Grignard reagents: the most popular

1
Grignard reagents the most popular

• possible with a great variety of R
• ethers as solvent are crucial to the success of
  the reaction

2
-d d
R - M M Mg, Li
The strong polarity of the M-C bond and the
consequent carbanionic character determines the
reactivity
1) superstrong base
3
-d d
R - M M Mg, Li
The strong polarity of the M-C bond and the
consequernt carbanionic character determines the
reactivity
2) very good nucleophiles
4
and of course E2 reactions
5
Nucleophilic Addition (prep. of ROH)
Use acid hydrolysis to avoid precipitation of
Mg(OH)2
6
Formation of alcohols
Formaldehyde Aldehyde ketone
7
Reaction with both esters and acyl halides
Two identical groups
8
Planning a Grignard Synthesis
We can synthesize ANY alcohol
9
Restrictions
Incompatible with any function that can be
deprotonated -OH, -NH2, -NHR, -CO2H, -SO3H,
-SH, -CC-H, aldehyde, ketone, esters,
amide -NO2, -CN, epoxide
Grignard carbonatation to lenght the chain by one
C atom
10
Reactivity of alcohols
Basic center
SN2
11
Acidity
CH3OH more acidic than H2O (just a
little) Crowded ROH less acidic than H2O
(solvation of the conjugated base RO-)
Acidity H2O gt ROH gt RCCH gt H2 gt NH3 gtgtgt
RH Basicity R- gtgtgt NH2- gt H- gt RCC- gt RO- gt OH-
Useful reagents in organic synthesis (E and SN
reactions)
12
Esterification
Ester of alkylsulfonic acid
ester
13
Mechanism of formation
14
Excellent leaving groups for SN2 reactions
15
Two-step substitution