Reactions in the presence of Lewis acids

Phosgene can react with arenes, when in the presence of a Friedel-Crafts catalyst such as aluminium(III) chloride [1556,2026], to give predominantly benzoyl chlorides or benzophenones, depending on the reaction conditions [2196]  

This system has been cited frequently (e.g. [96]) as a method for the production of aromatic acids. Hence, benzoic acid is formed from the hydroiysis of benzoyl chloride, prepared from benzene and an excess of liquid phosgene in the presence of dissolved aluminium(III) chloride [1754]. Toluene or chlorobenzene react similarly to give 4-chloro- or 4-methyIbenzoic acids via the corresponding acid chlorides. 

The acid chlorides CgH COCl [915,1753] and 4-ClCgH COCl [915] were also produced from CgHg and CgH Cl, respectively, by using an excess of COCl in the presence of aluminium(III) chloride at low temperatures, and by using CSj as a solvent. In early work [888], benzene is reported to react with COClj in the presence of sunlight to give an unspecified amount of CgHgCOCl. 

Upon protracted contact with aluminium(III) chloride at higher temperatures, and especially if the aromatic hydrocarbon is itself used as the solvent, the product of the reaction between phosgene and aromatic hydrocarbons is usually the corresponding benzophenone [2026]. Friedel and Crafts [686aa] found that COCI, reacts with benzene in the presence of a stoicheiometric amount of aluminium(III) chloride to give benzophenone  

Some of the 2,3,3, 4 -isomer was found as a minor product. Similarly, the products formed from the reaction of phosgene with 1,3-dimethylbenzene in the presence of aluminium(III) chloride were  

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Diels-Alder reactions in the presence of Lewis acids represent a case in which the Lewis acid is often used in catalytic quantities. The complexed ester (ethyl acrylate in the example given below) is substantially more reactive than the uncomplexed molecule, and the reaction proceeds through the complex. The reactive complex is regenerated by exchange of the Lewis acid from the adduct. 

Doubly activated imines undergo intramolecular electrophilic cyclization reactions in the presence of Lewis acids and this provides an efficient route to annulated pyrrolidine, piperidine and azepine lactones (Sch. 32) [143]. TMSOTf and GaCls give different product ratios and yields. 

The effect of auxiliary structure on the level of absolute stereochemical control was extensively studied, suggesting that the phenyl groups in both 5-methyl-2-(l -methyl-1-phenyl)cyclohexanol and tra .s-2-phenylcyclohexanol are important elements for practical levels of control87. Studies were also conducted to uncover the nature of the influence of the phenyl group on the competing transition states88. In all cases, those systems that provided high levels of control in ene reactions in the presence of Lewis acids afforded essentially no control when used in reactions under thermal conditions. 

The 2-oxopropanoate of 5-methyl-2-(l-methyl-l-phenylcthyl)cyclohcxanol undergoes mainly self-aldol reactions rather than ene reactions in the presence of Lewis acids and alkenes (the original report was incorrect92). Nonetheless, ene reactions between the 2-oxopropanoate of franj-2-phenylcydohexanol and both 1-hexene and 3-trimethylsilylpropene (see Table 4, entries 11,12) proceed with good yield and good to excellent absolute stereochemical control93. 

Guindon demonstrated that this reaction is not technically a fragmentation reaction either. Instead the reaction occurs by an atom transfer process. The atom transfer product undergoes an ionic elimination to form the final allylated product, 117. Similarly, Porter has used allyltrimethylsilane to carry out enantioselective allyla-tion reactions in the presence of Lewis acids and chiral ligands, L [69]. 

Similar redistribution reactions in the presence of Lewis acids take place at room temperature 32-34). This is of technical significance (Me4Pb + Et4Pb). The classical papers by Calingaert et al. 32-34) and some recent results are reviewed by Moedritzer 185). Besides radical reactions, polar reactions of the Pb—C bond can often be observed, i.e., cleavage with acids, halogens, and alkali metals 79, 110, 149, 161, 242). 

Seijas et al. [115] suggested microwave-assisted synthesis of Bemthsen reaction in the presence of Lewis acid catalyst ZnCl2 with shortened reaction time and increased yield (Scheme 11.57). The yield was 57-98% within 2.5-11 min. R was taken as alkyl or aiyl group. 

