Chemistry 125: Lecture 73April 25, 2011

-H Reactivity (J&F Ch. 19)

Condensations (J&F Ch. 19)

Fischer’s Glucose Proof - Introduction

This

For copyright notice see final page of this file

a-AlkylationKetones / Aldehydes

(e.g. J&F Sec.19.5a)

CH3-I ?

-170

HOMO favors C

Electrostatic Potential

s attack

p attack

favors O

-143

a-AlkylationKetones / Aldehydes

(e.g. J&F Sec.19.5a)

CH3

CH3-I(CH3)3Si-Cl

Si(CH3)3

Si(CH3)3

t-Bu

t-But-Bu

t-Bu negligible

85%negligible

major

a-AlkylationKetones / Aldehydes

(e.g. J&F Sec.19.5a)

+Ph3C

- K+

CH3OC2H4OCH3

22%

CH3I (2 eq)

41% 9% 21% 6%

added to enolate solution

pKa 32

pKa ~20

a-AlkylationKetones / Aldehydes

(e.g. J&F Sec.19.5a)

i-Pr2N- Li+

-78°C

MnCl2 • 2LiCl

-78°C

PhCH2Br (1.3 eq)

room temp

88% distilled“Org. Syn. Prep.”

“LDA”

a-AlkylationCarboxylic Acids

(e.g. J&F Sec. 19.5b)

i-Pr2N- Li+

“LDA”LDA

R-Br

R

a-Alkylation -Dicarbonyls

(e.g. J&F Sec.19.5c)

EtO- HO-R-L

EtO- HO-R-L

HO-EtO- R-L or

b-ketoester

malonic ester

cyanoacetic ester

(not HO-)

a-AlkylationDecarboxylation

(e.g. J&F Sec. 19.5d)

“Acetoacetic Ester Synthesis” of Ketone

“Malonic Ester Synthesis” of Acid

H+

H+

D

D

Arndt-Eistert, C N, Grignard/CO2 add one C to chain; these syntheses & add two.

The Aldol “Condensation”(e.g. J&F Sec 19.6)

-b Hydroxyaldehyde

HO-

acetaldehyde“aldol”

HOH

, -a b Unsaturated Aldehyde

-H2O

H+ catalysis also works for

both steps

favorable equilibrium

The Aldol “Condensation”(e.g. J&F Sec 19.6)

-b Hydroxyketone

HO- HOH

unfavorable equilibriumketone

Make tea by pouring hot water through tea

bag in funnel?

Better to use Soxhelet extractorcontaining solid base, Ba(OH)2

Boil

Condense

The Crossed Aldol “Condensation”(e.g. J&F Sec 19.6)

-b Hydroxyketone

HO- HOH

, -a b Unsaturated Ketone

-H2O

favorable equilibrium

can’t formenolate!

unfavorable equilibrium

Conjugate Addition (e.g. J&F Sec 19.6c)

Robinson Annulation - 1935(e.g. J&F Sec 19.11)

Methyl Vinyl Ketone

aldol

conjugate addition to

pinacolrearr.

pinacolreduction

Robert Robinson R. B. Woodward

by

perm

issi

on

J. D

. R

obe

rts

The Claisen “Condensation”(e.g. J&F Sec 19.8)

-b Ketoester

RO-

ester

-RO-

RO-

“eats the lye”

Drives the Equilibrium

starts like aldol but has a leaving group

HScoA =

Nature’s Claisen “Condensation”(e.g. J&F Sec 19.10)

Acetyl-coA

-CO2Drives the Equilibriumunfavorable equilibrium

Malonyl-coA

CO2-

2

CO2-

CO2-

H1) Reduce

2) Dehydrate3) Reduce

Natural fatty acids have even numbers of C atoms.

Couper1858

Carbohydrate(C•HOH)n

CHOH

CHOH

CHOH

CHOH

CHOH

CHOH

HOH

Carbohydrate(C•HOH)n

CHOH

CHOH

CHOH

CHOH

CHOH

CHOH

C=O

CHOH

CHOH

CHOH

CHOH

CHOH

H

H

CHOH

C=O

CHOH

CHOH

CHOH

CHOH

H

HCHOH

CHOH

C=O

CHOH

CHOH

CHOH

H

H

Heinrich Kiliani

1855-1945

End of Lecture 73April 25, 2011

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