Diels-Alder reaction activated dienes

Maleimides have three principal reaction pathways. These are radical addition to vinyl compounds the Michael addition with compounds having active hydrogens and the Diels-Alder reaction with dienes (Fig. 3). Any of the three can be tools for forming thermosetting adhesives. 

The study of the cycloaddition behavior of l,l-dichloro-2-neopentylsilene, C Si =CHCH2Bu (2) [3], reveals the high polarity of the Si=C bond and a strong electrophilicity. The [4+2] cycloaddition reactions with anthracene (3), cyclopentadiene (4) and fulvenes (5) proceed as expected surprising, however, the Diels-Alder reactions with dienes are of lower activity, like naphthalene (6) and furans (7). 

As a part of a broad study dealing with the development of synthetic methods for polycyclic aromatic compounds, Minuti and colleagues77 prepared some [5]phenacenes and fluorenoanthracenes via Diels-Alder reactions between dienes such as 59 and several activated dienophiles. Oxidation of the primary adducts with DDQ afforded the desired polycyclic aromatic compounds. Equation 21 shows the reaction between 3,4-dihydro-1-vinylanthracene (59) and in situ generated 2-inden-l-one (60) which afforded a 3 1 mixture of regioisomers 61 and 62 with 51% overall yield. 

Diels-Alder reactions between dienes and highly reactive dienophiles such as alkyl vinyl ketones can be carried out using the corresponding acetals in order to prevent polymerization of the dienophile. Activation of the masked dienophiles to undergo ionic [4 + 2] cycloadditions with dienes can be by EGA using the conditions in Scheme 18 [44]. Yields in the range 20 to 85% were obtained depending on the... 

The use of isopropylidine acetals (112) as tethers in the intramolecular Diels-Alder reactions of dienes with alkenes facilitates the formation of civ-fused cycloadducts (113) from an endo transition state (Scheme 41).218 The intramolecular Diels-Alder reaction of 4-[tris-(2-mcthylcthyl)silyl]oxy-2//-thiopyran derivatives with potential dienophiles tethered at C(2), C(3), C(5), and C(6) positions yielded cycloadducts when the dienophiles were activated with a carbomethoxy group.219 By the substitution of a phenylsulfonyl group on the dienophile of 2-benzopyran-3-ones, it is possible to enhance exo addition during intramolecular Diels-Alder cyclizations to yield a predominance of trans-fused hexaphenanthrenes related to natural products.220 The intramolecular Diels-Alder reaction of 2-furfuryl fumarates has been investigated by molecular mechanics (SIBFA)/continuum reaction field computations.221 The intramolecular 4 + 2-photo-cycloaddition of A-benzylcinnamamides (114) in the presence of C(,H6 gives 3-azatricyclo[5.2.2.01,5]undeca-8,10-dien-4-ones (115) with high stereoselectivity (Scheme 42).222... 

Saigo and co-workers reasoned that, by analogy, high levels of diastereofacial discrimination could be achieved in the Lewis acid-mediated Diels-Alder reaction of dienes with oxazolidinone 108-derived dienophiles. Indeed, excellent regioselectivities (endo. exo) and diastereoselectivities were reached in the Diels-Alder reaction of 109 with cyclic and acyclic dienes using Et2AlCl as the activator (Scheme 24.28).107 The selectivities obtained actually surpassed those reported with cis-1 -amino-2-indanol 1 as the chiral auxiliary (93% de) (see Scheme 24.16).82 The additional bulk... 

In order to test the iminium-activation strategy, MacMillan first examined the capacity of various amines to enantioselectively catalyze the Diels-Alder reaction between dienes and a,/ -unsaturated aldehyde dienophiles [6]. Preliminary experimental findings and computational studies proved the importance of four objectives in the design of a broadly useful iminium-activation catalyst (1) the chiral amine should undergo efficient and reversible iminium ion formation (2) high... 

The strong Lewis acids HC(py)3M (NO)2 (M = Mo, W) (see also Section 14.3.1), with Lewis acidities comparable with that of BF3, were shown by Faller et al. to coordinate and activate a,/8-unsaturated carbonyl compounds via formation of an M-O a-bond. These complexes, in nitromethane, catalyze Diels-Alder reactions with dienes (e.g. butadiene). They also readily polymerize butadiene when a less basic dienophile com-... 

Diels-Alder reactions. Activated carbonyl compounds condense with dienes to furnish dihydropyrans at room temperature when catalyzed by BiCl,. Conventional Diels-Alder reactions catalyzed by BiClj or Bi(OTf), have also been scrutinized. ... 

Langlois and coworkers [331, 339, 1008] proposed a,P-unsaturated oxa-zolines 9.70 bearing the bomane skeleton as dienophiles for asymmetric Diels-Alder reactions. Activation with trifluoroacetic anhydride generates N-acyi-imminium salts in situ. Their cycloadditions with a number of dienes take place with a high selectivity between -78°C and -15°C (Figure 9.37). However, the reaction with 2,3-dimethylbutadiene is not sdective. The removal of the chiral auxiliary is accomplished by sequential treatment of the products with aC00CH2Ph and dilute NaOH. 

