Professor David L.

Van Vranken
Chemistry 201: Organic Reaction Mechanisms I

Topic 14: Electrophilic Addition to C=C

Addition of Heteroatom Electrophiles
to Simple C=C Bonds

E+

Read:
F. A. Carey & R. J. Sundberg Advanced Organic Chemistry, Part A: Structure and
Mechanisms. 5th Ed. 5.1-5.9
I. Fleming Molecular Orbitals and Organic Chemical Reactions, 5.2.3, 5.2.4
M.O. Picture of the Pi Bond

■ Predicted EHOMO: πC=C > πC=N > πC=O

■ C=N and C=O usually react via lone pairs, not pi bonds (exception = pericyclic)
R+ R+ R+ E (+)
.. ..
C O N EMO πCC
C C C
πCN
Nucleophilicity: π < nO < nN πCO

■ Electrophiles attack alkenes in the middle of C C

Nu attacks 109° E+ attacks "middle" of π

Nu 109° E+
Burgi-Dunitz
trajectory R
C C C C
R

■ Electrophiles attack πCC on the face opposite from allylic σ donors

-OAc
.. Me Wickham, G.; Kitching, W.
Me Me JOC 1983, 48, 614.
O SnMe3 SnMe3
2 H + Me 3Sn-OAc
H
O + D
D
- TiCl -
4
O + OTiCl 4 OH
Me 3Si +
Me 3Si Hayashi, T.; Kebeta, K.; Yamamoto, T.;
Tamao, K.; Kumada, M. TL 1983, 24, 5661.

Kahn, S. D.; Pau, C. F.; Chamberlin, A. R.; Hehre, W. J. JACS 1987, 109, 663.
Halogen Addition

■ Mechanism often involves a charg-transfer complex. (Chem 201 arrow-pushers don’t have to draw
charge transfer complex)
Br cyclic bromonium
MP2
Br.. + H Br
Br
H R R
H R R anti addition
R H R H Br H
..
Br Br -

actually, via Br slow JACS 1994, 59, 7156.

Phys. Chem.-Chem. Phys
charge-transfer H R 2001, 2, 1397.
complex R H

R. S. Brown, H. Slebocka-Tilk, et. al. JACS 1990, 112, 6310.

■ More substituted double bonds are more reactive. Rates for Br2 in MeOH:
Et Me Me Me Me PhI Br Br
< < < <
Me Me Me
hexane
AcO
krel 1 100 1750 5700 138,000 -5 °C, 3 h
Br2
Dubois, J. E.; Mouvier, G. Bull. Soc. Chim. Fr. 1968, 1426. Fryberg, et al. Tetrahedron 1971, 27, 1261

■ Cyclic bromonium ion or not?

It's easy to guess for these cases... Not easy to guess w/o data S.M.
Br % anti + Nu
Br +Br Br .. Br
.. 100%
Bu Bu H R H +
R R R
83% H
Br Ph .. .. H
Br Nu Nu
.. Br
MeO MeO 68%
+ Ph 100% anti anti + syn
Addition of I2 to C=C

■ Addition of I2 is fast, but thermodynamically unfavorable (under most condns)

weak
Enthalpy change:
I
.. πcc 64 kcal/mol For special conditions:
+ I2 I—I 36 kcal/mol Barluenga, J.; et al.
I C-I 51 kcal/mol JCS Perkin 1 1990, 2807

■ Garegg-Samuelsson Olefination

OMe 4 equiv. Ph 3P OMe

2 Ph 3P
OH 4 equiv. imidizaole I 2 I2 OH
O 3 equiv. I 2 O

OH toluene I Appel OH
O O 120 °C, 3 h O O reaction
76%
Ph Ph
Cis diols require an extra I source;
-

Garegg, P. J.; Samuelsson, B. Synthesis 1979, 469

Appel, R. ACIEE 1975, 14, 801

■ Halolactonization

I
I2 H T.S.
O O I+
O
Ph OH CHCl3 Ph O Ph
61 °C H
O
..

Bartlett Org Syn 1985, 175.

HX Addition

■ Follows Markovnikov's rule; because the Hammond postulate says more stable carbocations form faster.

H H H
H A + H H Rates: H-I > H-Br > H-Cl
R R R
Nu
:Nu -

■ Stereospecific anti addition (unless stable carbocation possible)

Ph Br R Me Br
+ D—Br
.. 85% anti
D AcOD
D
Pasto, D. J.; Meyer, G. R.; Lepeska, B. JACS 1974, 96, 1858.

