Dienophiles synthesis

Gheneim R, Perez-Beramen C, Gandini A. Diels-Alder reactions with novel polymeric dienes and dienophiles synthesis of reversibly cross-linked elastomers. Macromolecules 2002 35 7246-7253. 

Chiral Aldehydes as Dienophiles Synthesis of Long-Chain Sugars... 

Chernov SV, Shults EE et al (2000) Synthetic transfoimatilevopimaric acid. Russ J Org Chem 36 1623-1633... 

Visnick M, Battiste MA (1985) Multistage cycloadducts firom the condensation of N, N -dipyrrolylmethane with acetylenic dienophiles synthesis of the 10,12-diazapentacyclo [7.3.1.04,1205,1306,10]trideca-2,7-diene ring system. J Chem Soc Chem Comm 1621-1622... 

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. 

The mechanism of the diene synthesis appears to involve an electron transfer from the diene to the dienophile, .e., it is initiated by an ionic reaction. The following scheme may represent the addition of 2 3-dimethylbutadiene to maleic anhydride ... 

In the Diels-Alder reaction (in older literature referred to as the diene synthesis ) a six-membered ring is fonned through fusion of a four-tt component, usually a diene and a two-7C component, which is commonly referred to as the dienophile (Scheme 1.1). 

Scheme 2.5. Synthesis of the ionic dienophiles 2.4f and 2.4g. features of the nncatalysed reaction will be discussed The kinetics of the Diels-Alder reaction of 2,4...

Within the cubane synthesis the initially produced cyclobutadiene moiety (see p. 329) is only stable as an iron(O) complex (M. Avram, 1964 G.F. Emerson, 1965 M.P. Cava, 1967). When this complex is destroyed by oxidation with cerium(lV) in the presence of a dienophilic quinone derivative, the cycloaddition takes place immediately. Irradiation leads to a further cyclobutane ring closure. The cubane synthesis also exemplifies another general approach to cyclobutane derivatives. This starts with cyclopentanone or cyclohexane-dione derivatives which are brominated and treated with strong base. A Favorskii rearrangement then leads to ring contraction (J.C. Barborak, 1966). 

Donor substituents on the vinyl group further enhance reactivity towards electrophilic dienophiles. Equations 8.6 and 8.7 illustrate the use of such functionalized vinylpyrroles in indole synthesis[2,3]. In both of these examples, the use of acetyleneic dienophiles leads to fully aromatic products. Evidently this must occur as the result of oxidation by atmospheric oxygen. With vinylpyrrole 8.6A, adducts were also isolated from dienophiles such as methyl acrylate, dimethyl maleate, dimethyl fumarate, acrolein, acrylonitrile, maleic anhydride, W-methylmaleimide and naphthoquinone. These tetrahydroindole adducts could be aromatized with DDQ, although the overall yields were modest[3]. 

Discussion of ladder polymers also enables us to introduce a step-growth polymerization that deviates from the simple condensation reactions which we have described almost exclusively in this chapter. The Diels-Alder reaction is widely used in the synthesis of both ladder and semiladder polymers. In general, the Diels-Alder reaction occurs between a diene [XVI] and a dienophile [XVll] and yields an adduct with a ring structure [XVlll] ... 

The synthesis of natural products containing the quinonoid stmcture has led to intensive and extensive study of the classic diene synthesis (77). The Diels-Alder cycloaddition of quinonoid dienophiles has been reported for a wide range of dienes (78—80). Reaction of (2) with cyclopentadiene yields (79) [1200-89-1] and (80) [5439-22-5]. The analogous 1,3-cyclohexadiene adducts have been the subject of C-nmr and x-ray studies, which indicate the endo—anti—endo stereostmcture (81). 

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). 

Oxidation of thiophene with peracid under carefully controlled conditions gives a mixture of thiophene sulfoxide and 2-hydroxythiophene sulfoxide. These compounds are trapped by addition to benzoquinone to give ultimately naphthoquinone (225) and its 5-hydroxy derivative (226) (76ACS(B)353). The further oxidation of the sulfoxide yields the sulfone, which may function as a diene or dienophile in the Diels-Alder reaction (Scheme 88). An azulene synthesis involves the addition of 6-(A,A-dimethylamino)fulvene (227) to a thiophene sulfone (77TL639, 77JA4199). 

Small unsaturated rings are usually very reactive undergoing ring opening in a number of ways, and this characteristic has been utilized in heterocyclic synthesis. In their role as dienophiles or dipolarophiles, the initial cycloaddition is usually followed by a valence tautomerism resulting in a six-membered or larger ring system. Several examples exist, however, where this does not occur, and these are described below. 

Cycloaddition involves the combination of two molecules in such a way that a new ring is formed. The principles of conservation of orbital symmetry also apply to concerted cycloaddition reactions and to the reverse, concerted fragmentation of one molecule into two or more smaller components (cycloreversion). The most important cycloaddition reaction from the point of view of synthesis is the Diels-Alder reaction. This reaction has been the object of extensive theoretical and mechanistic study, as well as synthetic application. The Diels-Alder reaction is the addition of an alkene to a diene to form a cyclohexene. It is called a [47t + 27c]-cycloaddition reaction because four tc electrons from the diene and the two n electrons from the alkene (which is called the dienophile) are directly involved in the bonding change. For most systems, the reactivity pattern, regioselectivity, and stereoselectivity are consistent with describing the reaction as a concerted process. In particular, the reaction is a stereospecific syn (suprafacial) addition with respect to both the alkene and the diene. This stereospecificity has been demonstrated with many substituted dienes and alkenes and also holds for the simplest possible example of the reaction, that of ethylene with butadiene ... 

Covalent fluondes of group 3 and group 5 elements (boron, tin, phosphorus, antimony, etc ) are widely used m organic synthesis as strong Lewis acids Boron trifluoride etherate is one of the most common reagents used to catalyze many organic reactions. A representative example is its recent application as a catalyst in the cycloadditions of 2-aza-l,3-dienes with different dienophiles [14] Boron trifluoride etherate and other fluonnated Lewis acids are effective activators of the... 

Applieation of this theory to the Boger pyridine synthesis reveals that it is a LUMOdiene-controlled Diels-Alder reaetion. Sinee the 1,2,4-triazine is eleetron defieient as a result of the ring nitrogen atoms, one must pair this diene with eleetron rieh dienophiles to allow optimal HOMO-LUMO pairing for this reaetion to beeome faeile. 

Snyder has conducted similar chemistry but with the goal of generating carbon skeletons for the total synthesis of alkaloids. Using indole 84 as a dienophile, the canthine alkaloid skeleton 85 was produced. Access to aspidosperma alkaloids was obtained when 86 was transformed into 87. 

The ability of 1,2 (or l,6)-dihydropyridines to undergo a Diels-Alder reaction with dienophiles such as methyl vinyl ketone, methyl acrylate, and acrylonitrile has been utilized in the synthesis of polyfunctional isoquinuclidine as a key intermediate in the synthesis of aspidosperma- and iboga-type alkaloids (66JA3099). 

---