Diels-Alder Cycloadditions pericyclic reactions

Pericyclic reactions, such as Diels-Alder cycloaddition, electrocyclic reactions, and ene reactions, are extremely effective tools in constructing complex products [18]. 

The Diels-Alder cycloaddition is one exanple of a pericyclic reaction, which is a one-step reaction that proceeds through a cyclic transition state. Bond formation occurs at both ends of the diene system, and the Diels-Alder transition state involves a cyclic ariay of six carbons and six tt electrons. The diene must adopt the 5-cis conformation in the transition state. 

The mechanism of the Diels-Alder cycloaddition is different from that of other reactions we ve studied because it is neither polar nor radical. Rather, the Diels-Alder reaction is a pericyclic process. Pericyclic reactions, which we ll discuss in more detail in Chapter 30, take place in a single step by a cyclic redistribution of bonding electrons. The two reactants simply join together through a cyclic transition state in which the two new carbon-carbon bonds form at the same time. 

Of course, this was only a theory—until in 1982 K.C. Nicolaou s group synthesized the proposed endiandric acid precursor polyene—and in one step made both endiandric acids D and E, plus endiandric acid A, which arises from a further pericyclic reaction, an intramolecular Diels-Alder cycloaddition of the acyclic diene on to the cyclohexadiene as dienophile. 

The synthesis of macropolycyclic arrays — both linear and cyclic — and their derivatives is an area of growing current interest since it provides compounds of considerable academic and technological interest [39]. Although several different synthetic strategies can be envisaged for the production of polyacene and cyclacene derivatives, none have surpassed the utilization of pericyclic reactions, most notably the Diels-Alder cycloaddition, for the construction [40] of the laterally-fused six-membered ring backbone. 

One of the very rare examples of a combination of a radical with a pericyclic reaction - in this case a [4+2] Diels-Alder cycloaddition - is depicted in Scheme 3.83 [133]. The seqrtence, elaborated by Malacria and coworkers, is based on the premise that the vinyl radical 3-341 formed from the substrate 3-340 using tributyltin hydride exists mainly in the Z -form. This is reduced by a hydrogen atom to form a 1,3-diene, which can undergo an intramolecular Diels-Alder reaction via an exotransition state reaction (the chain lies away from diene). 

Electron transfer to or from a conjugated tr-system can also induce pericyclic reactions leading to skeletal rearrangements. A typical example is the Diels-Alder cycloaddition occurring after radical-cation formation from either the diene or the dienophile [295-297], The radical cation formation is in most cases achieved via photochemically induced electron transfer to an acceptor. The main structural aspect is that the cycloaddition product (s Scheme 9) contains a smaller n-system which is less efficient in charge stabilization than the starting material. Also, the original radical cations can enter uncontrollable polymerization reactions next to the desired cycloaddition, which feature limits the preparative scope of radical-type cycloaddition. 

Since their original discovery [362] pericyclic radical cation reactions have been developed for various synthetic formats. The methodology nowadays is most advanced for intra- [363] and intermolecular Diels-Alder cycloadditions [364], and... 

Perhaps the most interesting reaction of all of the possible anion radical pericyclic reactions, a Diels-Alder cycloaddition, has not been definitively exemplified, but one potential example of such a reaction has been proposed [127],... 

Pericyclic reactions, such as the addition of a carbene to an alkene and the Diels-Alder cycloaddition (Review Table 1, reactions Ih and li), involve neither radicals nor nucleophile-electrophile interactions. Rather, these processes take place in a single step by a reorganization of bonding electrons through a cyclic transition state. We ll look at these reactions mate closely in Chapter 30. 

The Diels-Alder cycloaddition reaction (Section 14.8) is a pericyclic process that takes place between a diene (four it electrons) and a dienophile (two TT electrons) to yield a cyclohexene product. Thousands of examples of Diels-Alder reactions are known. They often take place easily at room temperature or slightly above, and they are stereospecific with respect to substituents. For example, room-temperature reaction between 1,3-butadiene and diethyl maleate (cis) yields exclusively the cis-disubstituted cyclohexene product. Similar reaction between 1,3-butadiene and diethyl fumarate (trans) yields exclusively the trans-disubstituted product (Figure 30.7),... 

