N‐Heterocyclic Carbene Catalyzed Photooxidation: Intramolecular Cross Dehydrogenative Coupling of Tetrahydroisoquinoline‐Tethered Aldehydes

Abstract

An N‐heterocyclic carbene catalyzed photooxidation reaction via intramolecular cross dehydrogenative coupling of tetrahydroisoquinoline‐tethered aldehydes was developed, giving the corresponding oxidative cyclization products in moderate to good yields. This reaction features mild conditions with oxygen as the terminal oxidant in the absence of photocatalyst.

Light opens a new window for N-heterocyclic carbene catalysis

“…Soon aer, a particularly NHC-catalyzed photooxidation reaction of tetrahydroisoquinoline (THIQ)-tethered aldehydes 85 was described by Ye and coworkers (Scheme 9). 24 In this intramolecular cross dehydrogenative coupling process, molecular oxygen was chosen as the optimal oxidant and a catalytic amount of NaI was necessary to improve the efficiency. Substrates with different substituents on the benzaldehyde and THIQ skeletons were compatible with this protocol and furnished various oxidative cyclization products 86 in moderate to excellent yields.…”

Light‐Promoted Organocatalysis with N‐Heterocyclic Carbenes

“…The Miyabe [15] and Ye [16,17] groups have combined NHC organocatalysis with photooxidation of aldehydes. These reactions exploit the typical umpolung reactivity of NHCs, where addition of the catalyst to the electron-deficient substrate and proton transfer provides an electron-rich enamine-like Breslow intermediate.…”

“…[16] While this reaction employs a cooperative NHC/photoredox strategy similar to those discussed in the previous section, in a very recent study, photooxidation of an aldehyde substrate was achieved without an additional photocatalyst. [17] Instead, the authors proposed a mechanism in which the Breslow intermediate derived from the tetrahydroisoquinoline-tethered aldehyde substrate 9 itself acts as the key photoactive species, absorbing light and undergoing oxidative quenching with O 2 (Scheme 5b). Further single electron oxidations facilitated by an iodide co-catalyst, hydrolysis of the resulting acyl azolium species and cyclisation afford the final tetracyclic products 10.…”

“…In an initial report by Ye and co‐workers incorporating a subsequent Smiles rearrangement of a salicylic acid derivative, a dual NHC/photoredox catalysis system was employed using the organic dye 9‐mesityl‐10‐methylacridinium perchlorate (Mes−Acr−Me + , Scheme a) . While this reaction employs a cooperative NHC/photoredox strategy similar to those discussed in the previous section, in a very recent study, photooxidation of an aldehyde substrate was achieved without an additional photocatalyst . Instead, the authors proposed a mechanism in which the Breslow intermediate derived from the tetrahydroisoquinoline‐tethered aldehyde substrate 9 itself acts as the key photoactive species, absorbing light and undergoing oxidative quenching with O 2 (Scheme b).…”

“… a) Dual‐catalyzed NHC/photooxidation/Smiles rearrangement . b) NHC‐Catalyzed photooxidation/cyclization in the absence of a photocatalyst . DABCO=1,4‐diazabicyclo[2.2.2]octane.…”