Diels-Alder reactions suprafacial addition

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 ... 

The suprafacial thermal addition of an allylic cation to a diene (a [3 -f- 4] cycloaddition) is allowed by the Woodward-Hoflfmann rales (this reaction would be expected to follow the same rules as the Diels-Alder reaction ). Such cyclo-... 

The Woodward-Hoffmann rules also allow the prediction of the stereochemistry of pericyclic reactions. The Diels-Alder reaction is an example of (re4s + re2s) cycloaddition. The subscript s, meaning suprafacial, indicates that both elements of the addition take place on the same side of the re-system. Addition to opposite sides is termed antarafacial. The Woodward-Hoffmann rules apply only to concerted reactions and are derived from the symmetry properties of the orbitals involved in the transition state. These rules may be summarised as shown in Table 7.1. 

The thermal reaction produced 5 and 6 in a 3 2 ratio but the Lewis acid-catalyzed reaction gave a 1 1 ratio. We could not separate the two cycloadducts, but based the indicated constitution on analysis of the mass spectrum and lH NMR spectrum of the mixture of the two compounds. The stereochemistry was assigned on the basis that the Diels-Alder reaction is normally suprafacial-suprafacial18 and that for other cycloaddition reactions of levoglucosenone (2) the addition anti to the 1,6-anhydro bridge is favored.13 15... 

In 1989, the irradiation of (E,E)-2,4-hexadiene S3 sensitized by meso-porphyrin IX dimethyl ester led to the formation of cis-3,6-dimethyl-l,2-dioxene (62), which was the major product detected at — 78 °C in Freon 11 [69]. Endoperoxide 62 was purified under vacuum at 0.75 mmHg, and collected in a trap (98% isolated yield). Dienes that can adopt a cisoid conformation, such as 53 or ( , )-l,4-di phenyl butadiene, were photooxidized by the corresponding endoperoxides in high or quantitative yield in a suprafacial Diels-Alder reaction [60, 70], Dienes that cannot readily adopt cisoid conformations, such as (fc, Z)-2,4-hexadienes and (Z, Z)-2,4-hexadienes, lose their stereochemistry in the singlet oxygen [2 + 4]-cyclo-addition [60], (E,Z)- and (Z,Z)-dienes give a complex mixture of hydroperoxides and aldehydes, which suggests the intervention of intermediate zwitterions or 1,4-diradicals [71]. 

Essentially, a suprafacial-suprafacial or an antarafacial-antarafacial cycloaddition is equivalent to a concerted syn addition. A suprafacial-antarafacial or an antarafacial-suprafacial process is equivalent to a concerted anti addition. The Diels-Alder reaction is suprafacial for both components, so that the stereochemical relationships among the substituents are maintained in the product. In Example 6.6, suprafacial addition to the dienophile component means that the two carbomethoxy groups that are cis in the starting material also are cis in the product. Suprafacial reaction at the diene component leads to a cis orientation of the two methyl groups in the product. 

Since its discovery over sixty years ago [1] the Diels-Alder reaction has lost none of its attraction. [2, 3] It enables, in a one-step inter- or intramolecular reaction, the rapid preparation of cyclic compounds having a six-membered ring. During the course of the [4 -I- 2] cycloaddition four new stereocenters can be introduced directly, and their stereo-control is a topic of major interest in modem synthetic chemistry. [4-6] In addition, in intermolecular reactions, the relative positions of the reaction partners (regiochemistry) must be taken into account. If a concerted reaction is assumed, both a cis addition (suprafacial mode) and a preferred endo orientation (Alder rules) can be expected. But how can the absolute configuration of the desired product be controlled There are three basic possibilities the use of a chirally modified diene, a chirally modified dienophile, or a chiral catalyst. Although the first successes resulted from the attractive, hut difficult, catalytic route, [4b, 7] the majority of the investigators are concerned with the stoichiometric... 

This equilibration takes place by rotation about the carbon-carbon single bond. Another requirement of the Diels-Alder reaction is that the diene must add onto the dienophile in a suprafacial process that is, both bonds are formed on the same face of the dienophile. The last requirement of the Diels-Alder reaction is that the addition of a diene to a dienophile bearing an unsaturated group will occur in an endo fashion that is, the unsaturated group will lie near the developing double bond in the diene portion. Cis,trans-2,4-hexadiene exists in s-trans - s-cis equilibriiara as shown ... 

The Diels—Alder reaction involves the addition of a dienophile, which is an olefinic or acetylinic compound, to the 1,4-position of a conjugated diene system to produce a cyclohexene. Since the reaction forms a cyclic product, via a cyclic transition state by the addition of a 47T-electron system (i.e., diene) to a 27t-electron system (i.e., dienophile), it can also be described as a [7t" s -I- TT s] cycloaddition reaction. Numbers 4 and 2 identify both the number of TT-electrons involved in the electronic rearrangement and the number of atoms in the cyclohexene ring. The letter s indicates that the reaction takes place suprafacially on both the components. The reaction between buta-1,3-diene and ethene to give cyclohexene is a typical example of Diels—Alder reaction (Scheme 4.5). 

Most of the ene reactions are concerted and orbital symmetry allowed processes involving all suprafacial transition states of 6e (4jt and 2endo orientations of the electron withdrawing group as depicted in (Fig. 5.1). The addition of the ene to the enophile is stereospecific syn. The TS requires higher activation energy compared to that of Diels-Alder reaction because two cr-electrons of the allylic CT-bond are involved instead of a rr-bond of a diene. 

Cycloaddition processes can be described by a symbolism which describes the type and number of electrons involved in the reaction and the topology of the reaction. Thus a Diels-Alder reaction is a [477 + 277 ] process, signifying addition of a four-77-electron and a two-77-electron system, with both sets of orbitals reacting in a suprafacial mode. The allowed 2 + 2 addition would be described as 2iTs + 277 ]. 

If butadiene and an appropriately substituted ethylene approach and begin to overlap as in Equation 5.2, there is a favorable phase relationship using the HOMO of the diene and the LUMO of ethylene (the frontier molecular orbitals) for a face-to-face joining. This is, of course, the familiar Diels-Alder reaction, and it is thermally allowed. With respect to both components of the reaction, the reaction occurs from the same face, termed suprafacial addition. Because there are four % electrons in butadiene and two % electrons in ethylene, the Diels-Alder reaction is named as a [ 4 -i- 2 ] reaction. The stereochemical consequences of this approach are further illustrated in Section 8.6. 

As both the n-systems are involved in the cyclo addition, it is essential to specify the modes with respect to each of them. Specification is made by placing subscript S or a after the number refering to n-component. For instance, suprafacial addition with respect to each component of Diels-Alder reaction is specified as n] +n J cycloaddition. Another way is simply writting it as 2s+4s cycloaddition. 

The high diastereoselectivity of reaction cascade 160 +161 163 +164 (Scheme 22.42) can be interpreted in terms of a highly diastereoselective (suprafacial) hetero-Diels-Alder addition of SO2 to diene 160 in which the C—H bond of the 1-phenylethyl ether residue resides in the 7i-plane of the i-cis-butadiene moiety (Scheme 22.43). Thus, the SO2 coordinated to the acid promoter attacks the face of the diene syn with respect to the methyl group of the phenylethyl group, giving a sultine that is immediately... 

---