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Electrophilic Addition to Alkenes & Alkynes

YX Y X X Y

This is a classical & apparently straightforward reaction

Questions: 1) stereochemistry

2) regiochemistry

3) mechanism

Stereochemistry of Addition

case A: H _ X

BrBr

H Br +

anti syn

9 1:

H H

Hammond, JACS 1954, 76, 4121

This is often (but not universally) true for unconjugated alkenes

Why?

1) kinetics are often termolecular: r = k3[alkene][H-X]2

implication:

H X

XH -simultaneous addition of two H-X

molecules

⇒sterically favors anti

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2) torsional strain

consider the transition states for syn & anti addition:

H

XH X

vs.

anti syn

anti

syn

staggered (favored)

eclipsed (disfavored)

Case B -Halogen Addition

Br2+

Br

Br

trans

Br2Br

Br

Br

Br

Br

Br

anti in sense of addition

H3CHCH2C

F

Br H3CHC CH2

BrSO2, -60o+

SbF5SbF6

⇑ can be observed by NMR

addition of Cl2, largely similar

addition of F2, degrades carbon chain

addition of I2, readily reversible (favors s.m.)

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other electrophiles:

sulfur / selenium

RCH CH2RCH CH2

S

R CH

SR

CH2

Cl

RCH CH2

S

ClR

+

R

sulfonium ion

sulfurane

RSCl

ClSN2

similar behavior for RSeCl

Iodination

While diiodo products are not stable, iodine is still a very useful electrophile -

iodolactonizations

OH O O O

I

O OH

I I

OH O

preference for five membered over six membered ring

O

O

OH

I

OH

O

O

OH

O

O

II

I

O

I2, I

6 memberedcyclization

H

H

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Addition of Metals

NaBH4

Hg(OAc)2

AcO-

Hg

O

O

Hg

O

O

O

O

Markownikoff regioselectivity and stereoselectivity

comparison of bridged cationic intermediates

H

a) H+ is a hard acid with no unshared electrons

b) either carbocation or hydrogen bridged cation is electron deficient

Br

a) Br+ is a soft acid

b) Bromonium ion can be represented having two covalent bonds to

bromine

Hg

a) Hg++ is a soft acid - strongly polarizing

b) electron deficient bridged structure

c) extent of bridging Br+ > Hg++ > H+

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Addenda

a variety of nucleophiles can participate in mercuration

R

R

NH

1) Hg(ClO4)2,

2) NaBH4

NH2

Second reduction step is not a trivial consideration

RHgX + NaBH4 → RHgH

RHgH → R. + IHgH

R. + RHgH → RH + Hgo + R.

Reduction with sodium borohydride is a radical process

Reduction with Na-Hg in protic solvent does not involve radical intermediates

Acetylenes & Allenes

AdE2

R R X Y RX

R

X

R

R

Y

Y

R

X

R

+

Y

R R

X Y

R R

XX

R

R

YY

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AdE3

R R

X

R

R

Y

X Y

X Y X

Y

In general, alkynes are much less reactive towards electrophiles than alkenes

R H RX

H

Xmuch less stable

R CH

CH2 R CH

XCH2X

Reaction Rxn. rate ratio terminal alkenes / alkynes

bromination 2 x 105

chlorination 5 x 105

H+ / hydration 4

Addition is Markownikoff

Impact of substitution:

syn

Cl

HCl

H

C C H + C C H

Cl H

H

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anti

C C CH3 +H3C C C CH3H3C

H Cl

H Cl

H

CH3

H3C

Cl

HCl

H2C C CH2

H2C CH

CH2

H3C C CH2

?+ HX

HH+

C C CH

HH

HC C C

H

HH

H

unstabilized primary carbocation

HCl

HCl

H2C C CH2 H3CCH2

Cl

H3C CH3

Cl

Cl

+

Hydroboration

CH3 H3C H3CH

BOH

H1) B2H6 2) H2O2

H

H

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C-B Bond Formation

regioselectivity: anti-Markownikoff addition

stereoselectivity: syn addition

H

C1C2

BR

R

C1 donates electrons to the empty orbital on boron while hydrogen

on boron donates electrons back to C2 on the alkene

NOTE: Hydrogen is not the electrophilic portion of the attacking group

concerted reaction dominated by steric interactions:

(BH3)2 43% 57%

HB

0.2% 99.8%

C-B Bond Breakage

R B

R

R

O OH R B

R

OR

RO B

OR

OR

R3B HOO+ + OH

H2OROH + B(OH)3

replacement of C-B bond with retention of configuration

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Elimination Reactions

E2

BH

X

H

R

RR

R

!

