Dienophiles intramolecular

In addition to intermolecular cycloaddition reactions of 1,2,4,5-tetrazines with various dienophiles, intramolecular cycloaddition reactions with alkene367 and acetylene 360 367 dienophiles or nitrile groups355-356 have also been reported. By this method condensed pyrid-azines 15 or 1,2,4-triazines 16 (see Section B.2.2.1.3.) are obtained. In most cases the side chain is bound to the 1,2,4,5-tetrazine ring by a heteroatom (O, S or In ). In a few cases the side chain is bound by a carbon atom or contains an additional heteroatom. The general reaction scheme is shown. 

All the diazines, providing they also have electron-withdrawing substituents, undergo Diels-Alder additions with dienophiles. Intramolecular reactions occur the most... 

All the diazines, providing they also have electron-withdrawing substituents, undergo Diels-Alder additions with dienophiles. Intramolecular reactions occur the most readily these do not even require the presence of activating substituents. The immediate products of such process usually lose nitrogen (pyridazine adducts) or hydrogen cyanide (adducts from pyrimidines and pyrazines) to generate benzene and pyridine products,respectively, as illustrated below. ... 

Cyclopolyenes as dienophiles Intramolecular diene synthesis Highly condensed polyisocyclics... 

Perfluorotetramethylthiadiphosphanorbornadiene and bis(trifluoromethyl) thiadiphosphole can be prepared by thermolysis of an adduct of methanol and hexakis(trifluoromethyl)-l,4-diphosphabarrelene with sulfur [113] (equation 23) Pyrolysis of the adduct of hexafluorinated Dewar benzene and phenyl azide results in ring expansion giving azepine, which photochemically yields an intramolecular 2-1-2 adduct, a good dienophile for the Diels-Alder reaction [114, //5] (equation 24) Thermolysis of fluonnated derivatives of 1,5-diazabicyclo-... 

The di-r-butylsilylene group has been used to connect a diene and a dienophile to control the intramolecular Diels-Alder reaction. ... 

The hetero Diels-Alder [4+2] cycloaddition (HDA reaction) is a very efficient methodology to perform pyrimidine-to-pyridine transformations. Normal (NHDA) and Inverse (IHDA) cycloaddition reactions, intramolecular as well as intermolecular, are reported, although the IHDA cycloadditions are more frequently observed. The NHDA reactions require an electron-rich heterocycle, which reacts with an electron-poor dienophile, while in the IHDA cycloadditions a n-electron-deficient heterocycle reacts with electron-rich dienophiles, such as 0,0- and 0,S-ketene acetals, S,S-ketene thioacetals, N,N-ketene acetals, enamines, enol ethers, ynamines, etc. 

Carbene complexes containing either the dienophile or the diene functionality bonded directly to the carbene carbon undergo intramolecular [4+2] cycloadditions under mild conditions [108] (Scheme 60). 

Carbene complexes which have an all-carbon tether between the diene and the dienophile react via intramolecular Diels-Alder reaction to give the corresponding bicyclic compound. The stereoselectivities of these reactions are comparable to those observed for the Lewis acid-catalysed reactions of the corresponding methyl esters and much higher than those of the thermal reactions of the methyl esters which are completely unselective. Moreover, the ris-sub-stituted complexes undergo endo-selective reactions where the corresponding reaction of the ester fails [109] (Scheme 61). 

Mathey et al. have described a quite unusual intramolecular [4+2] cycloaddition process. In this reaction the diene and the dienophile are part of two different ligands within the same complex. Thus, ris-(vinyl ethoxycarbene) (1-phenyl-3,4-dimethylphosphole)tetracarbonylchromium complex reacts at... 

Feringa-butenolide 114, in the presence of Dess-Martin periodinane reagent and 2,6-lutidine, gave the bis-ketone 115 which underwent intramolecular cycloaddition to afford endo-selectively the desired decalin-based lactone 116 (Equation 2.32) [114]. Double activation of butenolidic double bond strongly increases the reactivity of dienophile 115. 

The extensive study of Craig and coworkers [116] on the intramolecular Diels-Alder reactions of E- and Z-sulphonyl-substituted deca-, undeca- and dodecatrienes 120 (Figure 2.13) has opened a short route to trans- and cis-bridgehead hydrindanes and decalines and has given new insights into the role of dienophile substitution and geometry in determining the stereochemical outcome of these intramolecular cycloadditions. 

Tetraene 141 has been converted into various complex polycondensed adducts by reacting with a variety of dienophiles such as maleic anhydride, N-phenylmaleimide, N-phenyltriazolinedione,p-benzoquinone and tetracyano-ethylene carried out under thermal conditions. All cycloadditions occurred facial-diastereoselectively from an outside attack and provided monocycloadducts which had an exceptionally close relationship between diene and dieno-phile and then underwent intramolecular cycloaddition [125]. The reaction between 141 and p-benzoquinone is illustrated in Scheme 2.53. 

