Organic Chemistry

Organic Chemistry William H. Brown & Christopher S. Foote

OrganometallicCompounds Chapter 15

Organometallic Compounds • Organometallic compound: a compound that contains a carbon-metal bond • We focus on organometallic compounds of Mg, Li, Cu, Zn, Pd, and Ru • these classes illustrate the usefulness of organometallics in modern synthetic organic chemistry • they illustrate how the use of organometallics can bring about transformations that cannot be accomplished in any other way

Organometallic Compounds • Oxidative addition: a reagent adds to a metal or metal compound, causing its coordination to increase by two • Reductive elimination: a reagent is eliminated from a metal compound, causing its coordination to decrease by two • Ligand: a Lewis base bonded to a metal in a coordination compound

Grignard Reagent • Grignard reagent: an organomagnesium compound • prepared by addition of an alkyl, aryl, or alkenyl (vinylic) halide to Mg metal in diethyl ether or THF

RMgX and RLi • Grignard reagents dissolve as coordination compounds solvated by ether • ethylmagnesium bromide, EtMgBr

RMgX and RLi • Organolithium reagents • prepared by reaction of an alkyl, aryl, or alkenyl halide with lithium metal

RMgX and RLi • The carbon-metal bonds in RMgX and RLi are polar covalent

RMgX and RLi • RMgX and RLi are valuable in synthesis as nucleophiles • the carbon bearing the halogen is transformed from an electrophile to a nucleophile • their most valuable use is addition to the electrophilic carbon of a C=O group to form a new carbon-carbon bond

RMgX and RLi • Reaction with protic acids • RMgX and RLi are strong bases

RMgX and RLi • Reaction with protic acids • RMgX and RLi react readily with these proton donors

RMgX and RLi • Reaction with oxiranes (epoxides) • reaction of RMgX or RLi with an oxirane followed by protonation increases chain length by two carbons

RMgX and RLi • Reaction with oxiranes (epoxides) • the major product corresponds to SN2 attack of RMgX or RLi on less hindered carbon of the epoxide

Gilman Reagents • Lithium diorganocopper reagents, known more commonly as Gilman reagents • prepared by treating an alkyl, aryl, or alkenyl lithium compound with Cu(I) iodide

Gilman Reagents • Coupling within organohalogen compounds • form new carbon-carbon bonds by coupling with alkyl chlorides, bromides, and iodides

Gilman Reagents • coupling with a vinylic halide is stereospecific; the configuration of an alkene is retained

Gilman Reagents • A variation on the preparation of a Gilman reagent is to use a Grignard reagent with a catalytic amount of copper(I) salt

Gilman Reagents • Reaction with epoxides • regioselective ring opening

Heck Reaction • A palladium catalyzed reaction in which the carbon group of a haloalkene or haloarene is substituted for a vinylic H of an alkene

Heck Reaction • substitution is highly regioselective; at the less substituted carbon • substitution is highly stereoselective; where E,Z isomerism is possible in the product, the E configuration is often formed almost exclusively

Heck Reaction • reaction is stereospecific with regard to the haloalkene; the configuration of the double bond is retained

Heck Reaction • The catalyst • most commonly Pd(II) acetate • reduced in situ to Pd(0) • reaction of Pd(0) with good ligands gives PdL2 • The organic halogen compound • aryl, heterocyclic, and vinylic iodides, chlorides, and bromides • alkyl halides with an easily eliminated b hydrogen are rarely used because they undergo b-elimination to give alkenes • OH group, C=O groups of aldehydes & ketones, and esters unreactive under Heck conditions

Heck Reaction • The alkene • the less the crowding on the alkene, the more reactive it is • The base • triethylamine, sodium and potassium acetate, and sodium hydrogen carbonate are most common • The solvent • polar aprotic solvents such as DMF, acetonitrile, DMSO • aqueous methanol may also be used • The ligand • triphenylphosphine is one of the most common

Heck Reaction • the usual pattern of acyclic compounds is replacement of a hydrogen of the double bond with an R group • if the organopalladium group attacks a double bond so that the R group has no syn H for syn elimination, then the double bond may shift

Carbenes and Carbenoids • Carbene, R2C: a neutral molecule in which a carbon atom is surrounded by only six valence electrons • Methylene, the simplest carbene • prepared by photolysis or thermolysis of diazomethane • methylene prepared in this manner is so nonselective that it is of little synthetic use

Carbenes and Carbenoids • Dichlorocarbene • prepared by treating chloroform with potassium tert-butoxide

Carbenes and Carbenoids • Dichlorocarbene • reacts with alkenes to give dichlorocyclopropanes

Carbenes and Carbenoids • Simmons-Smith reaction • a way to add methylene to an alkene to form a cyclopropane • generation of the Simmons-Smith reagent • this organozinc compound reacts with a wide variety of alkenes to give cyclopropanes

Carbenes and Carbenoids • Simmons-Smith reagent

Carbenes and Carbenoids • Simmons-Smith reaction • the organozinc compound reacts with an alkene by a concerted mechanism

Stable Nucleophilic Carbenes • Stable nucleophilic carbenes • certain carbenes with strongly electron-donating groups are particularly stable • their stability is enhanced by bulky groups that hinder self-reactions; one such group is the 2,4,6-trimethylphenyl group • rather than behaving as electron-deficient reagents like most carbenes, these compounds are nucleophiles because of the strong electron donation by the nitrogens

Stable Nucleophilic Carbenes • this carbene is stabilized by the electron-donating nitrogens and the bulky 2,4,6-trimethylphenyl groups

Ring-Closing Alkene Metathesis • Alkene metathesis reaction: two alkenes interchange carbons on their double bonds • if the reaction involves 2,2-disubstituted alkenes, ethylene is lost to give a single alkene product

Ring-Closing Alkene Metathesis • a useful variant of this reaction uses a starting material in which both alkenes are in the same molecule, and the product is a cycloalkene

Ring-Closing Alkene Metathesis • a particularly useful alkene methathesis catalyst consists of ruthenium, Ru, complexed with a nucleophilic carbene and another carbenoid ligand. In this example, the other carbenoid ligand is a benzylidene group.

Ring-Closing Alkene Metathesis • Like the Heck reaction, alkene metathesis involves a catalytic cycle • addition of a metalocarbenoid to the alkene gives a four-membered ring • elimination of an alkene in the opposite direction gives a new alkene

Prob 15.9 Complete these reactions involving Gilman reagents.

Prob 15.13 Show reagents to synthesize this target molecule from cyclohexane.

Prob 15.14 Complete these equations.

Prob 15.15 Account for the stereospecificity of this reaction.

Prob 15.18 Account for the stereospecificity of this Heck reaction; that is, that the E alkene is formed exclusively.

Prob 15.19 Account for the formation of these isomeric alkenes in this Heck reaction.

Prob 15.20 Complete these Heck reactions.

Prob 15.21 Account for the formation of 3-phenylcyclohexene and the fact that no 1-phenylcyclohexene is formed.

Prob 15.22 Account for the formation of this product and the cis stereochemistry of its ring junction.

Prob 15.23 Account for the formation of the following product, including the cis stereochemistry at the ring junction.

Prob 15.24 Show how Exaltolide can be synthesized from the given starting material. Give the structure of R.

Prob 15.25 Propose a synthesis of spiro[2.2]pentane from organic compounds of three carbons or less.

Prob 15.26 Predict the product of each alkene metathesis reaction.

Organic Chemistry