Diels-Alder cycloaddition catalysis

Miscellaneous Reactions. Some hydantoin derivatives can serve as precursors of carbonium—immonium electrophiles (57). 5-Alkoxyhydantoins are useful precursors of dienophiles (17), which undergo Diels-Alder cycloadditions under thermal conditions or in the presence of acid catalysis (58). The pyridine ring of Streptonigrine has been constmcted on the basis of this reaction (59). 

Togni A., Pastor S. D. Cooperativity of Chirality in Homogeneous Catalysis The Gold(I)-Catalyzed Aldol Reaction and the Vanadium(IV)-Catalyzed Hetero-Diels-Alder Cycloaddition Chirality 1991 3 331-340... 

To date, hydrogen bond catalysis has been successfully utilized to facilitate enantioselective Michael additions, Baylis-Hillman reactions, Diels-Alder cycloadditions, and additions of 7i-nucleophiles to imines. 

Application to both Type I and Type II intramolecular Diels-Alder cycloaddition has also met with appreciable success, the most efficient catalyst for these reactions being imidazolidinone 21 (Scheme 7) [51, 52]. The power of the inttamolecular Diels-Alder reaction to produce complex carbocyclic ring structures from achiral precursors has frequently been exploited in synthesis to prepare a number of natural products via biomimetic routes. It is likely that the ability to accelerate these reactions using iminium ion catalysis will see significant application in the future. 

One of the most compelling features of iminium ion catalysis is the proposed mechanistic rationale for the transformations, which leads to highly predictable reaction outcomes. Despite impressive advances and the plethora of reactions reported efforts to provide a detailed mechanistic understanding of the catalytic cycle are limited. The reported work has focussed on the Diels-Alder cycloaddition and has provided useful indicators that could be used in design of more active catalysts. 

Unlike the impressive progress that has been reported with asymmetric catalysis in other additions to alkenes (i.e., the Diels-Alder cycloaddition, epoxidation, dihydroxylation, aminohydroxylation, and hydrogenation) so far this is terra incognita with nitrile oxide cycloadditions. It is easy to predict that this will become a major topic in the years to come. 

K. Mikami, Y. Motoyama, and M. Terada, Asymmetric catalysis of Diels-Alder cycloadditions by an MS-free binaphthol-titanium complex dramatic effect of MS, linear vs positive nonlinear relationship and synthetic applications, J. Am. Chem. Soc., 116 (1994) 2812-2820. 

Diels-Alder cycloaddition is one of the central reactions in organic synthesis and, despite its minor biological significance, has often been used in innovative approaches in catalysis research. In the context of the RNA world hypothesis, the formation of carbon-carbon bonds would be essential in anabolic pathways. 

Visnjevski A et al (2005) Catalysis of a Diels-Alder cycloaddition with differently fabricated molecularly imprinted polymers. Cat Commun 6 601-606... 

In addition to these intramolecular [2+2+2] cycloadditions, intramolecular [4+2] cycloaddition of yne-enones 29 leading to fused pyrans 30 has been achieved by means of the ruthenium catalysis with a cationic complex, CpRu(MeCN)3PF6 (Eq. 15) [24], Such hetero Diels-Alder cycloaddition was considered to proceed via an oxaruthenacycle 31. 

DIels-Alder catalyst. The furane 1 undergoes an intramolecular Diels-Alder cycloaddition to give 2 in 93% yield in florisil-CH2Cl2 at 20° in 6 days. In the absence of florisil, 2 is formed to the extent of 55% in the same time. The acidic nature of florisil may be involved in this catalysis in addition to the known effect of materials with high surface area. ... 

The more or less accidental discovery that fluorinated y9-diketonates of europium both effect the Lewis acid catalysis of Diels-Alder reactions [10] and interact with carbonyl functionalities of the substrates [102] emerged in a very prolific research. Despite the ready feasibility of homo-Diels-Alder reactions [103], hetero-Diels-Alder cycloadditions are preferentially mediated [104]. The endo select vities... 

Matsuoka, T., Harano, K., Uemura, T., Hisano, T. Hetero Diels-Alder reaction of N-acyl imines. I. The reaction of N -thiobenzoyl-N,N-dimethylformamidine with electron-deficient dienophiles. Stereochemical and mechanistic aspects. Chem. Pharm. Bull. 1993, 41, 50-54. Mikami, K., Motoyama, Y., Terada, M. Asymmetric Catalysis of Diels-Alder Cycloadditions by an MS-Free Binaphthol-Titanium Complex Dramatic Effect of MS, Linear vs Positive Nonlinear Relationship, and Synthetic Applications. J. Am. Chem. Soc. 1994, 116, 2812-2820. 

Michael condensations, together with the Diels-Alder cycloaddition and the aldol reactions, are the most powerful and useful bond-fonning reactions in synthetic organic chemistry. Like the nitro-aldol (Henry) additions, nitroalkanes are particularly appropriate reagents in Michael reactions they act as a-hydrogen donors. Nitroalkanes react easily with typical Michael acceptors such as a,p-unsaturated aldehydes or ketones under base or Lewis acid catalysis. ... 

