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 α,β-unsaturated β 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.


Br or I. . • Note that this means that using this methodology. • Tertiary (3° halides are too sterically hindered to react. 1° cyclic 2° vinyl and aryl halides can be used. 4 . Reactions with vinyl halides are stereospecific. . this method ultimately converts two organic halides (RX and R’X) into a hydrocarbon R—R’ with a new carbon—carbon bond. a given hydrocarbon can often be made by two different routes. • The halogen (X) may be Cl.Coupling Reactions of Organocuprates • Methyl. ) 3 Coupling Reactions of Organocuprates • Since organocuprate reagents are prepared in two steps from alkyl halides (RX).

Note that “Ac” is the abbreviation for the acetyl group. so OAc is the abbreviation for CH3CO2¯ . • A common electron donating ligand is phosphine. which donate electron density to (or sometimes withdraw electron density from) the metal.The Suzuki Reaction—A Reaction with a Pd Catalyst • Organopalladium compounds are compounds that contain a carbon—palladium bond. dominate many reactions of palladium compounds. Pd is coordinated to a variety of groups called ligands. called oxidative addition and reductive elimination. 6 . CH3C=O. only a catalytic amount of Pd reagent is used. • In most useful reactions. • Two common processes. • During a reaction. from another palladium reagent such as Pd(OAc)2 or Pd(PPh3)4.” Pd bonded to four ligands is denoted as PdL4. • Organopalladium compounds are generally prepared in situ during the course of a reaction. some derivatives of which are shown: 5 The Suzuki Reaction—A Reaction with a Pd Catalyst • A general ligand bonded to a metal is often designated as “L.

• Pd(PPh3)4 is the typical palladium catalyst. • The reaction is carried out in the presence of a base such as NaOH or NaOCH2CH3. • The Suzuki reaction is completely stereospecific.The Suzuki Reaction—A Reaction with a Pd Catalyst 7 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. and the halogen is usually Br or I. • Vinyl or aryl halides are most often used. 8 .

• Vinylboranes. are prepared by hydroboration using catecholborane. hydroboration always places the boron atom on the less substituted terminal carbon. With terminal alkynes.The Suzuki Reaction—Mechanistic Details 9 The Suzuki Reaction—Mechanistic Details The organoboranes used in the Suzuki reaction are acquired from two sources. a commercially available reagent. • Hydroboration adds H and B in a syn fashion to form a trans vinylborane. which have a boron atom bonded to a carbon—carbon double bond. 10 .

The Suzuki Reaction—Mechanistic 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 The Suzuki Reaction—Mechanistic Details 12 .

• The halogen is typically Br or I.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 C—C bond. 14 . the new C—C bond is formed on the less substituted carbon to afford a trans alkene. • Palladium(II) acetate [Pd(OAc)2] in the presence of a triarylphosphine [P(o-tolyl)3] is the typical catalyst. COOR or CN in a monosubstituted alkene. • When a vinyl halide is used as the organic halide. the reaction is stereospecific. • 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 reaction is carried out in the presence of a base such as triethylamine. 13 The Heck Reaction • The alkene component is typically ethylene or a monosubstituted alkene (CH2=CHZ). • When Z = Ph.

The Heck Reaction 15 The Heck Reaction • To use the Heck reaction in synthesis. and break the molecule into two components at the end of the C=C not bonded to one of these substituents. locate the double bond with the aryl. 16 . you must determine what alkene and what organic halide are needed to prepare a given compound. COOR. or CN substituent. • To work backwards.

with a vacant p orbital extending above and below the plane containing the C and the two R groups. • These three groups make the carbene carbon sp2 hybridized.The Heck Reaction 17 Carbenes and Cyclopropane Synthesis • A carbene. and two each from the two R groups. is a neutral reactive intermediate that contains a divalent carbon surrounded by six electrons—the lone pair. • The lone pair occupies an sp2 hybrid orbital. 18 . R2C:.

treatment of chloroform (CHCl3) with KOC(CH3)3 forms dichlorocarbene. • Loss of the two elements from the same carbon is called α elimination. e. • Dichlorocarbene is formed by a two-step process that results in the elimination of the elements of H and Cl from the same carbon.g.Carbenes and Cyclopropane Synthesis • Dihalocarbenes. 19 Carbenes and Cyclopropane Synthesis 20 . :CCl2. :CX2.. are especially useful reactive intermediates since they are readily prepared from trihalomethanes (CHX3) by reaction with strong base.

Carbenes and Cyclopropane Synthesis • Since dihalocarbenes are electrophiles. forming two new carbon—carbon bonds. • Carbene addition is a stereospecific reaction. since cis and trans alkenes yield different stereoisomers as products. so both bonds are formed in a single step. 22 . 21 Carbenes and Cyclopropane Synthesis • Carbene addition occurs in a syn fashion from either side of the planer double bond. they readily react with double bonds to afford cyclopropanes. • Cyclopropanation is a concerted reaction.

23 The Simmons-Smith Reaction 24 . • The reaction is stereospecific. in the presence of a copper-activated zinc reagent called zinccopper couple [Zn(Cu)].The Simmons-Smith Reaction • Nonhalogenated cyclopropanes can be prepared by the reaction of an alkene with diiodomethane. This is known as the Simmons-Smith reaction. CH2I2.

or molybdenum (Mo). • In a widely used catalyst called Grubbs catalyst. the metal is Ru. 25 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). 26 . • Metathesis catalysts are compatible with the presence of many functional groups (such as OH.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. OR. and C=O). • Two σ and two π bonds are broken and two new σ and two new π bonds are formed.

• However. it is useless for preparative processes. Thus. 27 Alkene Metathesis—Examples 28 .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. monosubstituted alkenes (RCH=CH2) and 2. which escapes from the reaction mixture and drives the equilibrium to the right. with terminal alkenes.2disubstituted alkenes (R2C=CH2) are excellent metathesis substrates because high yields of a single alkene product are obtained. one metathesis product is ethylene gas (CH2=CH2).

Alkene Metathesis—Drawing the Products Drawing the products of olefin metathesis using styrene (PhCH = CH2) as starting material 29 Alkene Metathesis—The Mechanism 30 .

High dilution favors intermolecular rather than intramolecular metathesis. ----. 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.Ring Closing Metathesis (RCM) When a diene is used as a starting material.*** ----- 31 . Virtually any ring size can be prepared.