E
A. R. White et al.
Letter
Synlett
substituted acridinium core, and benzyl-substituted nitro-
gen atom. The substitution effects appear to be additive,
eliciting an excited-state lifetime exceeding 25 ns, which is
longer than any of the acridinium salts studied in Scheme 3.
(2) (a) Fukuzumi, S.; Kotani, H.; Ohkubo, K.; Ogo, S.; Tkachenko, N.
V.; Lemmetylnen, H. J. Am. Chem. Soc. 2004, 126, 1600.
(b) Kotani, H.; Ohkubo, K.; Fukuzumi, S. J. Am. Chem. Soc. 2004,
126, 15999.
(3) Joshi-Pangu, A.; Lévesque, F.; Roth, H. G.; Oliver, S. F.; Campeau,
L.-C.; Nicewicz, D.; DiRocco, D. A. J. Org. Chem. 2016, 81, 7244.
(4) Acridinium 2 can be purchased for US $871/g from Sigma–
Aldrich at the time of this publication.
25% yield (2-steps)
E0,0 = 2.59 eV
Cl
Cl
(5) Romero, N. A.; Margrey, K. A.; Tay, N. E.; Nicewicz, D. A. Science
2015, 349, 1326.
tBu
tBu
E1/2(C/C–) = –0.39 V vs. SCE
(6) (a) Fischer, C.; Sparr, C. Angew. Chem. Int. Ed. 2018, 57, 2436.
(b) Fischer, C.; Sparr, C. Tetrahedron 2018, 74, 5486.
E1/2(C*/C–) = 2.20 V vs. SCE
N+
–BF4
τ = 25.7 ns
27
(7) (a) Katritzky, A. R.; Brownlee, R. T. C.; Musumarra, G. Tetrahe-
dron 1980, 36, 1643. (b) Katritzky, A. R.; Manzo, R. H.; Lloyd, J.
M.; Patel, R. C. Angew. Chem. Int. Ed. Engl. 1980, 19, 306.
(8) Wu, D.; Feng, X.; Takase, M.; Haberecht, M. C.; Müllen, K. Tetra-
hedron 2008, 64, 11379.
Ph
Figure 2 Custom acridinium salt designed to possess an enhanced ex-
cited-state lifetime
(9) Birman, V. B.; Chopra, A.; Ogle, C. A. Tetrahedron Lett. 1996, 37,
5073.
(10) Gram-Scale Preparation of Acridinium Salts; Typical Proce-
dure for Acridinium 2
In conclusion, an efficient reaction manifold has been
developed to access our most stable and potent acridinium
photocatalyst (2). This new approach is a marked improve-
ment over the previous generation synthesis in terms of
step count, time, overall yield, scalability, and cost of start-
ing materials.13 We have also applied this versatile strategy
to the synthesis of a library of novel acridinium salts and
measured their photophysical properties. The insights at-
tained from this study are guiding ongoing efforts in cata-
lyst design aiming to strike an optimal balance between
cost, ease of preparation, stability, and photophysical prop-
erties.
3,6-Di-tert-butyl-9-mesitylxanthylium Tetrafluoroborate (3)
To a flame-dried 250 mL round-bottom flask under argon were
added 4 (8.02 g, 28.4 mmol, 1 equiv), TMEDA (8.71 mL, 58.2
mmol, 2.05 equiv), and anhydrous n-hexane (28 mL). The
resulting solution was cooled in an ice bath and sec-butyllith-
ium (1.4 M solution in cyclohexane, 42.0 mL, 58.2 mmol, 2.05
equiv) was added dropwise. The ice bath was removed and the
reaction mixture was stirred at room temperature for 4 h. The
reaction was cooled to –78 °C and a solution of methyl 2,4,6-
trimethylbenzoate (5.11 g, 28.7 mmol, 1.01 equiv) in anhydrous
n-hexane (28 mL) was added slowly via cannula. After the addi-
tion, the mixture was allowed to slowly warm to room tempera-
ture and stirred for 12 h. The reaction was quenched with water
(25 mL) and the biphasic mixture was stirred vigorously for 30
min. The mixture was diluted with Et2O (100 mL) and the layers
were separated. The organic layer was washed with water
(2 × 150 mL) and brine (1 × 150 mL). The organic layer was
transferred to a 250 mL round-bottom flask equipped with a
stir bar. To the vigorously stirred solution was added conc. HCl
(12 mL), resulting in a bright-yellow precipitate. The suspension
was stirred vigorously for 30 min then diluted with water (150
mL). The layers were separated and the organic layer was
extracted with water (3 × 150 mL or until the washings become
colorless). To the combined aqueous layers was added solid
NaBF4 (9.35 g, 85.2 mmol, 3 equiv), resulting in a bright-yellow
precipitate. The resulting suspension was extracted with
dichloromethane (3 × 150 mL or until the washings become col-
orless). To the combined organic layers was added HBF4·Et2O
complex (3.46 mL, 28.4 mmol, 1 equiv). The solution was
swirled to achieve homogeneity then washed with water
(1 × 100 mL) and aq. NaBF4 (1 M, 1 × 100 mL). The organic layer
was dried over solid NaBF4, filtered, and concentrated to dry-
ness. The residue was purified by trituration with hexanes and
filtered. The solid was rinsed with n-pentane and dried in vacuo
to give xanthylium 3 (10.6 g, 21.3 mmol, 75% yield) as a yellow-
orange solid. 1H NMR (600 MHz, CDCl3): = 8.50 (s, 2 H), 7.97–
7.88 (m, 2 H), 7.76 (d, J = 8.9 Hz, 2 H), 7.17 (s, 2 H), 2.49 (s, 3 H),
1.87 (s, 6 H), 1.54 (s, 18 H). 13C NMR (151 MHz, CDCl3): =
174.2, 171.0, 158.4, 141.3, 135.3, 129.2, 129.1, 128.5, 127.4,
122.0, 116.7, 37.5, 30.4, 21.3, 20.1. 19F NMR (376 MHz, CDCl3):
= –153.90, –153.96. HRMS (ESI+): m/z [M]+ calcd for C30H35O:
411.2688; found: 411.2687.
Funding Information
This project was supported by Award No. R01 GM098340 from the
National Institute of General Medical Sciences and a Camille Dreyfus
Teacher-Scholar Award (D.A.N.). L.W. was supported by the Interna-
tional Postdoctoral Exchange Fellowship Program. Photophysical
measurements were performed in the UNC-ERFC Instrumentation Fa-
cility established by the UNC-EFRC (Center for Solar Fuels, an Energy
Frontier Research Center funded by the U.S. Department of Energy,
Office of Science, Office of Basic Energy Sciences under Award Num-
ber DE-SC0001011).
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References and Notes
(1) For recent reviews, see: (a) Prier, C. K.; Rankic, D. A.; MacMillan,
D. W. C. Chem. Rev. 2013, 113, 5322. (b) Narayanam, J. M. R.;
Stephenson, C. R. J. Chem. Soc. Rev. 2011, 40, 102. (c) Yoon, T. P.;
Ischay, M. A.; Du, J. Nat. Chem. 2010, 2, 527. (d) Nicewicz, D. A.;
Nguyen, T. M. ACS Catal. 2014, 4, 355. (e) Romero, N. A.;
Nicewicz, D. A. Chem. Rev. 2016, 116, 10075. (f) Shaw, M. H.;
Twilton, J.; MacMillan, D. W. C. J. Org. Chem. 2016, 81, 6898.
(g) Wang, C.-S.; Dixneuf, P. H.; Soulé, J.-F. Chem. Rev. 2018, 118,
7532.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, A–F