Sintesis Kimia Organik PDF 2

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Carbon—Carbon Bond-Forming Reactions in

Organic Synthesis

Coupling Reactions of Organocuprates

• Recall that organocuprate reagents react a variety of functional compounds including acid chlorides, epoxides and αααα,ββββ-unsaturated carbonyl compounds.

• Organocuprate reagents also react with organic halides R’—X to form coupling products R—R’ that contain a new C—C 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.

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SINTESIS KIMIA ORGANIK

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• 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.

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• Since organocuprate reagents are prepared in two steps

from alkyl halides (RX), this method ultimately converts two organic halides (RX and R’X) into a hydrocarbon

R—R’ with a new carbon—carbon bond.

• Note that this means that using this methodology, a

given hydrocarbon can often be made by two different routes.

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The Suzuki Reaction—A Reaction with a Pd Catalyst

• Organopalladium compounds are compounds that contain a carbon—palladium 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:

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• 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 situduring 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.

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The Suzuki Reaction—Mechanistic Details

• The Suzuki reaction is a palladium-catalyzed coupling of an organic halide (R’X) with an organoborane (RBY2) to form a product (R—R’) with a new C—C 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.

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• Vinylboranes, which have a boron atom bonded to a carbon—carbon double bond, are prepared by hydroborationusing 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.


The organoboranes used in the Suzuki reaction are acquired from two sources.

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• Arylboranes, which have a boron atom bonded to a benzene ring, are prepared from organolithium reagents by reaction with trimethyl borate [B(OCH3)3]


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• 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 C—C 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.

The Heck Reaction

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• The alkene component is typically ethylene or a

monosubstituted alkene (CH2=CHZ).

• The halogen is typically Br or I.

• When Z = Ph, COOR or CN in a monosubstituted alkene, the new C—C bond is formed on the less substituted

carbon to afford a trans alkene.

• When a vinyl halide is used as the organic halide, the reaction is stereospecific.

The Heck Reaction

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The Heck Reaction

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• 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.

The Heck Reaction

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The Heck Reaction

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• A carbene, R2C:, is a neutral reactive intermediate that contains a divalent carbon surrounded by six electrons—the 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.

Carbenes and Cyclopropane Synthesis

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• 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 ααααelimination.

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• Since dihalocarbenes are electrophiles, they readily react with double bonds to afford cyclopropanes, forming two new carbon—carbon bonds.

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• 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.

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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 zinc-copper couple [Zn(Cu)]. This is known as the Simmons-Smith reaction.

• The reaction is stereospecific.

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The Simmons-Smith Reaction

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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 σσσσ and two ππππ bonds are broken and two new σσσσ and two new ππππ bonds are formed.

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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).

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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 2,2-disubstituted alkenes (R2C=CH2) are excellent

metathesis substrates because high yields of a single alkene product are obtained.

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Alkene Metathesis—Examples

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Alkene Metathesis—Drawing the Products

Drawing the products of

olefin metathesis using

styrene (PhCH = CH2) as

starting material

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Alkene Metathesis—The Mechanism

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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.

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Sintesis Kimia Organik PDF 2

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