Diene conformations

Diels-Alder reaction, 492 characteristics of, 492-497 dienes in, 496-497 dienophiles in. 493-494 electrostatic potential map of. 493 endo stereochemistry of, 495 HOMO in. 1188-1189 LUMO in. 1188-1189 mechanism of. 493 s-cis diene conformation in, 496-497... 

In the third sequence, the diastereomer with a /i-epoxide at the C2-C3 site was targeted (compound 1, Scheme 6). As we have seen, intermediate 11 is not a viable starting substrate to achieve this objective because it rests comfortably in a conformation that enforces a peripheral attack by an oxidant to give the undesired C2-C3 epoxide (Scheme 4). If, on the other hand, the exocyclic methylene at C-5 was to be introduced before the oxidation reaction, then given the known preference for an s-trans diene conformation, conformer 18a (Scheme 6) would be more populated at equilibrium. The A2 3 olefin diastereoface that is interior and hindered in the context of 18b is exterior and accessible in 18a. Subjection of intermediate 11 to the established three-step olefination sequence gives intermediate 18 in 54% overall yield. On the basis of the rationale put forth above, 18 should exist mainly in conformation 18a. Selective epoxidation of the C2-C3 enone double bond with potassium tm-butylperoxide furnishes a 4 1 mixture of diastereomeric epoxides favoring the desired isomer 19 19 arises from a peripheral attack on the enone double bond by er/-butylper-oxide, and it is easily purified by crystallization. A second peripheral attack on the ketone function of 19 by dimethylsulfonium methylide gives intermediate 20 exclusively, in a yield of 69%. 

Aliphatic dienes undergo three main photochemical pericyclic processes, whose individual efficiencies depend largely on the torsional angle about the central bond in the specific diene conformer which is excited. These are (a) cyclobutene formation, (b) bicyclof 1.1.0] butane formation and (c) [l,5]-hydrogen migration. A fourth process, methylcyclopropene formation, has also been observed in minor amounts in several cases. 

The reactivity of dienes in Diels-Alder reactions is also controlled by the diene conformation. The two planar conformations of 1,3-butadiene are referred to as s-trans and s-cis (equation 16). Calculations have shown the s-trans conformation to be 2-5 kcalmol-1 more stable than the s-cis conformation. Open-chain dienes can only react in their cisoid conformation. Thus, 2-substituted dienes are generally more reactive than 1,3-butadiene due to their stronger preference for the s-cis conformation. 1 -Cis substituted 1,3-butadienes are almost exclusively in the s-trans conformation and are not reactive in Diels-Alder reactions. Highly substituted dienes may, however, be present in the s-cis conformation during a sufficient amount of time to participate in Diels-Alder reactions, even if a 1 -cis substituent is present62. 

Complexation of the s-cis 1,3-diene conformer has been described as a hybrid of two extreme coordination modes an j4-diene (2a) and a a2,jr metallacyclopent-3-ene (2b). 

Every discussion of the Diels-Alder reaction for 1,3-butadiene includes the observation that cycloaddition should occur only from the s-cis conformer to produce czs-cyclohexene. This conformational selectivity, however, further implies that cycloaddition of s-trans- 1,3-butadiene should lead to trans-cyclohexene, but the s-trans region of this potential surface has remained unexplored. A study of this problem shows that the concerted and stepwise reaction paths exist for both diene conformers, connecting them to the respective cyclohexene isomers.661 It is also demonstrated that the usual paradigm for the Diels-Alder reactions is incomplete a thorough understanding of this archetypal reaction requires consideration of the full range of processes shown in Scheme 6.10, not just those involving the s-cis conformer. 

The diene conformation and the endo transition state give this product. 

Tungsten j4-diene cations in both s-trans and s-cis forms have been synthesized and the influence of the diene conformation on the regiochemistry of nucleophilic attack has been demonstrated488. Application of nucleophilic additions to Mo-complexed olefins in the construction of quaternary carbon centres has been summarized489. 

Schleyer proposed one last alternative method for ganging ASE. Noting that many of these better methods (especially those analogons to Reaction 3.24) require computation of many compounds, he developed the isomerization stabilization energy (ISE) method, particularly useful for strained aromatic systems. ISE measures the energy realized when an isomeric compound converts into its aromatic analog. Benzene itself cannot be analyzed by the ISE method, however, toluene can, and the ASE values of toluene and benzene are expected to be quite similar. The conversions of two different isomers into toluene provide the ISE for toluene (Reactions 3.27a and 3.27b). Both of these reactions do not conserve s-cis/s-trans diene conformations. Reaction 3.28 can be added once to Reaction 3.27a and twice to Reaction 3.27b to give the corrected ISE values of -32.0 and -28.9 kcal mol , respectively. 

