Lunazzi et al.
As discussed in ref 14, it is impossible to assign which
rotation pathway corresponds to the measured barriers solely
on experimental ground. Conventional wisdom clearly suggests,
General Procedure for Compounds 1-4. To a solution of the
appropriate ortho-bromo acylphenone (1 mmol in 6 mL of benzene)
were added K
boronic acid (2.5 mmol, suspension in 4 mL of ethanol), and Pd-
(PPh (0.2 mmol) at ambient temperature. The stirred solution
was refluxed for 2-3 h, the reaction being monitored by GC-
MS. Subsequently, CHCl and H O were added, and the extracted
organic layer was dried (Na SO ) and evaporated. The crude
material was purified by chromatography on silica gel (hexane).
2 3
CO (2 M solution, 1.25 mL), 3-isopropylphenyl
t
however, that the Ph-C(CH2) Bu bond rotation of 6 should have
t
3 4
)
a barrier larger than that of the Ph-C(O) Bu bond rotation of
4
. The CdCH2 and CdO planes are orthogonal to the phenyl
3
2
ring in both cases, but the steric hindrance of the former is
2
4
21
obviously larger than that of the latter. Consequently, the larger
-1
t
barrier (12.5 kcal mol ) should be assigned to the Ph-C(CH2) -
Bu bond rotation. On the other hand, the Ar-Ar rotation should
have similar barriers in both 4 and 6, because the steric
hindrance should be nearly the same, in that the t-BuCdO and
t-BuCdCH2 moieties are both orthogonal to their phenyl rings.
Thus, the lower barrier of 6, almost equal to that measured in
1
3
′-Isopropyl[1,1′-biphenyl]-2-carbaldehyde (1). H NMR (600
MHz, CDCl , 25 °C, TMS): δ 1.28 (6H, d, J ) 7.0 Hz), 2.97 (1H,
3
1
3
septet, J ) 7.0 Hz), 7.20-8.03 (8H, m), 9.98 (1H, s, CHO).
NMR (150.8 MHz, CDCl , 25 °C, TMS): δ 23.9 (CH ), 34.0 (CH),
26.2 (CH), 127.4 (CH), 127.5 (CH), 128.3 (CH), 128.4 (CH), 130.7
CH), 133.4 (CH), 133.7 (q), 137.6 (q), 146.3 (q), 149.6 (q), 192.5
C
3
3
1
(
(
CHO). Anal. Calcd for C16
H
16O: C, 85.68; H, 7.19. Found: C,
4
(Table 1), should be assigned to the Ar-Ar rotation. This
8
5.45; H, 7.19.
assignment agrees with the results of DFT computations of 6
1
1-(3′-Isopropyl[1,1′-biphenyl]-2-yl)-1-ethanone (2). H NMR
t
that indicate the Ph-C(CH2) Bu bond rotation barrier to be
(
(
600 MHz, CDCl
s, 3H), 2.93 (1H, septet, J ) 7.0 Hz), 7.17-7.54 (8H, m).
, 25 °C, TMS): δ 24.0 (CH ), 30.4 (CH
4.1 (CH), 126.1 (CH), 126.3 (CH), 127.2 (CH), 127.3 (CH), 127.8
(CH), 128.7 (CH), 130.1 (CH), 130.6 (CH), 140.6 (q), 140.9 (q),
3
, 25 °C, TMS): δ 1.26 (6H, d, J ) 7.0 Hz), 1.96
-
1
larger (11.3 kcal mol ) than that for the Ar-Ar rotation (6.6
13
C
-
1
kcal mol ).
NMR (150.8 MHz, CDCl
3
3
3
3
),
Conclusion
141.1 (q), 149.4 (q), 205.0 (CdO). Anal. Calcd for C17H18O: C,
We have thus found at least two unusual examples where
85.67; H, 7.61. Found: C, 85.41; H, 7.61.
apparently bulkier substituents (i.e., the t-Bu-CdX groups in
1-(3′-Isopropyl[1,1′-biphenyl]-2-yl)-2-methyl-1-propanone (3).
