Components, pericyclic

Scheme 20. Stereoselective synthesis of polypropionate fragments by a three-component pericyclic domino reaction...

The Woodward-Hoffman rules (1) state that "A ground state pericyclic change is symmetry allowed when the total number of (4q + 2) suprafacial and (4r) antarafacial components is odd". 

The volume concludes with the preparation of four useful starting materials. The highly electrophilic tricarbonyl reagent DIMETHYL MESOXALATE finds application as a two-electron component in various pericyclic processes. 9-BROMO-9-PHENYL-FLUORENE is becoming increasingly used for the protection of primary amines, particularly amino acids and amino esters. Two methods for introducing the 9-phenylfluorenyl group are illustrated in the preparations of (S)-N-(9-PHENYLFLUOREN-9-YL)ALANINE AND (S)-DIMETHYL N-(9-PHENYLFLUOREN-9-YL)ASPARTATE. 

Lipids from marine products have been studied less frequently. The detection of co-(o-alkylphenyl)alkanoic acids with 16,18 and 20 carbon atoms together with isoprenoid fatty acids (4,8,12-trimethyltetradecanoic acid and phytanic acid) and substantial quantities of bones from fish and molluscs has provided evidence for the processing of marine animal products in vessels [58 60]. C16, C18, and C20 co-(o-alkylphenyl)alkanoic acids are presumed to be formed during the heating of tri-unsaturated fatty acids (C16 3, C18 3 and C20 3), fatty acyl components of marine lipids, involving alkali isomerization, pericyclic (intermolecular Diels-Alder reaction) and aromatization reactions. 

An efficient and also elegant synthesis of the active anti-influenza A virus indole alkaloid hirsu-tine 67 is performed by an inter-intermolecular anionic-pericyclic three- component domino reaction followed by solvolysis and hydrogenation (scheme 13).[261 The synthetic sequence developed by us contains first a Knoevenagel condensation of enantiopure 61 and 62 with the formation of the... 

An interesting pericyclic-anionic-pericyclic domino reaction showing a high stereoselectivity is the cycloaddition-aldol-retro-ene process depicted in scheme 20.1581 The procedure presumably starts with a [4+2]-cycloaddition of diene 98 and S02 in presence of a Lewis acid. After opening of the formed adduct reaction with (Z)-silyl vinyl ether 99 leads to a mixture of alk-2-enesulfinic acids 101. It follows a retro-ene reaction which affords a 7 3 mixture of the products 102 and 103. The reaction described by Vogel et al is a nice example for the efficient generation of polypropionate chains with the stereoselective formation of three stereogenic centers and one (0-double bond in a three-component domino reaction in its strict definition. 

Lallemand et al. have found a pericyclic-anionic domino three-component reaction to prepare highly functionalized alcohols.115931 This reaction was originally developed by Vaultier, Hoffmann et al.[59bl Diels-Alder reaction of a 1,3-dienylboronate with an acrylate yields a mixture of endo and exo diastereomers of the coupled allylboronate, which in the presence of an aldehyde such as 4-phenoxy-butyraldehyde undergoes an allylation reaction. After hydrolysis the resulting diastereomeric alcohols are obtained in about 50 % yield, whereby two new stereogenic centers are formed in a stereoselective fashion. 

In a cycloaddition reaction, the two active n systems may approach each other in either of two orientations, for example, head to head or head to tail. If one combination dominates, the reaction is said to be regioselective. In the course of the reaction, 4 new saturated centers are formed. With maximum labeling, a total of 16 (=24) stereo-isomeric forms, consisting of 8 enantiomeric pairs of diastereomers if neither polyene is chiral, may be formed. In pericyclic reactions, the stereochemistry is determined by specifying the stereochemical mode in which each component reacts. Each of the two... 

A component analysis of pericyclic reactions proceeds by the following steps, which are illustrated for each of the classes of reaction in Figure 12.4 ... 

Figure 12.4. Procedure for general component analysis illustrated for each of the three types of pericyclic reactions.

The general rule for all pericyclic reactions was formulated by Woodward and Hoffmann ([3], p. 169). A ground-state pericyclic change is symmetry allowed if the total number of (An + 2)s and (Am)a components is odd. 

Pericyclic reactions are described in Chapter 12 as a special case of frontier orbital interactions, that is, following Fukui [1]. However, the stereochemical nomenclature supra-facial and antarafacial and the very useful general component analysis of Woodward and Hoffmann [3] are also introduced here. 