Simple pyrroles do not react as 4n components in Diels-Alder cycloadditions exposure of pyrrole to benzyne, for example, leads only to 2-phenylpyrrole, in low yield. However A-substitution, particularly with an electron-withdrawing group, does allow such reactions to occur, for example adducts with arynes are obtained using l-trimethylsilylpyrrole. Whereas pyrrole itself reacts with dimethyl acetylenedicar-boxylate only by a-substimtion, even at 15 kbar, ° A-acetyl- and A-alkoxycarbonyl-pyrroles give cycload-ducts, addition being much accelerated by high pressure or by aluminium chloride catalysis. The most popular A-substituted pyrrole in this context has been A-Boc-pyrrole, with benzyne (from diazotization of anthranilic acid) for example, a 60% yield of the cycloadduct is obtained. ... 

Dibromo-l-methoxymethyl-l,2,3-triazole forms the 5-lithio compound with n-butyllithium at-80 °C and 4,5-dibromo-2-methoxymethyl-l,2,3-triazole undergoes a comparable exchange. l-Phenyl-1,2,3-triazoles participate in Diels-Alder cycloadditions with dimethyl acetylenedicarboxylate using aluminium chloride catalysis, producing l-phenylpyrazoles. " ... 

Diene (14) reacted with a series of aldehydes under BFj-OEt2 catalysis in CH2CI2 to give predominantly trans products (Table 10).31 32 Aldol-type products, such as p-hydroxy enones, are isolated (along with dihydropyrones) from the reaction mixtures. Using TFA as a catalyst, the p-hydroxy enones are, as previously described, converted into dihydropyrones. The stereoselectivity of these reactions is consistent with a Mukaiyama-aldol reaction rather than a Diels-Alder cycloaddition. The stereochemistry of the p hydroxy enones is also consistent with the observation that the (Z)-alkoxysilane reacts with the aldehyde in an extended transition state to give anti (threo) aldol products (Scheme 16). In the cases using ZnCh or lanthanide ions as catalysts aldol products have not been detected. 

Novel possibilities consisting in exploitation of coordination catalysis have been introduced. In addition, the traditional Diels-Alder cycloaddition reaction has been used in the last decade. 

Catalysis by LPDE was applied to some high-pressure reactions including Diels-Alder cycloadditions (entries 1-4), homo-Diels-Alder reactions (entry 5) and ene reactions (entry 6) (Table 10.4) [22]. 

Diels-Alder cycloaddition of the racemic butenolide reported in reaction C with an enantiomerically pure diene leads to the formation of a single cycloadduct and allows recovery of the unreacted (S)-enantiomer of the unsaturated lactone in 36% yield and > 98% e.e. High pressure and ZnCl2 catalysis were applied to ensure milder and more stereoselective reaction conditions [31]. 

During the last decade, use of oxazaborolidines and dioxaborolidines in enantioselective catalysis has gained importance. [1, 2] One of the earliest examples of oxazaborolidines as an enantioselective catalyst in the reduction of ketones/ketoxime ethers to secondary alco-hols/amines was reported by Itsuno et al. [3] in which (5 )-valinol was used as a chiral ligand. Since then, a number of other oxazaborolidines and dioxaborolidines have been investigated as enantioselective catalysts in a number of organic transformations viz a) reduction of ketones to alcohols, b) addition of dialkyl zinc to aldehydes, c) asymmetric allylation of aldehydes, d) Diels-Alder cycloaddition reactions, e) Mukaiyama Michael type of aldol condensations, f) cyclopropana-tion reaction of olefins. 

A method has been developed that combines the advantages of solid-supported catalyst extraction and solution-phase reactivity. By preparing a palladium complex bearing an anthracene tag, this can then be attached to a solid support via a chemoselective Diels-Alder cycloaddition to sequester the palladium catalyst along with any dissociated phosphine or phosphine oxide at the end of the reaction, leaving the desired catalysis product in the solution. The basis of the methodology is shown in Scheme 15. 

Cycloadditions Involving DMAP Catalysis. Bicyclic lactones containing a spirooxindole can be formed through a DMAP-catalyzed [4 + 2] Diels-Alder cycloaddition of pyrones and indole derivatives, resulting in both endo and exo products in approximately 2 1, 1 1, or 1 2 ratios in good yields. DMAP is proposed to abstract the proton on the pyrone, causing the initial cyclization to occur (eq 16). ... 

Even though the use of (S)-proline (1) for the synthesis of the Wieland-Miescher ketone, a transformation now known as the Hajos-Parrish-Eder-Sauer-Wiechert reaetion, was reported in the early 1970s, aminocatalysis - namely the catalysis promoted by the use of chiral second-aiy amines - was rediscovered only thirty years later. The renaissance of aminocatalysis was prompted by two independent reports by List et al. on the asymmetric intermolecular aldol addition catalysed by (S)-proline (1) and by MacMillan et al. on the asymmetric Diels-Alder cycloaddition catalj ed by a phenylalanine-derived imidazolidinone 2. These two reactions represented the archetypical examples of asymmetric carbonyl compound activation, via enamine (Figure ll.lA) and iminium-ion (Figure 11.IB), respectively. 

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