Enantioselective Organocatalytic Diels–Alder Trapping of Photochemically Generated Hydroxy‐o‐Quinodimethanes

Abstract

The photoenolization/Diels–Alder strategy offers straightforward access to synthetically valuable benzannulated carbocyclic products. This historical light‐triggered process has never before succumbed to efforts to develop an enantioselective catalytic approach. Herein, we demonstrate how asymmetric organocatalysis provides simple yet effective catalytic tools to intercept photochemically generated hydroxy‐o‐quinodimethanes with high stereoselectivity. We used a chiral organic catalyst, derived from natural cinchona alkaloids, to activate maleimides toward highly stereoselective Diels–Alder reactions. An unconventional mechanism of stereocontrol is operative, wherein the organocatalyst is actively involved in both the photochemical pathway, by leveraging the formation of the reactive photoenol, and the stereoselectivity‐defining event.

Doppelbindungen? Untersuchungen der Rotationsbarrieren von cumulenischen C=C‐Bindungen in Tetraaryl[n]cumulenen (n=3, 5, 7, 9)

“…Synthetisiert wurden diese Verbindungen ausgehend von den Diolen 1-4 nach der in Schema 1angegebenen Syntheseroute.K eton 5,d as die Endgruppe festlegt, wurde nach einer abgewandelten bekannten Vorschrift hergestellt [23] und anschließend in die Acetylenbausteine 6-8 umgewandelt (siehe die Hintergrundinformationen fürDetails). Synthetisiert wurden diese Verbindungen ausgehend von den Diolen 1-4 nach der in Schema 1angegebenen Syntheseroute.K eton 5,d as die Endgruppe festlegt, wurde nach einer abgewandelten bekannten Vorschrift hergestellt [23] und anschließend in die Acetylenbausteine 6-8 umgewandelt (siehe die Hintergrundinformationen fürDetails).…”

Light-Triggered Enantioselective Organocatalytic Mannich-Type Reaction

“…6 But methods that use substoichiometric chiral catalysts remained unprecedented until recently, when our research group reported an organocatalytic strategy for successfully trapping A in a stereoselective fashion. 7 Our approach relied on the use of a chiral organic catalyst which could effectively activate the dienophilic maleimide D (Figure 1c). Building upon this precedent, we wondered whether organocatalysis 8 could offer other effective tools to stereoselectively trap photogenerated hydroxy-o-quinodimethanes A with different dienophiles.…”

“…11 We also tested the catalytic profile of 5c, since it provided the best results in our previous study on the stereocontrolled trapping of photoenol A with maleimides of type D (Figure 1c). 7 The experiments were performed over 14 hours, in toluene, at ambient temperature, and under irradiation by a single black-light-emitting diode (black LED, λmax = 365 nm). Benzaldimines bearing commonly used N-protecting groups, including N-Boc, N-tosyl, and N-PMP imines (Boc = tert-butyloxycarbonyl; tosyl = toluenesulfonyl; PMP = p-methoxyphenyl), did not lead to the formation of any product, and were recovered untouched.…”

“…18 As for the mechanism of stereocontrol, we initially thought that (DHQ)2PHAL 6a could interact with the transient photoenol (E)-A. This idea was motivated by our precedent studies 7 demonstrating that the quinuclidine core within the cinchona-based catalyst 5c could reduce the formation of the photoenol derived from 1a by means of an electron transfer mechanism. To evaluate whether the cinchona moiety in 6a could participate in a similar pathway, we conducted laser flash photolysis studies.…”

“…(DHQ)2PHAL 6a was purchased from Sigma Aldrich. Cyclic imines 2 20 and benzophenones 7 were prepared according to procedures reported in the literature. Chromatographic purification of products was accomplished using force-flow chromatography (FC) on silica gel (35-70 mesh).…”