Acid catalysis ether formation

It is in the very nature of the catalytic process that the intermediate compound formed between catalyst and reactant is of extreme lability therefore not many cases are on record where the isolation by chemical means, or identification by physical methods, of intermediate compounds has been achieved concomitant with the evidence that these compounds are true intermediaries and not products of side reactions or artifacts. The formation of ethyl sulfuric acid in ether formation, catalyzed by HjSO , and of alkyl phosphates in olefin polymerization, catalyzed by liquid phosphoric acid, are examples of established intermediate compound formation in homogeneous catalysis. With regard to heterogeneous catalysis, where catalyst and reactant are not in the same... 

Claisen rearrangement of allyl phenolic ethers, followed by oxidation of the alkene generates ortbo-hydroxyarylacetaldehydes which close to give benzofurans under acid catalysis. The formation of 2-substituted benzofurans from 2- ortho-hydroxyaryl)-ketones is also very easy. 

Reactions of the Side Chain. Benzyl chloride is hydrolyzed slowly by boiling water and more rapidly at elevated temperature and pressure in the presence of alkaHes (11). Reaction with aqueous sodium cyanide, preferably in the presence of a quaternary ammonium chloride, produces phenylacetonitrile [140-29-4] in high yield (12). The presence of a lower molecular-weight alcohol gives faster rates and higher yields. In the presence of suitable catalysts benzyl chloride reacts with carbon monoxide to produce phenylacetic acid [103-82-2] (13—15). With different catalyst systems in the presence of calcium hydroxide, double carbonylation to phenylpymvic acid [156-06-9] occurs (16). Benzyl esters are formed by heating benzyl chloride with the sodium salts of acids benzyl ethers by reaction with sodium alkoxides. The ease of ether formation is improved by the use of phase-transfer catalysts (17) (see Catalysis, phase-thansfer). 

The mechanism for the formation of diethyl ether from ethanol under conditions of acid catalysis was shown in Figure 15.3. 

Recently, Akiyama et al. reported an enantiocontrolled [3+2] cycloaddition of chirally modified Fischer alkenylcarbene complexes 180 with aldimines 181 under Lewis-acid catalysis (Sn(OTf)2) to afford enantiomerically pure 1,2,5-trisubstituted 3-alkoxypyrrolines 182 (Scheme 40) [121]. The mode of formation of these products 182 was proposed to be a [4+2] cycloaddition, with the complexes 180 acting as a 1-metalla- 1,3-diene with subsequent reductive elimination. Upon hydrolysis under acidic conditions, the enol ethers give the enantiomerically pure 3-pyrrolidinones 183 (Table 9). 

Halide ions will also act as nucleophiles towards aldehydes under acid catalysis, but the resultant, for example, 1,1-hydroxychloro compound (35) is highly unstable, the equilibrium lying over in favour of starting material. With HC1 in solution in an alcohol, ROH, the equilibrium is more favourable, and 1,1-alkoxychloro compounds may be prepared, e.g. 1-chloro-l-methoxymethane (36, a-chloromethyl ether ) from CH20 and MeOH (cf. acetal formation, p. 209), provided the reaction mixture is neutralised before isolation is attempted ... 

The advantage of the LiC104/ether system is its equal or greater polarity compared to that of water. Therefore it promotes solvolysis of 12. Furthermore the Lewis acidity of the lithium cation activates the ketone.19 As expected, the addition occurred from the sterically less hindered a-face of the molecule. Previously these transformations could be carried out only thermally or under high pressure with the aid of Lewis acid catalysis, e. g. TiCl4 or Ti(OiPr)4. Grieco also points out that it is very important to keep the exact concentrations of before diluted substrate and added LiC104 in ether. In disrespect the rate of the formation of the 1,2 addition product is enhanced over that of the 1,4 adduct. 

The best alternatives to enamines for conjugate addition of aldehyde, ketone, and acid derivative enols are silyl enol ethers, Their formation and some uses were discussed in Chapters 21 and 26-28, but these stable neutral nueleophiles also react very well with Michael acceptors either spontaneously or with Lewis acid catalysis at low temperature,... 

In the first step the alcohol moiety of 32 is protected as tert-butyldi-methylsilyl ether (TBS). The TBSOTf / 2,6-lutidine system is one of the most powerful methods for the formation of TBS ethers. This silyl protecting group is quite stable to a variety of organic reaction conditions and is cleaved under strong acidic or strong basic conditions, under Lewis acid catalysis and in the presence of a fluorine source (e.g. TBAF). In the second step the methyl ester is hydrolyzed using standard saponification conditions to give 33. 

The stereoselective synthesis of (+)-trichodiene was accomplished by K.E. Harding and co-workers. The synthesis of this natural product posed a challenge, since it contains two adjacent quaternary stereocenters. For this reason, they chose a stereospecific electrocyclic reaction, the Nazarov cyclization, as the key ring-forming step to control the stereochemistry. The cyclization precursor was prepared by the Friedel-Crafts acylation of 1,4-dimethyl-1-cyclohexene with the appropriate acid chloride using SnCU as the catalyst. The Nazarov cyclization was not efficient under protic acid catalysis (e.g., TFA), but in the presence of excess boron trifluoride etherate high yield of the cyclized products was obtained. It is important to note that the mildness of the reaction conditions accounts for the fact that both of the products had an intact stereocenter at C2. Under harsher conditions, the formation of the C2-C3 enone was also observed. 

The homologation of ketones by the addition of diazoalkanes complements the Tiffeneau-Demjanov rearrangement. Epoxide formation is a side reaction which can be minimized if polar aprotic solvents are avoided (Scheme 7). Rearrangement i.e. homologation) is maximized in ether solvents or by Lewis acid catalysis. The reaction is most effective in the ring expansion of cyclic ketones. 

Problem 3.7. Dihydropyran (DHP) reacts with alcohols under acid catalysis to give tetrahydropyranyl (THP) ethers. The alcohols can be released again by treating the THP ether with MeOH and catalytic acid. Thus, the THP group acts as a protecting group for alcohols. Draw mechanisms for the formation and cleavage of the THP ether. 

An interesting rearrangement, which appears to be anion-accelerated, takes place in the enol thioether, anion-terminated vinylcyclopropanes of type 14. ° The rearrangement proceeds at — 78 C and is reasonably stereoselective with regard to the final cyclopentene products (syn selectivity 16 1). Regioisomers are encountered in the formation of the dihydrothiopyran cycloaddition adducts 13 in several instances. The mechanism of this rearrangement appears to involve the enol thioether anion in accord with the well-documented donor acceptor principles " and may be related to similar rearrangements observed with trimethylsilyl enol ether terminated vinylcyclopropanes under fluoride ion or Lewis acid catalysis." " ... 

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