Reactions with activated dienes

As noted in. Section 2.1.1.6.2.2.2. the imine bond of fluoroulkyl imines can be involved in [4 + 2] cycloaddition reactions with active dienes and. depending on the N-substitution, tri-fluoromethyl imines can also react as dienes with various dienophiles. 

Substituted cyclopropenones such as the diphenyl derivative undergo cycloaddition reactions with activated dienes either by [4 + 2] or [4 + 3] modes. For example, N-1,3-butadienyl-N,N-diethylamine adds to diphenylcyclopropenone via the normal [4 + 2]... 

Midland has used the cyclocondensation reaction with activated dienes to synthesize pstelotin A (165 Scheme 45). The key step in the Midland synthesis is the ACF addition of diene (162) with aldehyde (161) to give (164), using Eu(hfc)3 as catalyst. Deprotection of the benzyl group gave the target molecule (165). 

Kloek and Leschinsky299 studied the reaction of sulphonylamines (291) generated from ethylsulphamoyl chloride and triethylamine at low temperatures. Reaction with activated dienes leads to the formation of the 2-ethyl-1,2-thiazin-5(6tf)-one-1,1--dioxides (292) which, however, could only be isolated after acidic work-up of the mixture. The results from the studies of a range of activated dienes supports the conclusion that the reaction occurs in a stepwise fashion (equation 92). 

The mechanism by which Lewis-acids can be expected to affect the rate of the Diels-Alder reaction in water is depicted in Scheme 2.6. The first step in the cycle comprises rapid and reversible coordination of the Lewis-acid to the dienophile, leading to a complex in which the dienophile is activated for reaction with the diene. After the irreversible Diels-Alder reaction, the product has to dissociate from the Lewis-acid in order to make the catalyst available for another cycle. The overall... 

Chiral boron(III) Lewis acid catalysts have also been used for enantioselective cycloaddition reactions of carbonyl compounds [17]. The chiral acyloxylborane catalysts 9a-9d, which are also efficient catalysts for asymmetric Diels-Alder reactions [17, 18], can also catalyze highly enantioselective cycloaddition reactions of aldehydes with activated dienes. The arylboron catalysts 9b-9c which are air- and moisture-stable have been shown by Yamamoto et al. to induce excellent chiral induction in the cycloaddition reaction between, e.g., benzaldehyde and Danishefsky s dienes such as 2b with up to 95% yield and 97% ee of the cycloaddition product CIS-3b (Scheme 4.9) [17]. 

Danishefsky et al. were probably the first to observe that lanthanide complexes can catalyze the cycloaddition reaction of aldehydes with activated dienes [24]. The reaction of benzaldehyde la with activated conjugated dienes such as 2d was found to be catalyzed by Eu(hfc)3 16 giving up to 58% ee (Scheme 4.16). The ee of the cycloaddition products for other substrates was in the range 20-40% with 1 mol% loading of 16. Catalyst 16 has also been used for diastereoselective cycloaddition reactions using chiral 0-menthoxy-activated dienes derived from (-)-menthol, giving up to 84% de [24b,c] it has also been used for the synthesis of optically pure saccharides. 

Chiral salen-cobalt(III) complexes can also catalyze the reaction of glyoxylates with activated dienes to give the cycloaddition product in moderate yield and ee [29]. 

The absolute configuration of the cycloaddition product obtained by the reaction of ketones with activated dienes catalyzed by (S)-t-Bu-BOX-Cu(II) (S)-21b points also to an intermediate in which the geometry around the central copper atom is square-planar similar to 26 above, and that the diene approaches the carbonyl functionality in an endo fashion. 

Glutathione readily replaces the GSMe on platinum in the reaction with [Pt(dien)(GSMe)]2+ (GSMe = S-methylglutathione) - this system is claimed to be an effective model for cisplatin-protein interaction 224). Rate constants and activation parameters have been... 

The influence of hydrogen pressure, substrate and catalyst concentration has briefly been mentioned. The reaction rate is dependent upon the catalyst concentration and hydrogen pressure, but appears to be independent of substrate concentration. The mechanism is proposed to involve the activation of the parent [Pd(allyl)] species producing an unstable hydrido-Pd(II) species (71), ensued by a fast reaction with the diene to restore the [Pd(allyl)] moiety (72) (Scheme 14.21). The observation that most of the starting material is isolated after the reaction suggests that only a small portion of the catalyst is active under the reaction conditions. Although a complete selectivity for the monoene is observed (even after full conversion), the presence of catalytically active colloidal palladium has not been completely excluded. 

