Catalytic Asymmetric Bromine-Lithium Exchange: A New Tool to Build Axial Chirality
130.6, 136.3, 138.1, 140.3, 189.8; HR-MS: m/z=365.8892,
calcd. for C14H8Br2O2: 365.8891.
(CDCl3): d=2 (s, 6H), 7.55 (t, 2H, J=7.8 Hz), 7.65 (d, 2H,
J=7.6 Hz), 8 (d, 2H, J=7.6 Hz), 9.65 (s, 2H); 13C NMR
(CDCl3): d=19.7, 126.4, 128.6, 134.5, 135.9, 137.5, 140,
191.5; HR-MS: m/z=238.0994, calcd. for C16H14O2:
238.0994.
(S)-1,11-Dibromo-6-[(S)-3,3-dimethylbutan-2-yl]-6,7-
dihydro-5H-dibenzoACTHNUTRGNEUNG
[c,e]azepine (33)[11]
To dialdehyde 2 (crop of 44% ee) (60 mg) in CH3CN
(3.6 mL) was added (S)-dimethylbutan-2-amine (2 equiv.).
After 15 min of stirring, NaBH3CN (2 equiv.) was added and
the reaction stirred for 20 h before the addition of AcOH
(5 equiv.). Then the reaction was stirred for 1 h and the
product was quenched with 1M NaOH and extracted with
DCM/MeOH (98/2). Chromatographic filtration on silica gel
with DCM/MeOH (95/5), gave white solid with dr=1/2.6
measured by NMR in accordance with ee of the starting ma-
(S)-2,2’-Dibromo-6,6’-diiodobiphenyl (31)
Following the general procedure of asymmetric bromine-
lithium exchange using ent-14 as catalyst and as electrophile
I2 in 4 mL of THF. Chromatographic separation on silica gel
with pure pentane, gave a white solid with ee=80%; yield:
1
82%; [a]20: 5.28 (c 0.955, CHCl3). H NMR (CDCl3): d=7 (t,
2H, J=7D.8 Hz), 7.7 (dd, 2H, J=8.1 and 1 Hz), 7.95 (dd, 2H,
J=7.8 and 1 Hz); 13C NMR (CDCl3): d=100.1, 123.4, 131.3,
132.9, 138.5, 148.37; HR-MS: m/z=561.6923, calcd. for
C12H16Br2I2: 561.6926.
1
terial; yield: 93%. H NMR (CDCl3): d=0.8 (d, 2.13H, J=
7.1 Hz), 0.9 (2 s, 9H), 1.05 (d, 0.85H, J=7.1 Hz), 2.45 (q,
0.27H, J=7.1 Hz), 2.65 (q, 0.7H, J=7.1 Hz), 3.3–3.6 (m,
4H), 7.2 (m, 4H), 7.6 (m, 2H).
(S)-2,2’-Dibromo-6,6’-diphenylbiphenyl (36)
In a Schlenk tube, PdACHTNUGTRNEGNU(PPh3)4 (5 mol%), and 31 (70 mg)
(S)-6,6’-Dibromobiphenyl-2,2’-dicarboxylic Acid (29)
were mixed in THF (3 mL) and after 15 min PhZnCl·LiCl
[addition of PhLi (5 equiv.) to ZnCl2 (6 equiv.) in 1 mL of
THF at room temperature] was added dropwise. The reac-
tion was stirred at room temperature during 24 h. After
quenching with 1M HCl, the product was extracted with
ether followed by evaporation of solvent. Chromatographic
separation on silica gel with pure pentane, then pentane/
Following the general procedure of asymmetric bromine-
lithium exchange using ent-14 as catalyst, the electrophile
CO2 was bubbled into the Schlenk tube (dry ice in a syringe
with a long needle) for 30 min at À788C, then the mixture
was warmed up to rrom temperature. After quenching the
reaction, the organic layer was made basic (10% NaOH)
then extracted with ether. The aqueous phase was made
acid (1M HCl) then extracted EtOAc. Trituration with pen-
tane, then trituration in a minimum of DCM gave a white
powder with ee=80% (measured after formation of the
methyl diester); yield: 93%; [a]2D0: À2.58 (c 1.04, MeOH).