Substrate Selective Reactions in the Presence of Lewis Acids... 

Ene Reactions. In the presence of Lewis acids, isobutene adds to various enophiles to yield ene adducts. Enophiles such as alkoxyaldehyde (eq 13), dialkyl aminoaldehyde (eq 14), haloaldehyde (eq 15), and vinyl sulfoxides (eq 16) have been utilized. Chiral organoaluminum (eq 17) and organotitanium reagents (eq 18) have been reported to give high levels of asymmetric induction in the ene reaction of isobutene with activated aldehydes. 

As anticipated from the complexation experiments, reaction of 4.42 with cyclopentadiene in the presence of copper(II)nitrate or ytterbium triflate was extremely slow and comparable to the rate of the reaction in the absence of Lewis-acid catalyst. Apparently, Lewis-acid catalysis of Diels-Alder reactions of p-amino ketone dienophiles is not practicable. 

Epoxides and aziridines are also capable of electrophilic subsitution of indoles. Indolylmagncsium bromide and cyclohexene oxide react to give 3-(lrans-2-hydroxycyclohexyl)indole[14]. Reaction of indoles with epoxides also occurs in the presence of Lewis acids. For example, indole reacts with methyl 2S,3R-epoxybutanoate at C3 with inversion of configuration[15]. 

The generation of caibocations from these sources is well documented (see Section 5.4). The reaction of aromatics with alkenes in the presence of Lewis acid catalysts is the basis for the industrial production of many alkylated aromatic compounds. Styrene, for example, is prepared by dehydrogenation of ethylbenzene made from benzene and ethylene. 

A simple approach for the formation of 2-substituted 3,4-dihydro-2H-pyrans, which are useful precursors for natural products such as optically active carbohydrates, is the catalytic enantioselective cycloaddition reaction of a,/ -unsaturated carbonyl compounds with electron-rich alkenes. This is an inverse electron-demand cycloaddition reaction which is controlled by a dominant interaction between the LUMO of the 1-oxa-1,3-butadiene and the HOMO of the alkene (Scheme 4.2, right). This is usually a concerted non-synchronous reaction with retention of the configuration of the die-nophile and results in normally high regioselectivity, which in the presence of Lewis acids is improved and, furthermore, also increases the reaction rate. 

The Lewis acid-catalyzed 1,3-dipolar cycloaddition reaction of nitrones to a,/ -un-saturated carbonyl compound in the presence of Lewis acids has been investigated by Tanaka et al. [31]. Ab-initio calculations were performed in a model reaction of the simple nitrone 18 reacting with acrolein 1 to give the two cycloadducts 19 and 20 (Scheme 8.7). 

Nitro compounds have been converted into various cyclic compounds via cycloaddidon reactions. In particular, nitroalkenes have proved to be nsefid in Diels-Alder reactions. Under thermal conditions, they behave as electron-deficient alkenes ind react v/ith dienes to yield 3-nitrocy-clohexenes. Nitroalkenes c in also act as heterodienes ind react v/ith olefins in the presence of Lewis acids to yield cyclic alkyl nkronates, which undergo [3- 2 cycloaddidon. Nitro compounds are precursors for nitnie oxides, alkyl nitronates, and trialkylsilyl nitronates, which undergo [3- 2 cycloaddldon reacdons. Thus, nitro compounds play important roles in the chemistry of cycloaddidon reacdons. In this chapter, recent developments of cycloaddinon chemistry of nitro compotmds and their derivadves are summarized. 

The mechanism of chemical modification reactions of PS were determined using toluene as a model compound with EC in the presence of BF3-0(C2H5)2 catalyst and the kinetics and mechanism of the alkylation reaction were also determined under similar conditions [53-55]. The alkylation reaction of toluene, with epichlorohydrin, underwent polymerization of EC in the presence of Lewis acid catalysis at a low temperature (273 K) as depicted in Scheme (9). 

Several chlorophyll derivatives have been prepared by electrophilic substitution, inter alia by formylation reactions. Adopting methods from corrin chemistry.50 alkylation with chloro-methyl methyl ether (caution toxic),32k chloromethyl methyl sulfide,51 and dichloromethyl methyl ether (caution toxic)52 in the presence of Lewis acids are the methods of choice to introduce carbon residues into the chlorin frame work. The compounds listed below have been prepared by these methods. 

