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Chapter 24 - Catalytic Carbon-Carbon Bond Formation   

  • The traditional methods for forming carbon-carbon bonds during synthesis can be roughly classified as follows:

    • A carbon nucleophile displaces a leaving group (Gilman reagents, alkyne anions, enolate anions, and enamine alkylations)

    • The addition of a nucleophile to a carbonyl or carboxyl group, commonly employing enolate nucleophiles (Grignard, alkyne anion, cyanide, aldol, Claisen, enamine, and Wittig)

  • Addition of a conjugate to an a,b-unsaturated compound (Michael reaction)

    • Aromatic replacement (Friedel-Crafts)

    • Oxidative addition and its counterpart, reductive elimination, are two key transition metal and complex processes.

    • When a reagent adds to a metal, its coordination increases by two ligands, whereas reductive elimination is the inverse reaction.

  • The names oxidative and reductive relate to the change in formal charge that happens on the metal during these reactions.

    • Organohalogen, hydrogen, halogens, and many other reagents can react with metals in this manner.

    • The catalytic characteristics of transition metals are altered by the addition of various ligands, which are Lewis bases that coordinate with the metal.

    • In some cases, ligands can be utilized to affect the electrical characteristics, steric crowding, and even chirality surrounding the metal.

  • Green chemistry and atom economy are relatively new initiatives in the global chemical industry; their aims are strongly supported by organometallic catalytic reactions.

    • The Heck reaction involves the substitution of a haloalkene or haloarene for the H atom on an alkene (vinylic hydrogen) in the presence of a base and a little quantity of Pd catalyst.

    • When there is a difference, the substitution happens at the alkene's less substituted carbon and is frequently stereoselective for the E product.

  • When applicable, the haloalkene configuration is preserved.

    • The Heck reaction has the benefit of being compatible with alcohol, ether, aldehyde, ketone, and ester functional groups.

    • Stoichiometric quantities of organohalogen, alkene, and base are utilized, and the Pd catalyst is used.

  • A nucleophile, often an enolate of a doubly activated a-carbon, substitutes an allylic leaving group, typically a carboxylate such as acetate, in catalytic allylic alkylation.

    • The reaction takes place in the presence of a catalytic quantity of Pd(0). Unlike SN2 allylic alkylation, the stereochemistry at the alkylated carbon is preserved.

    • The mechanics of cross-coupling reactions are all extremely similar.

    • The initial step is to oxidatively add an R-X species to Pd, followed by transmetallation of a R9 group from a R9-metal/metalloid species.

    • The cycle is completed by the reductive removal of R-R9 from palladium.

  • To form a new carbon-carbon bond, a boron reagent (R9-BY2) is combined with an alkenyl, aryl, or alkynyl halide (typically Br or I) or triflate with a palladium salt.

    • Boron compounds can be borane (R93B), borate ester (R9-B(OR) 2), or boric acid (R9-B(OH) 2), with R9 being an alkyl, alkenyl, or aryl group.

    • Boranes are created by hydroboration alkenes or alkynes.

    • Borates are created by combining aryl or alkyl lithium compounds with trimethyl borate.

  • The metathesis reaction is often an equilibrium process that is pushed to completion by the use of two terminal alkenes, which yield gaseous ethylene as a result, which bubbles out of the reaction.

  • Ring-closing alkene metathesis is a particularly useful variant of the metathesis process that includes two terminal alkenes on the same molecule, resulting in an intramolecular reaction that produces a cycloalkene product.

    • Ring-closing alkene metathesis has been used to create extremely large ring sizes that are difficult to achieve in other means.

  • The alkene metathesis process is an organometallic-catalyzed reaction in which two alkenes swap double bond carbons.

    • Both alkenes are in the same molecule in a ring-closing alkene metathesis process, and the result is a cycloalkene.

    • Catalysts containing Ru are often utilized; a nucleophilic carbene complex of Ru is very helpful.

    • The metal catalyst reacts with the alkenes to generate a four-membered ring metallacycle, which decomposes to give starting materials or, by elimination in the other direction, to give a new alkene.

