Search

Diaddition of alkenyllithium to 1,2-diones induce dianionic oxy-Cope rearrangements. As 1,2-diones some 1,2-diarylethane-1,2-diones were treated with (4,5-dihydrofuran-2-yl)lithium. The reaction, which took place at -78 °C, stereoselctively afforded meso-3,3'-coupled bis(tetrahydrofurans), which, in contrast to their 2,2' counterparts, have so far hardly been investigated. Two of the reaction products were characterized by crystal structure analyses. Subsequent intramolecular aldol addition gave a highly substituted octahydro-2H-cyclopenta[1,2-b:4,3-b']difuran, whose constitution and relative configuration were determined by NMR including NOE measurements.

The oxy-Cope rearrangement of aldol products has been studied both experimentally and theoretically to gain insight into the aspects that are responsible for the exceptional rate and diastereoselectivity of this process. Kinetic studies as well as DFT calculations convincingly show that the activation barrier of this process is mainly dependent on the electronic nature of the oxy-substituent, with electron-withdrawing O-substituents raising this barrier. The diastereoselectivity, however, remains uniformly high for all derivatives investigated and steric factors are proposed to account for the selectivity to a large extent. The poor diastereoselectivity in the case of the anti-aldols was also found in our calculations and it appears to result from unfavorable gauche interactions between the oxy and carboximide groups in the transition state.

The sequential ester dienolate [2,3]-Wittig/oxy-Cope rearrangement/carbonyl ene reaction has been investigated. Acyclic α,β-unsaturated α-allyloxy-substituted esters 1a−j were transformed into cyclopentane- or cyclohexanecarboxylates 6a−f and 7a−7d. This study presents a domino ester dienolate [2,3]-Wittig/oxy-Cope rearrangement or a domino oxy-Cope rearrangement/carbonyl ene reaction, depending on the substrate structure. The thermal intramolecular type-I carbonyl ene reaction as the terminating ring-closing reaction proceeds with high simple diastereoselectivity, but low induced diastereoselectivity. The corresponding type-II ene reaction afforded the cyclohexanecarboxylates 7a−d in high yield with complete simple and induced diastereoselectivity. Unfortunately, an attempted auxiliary-controlled enantioselective sequence was inefficient.

Dianionic oxy Cope rearrangements have been shown to take place at low temperature upon syn double addition of alkenyllithium derivatives to cyclobutanedione compounds such as benzocyclobutenedione chromium complex 1 or squaric acid esters. In order to obtain some insight into the more general applicability of this type of reaction sequence beyond these special cases, a number of 1,2-diketones were treated with vinyllithium. The diketones tested include benzil derivatives, aliphatic acyclic 1,2-diketones, ortho-quinones, and cyclic aliphatic 1,2-diketones. With benzil and heterobenzil derivatives, the desired double addition/dianionic oxy Cope rearrangement was found to take place at low temperature, leading to 1,6-diketones and their intramolecular aldol adducts in up to 80% overall yield. With acyclic aliphatic 1,2-diketones as substrates, this reaction sequence was also found, albeit with somewhat lower yields and requiring higher temperatures than in the benzil cases. A brief investigation of the intramolecular aldol adduct/1,6-hexanedione equilibrium indicated that the preferential formation of intramolecular aldol adducts at lower temperatures and at shorter reaction times appears to be the result of kinetic reaction control, whereas the preference for 1,6-diketones at higher temperatures is caused by thermodynamic reaction control. ortho-Quinones reacted with vinyllithium only by addition; no dianionic oxy Cope rearrangement was observed. This was also the case for most aliphatic cyclic diketones; however, in the case of 1,2-indanedione, rearrangement products were obtained in moderate yield at elevated reaction temperatures.

The (Z)-(iodovinyl)oxetane 12 was prepared from D-glucose and the acyclic analog 18 was obtained from D-mannitol. Following the generation of their lithium derivatives by halogen−metal exchange, coupling to the enantiopure vinyl-substituted norbornanones 20, 23, and 29 proceeded exclusively via endo attack to deliver the targeted exo-carbinols. The anionic oxy-Cope rearrangements of 21 and 24 were seen to differ appreciably in rate. While the sulfur derivative 24 experiences [3,3] sigmatropy with a half-life of less than a minute at −78 °C, its oxygen analogue 21 proved unreactive below −20 °C under entirely comparable conditions. This phenomenon is critically examined in a synthetic context involving 26 and 30, where the heavily functionalized acyclic side chain involved previously is supplanted by an oxetane assembly. In the sulfur example, isomerization occurs very rapidly as before with 100% transfer of chirality. The kinetic response of vinyl ether 26 now proved to be entirely comparable. However, the pathway followed in this instance was intramolecular nucleophilic attack by the “naked” alkoxide at the less substituted C−O bond of the oxetane with ring cleavage and formation of alcohol 28. The global findings provide a glimpse of the subtle way in which [3,3]-sigmatropic transpositions can be modulated by heteroatomic substitution.