1
4
and 6) make the Ar-Ar rotation barriers lower than those
3
H NMR (600 MHz, CDCl , 25 °C, TMS): δ 0.80 (6H, d, J ) 6.7
occurring in apparently less crowded compounds (i.e., 1 and 5,
where the substituents are the “small” HCdX groups).
Hz), 1.26 (6H, d, J ) 6.8 Hz), 2.41 (1H, septet, J ) 6.8 Hz), 2.93
13
(
1H, septet, J ) 6.7 Hz), 7.15-7.49 (8H, m). C NMR (150.8
MHz, CDCl , 25 °C, TMS): δ 18.7 (CH ), 24.1 (CH ), 34.2 (CH),
0.3 (CH), 126.0 (CH), 126.3 (CH), 127.3 (CH), 127.4 (CH), 128.0
CH), 128.8 (CH), 130.1 (CH), 130.2 (CH), 140.1 (q), 140.6 (q),
3
3
3
4
(
Experimental Section
Materials. 2-Bromobenzaldehyde and 2′-bromoacetophenone
140.9 (q), 149.4 (q), 212.9 (CdO). Anal. Calcd for C19H22O: C,
85.67; H, 8.32. Found: C, 85.27; H, 8.36.
were commercially available and were used without further
22
purification. 1-(2-Bromo-phenyl)-2,2-dimethyl-propan-1-one and
-isopropyl-phenylboronic acid3b were prepared according to the
literature.
1-(3′-Isopropyl[1,1′-biphenyl]-2-yl)-2,2-dimethyl-1-pro-
1
3
panone (4). H NMR (300 MHz, CDCl
3
, 25 °C, TMS): δ 0.85
(9H, s), 1.25 (6H, d, J ) 6.9 Hz), 2.91 (1H, septet, J ) 6.9 Hz),
13
1-(2-Bromo-phenyl)-2-methyl-propan-1-one. To a solution of
7.12-7.43 (8H, m). C NMR (75.45 MHz, CDCl
3
, 25 °C, TMS):
isopropylmagnesium bromide (0.5 M, obtained from 3.69 g of
δ 24.1 (CH
3
), 27.4 (CH ), 34.2 (CH), 45.0 (q), 125.8 (CH), 125.9
3
2
-bromopropane and 0.73 g of Mg turnings in 60 mL of anhydrous
Et O) was slowly added, at 0 °C, a solution of o-bromobenzalde-
hyde (2.77 g in 40 mL of anhydrous Et O). After being stirred for
h, the solution was warmed to room temperature and quenched
(CH), 126.8 (CH), 127.1 (CH), 128.1 (CH), 128.6 (CH), 128.8 (CH),
129.8 (CH), 138.5 (q), 141.0 (q), 141.3 (q), 149.2 (q), 216.8 (Cd
2
O). Anal. Calcd for C20
H, 8.69.
