Lithium perchlorate Lewis acids

LP-DE has a weaker catalytic activity than BF3-Et20, AICI3 and TiCU because the Lewis acidity of the lithium cation is moderated by complex-ing with diethyl ether and perchlorate anion [37], but it becomes a highly oxophilic Lewis acid when concentrated solutions are used [38]. The concentration of LP-DE is therefore sometimes essential for the success of the reaction. 

Keywords imines derived from formylphosphonate undergo Diels-Alder reactions only in those cases which carry a strongly electron-withdrawing N-substituent. Lewis acidity, solvent effect, lithium perchlorate in diethyl ether... 

Good results were also obtained with lithium perchlorate in dichloromethane and diethyl ether. It has been shown that the lithium cation acts as a Lewis acid and the effects are not due to an internal pressure [80]. The acceleration is much more pronounced for hetero Diels-Alder reactions as compared to the allcarbon cycloadditions. With chiral aldehydes a high level of chelation control has been observed (see later) [81,82]. 

Much more impressive rate accelerations for several Diels-Alder (and other) reactions have been observed by employing solutions of lithium perchlorate (up to 5 m) in diethyl ether (LPDE solutions) [802-806]. The dramatic rate accelerations found for Diels-Alder reactions in LPDE solutions appear to stem from Lewis acid catalysis by the coordinative unsaturated Li+ ion (see the end of Section 3.1). The Lewis acid catalysis by LPDE is applicable to those Diels-Alder reactions in which the lithium cation can coordinate with suitable functional groups in the reactants e.g. Li+---0=C). Addition of lithium-specific crown ethers e.g. [12]crown-4) leads to a loss of the catalytic activity of the Li+. For a recent extensive review of salt effects on Diels-Alder reactions, see reference [802]. 

Epoxides may undergo rearrangement in the presence of protic or Lewis acids to give carbonyl compounds. However, the nature of the products may depend quite subtly on the reaction conditions. For example, 1-methylcyclohexene oxide has been reported to give the ring-contracted aldehyde as the major product with lithium bromide, but with lithium perchlorate, 2-methylcyclohexanone is the major product (Scheme 2.22a). In the presence of a strong base such as lithium diethylamide, an allylic alcohol may be formed from an epoxide (Scheme 2.22b). 

Cycloadditions. Oppolzer first used this chiral acrylate derivative as an auxiliary in the Diels-Alder reaction with cyclopen-tadiene. Promotion by Lewis acids such as TiCU SnCU, and Et2AlCl provides the adduct in greater than 90% de (eq 1). Lithium perchlorate-promoted [4 + 2] reaction between 1 and 1-acetoxybutadiene was similarly effective." More recently, an exo-selective Diels-Alder addition of 1 with 2-acylamino dienes provided a single diastereomer in 80% yield. Cyclopentane formation is possible through exposure of 1 to methylenecyclo-propane and Ni(0) (eq 2). An example of a higher-order cycloaddition with 1 gave only low diastereoselection (78 22) for the endo product. 

Aminoalkyl and Related Acids. - Further development of the classical three component approach to aminoalkylphosphonates (the Kabachnik-Fields reaction) has been reported. The reaction of aldehydes, hydroxylamines and dimethyltrimethylsilyl phosphite using lithium perchlorate/diethyl ether as a catalyst gives N-trimethylsilyloxy-a-aminophosphonate derivatives. The catalytic activities of various lanthanide triflates as well as indium trichloride have been examined for the Kabachnik-Fields type reactions of aldehydes, amines and the phosphorus nucleophiles HP(0)(0Et)2 and P(OEt)3 in ionic liquids. TaCb-Si02 has been utilized as an efficient Lewis acid catalyst for the coupling of carbonyl compounds, aromatic amines and diethyl phosphite to produce a-... 

Far fewer quantitative measurements have been made of Lewis acid strength compared to that of Brpnsted acids.A simple table of Lewis acidities based on some quantitative measurement (e.g., that given for Brpnsted acids in Table 8.1) is not feasible because Lewis acidity depends on the nature of the base and any solvent that can function as a base. For example, lithium perchlorate functions as a weak Lewis acid in ether. " Qualitatively, the following approximate sequence... 

The reaction between acyl halides and alcohols or phenols is the best general method for the preparation of carboxylic esters. It is believed to proceed by a Sn2 mechanism.As with 16-57, the mechanism can be S l or tetrahedral. ° Pyridine catalyzes the reaction by the nucleophilic catalysis route (see 16-58). Lewis acids such as lithium perchlorate can be used. 

The mildness of the lithium perchlorate-diethyl ether medium may be illustrated by the outcome of the reaction of aldehyde (7) in 5.0 M LPDE with 2.3 equivalents of allyltrimethyltin at ambient temperature (Scheme 6.3.4). After 4 h, a 77% yield of the differentially protected triol (8) was obtained as a single diastereomer. The use of conventional Lewis acids (e.g. TiCU, SnCU) in methylene chloride to bring about the above transformation leads to an extensive decomposition even at -78 °C. 

Lewis acids have been widely used to catalyze Diels-Alder reactions when thermal conditions were not efficient [43]. A limitation of the Lewis acid catalyzed Diels-Alder cycloaddition reaction has often been found to be due to the sensitivity of the substrates to the strongly acidic media. For instance, when considering the addition of phenylacetylene derivatives to 1-silyloxypyrrole, it was found that the Lewis acids (AICI3, BF3, TiCU) led to decomposition of starting materials, while the thermal processes afforded only negligible amounts of the desired cycloadduct [44]. The successful preparation of the cycloadduct product was achieved with lithium perchlorate in ether. This approach did not produce a very acidic reaction medium, but considerably lowered the LUMO pyrrole energy, almost as much as protonation by itself (Table 14). The final effect was that the reaction became a strongly LUMO diene controlled Diels-Alder reaction. 

Allylstannanes undergo similar reaction with a-alkoxy aldehydes under Lewis acid catalysis. The treatment of 464 with allyl tri- -butylstannane in the presence of either MgBr2 Et20 [150] or lithium perchlorate-diethyl ether [153] furnishes protected syn-dio 468 with a dia-stereoselectivity of at least 25 1. This intermediate has been carried on to TBS-protected L-( — )-rhodinose (302) in an overall yield of 46% starting from (9-benzyl ethyl lactate 271b [150] (Scheme 69). 

The Baylis-Hillman reaction involves the reaction of an aldehyde with an a,fi-unsaturated ketone in the presence of a tertiary amine. This results in the aldehyde adding at the a-position of the carbon-carbon double bond. The reaction is conventionally carried out without a solvent however this causes problems if the starting materials are solids. Hence the reaction was investigated in ionic liquids such as [BMIM][BF4] and [BMIMjjPFe] [210]. The reaction of methyl acrylate with ben-zaldehyde proceeded 11 to 34 times faster in the ionic liquids than in the solvent acetonitrile. Various Lewis acidic additives had little effect on the reaction, with the exception of lithium perchlorate, which gave a 53 times rate enhancement. This reaction is shown in Scheme 5.2-85. 

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