!

R

R

R

R

+

B

E1

X

H

R

RR

R

R

R

R

R

+

X

H

R

RR

RBH

B

E1cb

BHB

X

H

R

RR

R

R

R

R

R

+XR

RR

RX

α elimination:

R C X

H

R

R C

R

HX+

β elimination:

R R

XH

H H

RCH CHR + HX

γ elimination:

R CH

CHCH

R

R R

+ HX

H H X

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Regioselectivity:

E1 relative stability of product alkene is determining factor (gives more highly

stabilized olefin) ⇒reactions are of low regioselectivity

E1cb determined by kinetic acidity of β protons

alkyl substituents electronically and sterically retard proton removal

⇒ preferred formation of less substituted olefin

Saytzeff Rule: eliminations involving good leaving groups give more substituted olefin

Hofmann Rule: eliminations involving poor leaving groups give less substituted olefins

Stereochemistry:

anti elimination dominates particularly with good leaving groups

(syn elimination is possible and is important with poor leaving groups)

Ion pair hypothesis:

C C

H X

OR

M base & cation assist in departure of leaving group

syn elimination higher in benzene

anti elimination higher in DMSO

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Most reactions are neither pure E1, E2 or E1cb, but rather lie somwhere on a continuum between all 3. The question is how to visualize such a scenario...

X-

R1

H

X

R3 R4R2

B- +

E2E1cb

E1

C-H

bond c

leavage

C-X bond cleavage

R1X

R3 R4R2

BH +

R1

H

R3 R4R2

B- +

R1 R4

R3R2

+ BH

+ X-

but, most reaction pathways will lie in between these extrema:

TS1 TS2

TS2

TS1

C-H

bon

d c

leavag

e

C-X bond cleavage

E1cb/E2

E1/E2

these transition states will have differing amountsof bond breaking:

!-

R1R2

R4R3

H

X

B!- ‡

!+

R1R2

R4R3

B" ‡

X!-

H

If we add energy as a third dimension, these are known as More-O’Ferral diagrams

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Other β-Elimination Reactions

R OH

OH

H

(-H2O)

hydrate

R H

O

aldehyde

R OH

NH

H

(-H2O)

hemiaminal

R H

N

aldimine

R'R'

Another important version - alcohol oxidation

R R'

OHX+

(-H+) R R'

OX

H :B (-BH)

(-X-) R R'

O

X= R2S, CrO3, Cl, Br (for example)

• This is the predominant mechanism by which alcohols are oxidized to carbonyl compounds

Ex:

R OH1. (COCl)2, DMSO, -45°2. NEt3, -45° -> 0°

RCHO "Swern oxidation"

mechanism:

H3CS+

CH3

O-

+ Cl

O

O

Cl

H3CS+

CH3

ClCl-

+

R

O

HSN2

H3CS+

CH2

O

R

Cl-

H NEt3

H3CS+

CH2

O

RHH

ylide

!-elim.

-45° -> 0°

H3CS

CH3

O

R

H

(- Et3NH+ -Cl)

• This is also true for CrVI oxidations (H2CrO4, etc.) and most other common oxidants

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Fragmentation Reactions These are β-elimination reactions accompanied by cleavage of a carbon-carbon bond Grob (Wharton) Fragmentation

B-

O XH

O

+ + B+H

-X

- there are stereochemical requirements placed on this reaction:

KOH

KOH

OTs

OH O

OTs

OH

A)

B) no reaction

Why? Look at the conformations:

X

O-

X

O-

leaving group is anti to breaking C-C bond

leaving group is gauche to breaking C-C bond

A)

B)

The requirement for the anti relationship in the Grob is akin to the anti preference of the E2 Eschenmoser Fragmentation

O

NNHTs

H+, !

O

A. Eschenmoser, Helv. Chim. Acta

mechanism:

H+O

N N H

Ts

O

NN

Ts

H

O

-only works for cyclic epoxy ketones