H24O: C, 85.67; H, 8.63. Found: C, 85.50;
2
1
with aqueous NH
4
Cl. The mixture was then treated with H
SO ). After the solvent was
removed, the crude was purified by a silica gel chromatography
column (petroleum ether/Et O 4/1) to give 1-(2-bromo-phenyl)-2-
methyl-propan-1-ol. A solution of the alcohol (2.30 g, 10 mmol in
0 mL of CH Cl ) was then treated with pyridinium chlorochromate
4.30 g, 20 mmol), monitoring the reaction by TLC. The reaction
was complete in 3 h. After addition of 50 mL of Et O, the mixture
2
O,
General Procedure for Compounds 5 and 6. To a cooled (0
°C) solution of 3′-isopropyl[1,1′-biphenyl]-2-carbaldehyde (1) (224
mg, 1 mmol in 10 mL of n-hexane) was added 0.94 mL (1.5 mmol)
2
extracted (Et O), and dried (Na
2
4
of methyl-lithium (1.6 M in Et
terminated, the reaction was refluxed for 2 h and then quenched
with water (15-20 mL). The mixture was extracted with Et O,
dried (Na SO ), and the solvent removed at reduced pressure, and
192 mg (0.8 mmol) of pure 1-(3′-isopropyl-biphenyl-2-yl)-ethanol
was obtained. The crude was treated with P (0.50 g, 3.52 mmol
in CHCl ), and the solution was allowed to warm for 1 h. The
product was extracted with Et O, dried (Na SO ), and the solvent
2
O). When the addition was
2
2
2
2
2
(
2
4
2
was filtered on a short silica gel column and concentrated. The
crude was purified by a silica gel chromatography column
2 5
O
3
(
petroleum ether/Et
propan-1-one (2.05 g, overall yield 60%). H NMR (CDCl
MHz, 25 °C): δ 1.20 (6H, d, J ) 6.8 Hz), 3.33 (1H, septet, J )
2
O 10:1) to obtain 1-(2-bromo-phenyl)-2-methyl-
2
2
4
1
3
, 400
removed at reduced pressure to obtain 154 mg (0.7 mmol, 70%)
of 5. The same procedure was used to obtain 6 starting from 4
(yield 65%).
13
6
(
1
.8 Hz), 7.26-7.29 (2H, m), 7.36 (1H, m), 7.59 (1H, m). C NMR
CDCl , 100.6 MHz, 25 °C): δ 18.1 (2CH ), 40.1 (CH), 118.6 (CH),
27.2 (CH), 128.1 (CH), 131.0 (CH), 133.4 (Cq), 142.0 (Cq), 208.6
1
3-Isopropyl-2′-vinyl-1-1′-biphenyl (5). H NMR (300 MHz,
3
3
CDCl
J ) 7.0 Hz), 5.17 (1H, dd, J ) 10.9, 1.3 Hz), 5.69 (1H, dd, J )
7.5, 1.3 Hz), 6.73 (1H, dd, J ) 17.5, 10.9 Hz), 7.15-7.67 (8H,
3
, 25 °C, TMS): δ 1.28 (6H, d, J ) 7.0 Hz), 2.95 (1H, septet,
(CO).
1
13
20) At -147 °C, many other 13C lines of 6 split into two signals with
3 3
m). C NMR (75.45 MHz, CDCl , 25 °C, TMS): δ 24.2 (CH ),
(
a 75:25 proportion, due to two diastereomeric conformers being created by
two stereogenic axes. The major spectrum has been arbitrarily assigned to
the less hindered conformer, that is, that with the two substituents in an
anti relationship.
34.3 (CH), 114.0 (CH), 125.3 (CH), 125.8 (CH), 127.4 (CH), 127.5
(CH), 127.8 (CH), 128.0 (CH), 128.3 (CH), 130.2 (CH), 136.3 (CH),
1
40.1 (q), 140.6 (q), 140.9 (q), 148.7 (q). Anal. Calcd for C17
C, 91.84; H, 8.16. Found: C, 91.78; H, 8.35.
-[1-(tert-Butyl)vinyl]-3′-isopropyl-1-1′-biphenyl (6). H NMR
(600 MHz, CDCl , 25 °C, TMS): δ 0.76 (9H, s), 1.24 (6H, d, J )
6.8 Hz), 2.82 (1H, septet, J ) 6.8 Hz), 5.06 (1H, d, J ) 1.7 Hz),
18
H :
(21) Grilli, S.; Lunazzi, L.; Mazzanti, A.; Casarini, D.; Femoni, C. J.
1
2
Org. Chem. 2001, 66, 488-495. Coluccini, C.; Grilli, S.; Lunazzi, L.;
Mazzanti, A. J. Org. Chem. 2003, 68, 7266-7273.
3
(22) Cahiez, G.; Luart, D.; Lecomte, F. Org. Lett. 2004, 9, 4395-4398.
9300 J. Org. Chem., Vol. 71, No. 25, 2006