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13C NMR (CDCl3): d=128.3, 127.8, 127.7, 127.4, 126.9, 126.2, 125.5,
35.4, 33.4, 26.3 ppm; 13C NMR (CDCl3): d=180.6, 139.0, 133.9, 132.4,
128.3, 127.9, 127.8, 127.5, 126.9, 129.3, 125.6, 35.4, 33.7, 26.3 ppm;
MS (API/ES): m/z: 213.10 [MÀ1]; found: 213.0.
the weekend. NMR spectroscopic analysis revealed complete con-
version. The mixture was cooled to RT and filtered over celite. The
residual solids were washed with toluene, and the mother liquor
with 1m NaOH (31 L). The combined aqueous layers were ex-
tracted with toluene (1 L), dried over Na2SO4, and concentrated to
give biaryl compound 20 as a brown solid, which was used as
2,3-Dihydrophenanthren-4(1H)-one (14): MsOH (375 mL) was
stirred at 908C and acid 18 (71.6 g, 107 mmol) was added in one
portion. The mixture was stirred for 1 h at 90–958C and was subse-
quently cooled to RT. The mixture was poured slowly in ice/water
(4.5 L) and extracted with Et2O (3750 mL). The combined organic
layers were washed with NaHCO3 (750 mL) and water (750 mL),
dried over Na2SO4, and concentrated to give ketone 14 as a brown
oil, which crystallized upon standing (62.2 g, 95% yield). 1H NMR
(CDCl3): d=9.41 (1H, d), 7.92 (1H, d), 7.81 (1H, d), 7.63 (1H, t), 7.49
(1H, t), 7.32 (1H, d), 3.13 (2H, t), 2.79 (2H, t), 2.15–2.24 ppm (2H,
m); 13C NMR (CDCl3): d=200.7, 147.0, 134.4, 133.0, 131.6, 129.0,
128.5, 127.5, 127.2, 126.9, 126.0, 41.3, 31.8, 23.2 ppm; MS (API/ES):
m/z: 197.09 [M+1]; found: 197.1.
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such in the next reaction (16.7 g, 76% yield). H NMR (CDCl3): d=
9.48 (s, 1H), 8.28 (d, 1H), 8.19 (d, 1H), 8.09 (t, 2H), 7.80–7.91 (m,
3H), 7.48–7.57 (m, 2H), 7.38 (m, 3H), 7.29 (t, 1H), 7.18 (brs, 1H),
7.93 (t, 1H), 1.63 ppm (s, 9H); 13C NMR (CDCl3) d=193.1, 153.5,
143.1, 137.4, 134.7, 134.2, 133.9, 133.8, 132.8, 131.2, 131.1, 130.0,
129.8, 129.2, 128.8, 127.5, 127.4, 127.3, 127.0, 126.7, 126.6, 124.3,
121.0, 117.7, 81.3, 28.7 ppm; MS (API/ES): m/z: 470.17 [M+Na];
found: 470.1.
tert-Butyl 4-(3-ethynylphenanthren-4-yl)naphthalen-1-yl carba-
mate (9): K2CO3 (10.8 g, 78.4 mmol, 2.1 equiv), followed by dimeth-
yl 1-diazo-2-oxopropylphosphonate (9.5 g, 49.6 mmol, 1.33 equiv),
was added to aldehyde 20 (16.7 g, 37.3 mmol) in MeOH (735 mL).
The resulting mixture was stirred overnight at RT, after which NMR
spectroscopic analysis revealed complete conversion. Heptane
(900 mL), saturated NaHCO3 (900 mL), EtOAc (1.8 L), and water
(1.8 L) were added to the reaction mixture. The layers were sepa-
rated and the aqueous layer was extracted with EtOAc (900 mL).