The main stabilization in reactions with activated reaction partners, viz. when one partner is electron-rich and the other electron-poor, arises through interaction between the donor HOMO and the acceptor LUMO which are much closer in energy than the acceptor HOMO and the donor LUMO. Figure 2 illustrates which interactions between the frontier orbitals cause the main stabilization in normal, neutral and inverse Diels-Alder reactions. For example, the main stabilization in the reaction between an electron-rich diene and an electron-poor dienophile stems from the interaction of the diene HOMO with the dienophile LUMO. 

The cycloaddition of dienes to imines to form tetrahydropyridines (equation 46) has been investigated extensively40. Ordinary imines are not sufficiently reactive to add to dienes they have to be activated by the presence of electron-withdrawing substituents. Thus the triester 70 adds to cyclopentadiene under atmospheric pressure to form 71 (equation 47). The reactions with other dienes (cyclohexadiene, isoprene or 2,3-dimethylbuta-l,3-diene) require high pressures41. 

A DFT study of the polar Diels-Alder reaction of 4-aza-6-nitrobenzofuroxan with cyclopentadiene found only one highly asynchronous transition state structure associated with the formation of the 4 + 2-adduct.178 4-Nitrobenzodifuroxan has been shown to be a highly reactive nitroalkene in Diels-Alder reactions with common dienes (cyclopentadiene) to produce stable NED adducts and with ethyl vinyl ether to produce IED adducts.179 Unlike a-acylfuran, 2-nitrofurans have been shown to be active dienophiles in thermal NED Diels-Alder reactions with a variety of buta-1,3-dienes, including Danishefsky s diene.180... 

It was demonstrated some time ago that vinylic and cross-conjugated double bonds of protoporphyrin (IX) dimethyl ester (80a) constitute a diene system capable of undergoing Diels-Alder reactions with activated dieno-philes (68CC697). Isobacteriochlorins 81 and 82a were obtained in a reaction with dimethyl acetylenedicarboxylate (ACDE) and tetracyanoethene (TCNE), respectively (73JCS(PI)1424). 

Diels-Alder reaction of aldehydes with activated dienes. This lanthanide shift reagent can function as a Lewis acid catalyst in the cyclocondensation of l-methoxy-3-trimethylsilyloxy-1,3-diene (2) with aromatic aldehydes, and permits isolation of the initial... 

Bicyclic diazenes, in which the diazcnc group is not activated by acyl substituents, can act as dienophiles in the Diels-Alder reaction with cyclic dienes only in the presence of a stoichiometric amount of tetrafluoroboric acid to give. V,/V"-bicyclic hydrazines 111 . When two diastereomers can be produced, due to the nonsymmetric dienophile (i.e., when n 2), a single diastereomer is obtained ( H-NMR studies). 

The reaction of imines derived from ethyl glyoxylate with activated dienes afforded a 70% yield of the cycloadduct, but no asymmetric induction was observed (Scheme 10.24) [47]. 

Simonsen, K. B., Svenstrup, N., Roberson, M., Jorgensen, K. A. Development of an unusually highly enantioselective hetero-Diels - Alder reaction of benzaldehyde with activated dienes catalyzed by hyper-coordinating chiral aluminum complexes. Chem.- Eur. J. 2000, 6, 123-128. 

In contrast to nucleophilic addition reactions to activated dienes, the mechanism of 1,6-cuprate additions to acceptor-substituted enynes is quite well understood, the main tools being kinetic and NMR spectroscopic investigations. C-NMR spectroscopic studies have revealed that these transformations proceed via jr-complexes with an interaction between the jr-system of the C=C double bond and the nucleophiUc copper atom (a soft-soft interaction in terms of the HSAB principle), as well as a second interaction between the hard lithium ion of the cuprate and the hard carbonyl oxygen atom (Scheme 4) q of C-labeled substrates has confirmed that the cuprate does... 

Jurczak has reported an interesting approach to optically active 6-substituted-2-methoxy-5,6-dihydropyrans. The approach is based on a high-pressure catalysed hetero-Diels-Alder reaction of activated diene 49 with non-activated heterodienophile 52 (Scheme 7.13). These authors studied the eifects of catalyst... 

The modified organoaluminum reagent, BINAL, can be used as a chiral Lewis acid catalyst in the asymmetric hetero-Diels-Alder reaction [41]. Reaction of various aldehydes with activated dienes under the influence of catalytic BINAL (5-10 mol%) at -20 °C gave, after exposure of the resulting hetero-Diels-Alder adducts to tri-fluroacetic acid, predominantly c/v-dihydropyrone in high yield with excellent enan-tioselectivity. 

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