1H NMR (CDCl3): d=7.35 (t, 2H, J=8.1 Hz), 7.8 (dd, 2H,
J=7.8 and 1.3 Hz), 8.1 (dd, 2H, J=7.8 and 1.3 Nz);
13C NMR (CDCl3): d=126.1, 130, 133.4, 137.4, 144.5, 168.6;
HR-MS: m/z=396.8713, calcd. for C14H7O4Br2: 396.8716.
ether (9/1) gave
a white solid with ee=80%; yield:
1
70%;[a]25: À75.08 (c 0.625, CHCl3). H NMR (CDCl3): d=
6.65 (d,D4H, J=8.3 Hz), 7–7.2 (m, 8H), 7.25 (t, 2H, J=
7.8 Hz), 7.7 (dd, 2H, J=7.8 and 1 Hz); 13C NMR (CDCl3):
d=126.9, 127.1, 127.3, 129.1, 129.2, 129.3, 131.3, 139.4, 140.1,
143.4; HR-MS: m/z=461.9618, calcd. for C24H16Br2:
461.9619.
(S)-(6,6’-Dibromobiphenyl-2,2’-diyl)bis(trimethyl-
silane) (32)[16]
(S)-2,2’-Dibromo-6,6’-dimethylbiphenyl (30)[12]
Following the general procedure of asymmetric bromine-
lithium exchange using ent-14 as catalyst with as electrophile
TMSCl (5 equiv.) in 5 mL of THF. Chromatographic separa-
tion on silica gel with pure pentane, gave a colourless oil
with ee=80%; yield: 77%; [a]2D0: 2.98 (c 0.95, CHCl3).
1H NMR (CDCl3): d=0 (s, 18H), 7.25 (t, 2H, J=7.8 Hz),
7.6 (d, 2H, J=7.4 Hz), 7.7 (d, 2H, J=7.9 Hz); 13C NMR
(CDCl3): d=0.3, 125.9, 128.8, 132.9, 133.7, 143, 147.5.
Following the general procedure of asymmetric bromine-
lithium exchange using ent-14 as catalyst and as electrophile
MeI in 4 mL of THF. Chromatographic separation on silica
gel with pure pentane, gave a white solid with ee=81%;
yield: 85%. For ee=62% [a]2D0: À6.98 {c 0.62, EtOH) (lit.12
[a]2D0: 11.68 (c 1, EtOH) for (R) enantio-pure}; 1H NMR
(CDCl3): d=2.05 (s, 6H), 7.2 (t, 2H, J=7.7 Hz), 7.3 (d, 2H,
J=7.2 Hz), 7.6 (d, 2H, J=7.8 Hz); 13C NMR (CDCl3): d=
20.6, 123.9, 129.06, 129.1, 130.2, 138.4, 140.8.
(R)-6,6’-Dibromo-4,4’-dipropylbiphenyl-2,2’-di-
carbaldehyde (41)
(S)-6,6’-Dimethylbiphenyl-2,2’-dicarbaldehyde (34)
In a dry Schlenk tube was added 30 (50 mg) followed by
THF (2 mL). Then the mixture was cooled to À788C (dry
ice in acetone) for 10 min and t-BuLi (4 equiv.) was added
dropwise to it. After 1 h DMF (6 equiv.) was added and the
whole was allowed to warm to room temperature. Then
water was added (2 mL) and the product was extracted with
ether (3ꢄ2 mL). The organic phases were filtered through a
pad of Na2SO4 and solvents removed on a rotatory evapora-
tor. Chromatographic separation on silica gel, with pure
pentane, then pentane/ether (9/1), gave a white solid with
Following the general procedure of asymmetric bromine-
lithium exchange using 5 as catalyst, 40 as substrate and as
electrophile DMF. Chromatographic separation on silica gel
with pentane/ether (9/1), gave a white solid with ee=52%;
yield: 60% (absolute configuration was assigned by analogy
1
with 2); [a]20: +27.88 (c 0.795 in CHCl3). H NMR (CDCl3):
d=0.95 (t, D6H, J=7.3 Hz), 1.75 (m, 4H), 2.7 (t, 4H, J=
7.6 Hz), 7.8 (s, 2H), 7.85 (s, 2H), 9.55 (s, 2H); 13C NMR
(CDCl3): d=13.8, 24, 37.3, 125.7, 128, 136.3, 137.8, 138,
145.9, 190.2; HR-MS: m/z=472.97216, calcd. for
C20H20Br2Na1O2 [M+Na]+: 472.97223.
1
ee=80%; yield: 86%; [a]2D0: À53.98 (c 0.74, CHCl3). H NMR
Adv. Synth. Catal. 2010, 352, 2611 – 2620
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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