The chiral catalyst 142 achieves selectivities through a double effect of intramolecular hydrogen binding interaction and attractive tt-tt donor-acceptor interactions in the transition state by a hydroxy aromatic group [88]. The exceptional results of some Diels-Alder reactions of cyclopentadiene with substituted acroleins catalyzed by (R)-142 are reported in Table 4.21. High enantio- and exo selectivity were always obtained. The coordination of a proton to the 2-hydroxyphenyl group with an oxygen of the adjacent B-0 bond in the nonhelical transition state should play an important role both in the exo-endo approach and in the si-re face differentiation of dienophile. 

Among special chemical methods that facilitate the Diels-Alder reaction can be included the temporary metal connection strategy [101] that is illustrated in Table 4.27. Si, Mg and A1 are used as temporary connectors of diene and dienophile moieties. The cycloaddition occurs easily due to its intramolecular nature and because the dienophilic component of reagent is now formally a vinyl carbon ion (i.e. a vinyl carbanion in 154 with M = AlEt ). Thus the metal-tethered 154, prepared from lithium alkoxide of 153 with the suitable metal vinyl halide, gives, by heating, the cycloadducts 156 and 157, through the... 

Engberts [3e, 9] has extensively investigated the Diels Alder reaction in aqueous medium. Recently Engberts and colleagues reported [9c] a kinetic study of a Diels Alder reaction of N-alkyl maleimides with cyclopentadiene, 2,3-dimethyl-1,3-butadiene and 1,3-cyclohexadiene in different solvents. The reaction rates of the cycloadditions with the open-chain diene relative to w-hexane are reported in Table 6.3. The aqueous medium greatly accelerates the Diels Alder reaction and the acceleration increases as the hydrophobic character of the alkyl group of the dienophile increases. These and other kinetic data [3e, 9], along with the observation that the intramolecular Diels-Alder reaction is also accelerated in... 

The nitroso moiety of the N-acylnitroso function is a powerful dienophile and therefore N-acylnitroso compounds are trapped rapidly, especially in an intramolecular reaction, with a diene allowing the Diels Alder reaction to occur also in water, although N-acylnitroso compounds are short-lived in aqueous medium. 

Keywords carbonyl compounds, chiral dienophiles, chiral dienes, chiral catalysts, intramolecular cycloadditions, chiral Lewis acids... 

Nelson J. H. Transition Metal-Promoted Intramolecular [4 + 2 Diels-Alder Cycloadditions of Phospholes With Dienophilic Ligands in Phosphorus-31 NMR Spectral Prop. Compd. Charact. Struct. Anal. 1994 203, Ed. Quin L. and Verkade J. G., Pb. VCH N.Y. 

To avoid problems with the separation of regiomers, dimethyl acetylene dicarboxylate (DMAD) was chosen as a dienophile. The intermolecular Diels-Alder reactions were performed in refluxing dichlorobenzene (bp 132 °C), while the intramolecular reaction of alkyne tethered pyrazinone required a solvent with a higher boiling point (bromobenzene, bp 156 °C). In the case of 3-methoxy or 3-phenyl pyrazinones a mixture of pyridinones and pyridines was obtained, while for the alkyne tethered analogue only the di-hydrofuropyridinone was isolated as the single reaction product. 

Intramolecular versions of the Diels-Alder reaction are well known, and this is a powerful method for the synthesis of mono- and polycyclic compounds.There are many examples and variations. One interesting internal Diels-Alder reaction links the diene and dienophile by a C—O—SiR2—or a C—O—SiR2—O—C linkage. Internal cyclization to give a bicyclic product is followed by cleavage of the O-Si unit to give a monocyclic alcohol. 

When (62) was treated with ethyl vinyl ether the cycloadduct (63) is afforded. If (62) is reacted with electron donating dienophiles such as allyl alcohols, transesterification and intramolecular cycloaddition occurs in the presence of a catalytic amount of distannoxane catalyst to give cis-fused polycyclic systems such as (64) <96T733>. 

Schemes 10.1 and 10.4 of Part A, respectively, give the structure of a number of typical dienophiles and show representative D-A reactions involving relatively simple reactants. The D-A reaction is frequently used in synthesis and can either be utilized early in a process to construct basic ring structures or to bring together two subunits in a convergent synthesis. The intramolecular version, which will be discussed in section 6.1.7, can be used to construct two new rings.

Entry 9 uses the oxaborazolidine catalysts discussed on p. 505 with 2-bromopropenal as the dienophile. The aldehyde adopts the exo position in each case, which is consistent with the proposed TS model. Entry 10 illustrates the use of a cationic oxaborazolidine catalyst. The chirality is derived from trans-1,2-diaminocyclohcxanc. Entry 12 shows the use of a TADDOL catalyst in the construction of the steroid skeleton. Entry 13 is an intramolecular D-A reaction catalyzed by a Cu-Ws-oxazoline. Entries 14 and 15 show the use of the oxazaborolidinone catalyst with more complex dienes. 

The dihydropyrone ring then served as the dienophile in the intramolecular Diels-Alder (IMDA) cycloaddition that was conducted in a microwave oven. The cyclopentadiene... 

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