Lewis acid catalyzed cycloadditions

There have been few mechanistic studies of Lewis acid-catalyzed cycloaddition reactions with carbonyl compounds. Danishefsky et ah, for example, concluded that the reaction of benzaldehyde 1 with trans-l-methoxy-3-(trimethylsilyloxy)-l,3-di-methyl-1,3-butadiene (Danishefsky s diene) 2 in the presence of BF3 as the catalyst proceeds via a stepwise mechanism, whereas a concerted reaction occurs when ZnCl2 or lanthanides are used as catalysts (Scheme 4.3) [7]. The evidence of a change in the diastereochemistry of the reaction is that trans-3 is the major cycloaddition product in the Bp3-catalyzed reaction, whereas cis-3 is the major product in, for example, the ZnCl2-catalyzed reaction - the latter resulting from exo addition (Scheme 4.3). 

One cannot discuss Lewis acid-catalyzed cycloaddition reactions in the present context without trying to understand the reaction course mechanistically, e.g. using a frontier molecular orbital (FMO) point of reasoning, or theoretical calculations of transition state structures. 

Lewis-acid-catalyzed cycloadditions of dienophiles, such as a,/l-unsaturated carbonyl compounds, with open-chain carbon-dienes, are generally highly ortho-para regioselective because the oxygen complexation increases the difference of LUMO coefficients of the alkene moiety. 

Synthesis of highly functionalized 3,4-dihydro-2H-pyrans by high-pressure Lewis-acid-catalyzed cycloaddition of enol ethers and a,/i-unsaturated aldehydes [83]... 

The reaction of nitrostyrene with cyclopentadiene gives the normal Diels-Alder adduct. However, the Lewis acid-catalyzed cycloaddition affords two isomeric nitronates, syn and anti in an 80-to-20 ratio. The major isomer is derived from an endo transition state. The preference of yy/i-fused cycloadducts can be understood by considering secondary orbital interactions (Eq. 8.95).152... 

Nitrone 1,3-DC reactions are still the most general approach to isoxazolidines. The stereocontrol is usually achieved by the use of chiral nitrones and/or dipolarophiles, but new interesting achievements on Lewis acid catalyzed cycloadditions are also frequently reported. Tris(6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanatedionate) europium(III) [Eu(fod)3] selectively activated the Z-isomer of C-alkoxycarbonyl nitrone 75 existing as an E,Z-equilibrium mixture by forming the (Z)-75-Eu(fod)3 complex. (Z)-75-Eu(fod)3 reacted with electron-rich dipolarophiles such as vinyl ethers to give the trans-adducts with excellent diastereoselectivity <06T12227>. 

The nature of the substituents on the allene can have an impact on the outcome of a [2 + 2] cycloaddition reaction, as was illustrated by the Lewis acid catalyzed cycloadditions of l-thioaryl-3,3-dimethylallene (24) and 1 -methyl- 1-trimethylsilylallene to various 2-alkoxy-p-benzoquinones 25 (e.g. equation 8)17. The reactions were considered to proceed via carbocation intermediates formed by nucleophilic attack of the thioallene on the Lewis acid activated quinone. At lower temperatures, these carbocations closed to cyclobutanes 26, whereas at higher temperatures, the thermodynamically more stable benzofurans 27 were formed. 

The chiral Lewis acid catalyzed cycloaddition of methacrolein 310 to cyclopentadiene predominantly affording exo cycloadduct 322 together with some 323 has been extensively investigated. The application of menthoxyaluminum dichloride (324) as the chiral catalyst in this reaction represents one of the earliest examples of a chiral Lewis acid catalyzed Diels-Alder reaction206 (equation 90). The authors confirmed their results in 1987, but the ee was revised from 72% to 57%207. 

Scheme 11.45 shows a proposal for the transition state involved in a related Lewis acid catalyzed cycloaddition where a disubstituted dipolarophile is used and endo/exo issues are examined. By coordination of the bulky titanium Lewis acid catalyst, the a-carbon of the acceptor becomes sterically more hindered, disfavoring exo-approach, which involves a serious steric interaction of the benzylidene phenyl moiety with the ligands on the titanium ion. Accordingly, the endo-cycloadduct is the only product observed. 

Two strategies for accomplishing asymmetric hetero-IMDA reactions have been reported (Figure 44). First, Tietze has shown that (157), that includes an ephedrine auxiliary as a component of the heterodiene unit, undergoes a highly diastereoselecdve Lewis acid catalyzed cycloaddition, providing cycloadduct... 

