Amines Diels-Alder cycloaddition

An alternative approach to thionitrosoarenes involves the reaction of amines with SCla. This method has also been adapted to the production of selenonitrosoarenes ArN=Se by using the selenium(If) synthon PhSOaSeCl as the Se source (Scheme 10.2). It is likely that SeCla, generated in situ in THF, could also be used in this process. The Diels-Alder cycloaddition of ArN=Se species with dimethylbutadiene gives 1,2-selenazine derivatives in low yields. 

Diels-Alder cycloaddition reactions of enaminothiones153 155 or enamino thioesters154,156,157 as nucleophilic dienes with electrophilic dienophiles R4CH = CHX lead to appropriate 4-amino-2,3-dihydro-2//-thiopyran intermediates 110, which easily eliminate amines R2R3NH to give the corresponding 2//-thiopyrans 111. 

Heterocyclic azadienes like di- and triazines have been used in the synthesis of pyridine rings. In general terms the reaction involves a regiospecific inverse electron demand Diels-Alder cycloaddition between the heterocycle and the enamine 280 followed by elimination of HCN (diazines) or N2 (triazines) and an amine from the primary cycloadduct 281 or 283, respectively, to give pyridines 282 and 284 (equation 61). At least in one case the latter type of intermediate has been isolated and fully characterized148. 

On the other hand, conjugated nitroalkenes are very useful electron-poor alkenes, prone to act as nucleophilic acceptor, mainly in the Michael reaction (Berestovitaskaya et al., 1994) or in the Diels-Alder cycloaddition (Denmark and Thorarensen, 1996). Moreover, the nitro group can be easily turned into a respectable array of functional groups such as its reduction to a primary amine, replacement with hydrogen (Ballini et al., 1983 Ono, 2001), conversion into a carbonyl (Nef reaction) (Ballini and Petrini, 2004), and transformation into other important functionalities such as nitrile, nitrile oxide, oximes, hydroxylamines, and thiols (Colvin et al., 1979). 

The preferred auxiliaries in chemistry at NSC Technologies are oxazolidinones. Oxazolidinones have found widespread use as chiral auxiliaries. A wide range of reactions is available and well documented [5], including aldol alkylations oc-substitution with a heteroatom such as halogenation, aminations, hydroxyla-tions, and sulphenylations Diels-Alder cycloadditions and conjugate additions. 

Heating the diethanolamine or bis(2-chloroethyl)amine hydrochlorides with aniline derivatives gave 1-arylpiperazine derivatives. The 1-substituted piperazines were deuteromethylated. 1,4-Dithiocarbonyl piperazine was obtained from reaction of benzaldehyde with piperazine and sulfur. l,4-Diacetylpiperazine-2,5-dione were reacted with aldehydes to give the monoarylidene products and then 73. 4-Benzylpiperazine-2,5-dione was reacted with bromobenzene to give 74. Diels-Alder cycloaddition of pyrazinone with ethene gave 75 . ... 

Chiral secondary amines such as nonracemic imidazolidin-4-ones have been found to be effective asymmetric organocatalysts in the Diels-Alder cyclization of cyclopentadiene and a,p-unsaturated aldehydes [60]. A tyrosine-derived imidazoli-din-4-one was immobilized on PEG to provide a soluble, polymer-supported catalyst 110. In the presence of 110, Diels-Alder cycloaddition of acrolein 112 to 1,3-cyclohexadiene 111 proceeded smoothly to afford the corresponding cycloadduct 113 with high endo selectivity and enantioselectivity up to 92% ee (Scheme 3.31) [61]. 

A chiral zw a-metallocene triflate complex catalyzes the Diels-Alder cycloaddition reaction between an oxazolidinone-based dienophile and cyclopentadiene [206]. Triflate in titanocene and zirconocene complexes is labile [207,208] and thus the polarity of solvent influences the reactivity and enantioselectivity. Asymmetric hydrogenation of imines and enamines catalyzed by chiral aw a-titanocene catalyst provides amines with high enantioselectivity [209,210]. 

Furans are also useful 4ji components for tandem Ugi condensation/intra-molecular Diels-Alder cascade reactions. For example, stirring a methanolic mixture of compounds 127-129 and benzylamine at rt provided the Ugi condensation product 130 that underwent a subsequent intramolecular Diels-Alder cycloaddition to furnish 131 in 70-90% yield (Scheme 23) (99TL1851). This methodology also allowed for a solid phase synthesis by using an ArgoGel-Rink resin as the amine component, providing cycloadducts 131 (after cleavage from the resin) in ca. 90-95% yields. 

The Y zeolites have been identified as active catalysts for various reactions such as isomerisation, amination, alkylation and deamination [1-4]. Cu containing Y zeolites have been found particularly useful to catalyse Diels - Alder cycloaddition [5-6]. Dehydration of t-BuOH has been suggested as a model reaction for estimating the zeolite acidity [7]. The dehydration of t-BuOH has received particular attention as tertiary species gives the most stable carbonium ion. The dehydration of alcohols by zeolites has been extensively studied... 

Other applications of Evans oxazolidinones include alkylation, Diels-Alder cycloaddition, Michael addition, and electrophilic halogenation, hydroxylation, and amination reactions [15]. In all cases, the conformational rigidity of the reaction TS allows the substituents at the stereocenters to direct efficiently the reaction course. 

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. 

In solution, benzyne and its derivatives are strained, short-lived intermediates which react with a broad array of nucleophiles, including carbanions, amines, alcohols and their salts, water, and even ethers. They also undergo pericyclic reactions such as Diels-Alder cycloadditions, 1,3-dipolar cycloadditions or ene reactions. The instability of benzyne and its derivatives is due to the strain caused by the deformation of the linear geometry of the formal sp-hybridized carbons of the triple bond to the angles close to 120° imposed by the ring geometry [2,3]. 

Sc(OTf)3-catalyzed three-component coupling reactions of aldehydes, amines, and dienes have also been developed. In the presence of 10 mol % Sc(OTf)3 and magnesium sulfate, the reaction of benzaldehyde with aniline and Danishefsky s diene produces the tetrahydropyridine derivative in 83% yield, while the reaction with cyclopentadiene instead of Danishefsky s diene produces the tetrahydroquinoline derivative. Various combinations of aldehydes, amines, and alkenes are possible in these reactions to produce diverse tetrahydroquinoline derivatives in high yield. Moreover, the three-component coupling reactions proceed smoothly in aqueous solution, and commercial formaldehyde-water solution can be used directly (eq 19). Sc(OTf)3-catalyzed three-component aza Diels-Alder cycloadditions also proceed smoothly in an ionic liquid. ... 

Simple open-chain 2-bromoheptadienes have frequently been used as substrates to generate 1,2-dimethylenecyclopentanes (Tables 2 and 3), which in turn have served as valuable starting materials in Diels-Alder cycloadditions. It has turned out to be even more favorable to carry out the intramolecular Heck reaction and subsequent Diels-Alder reaction as a domino-type sequence in a single operation (see Table 6). In the presence of secondary amines, aminoalkylcyclopentanes are produced (Sect. IV.3.2). 

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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