The first step 202 is now a pericyclic reaction. It looks like a cycloaddition, though it involves a hydrogen transfer as well. It is in fact a carbonyl (or oxo- ) ene reaction. It is like a Diels-Alder cycloaddition in which a C-H bond has replaced one of the double bonds in the diene and a C=0 group is the dienophile. Many Prins reactions are probably carbonyl ene reactions. In his excellent review30 in Comprehensive Organic Synthesis, B. J. Snider says The (carbonyl) ene reaction and the Prins reaction are not mechanistically distinct . Though this step is pericyclic, it is very polar and the transition state 203 no doubt contains partial charges. It is therefore stabilised and the reaction accelerated by protic acids 205 and Lewis acids 207. 

The Diels-Alder cycloaddition is one example of a pericyclic reaction. A peri-cyclic reaction is a one-step reaction that proceeds through a cyclic transition state. Bond... 

The principle presented here on two pericyclic reactions (Diels-Alder cycloaddition and cyclobutene ring opening) can be successfully applied to studies of the reaction outcome for many other pericyclic reactions. 

Isopolar activated complexes differ very little or not at all in charge separation or charge distribution from the corresponding initial reactants. These complexes are implied in pericyclic reactions such as Diels-Alder cycloadditions and the Cope rearrangement. 

In solution, benzyne and its derivatives are strained, short-lived intermediates which react with a broad array of nucleophiles, including carbanions, amines, alcohols and their salts, water, and even ethers. They also undergo pericyclic reactions such as Diels-Alder cycloadditions, 1,3-dipolar cycloadditions or ene reactions. The instability of benzyne and its derivatives is due to the strain caused by the deformation of the linear geometry of the formal sp-hybridized carbons of the triple bond to the angles close to 120° imposed by the ring geometry [2,3]. 

Pericyclic reactions are concerted processes that occur by way of a cyclic transition state in which more than one bond is formed or broken within the cycle. The classic example of such a process is the Diels-Alder cycloaddition reaction, one of the most common and useful synthetic reactions in organic chemistry. Cycloaddition reactions, sigmatropic rearrangements and electrocyclic reactions all fall into the category of pericyclic processes, representative examples of which are given in Schemes 3.1-3.3. This chapter will discuss these reactions and their use in synthesis. 

Of all the pericyclic reactions, the Diels-Alder cycloaddition reaction is the most popular. In the Diels-Alder reaction, a 1,3-diene reacts with a dienophile to form a six-membered ring adduct (3.1). Two new a-bonds and a new rr-bond are formed at the expense of three tt-bonds in the starting materials. ... 

Using the Pericyclic module, the Diels-Alder cycloaddition reaction of 1,3-cyclohexadiene (8) with maleic anhydride (9) (a known synthesis of endo-bicyclo[2.2.2]oct-5-ene-2,3-dicarboxylic anhydride, 10 (70))y was properly predicted by CAMEO, but only as a minor product (Scheme 3). CAMEO pr cted the 3-(l,4-cyclohexadiene) succinic anhydride (11) adduct as the major product via a "forward ene" mechanism. 

The reaction occurs in a single step, without an intermediate, by a mechanism in which six atoms undergo bonding changes in the same transition state by way of cyclic reorganization of their tt electrons. Concerted (one-step) reactions such as the Diels-Alder cycloaddition that proceed through a cyclic transition state are called pericyclic reactions. 

Bauld, N. L., and Yang, J. "Stereospecificity and Mechanism in Cation Radical Diels-Alder and Cyclobutanation Reactions." Org. Lett, X 773-774 (1999). Gao, D., and Bauld, N. L. Mechanistic Implications of the Stereochemistry of the Cation Radical Diels-Alder Cycloaddition of 4-(cis-2-Deuteriovinyl)anisole to 1,3-Cyclopentadiene." /. Org. Chem., 65,6276-6277 (2000). Saettel, N. J., Oxsgaard, J., and Wiesl, O. "Pericyclic Reactions of Radical Cations." Eur. /. Cftem., 1429-1439 (2001). 

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