Presentation on theme: "Chapter 8. Reactions Involving the Transition Metals"— Presentation transcript:
1 Chapter 8. Reactions Involving the Transition Metals IntroductionMain group metals are used in stoichiometric reaction, but many of transition metal are used in catalytic process.Transition metals frequently involve oxidation state changes at the metal8.1 Organocopper IntermediatesPreparatioon and structure of Organocopper reagents.
2 1,2-addition reactioncatalytic amount1,4-addition reactionThe 2:1 species are known as cuprates and are the most important as syntheticreagents.
3 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).
5 An important type of mixed cuprates is prepared from a 2:1 ratio of an alkyllithium and CuCN: higher-order cyanocuprates.Same reactivity, but more stable than dialkyl cuprate.R2CuCNLi2 in THFCN 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
6 8.1.2. Reactions Involving Orgnocopper Reagents and Intermediates Metal-metal exchange reactionReactions Involving Orgnocopper Reagents and IntermediatesOrganocopper reagents: nucleophilic displacements on halides and sulfonates.Epoxide ring opening, conjugate additions to a,b-unsaturated carbonylcompounds, and additions to alkynes.
14 The addition of halides to transition-metal species with low oxidation states is 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.
15 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.
16 Halogens a to carbonyl groups can be successfully coupled with organocopper Reagents.Introduced at less hindered carbon of the epoxide ring.
17 The addition is accelerated by trimethylsilyl choride or a combination of trimethylsilyl 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.
18 The lithium ion also plays a key role, presumably by Lewis acid coordination at 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 a,b-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.
21 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 CuO3SCF3as catalyst in the presence of phosphines or phosphites.
27 Conjugate addition to a,b-unsaturated esters can often be effected by copper catalyzed reaction with Grignard reagent. Other reactions, such as epoxidering opening, can also be carried out under catalytic conditions. (Scheme 8.5)
30 Conjugate acetylenic esters react readily with cuprate reagents, with syn 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
34 Organocopper intermediates are also involved in several procedures for coupling 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.
36 Arylcopper intermediates can be generated from organolithium compounds as in the preparation of cuprates. These compounds react with a secondaryl halide to provide unsymmetrical biaryls.
37 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 hydrogenunder reductive conditionsIn the absence of a reducing reagent,an elimination of Pd(0) and a proton occurs.
38 A second type of organopalladium intermediates are p-allyl complexes A second type of organopalladium intermediates are p-allyl complexes. Thesecomplexes can be obtained from Pd(II) salts and allyl acetates and othercompounds with potential leaving groups in an allylic poistion.The p-allyl complexes can be isolated as halide-bridged dimers.
39 The third general process involves the reaction of Pd(0) species with halides or sulfonates by oxidative addition, generating reactive intermediates having theorganic group attatched to Pd(II) by s-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 presenceof 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 alkylpalladium species in which there is a b hydrogen.
40 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.EnolThe co-reagents CuCl2 and O2 serve to reoxidize the Pd(0) to Pd(II). Thenet reaction consumes only alkene and oxygen.
44 The Heck ReactionHeck Reaction: Aryl and alkenyl halides react with alkenes in the presence ofcatalytic amounts of palladium to give net substitution of the halide bythe alkenyl group.The reaction is quite general and has been observed for simple alkenes, arylsustituted alkenes, and electrophilic alkenes such as acrylic esters andN-vinylamides. The reactions are usually carried out in the presence of aphosphine ligand.
45 The reaction is initiated by oxidative addition of the halide to a palladium(0) species genreated in situ from the Pd(II) catalyst.The s-complex decomposes with regeneration ofPd(0) by b-elimination.
46 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 complexationwith electron-rich alkene.
47 Aryl chlorides are not very reactive under normal Heck reaction conditions, but reaction 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 a arylation by useof bidentate phosphine ligands such as dppe and dppp, using aryl triflates asreactants. Electronic factors favor migration of the aryl group to the a carbon.
50 8.2.3 Palladium-Catalyzed Cross Coupling Allylic silanes show a pronounced tendency to react at the a carbon. Thisregiochemistry is attributed to the stabilization of cationic character at theb carbon by the silyl substituent.8.2.3 Palladium-Catalyzed Cross CouplingCoupling with organometallic Reagents: cross-coupling reactionOrganomagnesium, organozinc, mixed cuprate, stanne, ororganoboron compoundsThe 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 b elimination
54 A promising development is the extension of Pd-catalyzed cross coupling to simple 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 inphenylation of the enolates of aromatic ketones and diethyl malonate.Arylation has also been observed with the diphosphine ligand, BINAP.
55 A combination of Pd(PPh3)4 and Cu(I) effects coupling of terminal alkynes with vinyl 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
56 22.214.171.124. Coupling with Stannes: Stille Coupling Use of alkenyl halides in this reaction has proven to be an effective methodfor the synthesis of enynes. The reaction can be carried out directly with thealkyne, using amines for deprotonation.Coupling with Stannes: Stille CouplingThe approximate order of effectiveness of transfer of groups from tin isalkynyl>alkenyl>aryl>methyl>alkyl, so unsaturated groups are normally transferredselectively.
57 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 formylgroups
63 Masked form of formyl group Alkenyl triflates are also reactive
64 126.96.36.199. Coupling with Organoboranes: Suzuki couling Cross coupling in which the organometallic component is an aryl or vinylboron compound: boronic acids, boronate esters, boranes.Transmetallation or oxidative addition can be the rate determining step
71 In some synthetic applications, specific bases such as Cs2CO3 or TlOH have been found preferable to NaOH.The reaction proceed with retention of double-bond configuration in both theboron derivative and the alkenyl halide.