Chemistry, Organic Second Edition
Janice Gorzynski Smith
University of Hawaii
Chapter 26
Lecture Outline
Prepared by Rabi Ann Musah
State University of New York at Albany
Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
1
CarbonCarbon Bond-Forming
Organic Synthesis
Reactions
in
Coupling Reactions of Organocuprates
Recall that organocuprate reagents react a variety of
functional compounds including acid chlorides,
epoxides and , -unsaturated carbonyl compounds.
Organocuprate reagents also react with organic halides
RX to form coupling products RR that contain a
new CC bond.
Only one R group of the organocuprate is transferred to
form the product, while the other becomes part of the
RCu, a reaction product.
2
CarbonCarbon Bond-Forming
Organic Synthesis
Reactions
in
Coupling Reactions of Organocuprates
Methyl, 1, cyclic 2, vinyl and aryl halides can be used.
Reactions with vinyl halides are stereospecific.
The halogen (X) may be Cl, Br or I.
Tertiary (3) halides are too sterically hindered to react.
3
CarbonCarbon Bond-Forming
Organic Synthesis
Reactions
in
Coupling Reactions of Organocuprates
Since organocuprate reagents are prepared in two steps
from alkyl halides (RX), this method ultimately converts
two organic halides (RX and RX) into a hydrocarbon R
R with a new carboncarbon bond.
Note that this means that using this methodology, a
given hydrocarbon can often be made by two different
routes.
4
CarbonCarbon Bond-Forming
Organic Synthesis
Reactions
in
The Suzuki ReactionA Reaction with a Pd Catalyst
Organopalladium compounds are compounds that contain a
carbonpalladium bond.
During a reaction, Pd is coordinated to a variety of groups
called ligands, which donate electron density to (or
sometimes withdraw electron density from) the metal.
A common electron donating ligand is phosphine, some
derivatives of which are shown:
5
CarbonCarbon Bond-Forming
Organic Synthesis
Reactions
in
The Suzuki ReactionA Reaction with a Pd Catalyst
A general ligand bonded to a metal is often designated as
L. Pd bonded to four ligands is denoted as PdL4.
Organopalladium compounds are generally prepared in situ
during the course of a reaction, from another palladium
reagent such as Pd(OAc)2 or Pd(PPh3)4. Note that Ac is the
abbreviation for the acetyl group, CH3C=O, so OAc is the
abbreviation for CH3CO2.
In most useful reactions, only a catalytic amount of Pd
reagent is used.
Two common processes, called oxidative addition and
reductive elimination, dominate many reactions of palladium
compounds.
6
CarbonCarbon Bond-Forming
Organic Synthesis
Reactions
The Suzuki ReactionA Reaction with a Pd Catalyst
7
in
CarbonCarbon Bond-Forming
Organic Synthesis
Reactions
in
The Suzuki ReactionMechanistic Details
The Suzuki reaction is a palladium-catalyzed coupling of an
organic halide (RX) with an organoborane (RBY2) to form a
product (RR) with a new CC bond.
Pd(PPh3)4 is the typical palladium catalyst.
The reaction is carried out in the presence of a base such as
NaOH or NaOCH2CH3.
Vinyl or aryl halides are most often used, and the halogen is
usually Br or I.
The Suzuki reaction is completely stereospecific.
8
CarbonCarbon Bond-Forming
Organic Synthesis
Reactions
The Suzuki ReactionMechanistic Details
9
in
CarbonCarbon Bond-Forming
Organic Synthesis
Reactions
in
The Suzuki ReactionMechanistic Details
The organoboranes used in the Suzuki reaction are
acquired from two sources.
Vinylboranes, which have a boron atom bonded to a carbon
carbon double bond, are prepared by hydroboration using
catecholborane, a commercially available reagent.
Hydroboration adds H and B in a syn fashion to form a trans
vinylborane. With terminal alkynes, hydroboration always
places the boron atom on the less substituted terminal
carbon.
10
CarbonCarbon Bond-Forming
Organic Synthesis
Reactions
in
The Suzuki ReactionMechanistic Details
Arylboranes, which have a boron atom bonded to a benzene
ring, are prepared from organolithium reagents by reaction
with trimethyl borate [B(OCH3)3]
11
CarbonCarbon Bond-Forming
Organic Synthesis
Reactions
The Suzuki ReactionMechanistic Details
12
in
CarbonCarbon Bond-Forming
Organic Synthesis
Reactions
in
The Heck Reaction
The Heck reaction is a Pd-catalyzed coupling of a vinyl or aryl
halide with an alkene to form a more highly substituted
alkene with a new CC bond.
Palladium(II) acetate [Pd(OAc)2] in the presence of a
triarylphosphine [P(o-tolyl)3] is the typical catalyst.
The reaction is carried out in the presence of a base such as
triethylamine.
The Heck reaction is a substitution in which one H atom of
the alkene starting material is replaced by the R group of the
vinyl or aryl halide.
13
CarbonCarbon Bond-Forming
Organic Synthesis
Reactions
in
The Heck Reaction
The alkene component is typically
monosubstituted alkene (CH2=CHZ).
ethylene
or
a
The halogen is typically Br or I.
When Z = Ph, COOR or CN in a monosubstituted alkene,
the new CC bond is formed on the less substituted
carbon afford to a trans alkene.
