Chapter 8. Reactions Involving the Transition Metals

• Introduction• Main group metals are used in stoichiometric reaction, b

ut many of transition metal are used in catalytic process.• Transition metals frequently involve oxidation state chang

es at the metal

• 8.1 Organocopper Intermediates• 8.1.1. Preparatioon and structure of Organocopper reage

nts.

catalytic amount 1,4-addition reaction

1,2-addition reaction

The 2:1 species are known as cuprates and are the most important as syntheticreagents.

In solution, lithium dimethylcuprate exists as a dimer, [LiCu(CH3)2]2.Four methyl groups are attached to a tetrahedral cluster of lithium and copperatoms. However, in the presence of LiI, the compound seems to be a monomerof compostition (CH3)2CuLi.

Cuprates with two different copper substituents have been developed(Table 8.1).

An important type of mixed cuprates is prepared from a 2:1 ratio of analkyllithium and CuCN: higher-order cyanocuprates.Same reactivity, but more stable than dialkyl cuprate.

R2CuCNLi2 in THF

CN doesn’t seem to be bounddirectly to the copper.Only one of two organic groups is tranferred.

2-thienyl group is not tranferred.

Selectively transfer the alkenyl group in conjugate addition reaction

Metal-metal exchange reaction

8.1.2. Reactions Involving Orgnocopper Reagents and Intermediates

Organocopper reagents: nucleophilic displacements on halides and sulfonates.Epoxide ring opening, conjugate additions to -unsaturated carbonyl compounds, and additions to alkynes.

The addition of halides to transition-metal species with low oxidation statesis a common reaction in transition-metal chemistry and is called oxidativeaddition. The formal oxidation state of copper after addition is 3+. This stepis followed by combination of two of the alkyl groups from copper: reductiveelimination.

Allylic halide give both SN2 products and products of substitution with andallylic shift (SN2’ products) although the mixed organocopper reagent RCu-BF3 isreported to give mainly the SN2’ product.

The reaction shows a preference for anti stereochemistry in cyclic systems.

Propargyl acetates, halides, and sulfonates also react with a double-bondshift to give allenes.

Halogens to carbonyl groups can be successfully coupled with organocopperReagents.

Introduced at less hindered carbon of the epoxide ring.

The addition is accelerated by trimethylsilyl choride or a combination oftrimethylsilyl chloride and HMPA. The rate enhancement is attributed totrapping or a reversibly formed complex between the enone and cuprate.

The efficiency of the reaction is improved by the addition of trialkylphosphinesto the reaction mixture.

The lithium ion also plays a key role, presumably by Lewis acid coordinationat the carbonyl oxygen.

Isotope effects indicate that the collapse of the adduct by reductive eliminationis the rate determining step.

The more easily reduced, the more reactive is the compound toward cupratereagents. Compounds such as -unsaturated esters and nitriles, whichare not as easily reduced as the corresponding ketones, do not react as readilywith dialkyl cuprates, even though they are good Michael acceptors in classicalMichael reactions with carbanions.

In the presence of LiI, TMS-Cl, and catalystic amount of (CH3)2Cu(CN)Li2,conjugate addition of organozinc reagents occurs in good yield.

Simple organozinc reagents undergo conjugate addition with CuO3SCF3 as catalyst in the presence of phosphines or phosphites.

Conjugate addition reactions involving organocopper intermediates can bemade enantioselective by using chiral ligands.

Conjugate addition to -unsaturated esters can often be effected by coppercatalyzed reaction with Grignard reagent. Other reactions, such as epoxidering opening, can also be carried out under catalytic conditions. (Scheme 8.5)

Conjugate acetylenic esters react readily with cuprate reagents, withsyn addition being kinetically preferred.

Mixed copper-magnesium reagents analogous to the lithium cuprates canbe prepared. These compounds are often called Normant reagents. Thereagents undergo addition to terminal alkynes to generate alkenylcopperreagents. The addition is stereospecifically syn.

protonolysis

Organocopper intermediates are also involved in several procedures forcoupling of two organic reactants to form a new carbon-carbon bond.Classical example of this type of reaction is the Ullman coupling, which isdone by heating an aryl halide with a copper-bronze alloy. Good yields bythis method are limited to halides with electron-attracting substituents.

I2Cu

CuI2 +

ICu

single electron transfer

Cu(I)I +Cu(II)I

SET

Cu(II)I

I

CuI2 +

mechanism

Ullmann reaction

Arylcopper intermediates can be generated from organolithium compoundsas in the preparation of cuprates. These compounds react with a secondaryl halide to provide unsymmetrical biaryls.

8.2 Reactions Involving Organopallasium Intermediates

Catalytic processes have both economic and environmental advantage.

Three types of organopalladium intermediates are of primary importance in thereactions that have found synthetic application.

Palladium can be replaced by hydrogen under reductive conditions

In the absence of a reducing reagent, an elimination of Pd(0) and a proton occurs.

A second type of organopalladium intermediates are -allyl complexes. Thesecomplexes can be obtained from Pd(II) salts and allyl acetates and othercompounds with potential leaving groups in an allylic poistion.