The combined organic layers were dried over Na2SO4 and concen-
trated to give the crude alkyne (17.6 g). This material was purified
over SiO2 (1 L; eluent: EtOAc/heptane 2:8) to give alkyne 9 as
4-Bromo-1,2-dihydrophenanthrene-3-carbaldehyde (11): PBr3
(28.7 mL, 306 mmol, 2.4 equiv) was added dropwise to dry DMF
(28.6 mL, 369 mmol, 2.9 equiv) in dry dichloromethane (550 mL) at
08C. Ketone 14 (25 g, 127 mmol) in dry dichloromethane (475 mL)
was added in one portion after 1 h at 08C. The mixture was heated
to reflux overnight. The reaction mixture was cooled with ice/
MeOH, saturated NaHCO3 was added to make the mixture basic,
and the layers were separated. The aqueous layer was extracted
with dichloromethane (750 mL) and the combined organic layers
were washed with water (400 mL), dried over Na2SO4, and concen-
trated to give the crude aldehyde 11 (20 g). The obtained material
was purified by column chromatography over SiO2 (1 kg; eluent=
EtOAc/heptane 1:9) to give aldehyde 11 as a yellow oil (15.6 g,
1
a yellow solid (15 g, 91% yield). H NMR (CDCl3): d=8.12 (brd, 1H),
7.97 (q, 2H), 7.80 (q, 4H), 7.30–7.53 (m, 5H), 7.26 (m, 1H), 7.05
(brs, 1H), 6.88 (t, 1H), 2.73 (s, 1H), 1.62 ppm (d, 9H); 13C NMR
(CDCl3): d=153.7, 141.5, 137.1, 133.8, 133.7, 133.3, 132.8, 130.4,
130.1, 129.1, 128.8, 128.5, 128.3, 127.6, 127.5, 126.9, 126.6, 126.5,
126.4, 126.2, 123.8, 120.8, 118.4, 114.4, 83.6, 82.0, 81.0, 28.7 ppm;
MS (API/ES): m/z: 444.19 [M+1]; found: 444.3.
1
43% yield). H NMR (CDCl3): d=10.33 (1H, s), 8.71 (1H, s), 7.85 (2H,
s), 7.47–7.60 (2H, m), 7.34 (1H, d), 2.85 (2H, t), 2.60 ppm (2H, t);
13C NMR (CDCl3) d=192.9, 141.1, 138.1, 135.8, 134.0, 132.0, 130.5,
130.3, 129.0, 126.6, 126.0, 125.9, 125.6, 29.9, 22.9 ppm; MS (API/ES):
m/z: 287.00 [M+1]; found: 287.1.
5-Boc-aminohexahelicene (21): Alkyne 9 (5.0 g, 11.3 mmol) and
PtCl2 (290 mg, 1.1 mmol, 10 mol%) were stirred overnight in tolu-
ene (415 mL) at 808C, after which NMR spectroscopic analysis re-
vealed complete conversion. The mixture was concentrated and tri-
turated from EtOAc/heptane (2:8) to give helicene 21 as a yellow/
tert-Butyl 4-(3-formyl-1,2-dihydrophenanthren-4-yl)naphthalen-
1-yl carbamate (19): Bromide 11 (15.6 g, 54 mmol) in toluene
(300 mL) was placed in a flame-dried flask, and N2 was bubbled
through the mixtue for 10 min. A few drops of water were added
to the reaction mixture, followed by K3PO4(23.1 g, 109 mmol,
2 equiv), boronic acid 10a (23.4 g, 81 mmol, 1.5 equiv), Pd(OAc)2
(122 mg, 0.5 mmol, 1 mol%), and S-Phos (558 mg, 1.4 mmol,
2.5 mol%). The resulting mixture was heated to reflux overnight.
