes
apply to nucleophilic, radical and cationic additions
apply also to SN2 reactions

consider: 1 - ring size:

5 > 6 > 3 > 7 > 4 > 8-10
Jack Baldwin
2 - hybridisation of carbon undergoing attack:
sp = dig; sp2 = trig; sp3 = tet

3 - endo or exo closure:

for example 5-exo-dig

4
 Baldwin's rules

Exo Endo
Ring size dig trig tetr dig trig
3 unfav fav fav fav unfav
4 unfav fav fav fav unfav
5 fav fav fav fav unfav
6 fav fav fav fav fav
7 fav fav fav fav fav
do not learn this table by heart

Unfavorable cases: Bürgi-Dunitz angle cannot be achieved

5-endo-trig

5-endo-dig

5
 Radical additions to unsaturated systems

Difference with electrophilic and nucleophilic addition

- no charged intermediates  bond polarisation less important
 steric effects relatively more important
- more alkyl substituted radical more stable (hyperconjugation)
reaction proceed through most substituted intermediate  anti Markovnikov

AdH2 = Addition, Homolytic, bimolecular

Example: Electron pushing for bromination of alkene by HBr (chain reaction)
Initiation:

Propagation

Termination

6
 Radical initiators

contain weak bond that can undergo homolysis (thermally or by light)

di-t-butyl peroxide benzoyl peroxide AIBN

Cage effects: give rise to geminate recombination = initial return

particularly in viscous solvents
R-N=N-R may give R-R + N2
By fragmentation of radical anions obtained from single-electron reductions

7
 Propagation

polymerisation vs HBr addition

which path dominates depends on [HBr]kct vs [alkene]kpolym

HCl additions more likely to give oligomerisation than HBr

Why?

8
 Termination

Combination

Disproportionation = reaction between two identical species that leads to

two different products

9
 Substituent effects on radical reactions

 effect: effect of substituent on the carbon to which the radical adds

electronic effects not very large (electron withdrawing groups accelerate)
explanation: radical builds up on adjacent carbon
steric effects significant (Taft parameter large;  = 1.4)

 effect: effect of substituent on the carbon next to the carbon

to which the radical adds
both electron donating and withdrawing subsituents accelerate the reaction
explanation: any electron delocalisation is stabilising independent of whether
electrons flow away from of towards the radical centre.

steric effects not very important (Taft parameter small;  = 0.28)

10
 Captodative effect

Definition: Radicals that have electron withdrawing AND electron donating

groups on the radical centre are exceptionally stable
explanation: many resonance structures possible and also the polar
ones are now contributing strongly

Examples:

Consequence: strong directing  effect

11
 Carbene additions
Carbene: sp2 carbon with two nonbonding electrons in:
- both in the  orbital = singlet carbene
- one in the  and one in the p orbital = triplet carbene

:CH2

Reactivity: addition reactions to alkenes and alkynes (sometimes even with arenes)
insertion reactions (a bit out of place in this chapter)
Singlet carbenes: concerted (formally pericyclic reaction – Ch 15)
Triplet carbenes: step-wise (biradical)

12
 Arrow pushing for carbene reactions

singlet addition to alkenes triplet addition to alkenes

singlet insertion into CH bond triplet insertion into CH bond

13
 Carbene generation

1 - Thermal decomposition of diazoalkanes

which can be made by elimination of N-nitrosoureas

Warning:
diazomethane is highly explosive (explodes on contact with ground
glass joints)

2 - Elimination of tosyl hydrazones

14
 Carbene generation (cntd)

3 – decomposition of diazirines

4 -  eliminations (= 1,1 elimination) of haloform reagents

Normal product = singlet carbenes

Triplet carbenes can be generated by photochemical treatment of precursor
using a sensitiser

15
Stereoselectivity
singlet carbene: concerted and 100% selective
triplet carbene: less selective
spin flip required for ring closure
bond rotation and ring closure at comparable rates

Substituent effects
normal singlet carbenes react faster with more nucleophilic alkenes
- carbene acts as electrophile

electron rich singlet carbenes may react as nucleophile

Reactivity
in the absence of addition partners: indiscriminate insertion into CH bonds
if no suitable CH bonds are available: reaction as carbanions or carbocations

16
 Elimination Reactions
Previous section: additions to carbonyls and alkenes/alkynes
Now: elimination to form carbonyls (or related species) and alkenes

acetal hydrolysis E1
oxidations (CrO3 and Swern) E2
E1cB
thermal
radical

17
 Eliminations to give carbonyl (like) compounds

acetal hydrolysis – electron pushing

H
H O
O O H

18
 Viable mechanisms for acetal hydrolysis

Specific acid
catalysis
SN1

Specific acid
catalysis
SN 2

General acid
catalysis

19
…which of these three mechanisms is followed depends on specific reaction:

Example 1:

H
X H O
OEt H

OEt

evidence: kinetic analysis: specific acid catalysis

Hammett  = -3.3

Example 2:

NO2

O O

evidence: general acid catalysis ( = 0.5)

20
 Stereoelectronic effects

Leaving group departure is promoted by lone pairs antiperiplanar to them

Antiperiplanar = two bonds in the same plane, but pointing in opposite directions

to endocyclic
to endocyclic C-N bond

to exocyclic

Same principle as the anomeric effect that favours  (axial) over  (equatorial)
glycosidic bonds

21