Lewis-acidic substrates

Secondary or tertiary alkyl halides are much less reactive. For example an alkyl dichloride with a primary and a secondary chloride substituent reacts selectively by exchange of the primary chloride. The reactivity with respect to the Finkelstein reaction is thus opposite to the reactivity for the hydrolysis of alkyl chlorides. For the Finkelstein reaction on secondary and tertiary substrates Lewis acids may be used," e.g. ZnCla, FeCls or MesAl. 

The development of catalytic asymmetric reactions is one of the major areas of research in the field of organic chemistry. So far, a number of chiral catalysts have been reported, and some of them have exhibited a much higher catalytic efficiency than enzymes, which are natural catalysts.111 Most of the synthetic asymmetric catalysts, however, show limited activity in terms of either enantioselectivity or chemical yields. The major difference between synthetic asymmetric catalysts and enzymes is that the former activate only one side of the substrate in an intermolecular reaction, whereas the latter can not only activate both sides of the substrate but can also control the orientation of the substrate. If this kind of synergistic cooperation can be realized in synthetic asymmetric catalysis, the concept will open up a new field in asymmetric synthesis, and a wide range of applications may well ensure. In this review we would like to discuss two types of asymmetric two-center catalysis promoted by complexes showing Lewis acidity and Bronsted basicity and/or Lewis acidity and Lewis basicity.121... 

A broad range of compounds can be O-alkylated with carbene complexes, including primary, secondary, and tertiary alcohols, phenols, enols, hemiaminals, hydroxylamines, carboxylic acids, dialkyl phosphates, etc. When either strongly acidic substrates [1214] and/or sensitive carbene precursors are used (e.g. aliphatic diazoalkanes [1215] or diazoketones) etherification can occur spontaneously without the need for any catalyst, or upon catalysis by Lewis acids [1216]. 

Nitrogen dioxide in the presence of ozone has been used for aromatic nitrations." Such conditions are useful for the nitration of reactive and acid sensitive substrates. Lewis acids have been used in ozone-mediated nitrations with nitrogen dioxide." ... 

Alkyl nitrates in the presence of sulfuric acid" and Lewis acids/ like SnCU, AICI3, and BF3, have been used as nitrating agents. Nitrations in the presence of Nafion-H acidic resin have also been reported." Alkyl nitrates do not effect the nitration of aromatic substrates in the absence of an acid catalyst. 

Acids and Lewis acids react with quinoline at the basic nitrogen atom to form quinolinium salts, and there is a question over the nature of the substrate for electrophilic attack, i.e. is it quinoline or the quinolinium cation The answer is not a simple one and appears to depend upon the reagents and reaction conditions. Thus, whereas acetyl nitrate at 20 °C gives mainly 3-nitroquinoline (Scheme 3.2), fuming nitric acid in concentrated sulfuric acid containing sulfur trioxide at 15-20 °C yields a mixture of 5-nitroquinoline (35%) and 8-nitroquinoline (43%) (Scheme 3.3). In the case of acetyl nitrate, the reaction may proceed by the 1,4-addition of the reagent to quinoline, followed by electrophilic attack upon the 1,4-dihydro derivative. 

A new, metal-free protocol involving (heteroaryl)oxazoline catalysts for the enantioselective reduction of aromatic ketones (up to 94% ee) and ketimines (up to 87% ee) with trichlorosilane has been developed. The reaction is characterized by an unusual, long-ranging chiral induction.The enantiodifferentiation is presumed to be aided by aromatic interactions between the catalyst and the substrate.360 Asymmetric reduction of A-arylketimines with trichlorosilane is catalysed by A-methyl-L-amino acid-derived Lewis-basic organocatalysts with high enantioselectivity (up to 92% ee) 61... 

After the formation of a 1 1 substrate - Lewis acid adduct, the rearrangement proceeds in two steps, beginning with the cleavage of the ester bond and the release of formyl chloride in situ, which, in turn, acts as a formylating agent, introducing... 

Lewis acid Substrate 344 antksyn Yield (%) Substrate 345 antr.syn Yield (%)... 

Evidently, however, the use of strong acids or stable dual-acid anions is only one of the necessary requirements to initiate carbonium ion reactions in general and cationic polymerizations in particular. A specific substrate (Lewis base) which is able to accept the proton (or carbonium ion) and can be converted into a new conjugated Lewis acid is equally important. This newly formed electrophile in conjunction with the deprotonated dual-acid will be the reactive species. 

Substrate Lewis Acid Solvent Yield (%) Ratio of Isomer ... 

The first step of the reaction is a single-electron oxidation of the aromatic substrate to form a cation-radical [193,194]. Oxidizing agents for this reaction include Bronsted acids, oxidative Lewis acids, halogens (i.e., Br2), metal salts (e.g., Ti(CF3C02)3), electron-donor-acceptor complexes, irra-... 