TLC analysis (eluent: EtOAc/heptane 2:8, detection: UV/CeMo dip)
revealed complete conversion. Water (750 mL) was added to the
mixture, which was extracted with EtOAc (2750 mL). The com-
bined organic layers were washed with water (500 mL), dried over
Na2SO4, and concentrated to give the crude coupled product
(35 g). The obtained material was purified over SiO2 (1 kg; eluent:
EtOAc/heptane 1:9) to give aldehyde 19 as a yellow product,
which was not pure according to TLC analysis, but contained only
a few minor impurities as determined by NMR spectroscopic analy-
sis (22.0 g, 91% yield). 1H NMR (CDCl3): d=9.52 (s, 1H), 8.07 (d,
1H), 7.86 (dd, 2H), 7.69 (d, 1H), 7.59 (d, 1H), 7.49–7.41 (m, 3H),
7.29 (d, 1H), 7.16 (t, 2H), 7.01 (brs, 1H), 6.81 (t, 1H), 3.07 (t, 2H,
2.89–2.84 (m, 1H), 2.74–2.63 (m, 1H), 1.59 ppm (s, 9H); 13C NMR
(CDCl3): d=193.6, 153.4, 152.2, 140.2, 137.9, 134.3, 133.9, 133.4,
132.1, 131.8, 131.6, 131.5, 129.5, 129.0, 128.3, 127.7, 127.1, 126.7,
126.3, 126.1, 125.1, 125.0120.8, 116.9, 81.3, 30.6, 28.6, 20.6 ppm; MS
(API/ES): m/z: 448.20 [MÀ1]; found: 448.2.
1
orange solid (4.8 g, 96% yield). H NMR (CDCl3): d=8.49 (brs, 1H),
7.88–8.00 (m, 5H), 7.82 (t, 2H), 7.69 (d, 1H), 7.59 (d, 1H), 7.17–7.29
(m, 3H), 7.11 (brs, 1H), 6.63–6.72 (m, 2H), 1.65 ppm (m, 9H);
13C NMR (CDCl3): d=153.7, 132.9, 132.0, 132.0 (2nd), 131.8, 131.6,
130.8, 130.1, 128.8, 128.0, 127.9, 127.7, 127.6, 127.5, 127.2, 127.0,
126.5, 125.9, 125.6, 125.3, 124.9, 124.8, 124.2, 122.5, 119.6, 81.2,
28.7 ppm; MS (API/ES): m/z: 442.19 [MÀ1]; found: 442.2.
5-Aminohexahelicene hydrochloride (22): Boc-amino helicene 21
(4.8 g, 10.8 mmol) was stirred overnight in 4n HCl in dioxane
(30 mL) at RT. The resulting solid was collected by filtration,
washed with Et2O, and dried on the rotary evaporator to give HCl
1
salt 22 as a yellow/brown solid. H NMR ([D6]DMSO): d=8.01–8.14
(m, 7H), 7.92–7.99 (d, 2H), 7.61 (brs, 1H), 7.45–7.52 (dd, 2H), 7.23–
7.35 (m, 2H), 6.64–6.75 ppm (m, 2H); 13C NMR ([D6]DMSO): d=
134.0, 133.4, 132.1, 131.8, 130.9, 130.7, 129.7, 128.8, 128.6, 128.2,
127.7, 127.6, 127.5, 127.1, 126.9, 126.8, 126.4, 125.6, 125.5, 123.5,
122.8 ppm; MS (API/ES): m/z: 344.14; found: 344.1.
5-Aminohexahelicene (8): Helicene salt 22 (3.0 g, 6.7 mmol) was
suspended in dichloromethane (100 mL) and was washed with sa-
turated NaHCO3 (50 mL). The aqueous layer was extracted with di-
chloromethane (50 mL) and the combined organic layers were
dried over Na2SO4 and concentrated to give amine 8 as a brown
solid (2.3 g, 85% yield). The material could be further purified by
column chromatography over SiO2 (dichloromethane with 0.5%
7n NH3 in EtOH) to provide a yellow–orange material. 1H NMR
tert-Butyl 4-(3-formylphenanthren-4-yl)naphthalen-1-yl carba-
mate (20): DDQ (13.9 g, 61 mmol, 1.25 equiv) was added to alkene
19 (22.0 g, 49 mmol) in benzene (1.5 L) and heated to reflux over
Chem. Eur. J. 2016, 22, 1484 – 1492
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