■ In some cases 2 H-Cl involved! (in MeNO2): rate ≈ k[C=C][HCl]2 in MeNO2 MeNO2 is
poor at H-bonding
Rules out:
Cl
Cl R
R H H H not for
R +
H R arrow-pushing
- Cl
Cl
..

: Cl -

■ Rates for acid-catalyzed hydration

only 60%
faster
Me Me Me Ph Me Me Me
< < <
Me Me
krel 1 10 7 10 9 1012

Chwang, W. K.; Nowlan, V. J.; Tidwell JACS 1977, 99, 7233.

Epoxidation

■ With peroxyacids
O H T.S. R
O O
O Cl O
H R H R O O
R H R' H
R H O
O OH
stereospecific m-CPBA

■ Rate depends on alkene HOMO ■ Arrow pushers: draw peracid tautomer

O key tautomer
weak R R R
> > > >> O-O O O O
Ph bond H O H - O+ H O
krel 5200 240 53 1 O O.. O

Swern Org. React. 1953, 378

■ Allylic OH directs strongly

R
OH OH O Henbest
H O transition state JOC 2000, 65, 2030.
m-CPBA H
24:1 O
O O
CH 2Cl 2 syn/anti
0 °C

■ Allylic ammonium makes alkenes unreactive (so use CF3CO3H)

CF3CO3H
+ +
R 2N R 2N R 2N
O
H unreactive H

Trost, B. M; Van Vranken, D. L. JACS 1993, 115, 444.

Hydroboration/Oxidation

■ Anti-Markovnikov addition? H.C. Brown Borane Reagents. AP, 1988.

+ H–BR 2 BR 2
R' R'

p
■ Concerted 4-membered T.S. (but not pericyclic)
"The transition structure corresponding to the highest barrier is a four-center one, which avoids orbital symmetry forbiddenness σ
since it is a 'pseudopericyclic' reaction' having little or no cyclic four-electron conjugation."
H H
H
B H H Arrow-pushers:
H B
H BH B H Don't draw the
2
C C C C pi complex intermediate
C C (but never forget it.)
π-complex concerted T.S.

Houk, K. Tetrahedron 1984, 2257

Electronegativity predicts nucleophilicity:
δ+ δ−
■ Boron = electrophile; H = Nu Li CH3
H–BX 2
H X H H Li B H C F
H–BX 2 + .. - approx. EN 1 2 2.2 2.5 4.0
B vs .. +
R R X R CH 2 - R CH 2
δ+ δ− δ+ δ−
more important
X2B H H F
res. structure

■ Regioselection
H H H
B B - + BH
H H or H 3B O BH 3
H
diborane 9-BBN

n-Bu 94% >99%

Ph 80% 99%

i-Pr 57% >99%

electronics + sterics
Migratory Displacement of Boronates

■ Addition and oxidation are stereospecific

B 2H 6 H 2O 2

CH 2Cl 2 aq. NaOH

H H
BR 2 OH
forms CH 2Cl 2•BH3
Kanth, Josyula V. B.; Brown, Herbert C. Tetrahedron Lett. 2000, 41, 9361.

■ Oxidation of B-C bond occurs with retention of configuration

boronate
D D D D D
–
+ OOH
..

B -B O R O R - O OH
R R R B B
R OH - +

..
OH R OH
R R
σBC σ*OO
B OH
R

■ Other migratory displacements with C-B Bonds

Me Me Me
OTs i) BH 3 OTs H

ii) NaOH R 2B – 100 °C

H H 75%
OH

Marshall, J. A. Synthesis 1971, 5, 229-35.

See Shea work on polymethylene

Addition of HgX2 and ArPdI

■ Oxymercuration with Hg(OAc)2

HgX 2
HgX HgO + 2 AcOH Hg(OAc) 2
Nu Nu

Mechanism (don’t use curved arrows when making or breaking dative bonds)
X
X X HgX
X Hg
.. X Hg Hg + anti R
addn R R
R H R R
H
HgX
H H
R H R R H O+ H R
H .. H OH
H 2O H
: A-
X
HgX
R H
R H
via π complex

■ Pd(OAc)2 acts a lot like Hg(OAc)2

Hg(OAc) 2 HgX

rt, 12h

Pd(OAc) 2 PdX
Inorg. Chim. Acta 1992, 213
95 °C, 20 min

■ Carbapalladation (olefin insertion) R-PdX cis addition to olefins

ArPdBr PdBr Ar PdX

Ar PdX
Ar
Nu
R R