G
Synthesis
D. E. Collin et al.
Paper
endo-2,4-Dibromocyclopentadiene-1,8-dione (6)
CAS Reg. No. 2408937-98-2]
Dimethyl 1,4-Cubanedicarboxylate (1)
[
[CAS Reg. No. 2408937-98-2]
To a 500 mL flask, endo-2,4-dibromodicyclopentadiene-1,8-dione
bisethylene ketal (12; 58.5 g, 0.144 mol, 1.0 equiv) was dissolved por-
tionwise in concd H SO (>95%, 180 mL) at r.t.. After 30 h stirring at
r.t., the solution was slowly poured into a vigorously stirred ice-water
bath (1 L), forming a beige precipitate. The resulting slurry was fil-
To 1,4-cubanedicarboxylic acid (15; 7.00 g) in anhyd MeOH (200 mL)
under argon in a 500 mL flask, was added concd HCl (2.0 mL, 66.0
mmol, 1.8 equiv) dropwise. After 16 h at reflux under argon, the sol-
vent was concentrated under vacuum and the obtained solid dis-
solved in CH Cl (150 mL). The organic phase was washed with H O (7
2
4
2
2
2
tered under vacuum, washed with cold H O, and dried under high
vacuum. The crude solid (47.2 g) was dissolved in EtOAc (472 mL) in a
× 100 mL), then the aqueous phases were combined and extracted
with CH Cl (4 × 150 mL). The organic phases were combined, dried
2
2
2
2
L beaker with heating and stirring, then hexane (236 mL) was add-
(MgSO ), and concentrated under vacuum. The obtained black solid
4
ed. The pale beige precipitate formed was isolated by vacuum filtra-
tion, washed with ice-cold hexane/EtOAc (75 mL, 1:1), dried under
vacuum, and recrystallised from EtOAc/hexane to yield the title com-
pound (28.15 g, 0.089 mol) as colourless crystals. Further evaporation
of the filtrate gave a second crop (10.49 g, 0.033 mol) of colourless
crystals to afford, overall, 6 as colourless crystals; yield: 38.64 g (121.0
mmol, 84%); mp 164–165 °C.
was dry-loaded and purified by flash column chromatography (8:2
hexane/EtOAc) to afford 1 (5.67 g, 25.7 mmol) as a white solid. This
was subsequently repeated with 1,4-cubanedicarboxylic acid (15;
8.56 g) in anhyd MeOH (245 mL) and concd HCl (2.45 mL, 0.081 mol,
1.8 equiv), as above, to afford 1 (7.12 g, 32.3 mmol). Dimethyl 1,4-
cubanedicarboxylate (1; 12.79 g, 58.1 mmol) was thus obtained in
54% overall yield from endo-2,4-dibromocyclopentadiene-1,8-one (6).
IR (ATR): 1789 (s), 1717 (s), 1580 (w), 1554 (w), 985 (m), 886 (m), 722
(
Mp 163–164 °C; R = 0.51 (8:2 hexane/EtOAc).
f
s), 684 cm–1 (s).
IR (ATR): 3000 (s), 2955 (w), 1717 (s), 1440 (s), 1323 (s), 1206 (s),
1
–1
H NMR (400 MHz, CDCl ): = 7.67 (d, J = 2.9 Hz, 1 H, H ), 6.36 (dd, J =
1089 cm (s).
3
3
7
3
5
.0, 3.9 Hz, 1 H, H ), 6.26 (dt, J = 6.8, 0.9 Hz, 1 H, H ), 3.59 (ddd, J = 4.8,
1
6
5
H NMR (400 MHz, CDCl ): = 4.25 (s, 6 H), 3.72 (s, 6 H).
3
.9, 0.9 Hz, 1 H, H ), 3.53 (dd, J = 6.5, 2.9 Hz, 1 H, H3a), 3.21 (dd, J = 6.4,
7
1
3
C NMR (101 MHz, CDCl ): = 172.0 (2C, CO), 55.8 (2 C, C cubyl), 51.6
3
.1 Hz, 1 H, H7a).
(
2 C, CO CH ), 47.1 (6 C, CH cubyl).
2 3
1
3
C NMR (101 MHz, CDCl ): = 197.0 (C O), 192.4 (C O), 156.4 (C H),
3
1
8
3
Formula: C12H12O ; MW: 220.22 g·mol–1
Data consistent with the literature.22
.
4
134.1 (C H), 133.9 (C H), 129.8 (C Br), 60.3 (C Br), 49.0 (C3aH), 47.3
5 6 2 4
(C7H), 44.1 (C7aH).
