Lithium-perchlorate-accelerated Diels-Alder

Lithium perchlorate in diethyl ether has also been reported to accelerate Diels-Alder reactions significantly and this system has been applied to obtain Diels-Alder adducts that were inaccessible via conventional means [213-219]. A linear dependence of kobs on [Li+] is observed for the Diels-Alder reaction of DMA with acrylonitrile in LiC104-Et20 solution, while a second-order dependence of koba on [Li+] is involved for the reactions with fumaronitrile and dimethyl acetylenedi-carboxylate [216]. This suggests the possible contribution of Li -catalyzed electron transfer step in the Diels-Alder reaction as the case of Mg +-catalyzed Diels-Alder reaction in Scheme 12. However, such an electron transfer mechanism has not been confirmed in the Li -catalyzed Diels Alder reactions. 

Dramatic rate accelerations of [4 + 2]cycloadditions were observed in an inert, extremely polar solvent, namely in 5 M solutions of lithium perchlorate in diethyl ether (= 532 g LiC104 per litre ). Diels-Alder additions requiring several days, 10 — 20 kbar of pressure, and/ or elevated temperatures in apolar solvents are achieved in high yields in some hours at ambient pressure and temperature in this solvent (P.A. Grieco, 1990). Also several other reactions, e.g., allylic rearrangements and Michael additions, can be drastically accelerated by this magic solvent. The diastereoselectivities of the reactions in apolar solvents and in LiClOi/Et O are often different or even complementary and become thus steerable. 

The kinetics of high-pressure cycloaddition reactions of tropone with dienophiles and enophiles have been reviewed.254 The Diels-Alder reaction of 9,10-dimethylanthracene with acrylonitrile has been investigated at high pressure in acetonitrile and in ethereal solutions of lithium perchlorate.255 The combination of high pressure and a solution of lithium perchlorate in diethyl ether is an excellent reaction rate accelerator in 4 + 2-cycloaddition reactions.256... 

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]. 

In a series of papers Desimoni and Righetti [158-160] have now shown that the addition of salts such as lithium perchlorate and magnesium perchlorate not only accelerates the reaction, but also has a high influence on the ratio of ene and Diels-Alder products. Reaction of the benzylidene-1,3-diketone 2-156 with LiC104 at 25 °C for 3 days a 85 15 ratio of 2-157 and 2-158 in 70% yield and with Mg(C104)2 at 25 °C for 20 h a 7 93 ratio in 100% yield was obtained (Fig. 2-44). However, as expected the corresponding benzylidene-malonate gives the ene product exclusively under all conditions. 

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]. 

Grieco, P. A. Nunes, J. J. Gaul, M. D. Dramatic rate accelerations of Diels-Alder reactions in 5 M lithium perchlorate-diethyl ether The cantharidin problmi reexamined, J. Am. Chem. Soc. 1990,112,4595-4596. 

Lithium perchlorate displays explosive properties. The hazards of LPDE accelerated the search for alternative lithium compounds. Lithium trifluoromethane sulfonamide was used in some Diels-Alder reactions [23]. The limited access to this compound prompted the consideration of other lithium salts such as lithium tetrafluoroborate (LB) and lithium triflate (LS) [24]. They have seemingly similar catalytic activity to LPDE. Table 10.5 compares the catalytic merits of these lithium... 

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