Olefins can add to double bonds in a reaction different from those discussed in 5-15, which, however, is still formally the addition of RH to a double bond. This reaction is called the ene synthesis44,1 and bears a certain similarity to the Diels-Alder reaction (5-47). For the reaction to proceed without a catalyst, one of the components must be a reactive dienophile (see 5-47 for a definition of this word) such as maleic anhydride, but the other (which supplies the hydrogen) may be a simple alkene such as propene. There has been much discussion of the mechanism of this reaction, and both concerted pericyclic (as shown above) and stepwise mechanisms have been suggested. The reaction between maleic anhydride and optically active PhCHMeCH=CH2 gave an optically active product,441 which is strong evi-... 

The conclusion we may draw from this analysis is that in pericyclic reactions of these kinds we shall always be able to discover the inherent symmetry of the interaction topologically by considering the system as being made up of suitable components, even when there is no actual symmetry maintained in the molecule as a whole. We shall therefore be able to analyze the situation in terms of the... 

A pericyclic reaction is allowed in the electronic ground state if the number of suprafacial two-electron components is odd. 

This argument demonstrates in an entirely general way that the number of phase inversions in the interaction diagram for a simply connected pericyclic transformation is zero if the number of antarafacial components is even and one if the number of antarafacial components is odd. In order to complete the link between the Woodward-Hoffmann and Dewar-Zimmerman points of view, it remains only to find the total number of electrons in the completed ring. A 4q system contains an even number of pairs and a 4q + 2 system an odd number of pairs therefore any system obtained by joining components will have a total number of electrons satisfying the formula 4q (even number of pairs total) if there are an even number of 4q + 2 components and a total number satisfying 4 + 2 (odd number of pairs total) if there are an odd number of 4q + 2 components. 

Consider now a pericyclic interaction diagram made up of the four possible kinds of components as follows ... 

Verify that the selection rules found for the two-component cycloadditions (Section 11.3, p. 594) agree with the general pericyclic selection rule. What can be said about all-antara 2 + 2 + 2 +. .. cycloadditions About all-supra 2 + 2 + 2 +. .. cycloadditions ... 

Two systems of nomenclature are in use for designating the components of a cycloaddition reaction. One, proposed by Huisgen,2 specifies the numbers of atoms in each component the other, introduced with the pericyclic theory3 and used in Chapter 11, shows the numbers of electrons contributed by each. 

The pericyclic theory predicts that cheleotropic reactions of four-electron with two-electron components may occur by the linear path (p. 628), that is, supra-facially on the one-atom component, if the diene enters also suprafacially (six-electron interaction diagram 28). A number of examples are known, most of... 

Cycloadditions are characterized by two components coming together to form two new o-bonds, at the ends of both components, joining them together to form a ring, with a reduction in the length of the conjugated system of orbitals in each component. Cycloadditions are by far the most abundant, featureful, and useful of all pericyclic reactions. 

Another rare kind of 6-electron ionic cycloaddition is that between a pentadienyl cation and an alkene. A telling example is the key step 2.66 — 2.67 in a synthesis of gymnomitrol 2.68, where the nature of the pericyclic step is heavily disguised, but all the more remarkable for that. Ionization of the acetal gives the cationic quinone system 2.66. That this is a pentadienyl cation can be seen in the drawing of a canonical structure on the left, with the components of the pericyclic cycloaddition emphasized in bold. Intramolecular [4+2] cycloaddition takes place, with the pentadienyl cation as the 4-electron component and the cyclopentene as the 2-electron component. Th is reaction is an excellent example of how a reaction can become embedded in so much framework that its pericyclic nature is obscured. 

The preliminary rules, thermal and photochemical, given on p.16, need now to be qualified—they apply only to cycloadditions that are suprafacial on both components. Nevertheless, almost all pericyclic cycloadditions are suprafacial on both components. It is physically difficult for one conjugated system to suffer antarafacial attack from another, since it implies that one or another of the components can reach round from one surface to the other 2,85. Only if at least one of the components has a long conjugated system can it twist enough to make this even remotely reasonable. Straightforward antarafacial attack in cycloadditions is therefore very rare indeed. Keep in mind, however, that these rules only apply to pericyclic cycloadditions— there are other kinds of cycloaddition, in which the two bonds are formed one at a time, and to which none of these rules applies. 

All the other kinds of pericyclic cycloaddition discussed so for, not just Diels-Alder reactions, are also suprafacial on both components. Thus, 1,3-dipolar cycloadditions involve suprafacial attack on the dipolarophile, as in... 

---