Lewis additive

Appreciating the beneficial influences of water and Lewis acids on the Diels-Alder reaction and understanding their origin, one may ask what would be the result of a combination of these two effects. If they would be additive, huge accelerations can be envisaged. But may one really expect this How does water influence the Lewis-acid catalysed reaction, and what is the influence of the Lewis acid on the enforced hydrophobic interaction and the hydrogen bonding effect These are the questions that are addressed in this chapter. 

A similar approach is followed in a recent study of the Lewis-acid catalysis of a Michael addition in acetonitrile. See Fukuzumi, S. Okamoto, T. Yasui, K Suenobu, T. Itoh, S. Otera, J. Chem. Lett. 1997, 667. 

On the basis of the studies described in the preceding chapters, we anticipated that chelation is a requirement for efficient Lewis-acid catalysis. This notion was confirmed by an investigation of the coordination behaviour of dienophiles 4.11 and 4.12 (Scheme 4.4). In contrast to 4.10, these compounds failed to reveal a significant shift in the UV absorption band maxima in the presence of concentrations up to one molar of copper(ir)nitrate in water. Also the rate of the reaction of these dienophiles with cyclopentadiene was not significantly increased upon addition of copper(II)nitrate or y tterbium(III)triflate. 

This goal might well be achieved by introducing an auxiliary that aids the coordination to the catalyst. After completion of the Diels-Alder reaction and removal of the auxiliary the desired adduct is obtained. This approach is summarised in Scheme 4.6. Some examples in which a temporary additional coordination site has been introduced to aid a catalytic reaction have been reported in the literature and are described in Section 4.2.1. Section 4.2.2 relates an attempt to use (2-pyridyl)hydrazone as coordinating auxiliary for the Lewis-acid catalysed Diels-Alder reaction. 

In a second attempt to extend the scope of Lewis-acid catalysis of Diels-Alder reactions in water, we have used the Mannich reaction to convert a ketone-activated monodentate dienophile into a potentially chelating p-amino ketone. The Mannich reaction seemed ideally suited for the purpose of introducing a second coordination site on a temporary basis. This reaction adds a strongly Lewis-basic amino functionality on a position p to the ketone. Moreover, the Mannich reaction is usually a reversible process, which should allow removal of the auxiliary after the reaction. Furthermore, the reaction is compatible with the use of an aqueous medium. Some Mannich reactions have even been reported to benefit from the use of water ". Finally, Lewis-acid catalysis of Mannich-type reactions in mixtures of organic solvents and water has been reported ". Hence, if both addition of the auxiliary and the subsequent Diels-Alder reaction benefit from Lewis-acid catalysis, the possibility arises of merging these steps into a one-pot procedure. 

Unfortunately, addition of copper(II)nitrate to a solution of 4.42 in water did not result in the formation of a significant amount of complex, judging from the unchanged UV-vis absorption spectrum. Also after addition of Yb(OTf)3 or Eu(N03)3 no indications for coordination were observed. Apparently, formation of a six-membered chelate ring containing an amine and a ketone functionality is not feasible for these metal ions. Note that 4.13 features a similar arrangement and in aqueous solutions, likewise, does not coordinate significantly to all the Lewis acids that have been... 

First of all, given the well recognised promoting effects of Lewis-acids and of aqueous solvents on Diels-Alder reactions, we wanted to know if these two effects could be combined. If this would be possible, dramatic improvements of rate and endo-exo selectivity were envisaged Studies on the Diels-Alder reaction of a dienophile, specifically designed for this purpose are described in Chapter 2. It is demonstrated that Lewis-acid catalysis in an aqueous medium is indeed feasible and, as anticipated, can result in impressive enhancements of both rate and endo-exo selectivity. However, the influences of the Lewis-acid catalyst and the aqueous medium are not fully additive. It seems as if water diminishes the catalytic potential of Lewis acids just as coordination of a Lewis acid diminishes the beneficial effects of water. Still, overall, the rate of the catalysed reaction... 

A regioselective aldol condensation described by Biichi succeeds for sterical reasons (G. Biichi, 1968). If one treats the diaidehyde given below with acid, both possible enols are probably formed in a reversible reaaion. Only compound A, however, is found as a product, since in B the interaction between the enol and ester groups which are in the same plane hinders the cyclization. BOchi used acid catalysis instead of the usual base catalysis. This is often advisable, when sterical hindrance may be important. It works, because the addition of a proton or a Lewis acid to a carbonyl oxygen acidifies the neighbouring CH-bonds. 

Phenyl-1,4-hcxadicnc (122) is obtained as a major product by the codimerization of butadiene and styrene in the presence of a Lewis acid[110]. Pd(0)-catalyzed addition reaction of butadiene and aiiene (1 2) proceeds at 120 C to give a 3 1 mixture of trans- and c -2-methyl-3-methylene-l,5.7-octatriene (123)[lll]. 