A similar approach to enantiomericaUy pure norbornene derivatives was developed by Nouguier et al. who employed l,3 2,4-di-0-methylene acetals of pentitols as chiral templates [62]. Hence, the 5-(5-acryloyl-D-arabinatol derivative 82 underwent highly stereoselective Lewis acid catalyzed cycloaddition with cyclopentadiene, giving 83 (Scheme 10.28). The stereochemical outcome of the reaction was explained in terms of the chelate complex 84, in which the chair-like dioxane ring and the acrylic moiety are fixed in two parallel planes, forcing the diene to approach the cisoid acrylate from the ii-face. The synthesis and utihty of various methylene protected glycosides have also been reported by this group [63-66]. 

Scheme 5. Lewis acid catalyzed cycloaddition in water...

The nature of the substituents on the lene can have an impact on the outcome of a [2 + 2] cycloaddition reaction, as was illustrated by the Lewis acid catalyzed cycloadditions of l-thioaryl-3,3-dimethylallene (24) and 1-methyl-1-trimethylsilylallene to various... 

The Lewis acid catalyzed cycloadditions of (Z)-dienophile 5 to cyclopentadiene (2) have been studied. Adduct 6 was obtained in 84% yield and with an endojexo ratio of 97 3 and d.r. [(5S, 67 ,6 S )/(5/ .65, 6 S)] 96 4 under ethylaluminum dichloridc catalysis193, and converted to homochiral polyfunctional norbornene and norbornane derivatives19a-b. 

A major advantage of the non-Lewis acid catalyzed cycloaddition is the possibility of carrying out the domino [4 + 2]/[3 + 2] cycloaddition in a one-pot fashion, since electron-poor alkenes react much faster with the nitronate formed in situ than electron-rich alkenes [14c, 20, 21[. This multicomponent reaction then provides the nitroso acetals in a single transformation, without the need to isolate the nitronate which was formed first, prior to the 1,3-dipolar cycloaddition. 

Opening of 2-iminooxetanes The easy availability of 2-iminooxetanes from Lewis acid-catalyzed cycloaddition of ketene imines and aldehydes makes it desirable to find some synthetic uses. 3-Iodocarboxamides, which are generated by reaction with HI, are sources of -lactams. Remarkably little hydroxy amides is formed. 

Moderate to high selectivities were obtained in Lewis acid-catalyzed cycloaddition reactions of the cyclic a,p-unsaturated compound A. However, high selectivities have been reported in catalyzed reactions of Meyers bicyclic lactam widi acyclic dienes. ... 

SYNTHESIS OF CLERODANE DITERPENES VIA LEWIS ACID CATALYZED CYCLOADDITIONS... 

The 1,3-DC of azomethine imines and alkenes provides a straightforward access to dihydropyrazoles. In 2005, Sibi and coworkers developed the first catalytic enan-tioselective [3 -l- 2] cycloadditions of hydrazonyl bromide or chloride 31 to olefins 30 [19]. The corresponding dihydropyrazoles 32 were obtained in highly enantioen-riched form with 82-98% yields (Scheme 2.10). A concerted reaction mechanism was proposed considering the fact that only anti diastereomers of the cycloaddition products were observed by NMR analysis. Besides, other alkenes such as vinyl ether [20] and methallyl alcohol ether [21 ] were also good partners in the chiral Lewis acid-catalyzed cycloadditions of azomethine imines. 

Scheme 2.11 Lewis acid-catalyzed cycloadditions of A -sulfonyl nitrones.

Lewis Acid-Catalyzed Cycloadditions of 2,6-Diazasemibullvalenes with Isocyanides, Azides, and Diazo Compounds Novel Reaction Patterns Leading to N-Heterocyclk Cage-Shaped Compounds... 

For the examples on Lewis acid catalyzed cycloaddition of nitrones with vinyl ethers, see (a) Seerden, J. G. Boeren, M M. M. Scheeren, H. W. Tetrahedron 1997, 53, 11843-11852... 

Chiral Lewis acid-catalyzed cycloaddition-dual activation... 

Chiral Lewis acid-catalyzed cycloadditions between NJf-cyclic azomethine imines and electron-deficient olefins by lowest unoccupied molecular orbital (LUMO) activation... 

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