6
D. T. SEIDENKRANZ ET AL.
Synthesis
(500 MHz, CDCl ) δ: 7.89 (t, J = 8.0 Hz, 4H), 7.51 (d,
3
J = 8.4 Hz, 2H), 7.39 (t, J = 7.5 Hz, 2H), 7.21 (t, J = 7.6 Hz,
Dibromomethylbinapthalene precursors were prepared
according to scheme S1 using a modified procedure as
reported by Ooi et al. The resultant compounds had
spectroscopic signals that matched the reported data (50).
13
2
H), 7.05 (d, J = 8.5 Hz, 2H), 2.04 (s, 6H). C NMR (126 MHz,
CDCl ) δ: 135.26, 134.42, 132.89, 132.35, 128.86, 128.06,
3
1
27.56, 126.21, 125.78, 125.02, 20.18.
S)-2,2′-Dimethyl-1,1′-binaphthyl, [(S)-II]. Was prepared
similar to (R)-2 using the following amounts: (S)-I (4.86 g,
.83 mmol), NiCl (dppp) (157 mg, 0.265 mmol), degassed
(
2
,2′-bis(trifluoromethanesulfonyloxy)-1,1′-binaphthyl,
(R)-I]. (R)-BINOL (2.01 g, 7.02 mmol), N-phenylbistri-
fluormethanesulfonamide (5.02 g, 14.1 mmol), DIPEA
3.60 mL, 21.7 mmol) were combined in 10 mL dry
[
8
2
Et O (40 mL), MeMgI (2 M in Et O, 13 mL, 26 mmol). The
2
2
(
final product was isolated as an oil that solidified upon
DMF and stirred at r.t. for 24 hours. The reaction was
diluted with Et O, washed 3x with H O and then with
1
standing (2.185 g, 88%) H NMR (500 MHz, CDCl ) δ: 7.89
3
2
2
(t, J = 8.0 Hz, 4H), 7.51 (d, J = 8.4 Hz, 2H), 7.39 (ddd, J = 8.1,
brine. The organic layer was dried over MgSO, filtered
and concentrated under vacuum. The crude product
was purified by column chromotography using hex-
anes:EtOAc gradiant (0% – 20%) as the eluent
6
.6, 1.1 Hz, 2H), 7.21 (ddd, J = 8.2, 6.8, 1.3 Hz, 2H), 7.05 (d,
13
1
J = 8.4 Hz, 2H), 2.04 (s, 6H). C{ H} NMR (126 MHz, CDCl )
3
δ: 135.27, 134.43, 132.90, 132.36, 128.86, 128.06, 127.57,
1
26.22, 125.78, 125.03, 20.18.
R)-2,2′-Bis(bromomethyl)-1,1′-binaphthyl, [(R)-III]. (R)-
II (428 mg, 1.52 mmol), N-bromosuccinimide (594 mg,
.34 mmol), and AIBN (24.3 mg, 0.148 mmol, 10%) were
dissolved in benzene (15 mL) and heated to reflux for
hours. The reaction was cooled to room temperature
(
Rf = 0.12, Hex; R = 0.45, 20% EtOAc) to yield the
f
(
final product as an oil that solidifies to a white solid
1
upon standing (3.27 g, 85%) H NMR (500 MHz, CDCl )
3
3
δ: 8.15 (d, J = 9.1 Hz, 2H), 8.02 (d, J = 8.3 Hz, 2H),
7
.66–7.57 (m, 4H), 7.43 (t, J = 7.6 Hz, 2H), 7.32–7.19
3
1
3
1
(m, 2H). C{ H} NMR (126 MHz, CDCl ) δ: 145.51,
3
and diluted with Et O. The organic layer was washed 3x
2
1
1
33.27, 132.48, 132.12, 128.48, 128.11, 127.45, 126.88,
23.57, 119.46, 118.26 (q, J = 320.7 Hz). F NMR
with H O, 3x brine, dried over MgSO and filtered. The
19
2
4
crude product was purified using column chromotogra-
(471 MHz, CDCl ) δ: −74.56.
