1,3-Butadienes 2+4 -cycloadditions

In this section we will present results33 from the MD simulations along the IRC performed for five model reactions the HCN CNH isomerization reaction, the conrotatory ring opening of cyclobutene, ethylene-butadiene cycloaddition, the prototype SN2 reaction Cl +CII3CI C1CH3- -Cr, and the chloropropene isomerization Cl - CH2 - CH=CH2 - CH2=CH - CH2C1. 

Figure 4-16. Ethylene-butadiene cycloaddition reactants, products and TS structures...

Figure 4-17. Ethylene-butadiene cycloaddition the changes in the interatomic distances (a), angles (b), and torsional angles (c) along the IRC and from a 300K MD simulation...

Figure 7-17. Orbital correlation diagram for the ethylene-butadiene cycloaddition. Adaptation of Figure 10.20 from reference [74] with permission.

The regioselectivity of the formal [3 + 2] cycloaddition reactions in Scheme 13 corresponds to the polarization of the olefinic bond and to partial charges in the ketocarbenoid. The only exception occurred with benzofuran, in agreement with the behavior of the carbenoid derived from ethyl 2-diazo-3-oxobutyrate As several examples in Scheme 13 show, the cycloaddition is sterospecific, i.e. the configuration about the enol ether double bond is retained in the dihydrofuran. The observation that in the case of 1-methoxy-1,3-butadiene highly selective cycloaddition of the unsubstituted double bond occurs, whereas for 2-methoxy-1,3-butadiene cycloaddition takes place at the more electron-rich double bond, finds a close analogy in the cyclopropanation of these same dienes with ethyl diazoacetate (see Table 9). 

The ethylene-butadiene cycloaddition is a good example to illustrate that symmetry allowedness does not necessarily mean that the reaction occurs easily. This reaction has a comparatively high activation energy, 144 kJ/mol [7-7]. A large number of quantum-chemical calculations has been devoted to this reaction with conflicting results (for recent references, see Ref. [7-18]). It seems, however, that the concerted nature of the prototype Diels-Alder reaction is well established. The reason for the relatively high activation energy is that substantial distortion must occur in the reactants before frontier orbital interactions can stabilize the product. 

A more demanding dynamical study aimed to rationalize the product distribution in photochemical cycloaddition, looking at butadiene-butadiene [82]. A large number of products are possible, with two routes on the excited Si state leading back to channels on the ground state. The results are promising, as the MMVB dynamics find the major products found experimentally. They also... 

Let us now examine the Diels-Alder cycloaddition from a molecular orbital perspective Chemical experience such as the observation that the substituents that increase the reac tivity of a dienophile tend to be those that attract electrons suggests that electrons flow from the diene to the dienophile during the reaction Thus the orbitals to be considered are the HOMO of the diene and the LUMO of the dienophile As shown m Figure 10 11 for the case of ethylene and 1 3 butadiene the symmetry properties of the HOMO of the diene and the LUMO of the dienophile permit bond formation between the ends of the diene system and the two carbons of the dienophile double bond because the necessary orbitals overlap m phase with each other Cycloaddition of a diene and an alkene is said to be a symmetry allowed reaction... 

Refer to the molecular orbital diagrams of allyl cation (Figure 10 13) and those presented earlier in this chapter for ethylene and 1 3 butadiene (Figures 10 9 and 10 10) to decide which of the following cycloaddition reactions are allowed and which are forbidden according to the Woodward-Floffmann rules... 

Concerted Nonpolar Reactions. Maleic anhydride exemplifies the model dienophile for cycloaddition with dienes such as 1,3-butadiene... 

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 ... 

How do orbital symmetry requirements relate to [4tc - - 2tc] and other cycloaddition reactions Let us constmct a correlation diagram for the addition of butadiene and ethylene to give cyclohexene. For concerted addition to occur, the diene must adopt an s-cis conformation. Because the electrons that are involved are the n electrons in both the diene and dienophile, it is expected that the reaction must occur via a face-to-face rather than edge-to-edge orientation. When this orientation of the reacting complex and transition state is adopted, it can be seen that a plane of symmetry perpendicular to the planes of the... 

Fig. 11.9. Symmetry properties of ethylene, butadiene, and cyclohexene orbitals with respect to cycloaddition.