In general, die influence of diene conformation on the rate of silico Diels-Alder reaction speaks for a concerted mechanism of the [4+2] cycloaddition. This mechanism is confirmed by the small influence of solvent polarity and radical trt s on the reaction rate, which speaks against a pronotmced ionic or radical multiple step mechanism. On the other hand, trans-piperylene reacts over 1000 times faster with the standard silaethene than does tra s,tra s-hexadiene, wh eas the opposite is true for ethenes [27]. This fact contradicts dramatically the carbon-analogy of silaethenes, fiom which either trans-piperylene reacts too fast, or trans.trans-hexadiene too slow with the silaethene. 

Characteristic chemical shift differences are observed between configurations 3 and 5. Relative to 5, the Cp resonances of (s-trans-dAene)-metallocene isomers (3) are shifted to high field. As shown for butadiene as an example (Table IV), complexation of the s-cis-diene conformer to the transition metal causes large chemical shift differences of meso, syn, and... 

Cycloheptadiene-l,3-dione iron tricarbonyl and the related 5,7-cyclooctadiene-l,4-dione complex were readily prepared . It is not surprising that these species do not tautomerize to form the enol-iron tricarbonyl complexes, i.e. of 3-hydroxytropone and 1,4-dihydroxycyclooctatetraene, because the dienes conform to the T 8-electron rule while their tautomers would not. 

HCl in Et0H/H20 (1 1, reflux, 30 h). In agreement with X-ray and NOE measurements of (451) and consistent with the assumed operation of an exo anomeric effect, reactive diene conformations (Q) and (R) were proposed. It was therefore inferred that the major cycloaddition pathway involves attack of the dienophile (452) at the least-hindered top face of conformer (Q). 

The addition of a C-2 (equation 1 R = H > alkyl, aryl > OMe NR2), C-3, or C-4 electron-donating substituent to a 1 -oxa-1,3-butadiene electronically decreases its rate of 4ir participation in a LUMOdiene-controlled Diels-Alder reaction (c/. Table 5). Nonetheless, a useful set of C-3 substituted l-oxa-l,3-buta-dienes have proven to be effective dienes ° and have been employed in the preparation of carbohydrates (Table 6). The productive use of such dienes may be attributed to the relative increased stability of the cisoid versus transoid diene conformation that in turn may be responsible for the Diels-Alder reactivity of the dienes. Clear demonstrations of the anticipated [4 + 2] cycloaddition rate deceleration of 1-oxa-1,3-butadienes bearing a C-4 electron-donating substituent have been detailed (Table 6 entry 4). >> "3 In selected instances, the addition of a strong electron-donating substituent (OR, NR2) to the C-4 position provides sufficient nucleophilic character to the 1-oxa-1,3-butadiene to permit the observation of [4 + 2] cycloaddition reactions with reactive, electrophilic alkenes including ketenes and sul-fenes, often in competition with [2 + 2] cycloaddition reactions. ... 

The examples of 2,3-diaza-1,3-butadienes participating as 4tt components of Diels-Alder reactions are rare, and each successful case constitutes the reaction of a cyclic diene confined to an s-Z (cisoid) diene conformation (Table 12). Typical efforts to promote the Diels-Alder reactions of 2,3-diaza-l,3-buta-dienes provide simple imine addition products, e.g. 2 1 adducts, or [3 + 2] criss-cross products that may be attributed to the strong preference for simple acyclic 2,3-diaza-1,3-butadienes to adopt an s-E (trans-oid) diene conformation. 

Photodimerization of simple 1,3-dienes in a 4 1 + 4 r cycloaddition process is typically an inefficient process . This is not surprising, given the highly ordered transition state for [4+4]-cycloadditions, and the predominance of the unreactive s-trans conformation . As a result, as noted above [2 + 2]-cycloadducts are often the major product, accompanied by varying amounts of vinylcyclohexenes and cyclooctadienes. Crossed photocycloadditions employing 1,3-dienes with substituents at the 2- or 3-positions can furnish greater amounts of cyclooctadiene products (equation This presumably results from a perturbation of the diene conformational equilibration to provide a higher proportion of the s-cis conformer. 

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