On the other hand, in the presence of Lewis acids such as titanium(lV) chloride or eerium(TIT) chloride, the (S)-e s-conformer predominates via chelation of the two carbonyl groups and a reversed stereochemistry of the addition reaction is observed1 °. 

Allylsilanes react with carbonyl compounds to transfer the allyl group with 1,3-transposition, in the presence of Lewis acids, typically titanium(IV) chloride47. Recently this reaction has been carried out under super-acid catalysis48. Transfer of the allyl group is also induced by tetrabutylammonium fluoride, but in this case reaction takes place regioselectively at the less substituted end of the allyl fragment49. 

Allyl(trimethyl)silanes react efficiently with Lewis acids to give the corresponding tertiary alcohols67. Although only modest diastereofacial selectivity was observed for reaction with menthyl esters67, improved selectivity was found for chiral a-oxo imides68 and a-oxo amides derived from proline69. 

The primary aim of most studies on Lewis acid controlled copolymerization has been the elucidation of mechanism and only low conversion polymerizations are reported. Sherrington et al.m studied the high conversion synthesis of alternating MMA-S copolymers in the presence of Lewis acids on a preparative scale. Many Lewis acids were found lo give poor control (i.e. deviation from 50 50 composition) and were further complicated by side reactions including cross-linking. They found that the use of catalytic BCI- as the Lewis acid and photoinitiation gave best results. 

Photolysis of chromium alkoxycarbene complexes with aldehydes in the presence of Lewis acids produced /J-lactones [83]. Intermolecular reactions were slow, low-yielding, and nonstereoselective, while intramolecular reactions were more efficient (Eqs. 19 and 20). Subsequent studies showed that amines, particularly DMAP, could also catalyze this process (Table 13) [84], resulting in reasonable yields and diastereoselectivity in intermolecular cases. 

Step-growth polymerization processes must be carefully designed in order to avoid reaction conditions that promote deleterious side reactions that may result in the loss of monomer functionality or the volatilization of monomers. For example, initial transesterification between DMT and EG is conducted in the presence of Lewis acid catalysts at temperatures (200°C) that do not result in the premature volatilization of EG (neat EG boiling point 197°C). In addition, polyurethane formation requires the absence of protic impurities such as water to avoid the premature formation of carbamic acids followed by decarboxylation and formation of the reactive amine.50 Thus, reaction conditions must be carefully chosen to avoid undesirable consumption of the functional groups, and 1 1 stoichiometry must be maintained throughout the polymerization process. 

Fully acetylated hexopyranoses react with thiols in the presence of Lewis acids, such as BF3-Et20.32,33 The reaction is faster with 1,2-trans acetates than with the corresponding 1,2-cij ones and 1,2-trans products predominate. Alkyl, alkenyl, and aryl thioglycosides are produced by this method. Variations on this method include the use of trimethylsilyl34 or stannyl derivatives35 of the thiols. 

Microwave-assisted Diels-Alder reactions have been performed in solvents [38, 39], in free solvent conditions [38c, 40], in solid phase [39, 41] and in the presence of Lewis acids [38c]. Sometimes some of these reaction conditions were combined. 

Allylic silanes react with aldehydes, in the presence of Lewis acids, to give an allyl-substituted alcohol. In the case of benzylic silanes, this addition reaction has been induced with Mg(C104)2 under photochemical conditions. The addition of chiral additives leads to the alcohol with good asymmetric induction. In a related reaction, allylic silanes react with acyl halides to produce the corresponding carbonyl derivative. The reaction of phenyl chloroformate, trimethylallylsilane, and AICI3, for example, gave phenyl but-3-enoate. ... 

Danshefsky s diene [19] is the 1,3-butadiene with amethoxy group at the 1-position and a trimethylsiloxy group at the 3-position (Scheme 18). This diene and Lewis acids extended the scope of hetereo-Diels-Alder reactions with aldehydes [20], This diene reacts with virtually any aldehyde in the presence of Lewis acids whereas dienes usually react with only selected aldehydes bearing strongly electron accepting a-substituents. There are two (Diels-Alder and Mukaiyama aldol) reaction pathways (Scheme 18) identified for the Lewis acids catalyzed reactions of Danishefsky diene with aldehydes [21, 22]. The two pathways suggest that these reactions occur on the boundary between the delocahzation band (the pericyclic... 

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