3
phy (R = 0.23, Hex). The combined fractions were con-
f
2,2′-bis(trifluoromethanesulfonyloxy)-1,1′-binaphthyl,
centrated and the product was triturated in hexanes and
[(S)-I]. Was prepared similar to (R)-I using the following
then filtered to yield the final product as a white solid
amounts: (S)-BINOL (996 mg, 3.48 mmol), N-phenylbistri-
fluormethanesulfonamide (2.50 g, 7.00 mmol), DIPEA
1
(
302 mg, 45%) H NMR (500 MHz, CDCl ) δ: 8.02 (d,
3
J = 8.6 Hz, 2H), 7.93 (d, J = 8.2 Hz, 2H), 7.75 (d, J = 8.6 Hz,
(
1.8 mL, 10 mmol) in 5 mL DMF. The product was isolated
2
7
H), 7.49 (ddd, J = 8.2, 6.7, 1.0 Hz, 2H), 7.32–7.18 (m, 2H),
.08 (d, J = 8.5 Hz, 2H), 4.26 (s, 4H). C{ H} NMR (126 MHz,
1
as a white solid (1.35 g, 71%). H NMR (500 MHz, CDCl ) δ:
3
13
1
8.15 (d, J = 9.1 Hz, 2H), 8.01 (d, J = 8.3 Hz, 2H), 7.62 (d,
CDCl ) δ: 134.33, 134.23, 133.41, 132.66, 129.52, 128.17,
3
J = 9.1 Hz, 2H), 7.59 (ddd, J = 8.1, 6.7, 1.0 Hz, 2H), 7.42 (ddd,
1
27.89, 126.99, 126.97, 126.94, 32.78.
S)-2,2′-Bis(bromomethyl)-1,1′-binaphthyl, [(S)-III]. Was
prepared similar to (R)- III using the following amounts:
S)-II (501 mg, 1.77 mmol), N-bromosuccinimide (668 mg,
.75 mmol), and AIBN (32.0 mg, 0.195 mmol), and
13
1
J = 8.2, 6.8, 1.2 Hz, 2H), 7.32–7.19 (m, 2H). C{ H} NMR
(
(
126 MHz, CDCl ) δ: 145.51, 133.28, 132.48, 132.12, 128.48,
3
1
28.11, 127.45, 126.89, 123.57, 119.53, 118.26 (q, J = 320.7).
(
3
1
9
F NMR (471 MHz, CDCl ) δ: −74.57.
3
(R)-2,2′-Dimethyl-1,1′-binaphthyl, [(R)-II]. (R)-I (2.502 g,
benzene(15 mL). After 3 hours 125 mg (0.702 mmol)
NBS and 5.0 mg (3.0 µmol) AIBN were added and heated
to reflux for an additional hour. The final product was
4
.54 mmol) and NiCl (dppp) (82.0 mg, 0.139 mmol) were
2
combined in a Schlenk and evacuated/refilled 3x with and
atmosphere of N . Dry and degassed Et O (25 mL) was
2
2
1
isolated as a white solid (294 mg, 38%). H NMR (500 MHz,
added via cannula and cooled to 0 °C. MeMgI (2 M in Et O,
2
CDCl ) δ: 8.02 (d, J = 8.6 Hz, 2H), 7.93 (d, J = 8.2 Hz, 2H),
3
6
.8 mL, 14 mmol) was added slowly. The reaction mixture
7
.75 (d, J = 8.6 Hz, 2H), 7.49 (t, J = 7.5 Hz, 2H), 7.28 (t,
was then heated to reflux and stirred for 19 hours. The
reaction was then cooled to 0 °C and quenched with 2 mL
1
3
J = 7.9 Hz, 2H), 7.08 (d, J = 8.5 Hz, 2H), 4.26 (s, 4H). C NMR
126 MHz, CDCl ) δ: 134.33, 134.23, 133.40, 132.65, 129.51,
(
3
of 1 M HCl (aq), diluted with Et O, and filtered through
2
1
28.17, 127.89, 126.99, 126.96, 126.94, 32.78.
celite. The organic layer was then washed 3x with H O and
2
brine, dried over MgSO , filtered, and concentrated under
4
vacuum. The crude mixture was dissolved in hexanes and
the risdual salts removed via filtration. The product was
purified using column chromotograpny using hexanes as
General synthesis of barbituric acid derivatives 1–3
To a solution of barbituric acid (1 equiv.) in DMSO was
added diisopropylethylamine (DIPEA, 2.3 equiv.) The
mixture was stirred at room temperature for 10 min,
the eluent (R = 0.23) to yield the final product as a color-
f
1
less oil that solidifies upon standing (1.08 g, 84%). H NMR