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.