Industrielle Anwendungen der Diels‐Alder‐Reaktion

Abstract

Die Diels‐Alder‐Reaktion ist eine der beliebtesten Reaktionen aus dem Repertoire des Synthesechemikers zum effizienten Aufbau komplexer Moleküle. Überraschenderweise ist aber nur wenig zu ihrer industriellen Anwendung bei der Synthese von pharmakologischen Wirkstoffen, Agrochemikalien oder Riech‐ und Aromastoffen bekannt. Dieser Aufsatz behandelt ausgewählte Beispiele, mit einem Schwerpunkt auf Anwendungen in größerem Maßstab (>1 kg) aus Sicht der Prozessforschung und –entwicklung.

Deeper Insight into the Diels–Alder Reaction through the Activation Strain Model

“…[36,37] In order to understand what is behindt he above computed ratherd ifferent activation barriers, the ASM was applied next. As clearly seen in the ASD depicted in Figure5,t he strain energy remains nearly identical(or even, slightly less destabilizing for the [5,6]-pathway)f or both approaches, thus indicating that the energy required to deform the reactants is not the factor controlling the regioselectivity of the process. In contrast, the interaction energy between the deformed reactants becomes the differential factor favoring the [6,6]-cycloaddition along the entire reactionc oordinate, that is, from the correspondingr eactantc omplexes to the transition state region.…”

“…[32] 3.3. [6,6]-over [5,6]-bond preference in the DA reactions in-volvingC 60 fullerene It is very well established that cycloaddition reactions in empty fullerenes, such as C 60 fullerene, show aremarkable or even exclusive preference towards [6,6]-corannulenicb onds over [5,6]pyracylenic bonds. [33,34] Despite that, the reasons behind this [6,6]-selectivity were not fully understood until our recent study based on the combinationo ft he ASM and EDA methods.…”

“…The other energy terms remainpractically identical. The more stabilizingo rbital interactions for the [6,6] pathway can be ascribed to the shape of the triply degenerated LUMO of C 60 ,w hich has the appropriate p*c haracter on [6,6]-bonds but not on [5,6]-bonds.A saconsequence, am uch better < HOMO(cyclopentadiene) j LUMO(C 60 ) > overlap was computed for the [6,6]-cycloaddition from the initially formed reactant complext ot he corresponding transitionstate.…”

“…Figure 6. Comparative decomposition of the interactionenergy for the [6,6] (solid lines) and [5,6] (dashedlines) approaches of the DA reaction between cyclopentadiene and C 60 alongt he reactionc oordinate projectedo nto the forming C···Cb ond distance. Data taken from reference [35].…”

“…[2] For all these reasons, it is not surprising that this [4+ +2]-cycloaddition reaction has attracted considerable attention since its discovery in 1928 [3] from both experimental and theoretical points of view.I nt his sense, different aspects of this useful reaction have been studied, including asymmetric catalysis [4] and even, industrial applications. [5] Regarding the mechanisms of this transformation,w hich span from concertedt os tepwise processes (either involving diradical or zwitterionici ntermediates), theory has played an important role in understanding this process. For concerted reactions in particular, Fukui's frontier molecular orbital (FMO) [6,7] theory and Woodward-Hoffmann rules [8] have been traditionally used to interpret reactivity trends and regioselectivity patterns of different cycloaddition reactions.…”