Functional group interconversion by
substitution reaction at saturated
carbon
TOSYLATES
TOSYLATES
ALCOHOL + p-TOLUENESULFONYL CHLORIDE
TsCl
+
TOSYL
CHLORIDE
pyridine
ROTs
TOSYLATE ESTER
CONVERSION TO A TOSYLATE WITH TsCl AND PYRIDINE
Poor leaving TsC
group l ..
.. +
* : -
.. C
l
R-OT pyridine
s
*
+C-
If the alcohol is Good leaving group
chiral, the conversion for both SN1 and l
to a tosylate retains
configuration.
SN2
EXAMPLE OF THE USE OF A TOSYLATE
(R (R
TsC
CH)3-CH-O l CH) 3-CH-O
H Ph pyridine Ts Ph
RETENTIO
N NaCN
SN
acetone
2
INVERSIO
N
(S
CH) 3-CH-C
N Ph
EXPLANTION OF STEREOCHEMISTRY
Same configuration
as the starting alcohol.
..
: pyridine
NaC
The first reaction step N
acetone
does not involve the
carbon stereocenter - This step is an
the atom oxygen reacts. SN2 reaction
with inversion
of
configuration.
BROSYLATES
BROSYLATES WORK LIKE TOSYLATES
p -bromobenzenesulfonyl
+ chloride
“Brosyl Chloride”
pyridine BsCl
a p -bromobenzensulfonate
“Brosylate”
R-OBs
a good leaving group
Influencing Factors of Leaving groups
a) The strength of R-X bond
b) The polarisability of the bond
c) The stability of X(-)
d) The degree of stabilisation through solvation of X(-)
For halides (a) & (b) are more imporatnt
(c) & (d) becomes more important for following groups
CF3SO3-
triflate ion
p-toluenesulfonate ion (a “super”leaving group)
(Tosylate)
Conversion of alcohols to alkylating agents
Another way to convert OH group into a better leaving group
Combination with an element that forms strong bonds with oxygen
¨
SN2 at P
Stable anion
Alkyl dibromophosphite Better leaving group
HOPBr2 H3PO3
Appel
Reaction
Nucleophilic catalysis
Outer shell electrons in
I- are loosely held hence
it is highly polarisable
It is a good leaving and
good entering group.
Finkelstein
Reaction
t-BuCH2 CH2=CH PhCH2– EtOC(O)
Me–Cl Bu–Cl i-Pr–Cl MeC(O)CH2–Cl
–Cl –CH2–Cl Cl CH2–Cl
179 1 0.0146 0.00003 64 179 1600 33000
A modern SN2 reaction: Mitsunobu reaction
DEAD +Ph3P
+ HNu
PhCOOH
DEAD +Ph3P
Normal ester formation leads with retention 100% inversion
Mechanism: First step involves neither the Nu nor the alcohol
Stable anion
Ph3P=O
+
One step process for esters, all four reagents are taken together
Problem:
HNu
-H2O
Strong bond
Acidic proton
to be broken
Solution:
Ph3P Ph3P=O Strong bond formed
Weak bond
Strong bonds formed
Problem:
Miscellaneous conditions for Mitsunobu reaction
Miscellaneous examples of Mitsunobu reaction
Miscellaneous examples of Mitsunobu reaction
Regioselectivity of epoxide opening
Attack of powerful Nu Acid catalysis
basic
1,1,2-trisubstituted epoxide
Regeiochemistry reverses with conditions!!!
Pure SN2
Nu- attacks at
less substituted
C-atom
Opening happens at the more substituted end
State with reasons whether these reactions will be either SN1 or SN2.
SN2 due to carbonyl
S N1
Acid catalysis makes better LG, inversion unusual, but due to OH group hindrance
S N2
base catalysis makes better Nu, inversion usual