Nitrile, azo, and nitroso groups, and even the oxygen molecule, take part in such reactions, and acetylenic triple bonds in particular confer reactivity as philodiene. As for dienes, so for philodienes the reactivity depends on the constitution. Activating groups particularly favor addition. The most reactive components include <%,/ -unsaturated carbonyl compounds such as acrolein, acrylic acid, maleic acid and its anhydride, acetylenedicarboxylic acid, p-benzo-quinone and cinnamaldehyde, as well as saturated nitriles and <%,/ -unsaturated nitro compounds. Tetracyanoethylene also reacts with dienes.41,42 Conjugation of the double bond to an active group is not absolutely essential for a philodiene, for dienes add under certain conditions also to philodienes with isolated double bonds examples of the latter type are vinyl esters and vinyl-acetic acid. Ketenes do not undergo the Diels-Alder reaction with dienes, but instead yield cyclobutanone derivatives 43,44... 

An alternative synthesis of pumiliotoxin C makes use of a related, but intramolecular Diels-Alder reaction. The diene 39, prepared in optically active form from (5)-norvaline, cyclized to the octahydroquinoline 40 with high selectivity (3.40). In this chemistry, the chiral centre in 39 controls the formation of the three new developing centres in 40. 

In 2004 the same research group showed that TADDOLs 2 were able to catalyse other reactions via hydrogen-bonding activation, for example the Diels-Alder reaction between diene 1 and substituted acroleins 5 (Scheme 24.3), for this reaction 1-naphthyl-TADDOL 2a was the best catalyst. 

Table 4 Influence of additives on the rate constants and activation parameters of the aqueous Diels-Alder reaction of diene 2 with methylvinylketone at 25 °C.

In both cases, the mechanism of the reactions can be described like an ene-yne metathesis catalyzed by the Ru-NHC complex [82], followed by a Diels-Alder reaction. The mechanism of these reactions (exemplified for the synthesis of 81) is depicted in Scheme 5.59. Initial [2+2] cycloaddition between the alkyne and the olefin stemming from the metallic carbene achieves metallacyclobutene 158. Subsequently, cycloelimination and [2+2] cycloaddition with the alkene reagent give 159. A second cycloelimination generates a diene (by-product) and the active catalytic species 160, which initiates the catalytic cycle following successive cycloadditions and cycloeliminations up to afford diene 82. Finally, a Diels-Alder reaction between diene 82 and a,p-nnsatnrated carbonyls (dienophile) produces exclusively the syn-(endo-)ptod ict 81. 

In 2003, Rawal reported the use of TADDOLs 177 as chiral H-bonding catalysts to facilitate highly enantioselec-tive hetero-Diels-Alder reactions between dienes 181 and different aldehydes 86 (Scheme 6.29A) [82], and also BINOL-based catalysts 178 were found to facilitate this reaction with excellent selectivities [83]. TADDOLs were also successfully used as organocatalysts for other asymmetric transformations like Mukaiyama aldol reactions, nitroso aldol reactions, or Strecker reactions to mention a few examples only [84]. In addition, also BINOL derivatives have been employed as efficient chiral H-bonding activators as exemplified in the Morita-Baylis-Hilhnan reaction of enone 184 with different carbaldehydes 86 [85]. The use of chiral squaramides for asymmetric reactions dates back to 2005 when Xie et al. first used camphor-derived squaric amino alcohols as ligands in borane reductions [86]. The first truly organocatalytic application was described by Rawal et al. in 2008 who found that minute amounts of the bifunctional cinchona alkaloid-based squaramide 180 are... 

The Diels-Alder Reaction consists in the direct combination of a compound containing a conjugated diene system u ith a reagent which possesses a double or triple bond activated bj suitable adjacent groups. Examples of such reagents are maleic anhydride, p-benzoquinone, acraldehyde and acetylene dicarboxylic esters. Combination always occurs at the 1,4 positions of the diene system ... 

Compounds containing a double or triple bond, usually activated by additional unsaturation (carbonyl, cyano, nitro, phenyl, etc.) In the ap position, add to the I 4-positions of a conjugated (buta-1 3-diene) system with the formation of a ax-membered ring. The ethylenic or acetylenic compound is known as the dieTwphile and the second reactant as the diene the product is the adduct. The addition is generally termed the Diels-Alder reaction or the diene synthesis. The product in the case of an ethylenic dienophile is a cyctohexene and in that of an acetylenic dienophile is a cyctohexa-1 4-diene. The active unsaturated portion of the dienophile, or that of the diene, or those in both, may be involved in rings the adduct is then polycyclic. 

Figure 1.2. Endo and exo pathway for the Diels-Alder reaction of cyclopentadiene with methyl vinyl ketone. As was first noticed by Berson, the polarity of the endo activated complex exceeds that of the exo counterpart due to alignment of the dipole moments of the diene and the dienophile K The symmetry-allowed secondary orbital interaction that is only possible in the endo activated complex is usually invoked as an explanation for the preference for endo adduct exhibited by most Diels-Alder reactions.

In 1961 Berson et al. were the first to study systematically the effect of the solvent on the endo-exo selectivity of the Diels-Alder reaction . They interpreted the solvent dependence of the endo-exo ratio by consideririg the different polarities of the individual activated complexes involved. The endo activated complex is of higher polarity than the exo activated complex, because in the former the dipole moments of diene and dienophile are aligned, whereas in the latter they are pointing in... 

Furthermore, the number of diene - dienoplrile combinations that can be expected to undergo a Lewis-acid catalysed Diels-Alder reaction is limited. Studies by Wijnen leave little doubt that the rate of typical Diels-Alder reactions, where the dienophile is activated by one or more carbonyl functionalities, does not respond to the presence of Lewis acids in aqueous solution , at least not beyond the extent that is expected for non-specific interactions (salt effects). No coordination of the Lewis acid to the dienophile was observed in these cases, which is perhaps not surprising. Water is... 

---