Carbon-carbon Bond Formation
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Transcript of Carbon-carbon Bond Formation
Carbon-carbon bond formation
O C-C Bond Formation
O Alkylation of enolates, enamines and
hydrazones
O Alkylation of heteroatom stabilized
anions
O C=C Bond Formation
O Claisen rearrangement
O Wittig reaction
O Peterson olefination
Alkylation of enolates
O Enolates:
O α-deprotonation of a ketone, aldehyde or ester by
treating with a strong non-nucleophilic base
O The carbonyl group will stabilizes the resulting
negative charge
O Common bases: NaH, EtONa, NaNH2
-base
enolate
O Enolate formation
O Acid catalyzed (thermodynamic)
O Based induced (thermodynamic or
kinetic)
H+
-
more substituted
Base
-
less substituted
O Regioselective Enolate Formation
O Kinetic enolate – deprotonation of the
most accessable proton
O Typical condition: a strong hindered (non-
nucleophilic base)
LDA/THF, -78°C
-Li+
O Themodynamic enolate – reversible deprotonation
to give the most stable enolate; more highly substituted
C=C of the enol form
O Typical Condition: RO-M+ in ROH, protic solvent allows
reversible enolate formation
-K+
K+
tBuO-K+, tBuOH
thermodynamic enolate
more substituted alkene
-
kinetic
O Alkylation of enolates:
O Primary alkyl halides, alylic and benzylic halides work well
O Secondary halides can be troublesome
O Tertiary halides dont work
O Rate of alkylation is increased in more polar solvents
1. LDA, THF, -78°C
2. Me-I
O C-C bond formation using enamines
O Advantages: mono alkylation usually gives product from
kinetic enolization
enamine
acid
more stable, kineticless stable, thermodynamic
enamine
O C-C bond formation using hydrazones
O Hydrazones are isoelectronic with ketones
O Hydrazone anions are more reactive than corresponding
ketone or aldehyde enolate
O Drawback: can be difficult to hydrolyze
-
Me2N.NH2
H+, -H2O
LDA/THF -
E+
hydrolysis
E+
O C-C bond formation using heteroatom stabilized anions
O Sulfones
O Sulfoxides
LDA/THF -
Al(Hg)
LDA/THF -
Raney Ni
C=C Bond Formation
O Aldol condensation
O Wittig reaction
O Peterson olefination
O Aldol condensation
O Initially give b-hydroxy ketones which under
certain conditions readily eliminated to give a,b-
unsaturated carbonyls
LDA, THF, -78°C elimination of H2O
O Mannich reaction – formation of a,b-
unsaturated carbonyls or a-methylene
carbonyls
H2C=O, Me2NH.HCl
O Wittig Reaction
O Reaction of phosphonium ylide with aldehydes
and ketones
-Ph3P=O
Ph3P
X-
strong base -
-
ylidephosphorane
betaine oxaphosphetane
O Geometry of olefin
Z-olefin
E-olefin
non-stablilized ylide
stabilized ylide
+ -
-
E-olefin
O Peterson Olefination
-LDA/THF
negative chage stabilized by Si
-
-Me3SiO
mixture of E and Z alkenes
Show an arrow mechanism for the following reactions.
O
Ph3P=CHCH2CH3
Predict the product(s) or reactant(s) for the following reactions.
O
1. LDA
2. CH3CH2I?