Retro-D-A reaction

Arndtsen and co-workers developed an isocyanide-mediated three-component synthesis ofthe polysubstituted pyrroles 97, wherein an acyclic imine was activated in situ by acylation [54]. Thus, reaction of an imine, an acyl chloride, an alkyne, and an isocyanide in the presence of PrNEt2 afforded 97 in good to excellent yields (Scheme 5.29). A complex reaction sequence involving formation ofthe N-acyliminium by [4 + 1] followed by [3 + 2] cycloadditions and a retro-cycloaddition was proposed to account the formation of 97. The isocyanide participated actively in this reaction sequence however, it was not incorporated in the final adduct since it was lost as isocyanate by a retro-D-A reaction. The aliphatic imine was shown to be an appropriate substrate, at least in one case, leading to the corresponding pyrrole (R2 = isopropyl) in 72% yield. Azenes participated in this reaction in a similar manner. Thus, the isoquinoline 94 was converted to the benzo-fused pyrrole 98 in 50% yield. 

The reverse reactions of Diels-Alder reactions for thermal dissociations of cycloadducts in to dienes and dienophiles at higher temperatures or in the presence of Lewis acid or base are known as the retro-Diels-Alder (rDA) reactions. These reactions in most cases proceed in a concerted process. These reactions are often used for separation of diene or dienophile from their mixture with other compounds. Proper selection of conditions of these reactions provides new dienes and dienophiles, which are important synthons for synthesis of several bioactive natural products and organic molecules of complex structures. For example, the D-A adduct of 4-phenyl oxazole 110 with methyl acetylene dicarboxylate, on retro-D-A reaction gives new compounds, benzonitrile, and furan 3,4-dicarboxylic acid methyl ester 111 [65]. 

G) D-A cycioaddition and then retro D-A reaction and electrocyclic ring opening of trani-3,4-diacetoxycyclobutene. 

Interestingly, we were intrigued by the ESI mass spectrum of the compound, as the observed base peak consisted of [M-S02+Na]+. This led us to explore a thermal retro-Diels-Alder reaction that could afford the desired enone 69. It is noteworthy that the chemistry of cyclic enol-sulfites would appear to be an under-explored area with a few references reporting their isolation being found [57]. At last, we were also able to prepare epoxy ketone 70 from 69 in three steps, albeit epoxidation did not take place unless the TES group was removed. Spartan models reaffirmed our initial conformational assessment of enone 69 and epoxy ketone 70, which contain sp3-hybridized C8a and s/r-hybridized C8b (p s e u d o-. v/r - h y b r i d i zed C8b for 70) at the AB-ring junction (Fig. 8.12) and displayed the desired twisted-boat conformation in A-ring. 

The mechanism of Step 4 involves a retro-aldol condensation reaction on the open-chain form of D-fructose 1,6-bisphosphate. This reaction, and the origin of the carbon atoms in the products, is shown below. 

If D-A adduct 1 contains some 1 2 adducts as impurities, 1,4-benzoquinone is formed by a retro-Diels-Alder reaction during the pyrolytic distillations. In this case, a dark yellow solid of benzoquinone can be seen on the walls of the air condenser, and the distillate has a deeper yellow color. Contamination with a small amount of 1,4-benzoquinone apparently does not interfere with photochemical [2+2] cycloadditions of enedione 3 with alkenes and alkynes, an important application of 3. Fractional distillation of the benzoquinone-contaminated 3 as described for the second distillation of 3 can remove the benzoquinone with some loss of enedione 3. The benzoquinone deposits initially as a dark yellow solid on the walls of the distillation head and air condenser during early fractions. 

A referee of this communication, later identified as Dan Singleton, proffered an alternative mechanism (Scheme 8.14) for the creation of 102. This is apseudoper-icyclic reaction (see Section 4.5 for a detailed discussion of this type of reaction) that leads from 98 directly to 102. In fact, the TS for this pseudopericyclic reaction is 19.0 kcal mol (MPWBIK/ 6-31-l-G(d,p)) lower in energy than the TS for the retro-Diels-Alder reaction of Scheme 8.11. 

The quinone methide (11) derived from flavan by a retro-Diels-Alder reaction gives only a 4% yield of acridine when heated with aniline. However, the other products include the diphenylmethane (12) and the Mannich base (13) both of which yield the tricyclic compound upon pyrolysis (J.L. Asherson. 0. Bilgic and D.W. Young, J. chem. Soc. Perkin I, 1980, 522). 

Only in the retro Diels-Alder reaction of cyclohexene at 1000 °C do isotope effects provide some support for part of the reaction not being concerted, see D. K. Lewis, B. Brandt, L. Crockford, D. A. Glenar, G. Rauscher, J. Rodriguez and J. E. Baldwin, J. Am. Chem. Soc., 1993,115, 11728. 

More recently, a Pd(II) salt was shown to catalyze the 1,2-insertion polymerization of a 7-oxanorbornadiene derivative (Fig. 10-16) [50]. The resulting saturated polymer, when heated, gives polyacetylene via a retro-Diels-Alder reaction. (This reaction is reminiscent of the Durham route to polyacetylene discussed below). One advantage of this technique over other routes is that it employs a late transition metal polymerization catalyst. Catalysts using later transition metals tend to be less oxophilic than the d° early transition metal complexes typically used for alkene and alkyne polymerizations [109,110]. Whereas tungsten alkylidene catalysts must be handled under dry anaerobic conditions, the Pd(II)-catalyzed reaction of water-insoluble monomers may be run as an aqueous emulson polymerization. 

The "cracking" of dicyclopentad iene to two moles of 1,3-cyclopentadiene (Eq. 12.8) is an example of a retro-Diels-Alder reaction. Predict the products to be anticipated from an analogous reaction with the compounds a-d. 

Toure, B. B., Hall, D. G. (2004). Three-component seqnential aza[4-l-2] cycloaddition/allylboration/retro-sulfinyl-ene reaction a new stereocontroUed entry to palustrine alkaloids and other 2,6-disubstituted piperidines. Angewandte Chemie International Edition, 43, 2001-2004. 

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