Organic Chemistry

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Organic Chemistry
William H. Brown Christopher S. Foote
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OrganometallicCompounds

• Chapter 15

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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

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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

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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

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RMgX and RLi

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

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RMgX and RLi

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

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RMgX and RLi

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

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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 CO group to form a new
  carbon-carbon bond

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RMgX and RLi

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

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RMgX and RLi

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

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RMgX and RLi

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

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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

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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

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Gilman Reagents

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

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Gilman Reagents

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

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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

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Gilman Reagents

• Reaction with epoxides
• regioselective ring opening

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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

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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

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Heck Reaction

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

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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, CO groups of aldehydes ketones, and
  esters unreactive under Heck conditions

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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

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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

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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

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Carbenes and Carbenoids

• Dichlorocarbene
• prepared by treating chloroform with potassium
  tert-butoxide

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Carbenes and Carbenoids

• Dichlorocarbene
• reacts with alkenes to give dichlorocyclopropanes

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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

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Carbenes and Carbenoids

• Simmons-Smith reagent

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Carbenes and Carbenoids

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

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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

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Stable Nucleophilic Carbenes

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

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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

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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

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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.

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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

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Prob 15.9

• Complete these reactions involving Gilman
  reagents.

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Prob 15.13

• Show reagents to synthesize this target
  molecule from cyclohexane.

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Prob 15.14

• Complete these equations.

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Prob 15.15

• Account for the stereospecificity of this
  reaction.

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Prob 15.18

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

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Prob 15.19

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

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Prob 15.20

• Complete these Heck reactions.

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Prob 15.21

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

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Prob 15.22

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

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Prob 15.23

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

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Prob 15.24

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

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Prob 15.25

• Propose a synthesis of spiro2.2pentane from
  organic compounds of three carbons or less.

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Prob 15.26

• Predict the product of each alkene metathesis
  reaction.

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• Organometallic
• Compounds
• End Chapter 15