Picomole‐Scale Real‐Time Photoreaction Screening: Discovery of the Visible‐Light‐Promoted Dehydrogenation of Tetrahydroquinolines under Ambient Conditions

Abstract

The identification of new photocatalytic pathways expands our knowledge of chemical reactivity and enables new environmentally friendly synthetic applications. However, the development of miniaturized screening procedures/platforms to expedite the discovery of photochemical reactions remains challenging. Herein, we describe a picomole-scale, real-time photoreaction screening platform in which a handheld laser source is coupled with nano-electrospray ionization mass spectrometry. By using this method, we discovered an accelerated dehydrogenation pathway for the conversion of tetrahydroquinolines into the corresponding quinolines. This transformation is readily promoted by an off-the-shelf [Ru(bpy)3 ]Cl2 ⋅6 H2 O complex in air at ambient temperature in direct sunlight, or with the aid of an energy-saving lamp. Moreover, radical cations and trans-dihydride intermediates captured by the screening platform provided direct evidence for the mechanism of the photoredox reaction.

Flavinium Catalysed Photooxidation: Detection and Characterization of Elusive Peroxyflavinium Intermediates

“…We varied the reaction time by irradiating the infused solution either in the vial, along the silica capillary,oratthe tip of the capillary (Figure 2and Figures S2, S15, S16 in the Supporting Information). [11] Thei rradiation at the tip of the capillary, right before it evaporates into the gas phase,a llowed us to observe short-lived intermediates.T hese intermediates were formal adducts of flavinium cation (1a + )w ith:h ydrogen peroxide,[ 1a+ 2H,2 O] + (m/z 455), benzylhydroperoxide, [1a+ Bn,H,2 O] + (m/z 545), and dibenzylperoxide,[ 1a+ 2Bn,2 O] + (m/z 635) ( Figure 2b). Signals of these intermediates disappear if the irradiation is blocked or if we irradiate further along the capillary,t hereby prolonging the reaction time.…”

Detection of Fleeting Amine Radical Cations and Elucidation of Chain Processes in Visible-Light-Mediated [3 + 2] Annulation by Online Mass Spectrometric Techniques

“…Finally, this study provides another good example of using MS to detect elusive and transient reaction intermediates in low quantity. 7,8 We believe that we have just scratched the surface of ESI-MS with online irradiation’s and online electrolysis’ potential in studying visible light photocatalysis, and more new applications are anticipated to come.…”

“…4,6 However, these spectroscopic methods usually lack structural information of the transient intermediates. Mass spectrometry (MS) has become a powerful technique for detecting and characterizing short-lived reaction intermediates as well as studying reaction mechanisms, since the advent of soft ionization methods such as electrospray ionization (ESI) 7 and desorption electrospray ionization (DESI) 8 . The inherent high sensitivity and rich mass information provided by MS measurements distinguish it from other commonly used methods.…”

“…9 Although MS in combination with online photolysis (e.g., using lamp or laser to irradiate a reaction mixture prior to MS detection) has been previously reported in literature, 7q,13 this type of setup has been rarely used to study the mechanism of visible-light triggered photoredox reactions. 7q Moreover, none of the reported MS studies provided any conclusive evidence for the chain reaction mechanism involved in photoredox reactions. Our setup not only allows for the direct detection of elusive reaction intermediates via online photolysis using a laser pointer (Figure 1a), but also enables coupling with an online microreactor to study the reactivities of the reaction intermediates.…”

High throughput reaction screening using desorption electrospray ionization mass spectrometry

“… 21 , 22 The combination of another ambient method, paper spray, with in situ analysis has also been reported. 23 …”