Dienophiles activated alkynes

A -Amino- and A-substituted amino-pyrroles readily undergo Diels-Alder additions and add to activated alkynes at room temperature. The resulting azanorbornadienes extrude A-aminonitrenes and this forms the basis of an unusual synthesis of benzene derivatives (81S753,81TL3347). It has been found that ethyl/3-phenylsulfonylpropiolate (135) is a superior dienophile to DMAD (Scheme 50). 

Dienophiles like phosphaalkyne 44a or activated alkynes and triphosphadewarbenzene 45 undergo a [2+2+2] homo-Diels-Alder reaction that leads to C3P4 cage 46. Cyclic dienophiles yield pentacycles (Scheme 13) <1997JOM(529)215, 1999S1363>. 

The reactivity of dienophiles may be increased by conjugation with additional electron-withdrawing groups. Doubly activated alkynes and 1,4-benzoquinones are particularly good participants in the Diels-Alder reaction." ... 

Enaminothiones, prepared from acetophenones by Vilsmeier methodology, give substituted 2//-thiopyrans on reaction with various dienophiles as a consequence of elimination of dimethylamine (94JPR434). 3-Thioacetyindoles behave in a similar manner and yield thiopyrano[4,3-l ]indoles (94H725). 3-Aryl-2-cyanothioacrylamides form 4-aryl-4W-thiopyrans on treatment with activated alkynes (94JCS(P1)989). 

The behavior of strained,/Zuorimiret/ methylenecyelopropanes depends upon the position and level of fluorination [34], l-(Difluoromethylene)cyclopropane is much like tetrafluoroethylene in its preference for [2+2] cycloaddition (equation 37), but Its 2,2-difluoro isomer favors [4+2] cycloadditions (equation 38). Perfluoromethylenecyclopropane is an exceptionally reactive dienophile but does not undergo [2+2] cycloadditions, possibly because of stenc reasons [34, 45] Cycloadditions involving most possible combinations of simple fluoroalkenes and alkenes or alkynes have been tried [85], but kinetic activation enthalpies (A/f j for only the dimerizations of tetrafluoroethylene (22 6-23 5 kcal/mol), chlorotri-fluoroethylene (23 6 kcal/mol), and perfluoropropene (31.6 kcal/mol) and the cycloaddition between chlorotnfluoroethylene and perfluoropropene (25.5 kcal/mol) have been determined accurately [97, 98] Some cycloadditions involving more functionalized alkenes are listed in Table 5 [99. 100, 101, 102, 103]... 

The cycloaddition-isomerization procedure can be accomplished in the presence of a catalytic amount of a transition metal salt. The reactions proceed at room temperature, neither air nor water needed to be excluded. The presence of an electron-withdrawing group is not necessary to activate the dienophile as the example below shows that gold coordination increases the electrophilicity of the triple bond. The presence of a terminal alkyne should also be important. In the case of a disubstituted alkyne no reaction can be observed <00JA11553>. 

Triazines are reactive electron-deficient dienes in Diels-Alder reactions with inverse electron demand. They react with alkenes, strained double bonds, electron-rich and electron-deficient alkynes and C=N double bonds. In most cases it is found that the dienophile addition occurs across the 3- and 6-positions of the triazine ring, but ynamines can also add across the 2- and 5-positions. The reactions are still under active theoretical and practical investigation. 

Different results were obtained when the vinylindole 54b, dissolved in the liquid dienophile (MP), was treated with a 20-fold (by weight) amount of activated silica gel 60 and the mixture was allowed to stand at room temperature for 3 days. In this case the reaction with the alkyne proceeded with regio- and stereoselectivity to give the Michael adduct 56 (90JOC5368). 

Isolated alkenes and alkynes, such as ethylene and acetylene, are notoriously poor dienophiles. This limitation has been laigely overcome by Ae development of dienophiles containing an activating moiety (e.g. NO2, S02Ar) which is readily removed after cycloaddition, with or without introduction of further functionality. These reactive dienophiles can, accordingly, be regarded as synthetic equivalents of unreactive or inaccessible species (Section 4.1.2). 

Dienophiles substituted with appropriate heteroatoms may offer a number of advantages such as (1) provide dienophilic equivalents of C-—C and moieties which do not undergo [4 + 2] cycloadditions to 1,3-dienes because of low (e.g. isolated alkenes, alkynes, allenes) or different reactivities (e.g. ketenes) (2) enhance or invert the regiochemistry of the Diels-Alder process (3) permit facile removal of the activating and/or regiocontrolling group after cycloaddition with or without introduction of further functionalities. The use of nitroalkenes as dienophiles demonstrates these issues most strikingly. 

The role of sulfur functionalities in activating alkenic and alkynic dienophiles, and directing their cycloadditions to 1,3-dienes, has been recently reviewed and only some essential points are outlined here. Depending on the oxidation state of sulfur, its vinyl derivatives range from strongly or weakly electron-deficient (sulfones or sulfoxides) to electron-rich (sulfides) dienophiles. 

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