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?