1,3-Butadiene with substituted 1,3-dienes

A process has been disclosed in which the mixture of naphthoquinones is reacted with a diene such as butadiene. Owing to the fact that the undesked product is an unsubstituted naphthoquinone, this dieneophile readily reacts to form a Diels-Alder adduct. By appropriate control of reaction parameters, Htde reaction is observed with the substituted naphthoquinone. Differential solubiUty of the adduct and vitamin allows for a facile separation (57,58). 

Since diazaquinones are among the most powerful dienophiles, they undergo [4+2] cycloaddition (Diels-Alder) reactions with a great variety of dienes to give various heterocyclic systems accessible with difficulty by other methods. Diazaquinone reacts with butadiene and substituted butadienes, carbocyclic and heterocyclic dienes, 1-vinylcycloalkenes, polyaromatic compounds and vinylaromatic compounds to afford bicyclic and polycyclic bridgehead diaza systems, including diazasteroids (Scheme 56). 

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 ... 

Amino-substituted dienes are also important dienophiles in Diels-Alder reactions. Recently, chiral and achiral 2-amino-l,3-dienes have been prepared to study their reactivity (see also asymmetric Diels-Alder reaction Section 8.1.2). The reaction of 2,3-diamino-l,3-butadienes with nitrostyrene gives unusual [3+2]carbocyclization products, 2-aminocyclopentanones, which are not formed by the direct cycloaddition but derived from the Michael addition products (see section discussing the Michael addition Section 4.1.3).42... 

In this equation the —225.7 1.3 kJ mol 1 is the hydrogenation enthalpy of 1,3-butadiene to n-butane. This last expression speaks to substituent/diene interactions and to substituent-substituent interactions. Both electronic and steric effects contribute. Again, this allows calibration of a substituted diene with 1,3-butadiene itself. A positive sign can be interpreted as the substituted species being more stabilized than the archetype. 

The nickel-catalyzed [4 + 4]-cycloaddition of butadiene to form cyclooctadiene was first reported by Reed in 1954.90 Pioneering mechanistic and synthetic studies largely derived from the Wilke group advanced this process to an industrially important route to cyclodimers, trimers, and other molecules of interest.91-94,943 95,96 While successful with simple dienes, this process is not useful thus far with substitutionally complex dienes as needed in complex molecule synthesis. In 1986, Wender and Ihle reported the first intramolecular nickel-catalyzed [4 + 4]-reaction of... 

At variance with the earlier study58 on butadiene, the data related to halogenation of these substituted dienes reveal also that solvents have striking effects on product ratios,... 

The behavior described above has been verified by experiment and calculation on numerous substituted dienes and dienophiles. For example Fig. 10.13 shows results for 2°-D isotope effects on Diels-Alder reactions of 2-methyl-butadiene with cyano-ethylene and 1,1-dicyano-ethylene. The calculated and experimental isotope effects are in quantitative agreement with each other and with the results on (butadiene + ethylene). In each case the excellent agreement between calculated and observed isotope effects validates the concerted mechanism and establishes the structure of the transition state as that shown at the bottom center of Fig. 10.11 and the left side of Fig. 10.12a. 

Heteroatom-substituted vinylcarbene complexes react particularly well with donor-substituted 1,3-butadienes to yield the corresponding cycloheptadienes [264]. Some of these reactions proceed at room temperature. The intermediate divinylcyclopropanes have occasionally been isolated [264]. As indicated in Figure 2.37, for donor-substituted dienes in particular the formation of zwitterionic intermediates... 

A few experiments have been tried with conjugated dienes in the substitution reaction. Preliminary results indicate that they too may react normally. Using palladium acetate in a stoichiometric reaction, benzene and butadiene were found to form 1-phenylbutadiene in about 25% yield (41). Iodobenzene and isoprene react with triethylamine and Pd(PPh3)2(OAc)2 as catalyst at 100° to form ( )-3-methyl-l-phenyl-1, 3-butadiene in 52% yield (42) ... 

Cycloadditions are called Diels-Alder reactions in honor of Otto Diels and Kurt Alder, the chemists who carried out the first such reaction. The substrate that reacts with the diene in these cycloadditions is called the dienophile. As you saw in Figure 15.1, the simplest Diels-Alder reactions, i.e., the ones between ethene and butadiene and between acetylene and butadiene, respectively, occur only under drastic conditions. Well-designed Diels-Alder reactions, on the other hand, occur much more readily. In the vast majority of those cases, acceptor-substituted atkenes serve as dienophiles. In the present section, we will be concerned only with such Diels-Alder reactions (see Figures 15.16, 15.17, and 15.23 for exceptions). 

Diels-Alder reactions of the type shown in Table 12.1, that is, Diels-Alder reactions between electron-poor dienophiles and electron-rich dienes, are referred to as Diels-Alder reactions with normal electron demand. The overwhelming majority of known Diels-Alder reactions exhibit such a normal electron demand. Typical dienophiles include acrolein, methyl vinyl ketone, acrylic acid esters, acrylonitrile, fumaric acid esters (fnms-butenedioic acid esters), maleic anhydride, and tetra-cyanoethene—all of which are acceptor-substituted alkenes. Typical dienes are cy-clopentadiene and acyclic 1,3-butadienes with alkyl-, aryl-, alkoxy-, and/or trimethyl-silyloxy substituents—all of which are dienes with a donor substituent. 

As a rule, C-1 substituted dienes form ort/zo-adducts predominantly for example, 1-methoxy-1,3-butadiene reacts with acrylonitrile to give 3-methoxy-4-cyanocyclohexene (8.7) in a major amount. 

On the other hand, C-2 substituted dienes produce para-adducts as the major product. For example, 2-methyl-1,3-butadiene reacts with methylacrylate to give 8.8 in a major amount. Diels-Alder reactions can be catalyzed by Lewis acids and there may be improvement in yield of 8.8 product (Scheme 8.1). 

Further extension of the reaction pool of Schilf bases 138 was achieved by their reaction with tran -l-methoxy-3-(trimethylsilyloxy)-1,3-butadiene (Danishefsky s diene) to give 2-substituted 5,6-didehydro-piperidin-4-ones 164 [135,136] (Scheme 10.54). The reaction is considered to be a sequence of an initial Mannich reaction between the imine and the silyl enol ether, followed by an intramolecular Michael addition and subsequent elimination of methanol. If the reaction was terminated by dilute ammonium chloride solution, then the Mannich bases 163 could be isolated and further transformed to the dehydropiperidinones 164 by treatment with dilute hydrochloric acid. This result proved that the reaction pathway is not a concerted hetero Diels-Alder type process between the electron-rich diene and the activated imine. The use of hydrogen chloride as a terminating agent resulted in exclusive isolation of the piperidine derivatives 164 formed with... 

Craig and coworkers have reported rate constants for the reaction of 2-substituted 1,3-butadienes with maleic anhydride in benzene at 25 °C their values are X, k Cl, 0,019 H, 0.19 Me, 0,57 Et, l.l5 /-Pr, 2.2 t-Bu, 5.6 OMe, 1.9. As the Diels-Alder reaction proceeds through the s-cis conformation of the diene, and substituents in the 2-and 3-positions can affect the fraction of the diene in this conformation, steric effects must be considered. The data set was correlated therefore with the CRS equation ... 

---