When a vinyl halide is used as the organic halide, the
reaction is stereospecific.
14
CarbonCarbon Bond-Forming
Organic Synthesis
Reactions
The Heck Reaction
15
in
CarbonCarbon Bond-Forming
Organic Synthesis
Reactions
in
The Heck Reaction
To use the Heck reaction in synthesis, you must determine
what alkene and what organic halide are needed to prepare a
given compound.
To work backwards, locate the double bond with the aryl,
COOR, or CN substituent, and break the molecule into two
components at the end of the C=C not bonded to one of these
substituents.
16
CarbonCarbon Bond-Forming
Organic Synthesis
Reactions
The Heck Reaction
17
in
CarbonCarbon Bond-Forming
Organic Synthesis
Reactions
in
Carbenes and Cyclopropane Synthesis
A carbene, R2C:, is a neutral reactive intermediate that
contains a divalent carbon surrounded by six electronsthe
lone pair, and two each from the two R groups.
These three groups make the carbene carbon sp2 hybridized,
with a vacant p orbital extending above and below the plane
containing the C and the two R groups.
The lone pair occupies an sp2 hybrid orbital.
18
CarbonCarbon Bond-Forming
Organic Synthesis
Reactions
in
Carbenes and Cyclopropane Synthesis
Dihalocarbenes, :CX2, are especially useful reactive
intermediates since they are readily prepared from
trihalomethanes (CHX3) by reaction with strong base, e.g.,
treatment of chloroform (CHCl3) with KOC(CH3)3 forms
dichlorocarbene, :CCl2.
Dichlorocarbene is formed by a two-step process that results
in the elimination of the elements of H and Cl from the same
carbon.
Loss of the two elements from the same carbon is called
elimination.
19
CarbonCarbon Bond-Forming
Organic Synthesis
Reactions
Carbenes and Cyclopropane Synthesis
20
in
CarbonCarbon Bond-Forming
Organic Synthesis
Reactions
in
Carbenes and Cyclopropane Synthesis
Since dihalocarbenes are electrophiles, they readily react
with double bonds to afford cyclopropanes, forming two new
carboncarbon bonds.
21
CarbonCarbon Bond-Forming
Organic Synthesis
Reactions
in
Carbenes and Cyclopropane Synthesis
Carbene addition occurs in a syn fashion from either side of
the planer double bond.
Carbene addition is a stereospecific reaction, since cis and
trans alkenes yield different stereoisomers as products.
Cyclopropanation is a concerted reaction, so both bonds are
formed in a single step.
22
CarbonCarbon Bond-Forming
Organic Synthesis
Reactions
in
The Simmons-Smith Reaction
Nonhalogenated cyclopropanes can be prepared by the
reaction of an alkene with diiodomethane, CH2I2, in the
presence of a copper-activated zinc reagent called zinccopper couple [Zn(Cu)]. This is known as the Simmons-Smith
reaction.
The reaction is stereospecific.
23
CarbonCarbon Bond-Forming
Organic Synthesis
Reactions
The Simmons-Smith Reaction
24
in
CarbonCarbon Bond-Forming
Organic Synthesis
Reactions
in
Alkene Metathesis
Alkene or olefin metathesis is a reaction between two
alkene molecules that results in the interchange of the
carbons of their double bonds.
Two and two bonds are broken and two new and
two new bonds are formed.
25
CarbonCarbon Bond-Forming
Organic Synthesis
Reactions
in
Alkene Metathesis
Olefin metathesis occurs in the presence of a complex
transition metal catalyst that contains a carbon-metal
double bond. The metal is typically ruthenium (Ru),
tungsten (W), or molybdenum (Mo).
In a widely used catalyst called Grubbs catalyst, the
metal is Ru.
Metathesis catalysts are compatible with the presence
of many functional groups (such as OH, OR, and C=O).
26
CarbonCarbon Bond-Forming
Organic Synthesis
Reactions
in
Alkene Metathesis
Because olefin metathesis is an equilibrium process and
with many alkene substrates yields a mixture of starting
material and two or more alkene products, it is useless
for preparative processes.
However, with terminal alkenes, one metathesis product
is ethylene gas (CH2=CH2), which escapes from the
reaction mixture and drives the equilibrium to the right.
Thus, monosubstituted alkenes (RCH=CH2) and 2,2disubstituted
alkenes
(R2C=CH2)
are
excellent
metathesis substrates because high yields of a single
alkene product are obtained.
27
CarbonCarbon Bond-Forming
Organic Synthesis
Reactions
Alkene MetathesisExamples
28
in
CarbonCarbon Bond-Forming
Organic Synthesis
Reactions
Alkene MetathesisDrawing the Products
Figure26.2
Drawing the products of
olefin metathesis using
styrene (PhCH = CH2) as
starting material
29
in
CarbonCarbon Bond-Forming
Organic Synthesis
Reactions
Alkene MetathesisThe Mechanism
30
in
CarbonCarbon Bond-Forming
Organic Synthesis
Reactions
in
Ring Closing Metathesis (RCM)
When a diene is used as a starting material, ring closure occurs.
These reactions are typically run in very dilute solution so that the
reactive ends of the same molecule have a higher probability of
finding each other. High dilution favors intermolecular rather than
intramolecular metathesis. Virtually any ring size can be prepared.
31