Wavelength-Gated Photochemical Synthesis of Phenalene Diimides

Abstract

Herein, we pioneer a wavelength-gated synthesis route to phenalene diimides. Consecutive Diels-Alder reactions of methylisophthalaldehydes and maleimides afford hexahydro-phenalene-1,6-diol diimides via 5-formyl-hexahydro-benzo[f]isoindoles as the intermediate. Both photoreactions are efficient (82-99 % yield) and exhibit excellent diastereoselectivity (62-98 % d.r.). The wavelength-gated nature of the stepwise reaction enables the modular construction of phenalene diimide scaffolds by choice of substrate and wavelength. Importantly, this synthetic methodology opens a facile avenue to a new class of persistent phenalenyl diimide neutral radicals, constituting a versatile route to spin-active molecules.

Keywords: Diels-Alder reaction; ortho-quinodimethane; persistent neutral radicals; phenalene diimide; wavelength-gated synthesis.

Scheme 1

Top: Previously reported synthesis routes for polycyclic aromatic diimides via photoinduced Diels–Alder reaction of o‐QDMs and maleimides and subsequent elimination and oxidation reactions.^[12] It is important to note that diimides with two differing R groups could not be prepared by this method. Bottom: Herein presented wavelength‐gated, step wise synthesis of phenalenyl diimide scaffolds. The first addition of one equivalent of maleimide to photoreactive 2‐methylisophthalaldehydes (MIAs) at higher wavelength leads to the formation of 5‐formyl‐hexahydro‐benzo[f]isoindoles (FBIs). Subsequent addition of a second equivalent of maleimide at lower wavelength affords hexahydro‐phenalene‐1,6‐diol diimides (HPDDs). Acid‐catalyzed E1 elimination and subsequent 3‐electron oxidation leads to phenalenyl diimide neutral radicals (PLYD). The annulated ring systems marked grey cannot host a neutral radical. In contrast, the radical hosting phenalene ring system is highlighted turquoise.

Figure 1

A) ¹H NMR spectra and assigned resonances of the reaction between MIA 1 a and maleimide 2 a affording cycloadduct 3 a under irradiation with a 385 nm LED and subsequently to form cycloadduct 4 a under irradiation with a 365 nm LED (LED‐emission spectra Supporting Information Figure S1). The NMR spectra were recorded after removing the solvent from the respective batch photoreactions without further purification (excess N‐ethylmaleimide is removed in vacuo). For detailed characterization data (¹³C, 2D‐NMR spectra, and LC–HRMS) of all compounds as well as experimental details refer to the Supporting Information Figures S20, S21, S27, S28, S36–S40, S90, S96 and Supporting Information Section VI. B) Molar extinction coefficients of 1 a (solid black), 3 a (dashed blue) and 4 a (dash–dot brown) overlaid with the wavelength‐dependent reactivity of the substrate 1 a (1.6 mmol L⁻¹ of 1 a with 2.20 equiv of 2 a in CD₃CN) after irradiation with (9.4±0.2)×10¹⁸ photons of each wavelength from a 20 Hz, 7 ns tunable OPO laser. The conversions are determined by ¹H NMR spectroscopy (Supporting Information Figures S87 and S88).

Figure 2

A) Proposed mechanism of the light‐induced (Z)‐enol formation of MIA 1 a, transition state of the subsequent Diels–Alder reaction with maleimides forming endo‐FBIs and light‐induced (E)‐enol formation of FBIs, transition state of subsequent Diels–Alder reaction with second maleimide resulting in the formation of endo/endo‐HPDDs. B) Not observed FBI regioisomers by initial enolization of the p‐formyl instead of the o‐formyl moiety. C) Exo‐addition to MIA forming exo‐FBI and subsequent anti‐endo addition. This reaction sequence is realized in HPDD exo‐4 b. D) Observed anti‐exo addition transition state forming the endo/exo diastereomer, realized in exo‐4 e and not observed syn‐endo addition from the sterically disfavoured trajectory. E) Influence of the non‐planarity of maleimide substrate 2 c on the endo/exo selectivity of the Diels–Alder reaction. F) Substrates: MIAs 1 a, 1 b and maleimides 2 a–2 d. G) Isolated FBIs 3 a, endo/exo‐3 b, and 3 c. H) Isolated HPDDs 4 a–4 g. Triclinic crystal structure (ellipsoids with 50 % probability) of HPDD 4 a, displayed as pair of enantiomers within the asymmetric unit. ^[33] Stereocentres in the molecules depicted in (C–H) represent one enantiomer of the obtained racemic mixture. ¹ Yield of isolated product after diastereomer separation. ² Yield of isolated product from two separate reactions (substrates endo ‐3 b and exo ‐3 b).

Figure 3

A) Synthesis of phenalenyl diimide neutral radical 6 a from HPDD 4 a. B) EPR spectrum of 6 a in toluene at 25 °C (black line) and simulation of the spectrum (blue dotted line) C) Most stable phenalenyl diimide neutral radical 6 g. D) Selected examples of persistent phenalenyl neutral radicals (PLY1‐6) from literature.[ ¹⁰ , ²⁷ , ²⁸ , ²⁹ , ³⁰ , ³¹ ]