The -allyl complexes can be isolated as halide-bridged dimers.

The third general process involves the reaction of Pd(0) species with halides orsulfonates by oxidative addition, generating reactive intermediates having theorganic group attatched to Pd(II) by -bond. The oxidative addition reaction isvery useful for aryl and alkenyl halides, but the products form saturated alkylhalides usually decompose by elimination.

The reactions involving organopalladium intermediates are done in the presence of phosphine ligands. These ligands coodinate at palladium and play a key rolein the reaction by influencing the reactivity. Another general point concerns therelative weakness of the C-Pd bond and, especially, the instability of alkyl palladium species in which there is a hydrogen.

8.2.1. Palladium-catalyzed Nucleophilic Substitution and Alkylation.

Wacker reaction: catalytic method for conversion of ethylene to acetaldehyde.

The first step is addition of water to the Pd-activated alkene.

Enol

The co-reagents CuCl2 and O2 serve to reoxidize the Pd(0) to Pd(II). Thenet reaction consumes only alkene and oxygen.

8.2.2. The Heck Reaction

Heck Reaction: Aryl and alkenyl halides react with alkenes in the presence of catalytic amounts of palladium to give net substitution of the halide by the alkenyl group.

The reaction is quite general and has been observed for simple alkenes, arylsustituted alkenes, and electrophilic alkenes such as acrylic esters and N-vinylamides. The reactions are usually carried out in the presence of aphosphine ligand.

The reaction is initiated by oxidative addition of the halide to a palladium(0)species genreated in situ from the Pd(II) catalyst.

The -complex decomposes with regeneration ofPd(0) by -elimination.

High halide concentration promotes formation of the anionic species [PdL2X]-

by addition of a halide ligand. Use of trifluoromethanesulfonate anions promotesdissociation of the anion from the Pd(II) adduct and accelerates complexation with electron-rich alkene.

Aryl chlorides are not very reactive under normal Heck reaction conditions, butreaction can be achieved by inclusion of triphenylphosphonium salts withPd(Oac)2 or PdCl2 as the catalyst.

With vinyl ethers and N-vinylamides, it is possible to promote arylation by useof bidentate phosphine ligands such as dppe and dppp, using aryl triflates as reactants. Electronic factors favor migration of the aryl group to the carbon.

Allylic silanes show a pronounced tendency to react at the carbon. Thisregiochemistry is attributed to the stabilization of cationic character at the carbon by the silyl substituent.

8.2.3 Palladium-Catalyzed Cross Coupling

8.2.3.1 Coupling with organometallic Reagents: cross-coupling reaction

Organomagnesium, organozinc, mixed cuprate, stanne, or organoboron compounds

The reaction is quite general for formation of sp2-sp2 and sp2-sp bonds inbiaryls, dienes and polyenes and enyenes. There are also some conditionswhich can couple alkyl organometallic reagents, but these reactions are lessgeneral because of the tendency of alkylpalladium intermediates to decomposeby elimination

Pd-catalyzed cross-coupling of organometallic reagents

A promising development is the extension of Pd-catalyzed cross coupling tosimple enolates and enolate equivalent, which provides an important way ofarylating enolates which is normally a difficult transformation to accomplish.

Use of tri-t-butylphsophine with a catalytic amount of Pd(OAc)2 results in phenylation of the enolates of aromatic ketones and diethyl malonate.

Arylation has also been observed with the diphosphine ligand, BINAP.

A combination of Pd(PPh3)4 and Cu(I) effects coupling of terminal alkynes withvinyl or aryl halides. The alkyne is presumably converted to the copper acetylide.The halide reacts with Pd(0) by oxidative addition. Transfer of the acetylidegroup to Pd results in reductive elimination and formation of the observedproduct.

Sonogashira Coupling

Use of alkenyl halides in this reaction has proven to be an effective method for the synthesis of enynes. The reaction can be carried out directly with thealkyne, using amines for deprotonation.

8.2.3.2. Coupling with Stannes: Stille Coupling

The approximate order of effectiveness of transfer of groups from tin isalkynyl>alkenyl>aryl>methyl>alkyl, so unsaturated groups are normally transferredselectively.

Subsequent studies have found improved ligands, including tri-2-furylphsophine and triphenylarsine. Aryl-aryl coupling rates are increased by the presence ofCu(I) co-catalyst.

The reactions occur with retention of configuration at both the halide and thestanne. Very useful in stereospecific construction of dienes and polyenes.Tolerant to the various functional groups: ester, nitrile, nitro, cyano, and formyl groups

Masked form of formyl group

Alkenyl triflates are also reactive

8.2.3.3. Coupling with Organoboranes: Suzuki couling

Cross coupling in which the organometallic component is an aryl or vinyl boron compound: boronic acids, boronate esters, boranes.