In the bacterial PI-PLC structures, the top of the barrel rim has several hydrophobic residues that are fully exposed to solvent and poorly defined in the crystal structures (implying significant mobility). The active site of PI-PLC is accessible and well-hydrated, and these mobile elements at the top of the barrel offer a different motif for interactions of the protein with phospholipid interfaces. The PI-PLC from B. thuringiensis (nearly identical in sequence to the enzyme from B. cereus whose crystal structure was determined) exhibits the property of interfacial activation, where enhanced activity is observed when the substrate PI is present in an interface compared to monomeric substrate (Lewis et al., 1993). However, other non-substrate lipids such as phosphatidylcholine (PC), phosphatidic acid (PA), and other anionic lipids have an effect on the activity of PI-PLC toward both substrates PI and water-soluble cIP (Zhou et al., 1997). In particular, the presence of PC enhances the catalytic activity of... 

The reactivity of the cationic Zr complexes is a direct consequence of their Lewis acidity see Lewis Acids Bases) (i) various substitution reactions can occur into the Zr-solvent weak bond, (ii) unsatnrated substrates (CO, alkenes, alkynes, or ketones) insert into the Zr-C bond, potentially leading to polymerization reactions (see Section 8.2), (iii) new organic ligands obtained after reaction in the coordination sphere of the metal can be spontaneously released by /3-H elimination see -Hydride Elimination), or (iv) C-H bond activation of suitable ligands can occur. 

There is direct evidence, from ir and nmr spectra, that the fert-butyl cation is quantitatively formed when ferf-butyl chloride reacts with AICI3 in anhydrous liquid HCl. In the case of alkenes, Markovnikov s rule (p. 1019) is followed. Carbocation formation is particularly easy from some reagents, because of the stability of the cations. Triphenylmethyl chloride and 1-chloroadamantane alkylate activated aromatic rings (e.g., phenols, amines) with no catalyst or solvent. Ions as stable as this are less reactive than other carbocations and often attack only active substrates. The tropylium ion, for example, alkylates anisole, but not benzene. It was noted on p. 476 that relatively stable vinylic cations can be generated from certain vinylic compounds. These have been used to introduce vinylic groups into aryl substrates. Lewis acids, such as BF3 or AIEta, can also be used to alkylation of aromatic rings with alkene units. 

Eisch, J. J., Gitua, J. N., Otieno, P. O., Shi, X. Carbon-carbon bond formation via oxidative-addition processes of titanium(ll) reagents with 7i-bonded organic substrates. Reactivity modifications by Lewis acids and Lewis bases Part 22. Organic chemistry of subvalent transition metal complexes. J. Organomet. Chem. 2001, 624, 229-238. 

The catalytic, enantioselective, vinylogous Mannich reaction has recently emerged as a very powerful tool in organic synthesis for the assembly of highly functionalized and optically enriched 6 amino carbonyl compounds. Two distinctly different strategies have been developed. The first approach calls for the reaction of preformed silyl dienolates as latent metal dienolates that react in a chiral Lewis acid or Bronsted acid catalyzed Mukaiyama type reaction with imines. Alternatively, unmodified CH acidic substrates such as a,a dicyanoalkenes or 7 butenolides were used in vinylo gous Mannich reactions that upon deprotonation with a basic residue in the catalytic system generate chiral dienolates in situ. 

Some thermally forbidden [2 + 2]-cycloaddition reactions can be promoted by Lewis acids1-6. With chirally modified Lewis acids, the opportunity for application in asymmetric synthesis of chiral cyclobutanes arises (for a detailed description of these methods see Sections D.l. 6.1.3.. D.l. 61.4. and references 7, 28-30). Thus, a chiral titanium reagent, generated in situ from dichloro(diisopropoxy)titanium and a chiral diol 3, derived from tartaric acid, catalyzes the [2 + 2]-cycloaddition reaction of 2-oxazolidinone derivatives of a,/ -unsalurated acids 1 and the ketene thioacetal 2 in the presence of molecular sieves 4 A with up to 96 % yield and 98% ee. Fumaric acid substrates give higher yields and enantiomeric excesses than acrylic acid derivatives8. Michael additions are almost completely suppressed under these reaction... 

If the acid H -X is also furnished with a lone electron pair, the following two-step mechanism appears feasible in case of strongly Lewis-acidic substrates such as Cp3% ... 

Since Diels-Alder reactions are activated by pressure and by Lewis acids, the combination of both has been applied in transformations that were particularly difficult to achieve otherwise. There has been no conclusive evidence about how pressure affects the reactivity and selectivity in such reactions. One can assume that the formation of Lewis acid/substrate complexes are favored by pressure, although in most cases under normal pressure the equilibrium already lies strongly on the side of such complexes. Consequently, it appears reasonable to assume that the reacting species are the same, both under ambient and high pressure (cf. Chapter 11) [3]. 

Reductions. Ionic reduction by EtjSiH usually requires a protic acid or Lewis acid to help ionize the substrate. Thus reduction of vinylstannanes to alkylstannanes uses a EtsSiH-TMSOTf combination. A preparation of 4-hydroxy a-amino acid... 

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