Formula: C10H Br O ; MW: 317.96 g·mol–1.
6
2
2
Data consistent with the literature.22
Funding Information
1
,4-Cubanedicarboxylic Acid (15)
CAS Reg. No. 29412-62-2]
In a 2 L flask, endo-2,4-dibromocyclopentadiene-1,8-one (6; 34.31 g,
08.0 mmol, 1.0 equiv) was dissolved in MeOH (907 mL), H O (163
The authors acknowledge financial support from the ERDF (LabFact:
InterReg V project 121) and EPSRC (Photo-Electro Programme Grant
[
EP/P013341/1, and EP/K039466/1).
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mL), and H SO (1.36 mL), then degassed with bubbling argon for 15
2
4
Supporting Information
min. The resulting colourless solution was pumped (flow rate of 1.8
mL·min–1) through the photoflow microreactor (V = 54 mL) using a
i
Supporting information for this article is available online at
https://doi.org/10.1055/s-0040-1705964. Su
peristaltic pump and a 36 W UV-B narrowband lamp. After reaching
the steady-state (≈ 50 min), the product stream was collected until
the solution had passed through the photoreactor. Pure MeOH was
then pumped through for 50 min. The resulting yellow solution was
concentrated under vacuum and the obtained solid was heated at re-
p
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orting Inform atio
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Su
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p
orting Inform atio
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References
flux in H O (312 mL) for 3.5 h to ensure full hydrolysis of any remain-
(1) Eaton, P. E.; Cole, T. W. J. Am. Chem. Soc. 1964, 86, 962.
(2) Zhang, M.; Eaton, P. E.; Gilardi, R. Angew. Chem. Int. Ed. 2000, 39,
401.
(3) Eaton, P. E. Angew. Chem. Int. Ed. 1992, 31, 1421.
(4) Macreadie, L. K.; Mensforth, E. J.; Babarao, R.; Konstas, K.; Telfer,
S. G.; Doherty, C. M.; Tsanaktsidis, J.; Batten, S. R.; Hill, M. R.
J. Am. Chem. Soc. 2019, 141, 3828.
2
ing dimethyl ketal. On cooling to r.t., aq NaOH (81.12 g, 26% w/v, 312
mL) was added portionwise to the mixture, and the dark brown solu-
tion stirred for 15 h at reflux. The solution was cooled to 0 °C, and
concd HCl (160 mL) was added dropwise until a pH ≈ 1–2 was
reached. The brown precipitate was filtered and washed successively
with ice-cold H O (200 mL) and ice-cold MeOH (15 mL). The crude
2
solid was concentrated under high vacuum for 6 h, then transferred to
a 250 mL flask and heated under reduced pressure for several hours
(5) Huang, H.-T.; Zhu, L.; Ward, M. D.; Wang, T.; Chen, B.; Chaloux,
B. L.; Wang, Q.; Biswas, A.; Gray, J. L.; Kuei, B.; Cody, G. D.;
Epshteyn, A.; Crespi, V. H.; Badding, J. V.; Strobel, T. A. J. Am.
Chem. Soc. 2020, 142, 17944.
(60 °C) to afford 1,4-cubanedicarboxylic acid 15 (≈ 17.93 g) as a
brown crude solid.
1
(6) Locke, G. M.; Bernhard, S. S. R.; Senge, M. O. Chem. Eur. J. 2019,
H NMR (400 MHz, CD OD): = 4.19 (s, 6 H).
3
2
5, 4590.
1
3
C NMR (101 MHz, CD OD): = 175.5 (2 C, C=O), 57.8 (2 C, C cubyl),
3
(7) Biegasiewicz, K. F.; Griffiths, J. R.; Savage, G. P.; Tsanaktsidis, J.;
48.3 (6 C, CH cubyl).
Priefer, R. Chem. Rev. 2015, 115, 6719.
Formula: C10H O ; MW: 192.17 g·mol–1.
8
4
(8) (a) Flanagan, K. J.; Bernhard, S. S. R.; Plunkett, S.; Senge, M. O.
Chem. Eur. J. 2019, 25, 6941. (b) Grover, N.; Locke, G. M.;
Flanagan, K. J.; Beh, M. H. R.; Thompson, A.; Senge, M. O. Chem.
Eur. J. 2020, 26, 2405.
Data consistent with the literature.22
©
2020. Thieme. All rights reserved. Synthesis 2020, 52, A–H