When the orbitals have been classified with respect to symmetry, they can be arranged according to energy and the correlation lines can be drawn as in Fig. 11.10. From the orbital correlation diagram, it can be concluded that the thermal concerted cycloadditon reaction between butadiene and ethylene is allowed. All bonding levels of the reactants correlate with product ground-state orbitals. Extension of orbital correlation analysis to cycloaddition reactions involving other numbers of n electrons leads to the conclusion that the suprafacial-suprafacial addition is allowed for systems with 4n + 2 n electrons but forbidden for systems with 4n 7t electrons. 

Fluorinaied dienophiles. Although ethylene reacts with butadiene to give a 99 98% yield of a Diels-Alder adduct [63], tetrattuoroethylene and 1,1-dichloro-2,2-difluoroethylene prefer to react with 1,3-butadiene via a [2+2] pathway to form almost exclusively cyclobutane adducts [61, 64] (equation 61). This obvious difference in the behavior of hydrocarbon ethylenes and fluorocarbon ethylenes is believed to result not from a lack of reactivity of the latter species toward [2+4] cycloadditions but rather from the fact that the rate of nonconcerted cyclobutane formation is greatly enhanced [65]... 

In a definitive study of butadiene s reaction with l,l-dichloro-2,2-difluoio-ethylene, Bartlett concluded that [2+4] adducts of acyclic dienes with fluorinated ethylenes are formed through a mixture of concerted and nonconcerted, diradical pathways [67] The degree of observed [2+4] cycloaddition of fluorinated ethylenes IS related to the relative amounts of transoid and cisoid conformers of the diene, with very considerable (i.e., 30%) Diels-Alder adduct being observed in competition with [2+2] reaction, for example, in the reaction of 1,1 -dichloro-2,2-difluoro-ethylene with cyclopentadiene [9, 68]... 

An interesting probe of reactivity was presented by Burton in his study of cycloadditions of l,2-disubstituted-3,3,4,4-tetrafluorocyclobutenes and 1,2-disub-stituted-3,3,4,4,5,5-hexaf1uorocyclopentenes with butadiene, 2-methylbutadiene, and 2,3-dimethylbutadiene [86], On the basis of the extent of their conversions to adducts, the relative reactivities of the cyclobutenes and of the cyclopentenes are as shown in equation 74. A typical reaction is shown in equation 75. 

One of the features of Diels-Alder reactions with most alkyl and aryl nitriles that has made them rather unattractive as dienophiles is the requirement of very high reaction temperatures Again, only when electron-withdrawing substituents are directly bonded to the nitnle function do [4+2] cycloaddition reactions occur at reasonably low temperatures [ 48, 231, 232] A high yield [4+2] cycloaddition was observed on reaction of 4,4-bis(trifluoromethyl) 1 thia-3-aza-l,3-butadienes with trifluoroacetonitrile at 150 °C [225]... 

Recall from Section 7.13 that a stereospecific reaction is one in which each stereoisomer of a particular starting material yields a different stereoisomeric form of the reaction product. In the examples shown, the product from Diels-Alder cycloaddition of 1,3-butadiene to c/s-cinnamic acid is a stereoisomer of the product from trans-cinnamic acid. Each product, although chiral, is formed as a racemic mixture. 

Dienamines undergo 1,4 cycloaddition with sulfenes as well as 1,2 cycloaddition. For example, l-(N,N-diethylamino)butadiene (111), when treated with sulfene (generated from methanesulfonyl chloride and triethyl-amine), produces 1,4 cycloadduct 116 in an 18 % yield and di-1,2-cycloadduct 117 in a 60 % yield (160). Cycloadduct 116 was shown not to be the precursor for 117 by treating 116 with excess sulfene and recovering the starting material unchanged (160). This reaction probably takes place by way of zwitterion 115, which can close in either a 1,4 or 3,4 manner to form cycloadducts 116 and 118, respectively. The 3,4 cycloaddition would then be followed by a 1,2 cycloaddition of a second mole of sulfene to form 117. Cycloadduct 117 must form in the 3,4 cycloaddition followed by a 1,2-cycloaddition sequence rather than the reverse sequence since sulfenes undergo cycloaddition only in the presence of an electron-rich olefinic center (159). Such a center is present as an enamine in 118, but it is not present in 119. 

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