Transmetallation or oxidative addition can be the rate determining step

Suzuki Cross Coupling

R-X

R= Alkenyl, aryl, allyl; X=halogen

+ R1

BY2

Pd(0) (cat)

NaOR2 or NaOH R1

R

R1

R Pd(0)

R-PdL2-X

R-PdL2-OR2

R1

PdR

L2

R-X

R2ONa

NaXR1

BY2

R2O-BY2

Special case

In some synthetic applications, specific bases such as Cs2CO3 or TlOH havebeen found preferable to NaOH.

The reaction proceed with retention of double-bond configuration in both theboron derivative and the alkenyl halide.

8.2.4. Carbonylation Reactions

The detailed mechanism of such reactions have been shown to involveaddition and elimination of phosphine.

These reactions can be carried out with stannes or boronic acids as thenucleophilic component.

Tandem carbonylation reaction

+ CORh cat./I-

180oC/ 30 barCH3COOHCH3OH

CH3OH CH3I

HI H2OI

RhCO

I CO

IRh

CO

I COI

CH3

-

-

IRh

I COI

-O

CH3

IRh

OC COI

-O

CH3

II

O

CH3CH3COOHCO

Monsanto Process (Acetic acid Synthesis): 150-200oc, 1-40 atmRef: BASF process: cobalt-based high pressure process (200-250oC, 500-700 atm)

8.3 Reactions Involving Organonickel Compounds

Allylic halides react with nickel carbonyl, Ni(CO)4 to give -allyl complexes.

These reactions are believed to involve Ni(I) and Ni(III) intermediates in achain process which is initiated by formation of a small amount of a Ni(I) sepcies.

This couplig reaction has been used intramolecularly to bring about cyclization of bis-allylic halides and was found useful in the preparationof large rings.

Nickel carbonyl is an extremely toxic compound, and a number of other nickelreagents with generally similar reactivity can be used in its place.

Mediun sized ring can be formed in intramolecular reaction.

The key aspects of the mechanism are (1) the reductive elimination whichoccurs via a diaryl Ni(III) intermediates and (2) the oxidative addition whichinvolves a Ni(I) species.

A soluble bis-phosphine complexes, Ni(dppe)2Cl2, is a particularly effective catalyst. The main distinction between this reaction and Pd-catalyzed crosscoupling is that the nickel reaction can be more readily applied to saturatedalkyl groups because of a reduced tendency for -elimination.

The synthesis of cyclophane-type structures by use of dihaloarenes andGrignard reagents from -dihalides.

When secondary Grignard reagents are used, the coupling product sometimesis derived from the corresponding primary alkyl group. This transformation canoccur by reversible formation.

Styrene serves to stabilize the active catalytic species, and among the styrenederivatives, m-trifluoromethylstyrene was the best.

The main advantage of nickel is that it reacts more readily with arylchlorides andmethanesulfonates than does the Pd system. These reactants may be moreeconomical than iodides or triflates in large-scale synthesis.

Vinyl phosphates can be used, and these are in some cases more readilyobtained and handled than vinyl triflates.

8.4 Reactions Involving Rhodium and Cobalt

Hydroformylation

The key steps in reaction are addition of hydridorhodium to the double bond ofthe alkene and migration of the alkyl group to the complexed carbon monoxide.

The acylrhodium intermediate is trapped by internal nucleophiles.

Fischer-Tropsch Process: reductive conversion of carbon monoxide to alkaneby reacting with hydrogen gas. Synthetic hydrocarbon fuels.(1923-1925)In1944, 600,000 ton/yr was produced. Since 1957 South Africa use this method, Sasol Process.

Under appropriate conditions, rhodium catalyst can be used for the decarbonylationof aldehyde and acyl chlorides.

The use of cobalt for synthetic purpose is quite limited. Vinyl bromides andidodides couple with Grignard reagents in good yields, but a good donorsolvent such as NMP or DMPU is required as a cocatalyst.

8.5 Organometallic Compounds with bonding

Among the classes of organic compounds that serve as ligands are alkene,allyl, dienes, cyclopentadiene anion, and aromatic compounds.

a) The number of electrons that can be accommodated by the metal orbitalsb) the oxidation level of the metal, c) the electron character of other ligands on the metal

The reactivity depends on the following factors

Both thermal and photochemical reactions are used.

-allyl complexes of nickel can be prepared either by oxidative addition onNi(0) or by transmetallation of a Ni(II) salt.

Oxidative decomposition

Trapping experiments

In 1956, Longuet and Orgel propose the complex compound.In 1959, Criegee isolated the complex.

One of the best known of the -organometallic compounds is ferrocene.

The molecules behave as an electron-rich aromatic system, and electrophilicsubstitution reactions occur readily. Reagents that are relatively strong oxidizingagents, such as the halogens, effect oxidation at iron and destroy the compound.

Effective Atomic Number: 18

One of the most useful types of -complexes of aromatic compounds from thesynthetic point of view are chromium complexes obtained by heating benzeneor other aromatics with Cr(CO)6.

The Cr(CO)3 unit is strongly electron-withdrawing and activates the ring tonucleophilic attack.

oxidize

Existing substituent groups such as CH3, OCH3, and +NMe3 exert a directiveeffect, often resulting in a major amount of the meta substitution product.