  • The traditional methods for forming carbon-carbon bonds during synthesis can be roughly classified as follows:

    • A carbon nucleophile displaces a leaving group (Gilman reagents, alkyne anions, enolate anions, and enamine alkylations)

    • The addition of a nucleophile to a carbonyl or carboxyl group, commonly employing enolate nucleophiles (Grignard, alkyne anion, cyanide, aldol, Claisen, enamine, and Wittig)

  • Addition of a conjugate to an a,b-unsaturated compound (Michael reaction)

    • Aromatic replacement (Friedel-Crafts)

    • Oxidative addition and its counterpart, reductive elimination, are two key transition metal and complex processes.

    • When a reagent adds to a metal, its coordination increases by two ligands, whereas reductive elimination is the inverse reaction.

  • The names oxidative and reductive relate to the change in formal charge that happens on the metal during these reactions.

    • Organohalogen, hydrogen, halogens, and many other reagents can react with metals in this manner.

    • The catalytic characteristics of transition metals are altered by the addition of various ligands, which are Lewis bases that coordinate with the metal.

    • In some cases, ligands can be utilized to affect the electrical characteristics, steric crowding, and even chirality surrounding the metal.

  • Green chemistry and atom economy are relatively new initiatives in the global chemical industry; their aims are strongly supported by organometallic catalytic reactions.

    • The Heck reaction involves the substitution of a haloalkene or haloarene for the H atom on an alkene (vinylic hydrogen) in the presence of a base and a little quantity of Pd catalyst.

    • When there is a difference, the substitution happens at the alkene's less substituted carbon and is frequently stereoselective for the E product.

  • When applicable, the haloalkene configuration is preserved.

    • The Heck reaction has the benefit of being compatible with alcohol, ether, aldehyde, ketone, and ester functional groups.

    • Stoichiometric quantities of organohalogen, alkene, and base are utilized, and the Pd catalyst is used.

  • A nucleophile, often an enolate of a doubly activated a-carbon, substitutes an allylic leaving group, typically a carboxylate such as acetate, in catalytic allylic alkylation.

    • The reaction takes place in the presence of a catalytic quantity of Pd(0). Unlike SN2 allylic alkylation, the stereochemistry at the alkylated carbon is preserved.

    • The mechanics of cross-coupling reactions are all extremely similar.

    • The initial step is to oxidatively add an R-X species to Pd, followed by transmetallation of a R9 group from a R9-metal/metalloid species.

    • The cycle is completed by the reductive removal of R-R9 from palladium.

  • To form a new carbon-carbon bond, a boron reagent (R9-BY2) is combined with an alkenyl, aryl, or alkynyl halide (typically Br or I) or triflate with a palladium salt.

    • Boron compounds can be borane (R93B), borate ester (R9-B(OR) 2), or boric acid (R9-B(OH) 2), with R9 being an alkyl, alkenyl, or aryl group.

    • Boranes are created by hydroboration alkenes or alkynes.

    • Borates are created by combining aryl or alkyl lithium compounds with trimethyl borate.

  • The metathesis reaction is often an equilibrium process that is pushed to completion by the use of two terminal alkenes, which yield gaseous ethylene as a result, which bubbles out of the reaction.

  • Ring-closing alkene metathesis is a particularly useful variant of the metathesis process that includes two terminal alkenes on the same molecule, resulting in an intramolecular reaction that produces a cycloalkene product.

    • Ring-closing alkene metathesis has been used to create extremely large ring sizes that are difficult to achieve in other means.

  • The alkene metathesis process is an organometallic-catalyzed reaction in which two alkenes swap double bond carbons.

    • Both alkenes are in the same molecule in a ring-closing alkene metathesis process, and the result is a cycloalkene.

    • Catalysts containing Ru are often utilized; a nucleophilic carbene complex of Ru is very helpful.

    • The metal catalyst reacts with the alkenes to generate a four-membered ring metallacycle, which decomposes to give starting materials or, by elimination in the other direction, to give a new alkene.