Another category Ic indole synthesis involves cyclization of a-anilino aldehydes or ketones under the influence of protonic or Lewis acids. This corresponds to retro.synthetic path d in Scheme 4.1. Considerable work on such reactions was done in the early 1960s by Julia and co-workers. The most successful examples involved alkylation of anilines with y-haloacetoacetic esters or amides. For example, heating IV-substituted anilines with ethyl 4-bromoacetoacetate followed by cyclization w ith ZnClj gave indole-3-acetate esterfi]. Additional examples are given in Table 4.3. 

Boron trichloride, usually in conjunction with an additional Lewis acid, effects o-chloroacetylation of anilines. The resulting products are converted to indoles by reduction with NaBH4.[l], The strength of the Lewis acid required depends upon the substitution pattern on the ring. With ER substituents no additional... 

If the Lewis base ( Y ) had acted as a nucleophile and bonded to carbon the prod uct would have been a nonaromatic cyclohexadiene derivative Addition and substitution products arise by alternative reaction paths of a cyclohexadienyl cation Substitution occurs preferentially because there is a substantial driving force favoring rearomatization Figure 12 1 is a potential energy diagram describing the general mechanism of electrophilic aromatic substitution For electrophilic aromatic substitution reactions to... 

Alkyl halides by themselves are insufficiently electrophilic to react with benzene Aluminum chloride serves as a Lewis acid catalyst to enhance the electrophihcity of the alkylating agent With tertiary and secondary alkyl halides the addition of aluminum chlonde leads to the formation of carbocations which then attack the aromatic ring... 

Electrophile (Section 4 8) A species (ion or compound) that can act as a Lewis acid or electron pair acceptor an elec tron seeker Carbocations are one type of electrophile Electrophilic addition (Section 6 4) Mechanism of addition in which the species that first attacks the multiple bond is an electrophile ( electron seeker )... 

The selective addition of the second HCN to provide ADN requires the concurrent isomerisation of 3PN to 4-pentenenitrile [592-51 -8] 4PN (eq. 5), and HCN addition to 4PN (eq. 6). A Lewis acid promoter is added to control selectivity and increase rate in these latter steps. Temperatures in the second addition are significandy lower and practical rates may be achieved above 20°C at atmospheric pressure. A key to the success of this homogeneous catalytic process is the abiUty to recover the nickel catalyst from product mixture by extraction with a hydrocarbon solvent. 2-Methylglutaronitrile [4553-62-2] MGN, ethylsuccinonitfile [17611-82-4] ESN, and 2-pentenenitrile [25899-50-7] 2PN, are by-products of this process and are separated from adiponitrile by distillation. 

Uses. Fluorosulfuric acid serves as catalyst in the alkylation (qv) of branched-chain paraffins (53—58) and aromatic compounds (59), and in the polymeriza tion of monoolefins (60) and rosin (61). Addition of strong Lewis acids, such as SbF, TaF, and NbF, to fluorosulfuric acid markedly increases... 

The HCFC-225 isomers designed to replace CFC-113 are manufactured by Lewis acid promoted addition of HCFC-21 to tetrafluoroethylene... 

Evidence supporting the formation of 1 1 addition compounds is substantiated by the actual isolation of stable acyl haUde—Lewis acid complexes. 

In addition, boron, aluminum, and gallium tris(triduoromethanesulfonates) (tridates), M(OTf)2 and related perduoroalkanesulfonates were found effective for Friedel-Crafts alkylations under mild conditions (200). These Lewis acids behave as pseudo haUdes. Boron tris(tridate) shows the highest catalytic activity among these catalysts. A systematic study of these catalysts in the alkylation of aromatics such as benzene and toluene has been reported (201). 

Ultimately, as the stabilization reactions continue, the metallic salts or soaps are depleted and the by-product metal chlorides result. These metal chlorides are potential Lewis acid catalysts and can greatiy accelerate the undesired dehydrochlorination of PVC. Both zinc chloride and cadmium chloride are particularly strong Lewis acids compared to the weakly acidic organotin chlorides and lead chlorides. This significant complication is effectively dealt with in commercial practice by the co-addition of alkaline-earth soaps or salts, such as calcium stearate or barium stearate, ie, by the use of mixed metal stabilizers. 

Displacement of activated chlorine atoms also proceeds with certain types of organic compounds, but only in the presence of Lewis acid catalysts. Particular examples include epoxides, polyhydric alcohols, trialkylphosphites (12), and P-aminocrotonates (13). These additives are commonly used in conjunction with metallic stabilizers to provide complete, high performance, commercial stabilizer packages. 

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