The Journal of Organic Chemistry
Article
0
.088 mmol, 59%) as a colorless oil. Characterization data for 17 are
Deuterium Incorporation in Product 9 Using 4,4-d -
2
6
included in the preceding article.
E)-(2-(1-Methylcyclohexyl)vinyl)benzene (18). In an identical
fashion, N-(acyloxy)phthalimide 4 (43 mg, 0.15 mmol, 1 equiv) was
coupled with β-bromostyrene (97 μL, 0.75 mmol, 5 equiv) to give a
crude residue, which was purified by silica gel chromatography (100%
pentane) to provide 18 (18 mg, 0.089 mmol, 59%) as a colorless oil.
Hantzsch Ester 23. A 1-dram vial was charged with N-(acyloxy)-
(
phthalimide 4 (75 mg, 0.26 mmol, 1 equiv), Ru(bpy)
2.6 μmol, 0.01 equiv), 4,4-d -Hantzsch ester 23 (100 mg, 0.39 mmol,
1.5 equiv), and a magnetic stir bar under argon. After sequential
addition of CH Cl (1.7 mL, sparged with Ar for 5 min), methyl vinyl
ketone (32 μL, 0.39 mmol, 1.5 equiv), and i-Pr NEt (100 μL, 0.57
3 6 2
(PF ) (3 mg,
2
2
2
2
6
Characterization data for 18 are included in the preceding article.
mmol, 2.2 equiv), the vial was capped and placed in the center of a 30
cm loop of blue LEDs. The reaction mixture was stirred for 18 h, after
which time it was concentrated under reduced pressure. Purification by
silica gel chromatography (2.5% EtOAc/hexanes) provided ketone 9
(21 mg, 0.13 mmol, 48%) as a colorless oil. Deuterium incorporation
1-(2-Phenylallyl)adamantane (19). In an identical fashion, N-
(
acyloxy)phthalimide 1 (49 mg, 0.15 mmol, 1 equiv) was coupled with
α-(bromomethyl)styrene (14) (33 μL, 0.23 mmol, 1.5 equiv) to give a
crude residue, which was purified by silica gel chromatography (100%
pentane) to provide 19 (27 mg, 0.11 mmol, 72%) as a colorless solid.
1
was determined by comparing the relative H NMR integrations of the
6
Characterization data for 19 are included in the preceding article.
α-keto methyl singlet resonance with the multiplet signal correspond-
1
2-((4,4-Dimethyl-6-phenylhept-6-en-1-yl)oxy)-1,4-dimethyl-
ing to protons at C2 (see ref 6 for an H NMR spectrum of this
1
benzene (20). In an identical fashion, N-(acyloxy)phthalimide 3 (59
mg, 0.15 mmol, 1 equiv) was coupled with α-(bromomethyl)styrene
product with high deuterium incorporation). H6 NMR analysis
determined the deuterium incorporation to be 33%.
(
14) (33 μL, 0.23 mmol, 1.5 equiv) to give a crude residue, which was
Preparation of the Product of Reductive Coupling 25 and
purified by silica gel chromatography (0−2% diethyl ether/pentane) to
provide 20 (44 mg, 0.14 mmol, 91%) as a colorless oil. R 0.16 (100%
hexanes); H NMR (500 MHz, CDCl ): δ 7.41 (d, J = 7.4, 2H), 7.33
(
7
6
1
1
1
Allylation 26 (Scheme 2). A 1-dram vial was charged with N-
(acyloxy)phthalimide 4 (75 mg, 0.26 mmol, 1 equiv), Ru(bpy) (PF )
3 6 2
(3 mg, 2.6 μmol, 0.01 equiv), Hantzsch ester 8 (100 mg, 0.39 mmol,
f
1
3
t, J = 7.5, 2H), 7.28−7.25 (m, 1H), 7.04 (d, J = 7.5, 1H), 6.69 (d, J =
.5, 1H), 6.61 (s, 1H), 5.28 (d, J = 1.9, 1H), 5.07 (s, 1H), 3.81 (t, J =
1.5 equiv), and a magnetic stir bar under argon. After sequential
6
addition of CH
Cl
2
(1.7 mL, sparged with Ar for 5 min), acceptor 24
2
.6, 2H), 2.54 (s, 2H), 2.34 (s, 3H), 2.21 (s, 3H), 1.79−1.72 (m, 2H),
(84 mg, 0.39 mmol, 1.5 equiv), and i-Pr
2
NEt (100 μL, 0.57 mmol, 2.2
1
3
.37−1.31 (m, 2H), 0.82 (s, 6H); C NMR (125 MHz, CDCl ): δ
equiv), the vial was capped and placed in the center of a 30 cm loop of
blue LEDs. The reaction mixture was stirred for 18 h, after which time
3
57.2, 147.4, 144.0, 136.5, 130.4, 128.3, 127.1, 126.7, 123.7, 120.7,
16.9, 112.1, 68.7, 47.0, 38.6, 34.2, 27.8, 24.5, 21.6, 16.0; IR (thin
it was diluted with Et
funnel. The ether layer was washed with aqueous 4 N HCl (4 × 20
mL) and aqueous 2 N NaOH (3 × 20 mL) and dried over MgSO
O (30 mL) and transferred to a separatory
2
film): 2953, 2925, 2867, 1616, 1585, 1509, 1469, 1265, 1157, 1130,
1
3
−1
+
044 cm ; HRMS-CI (m/z) [M + H] calculated for C H OH
.
4
23
30
23.2375, found 323.2386.
-Phenylallylation of the N-(Acyloxy)phthalimide Derivative
of 18β-Glycyrrhetinic Acid to Form 21. In an identical fashion,
The organic layer was filtered and concentrated under reduced
pressure. The crude residue was subjected to silica gel chromatography
(4% acetone/hexanes) to provide 25 (23 mg, 0.07 mmol, 29%, dr
8:2:1:1) and 26 (25 mg, 0.13 mmol, 51%) as colorless oils.
Characterization data for 25 and 26 are included in the preceding
2
5
N-(acyloxy)phthalimide 5 (92 mg, 0.15 mmol, 1 equiv) was coupled
with α-(bromomethyl)styrene (14) (33 μL, 0.23 mmol, 1.5 equiv).
After 18 h, the reaction mixture was diluted with CH Cl , the resulting
6
article.
2
2
organic phase was washed with 4 M HCl (3 × 10 mL), dried over
Preparation of Reductive-Coupling Product 25 (eq 5). A 1-
dram vial was charged with N-(acyloxy)phthalimide 4 (100 mg, 0.35
Na SO , and evaporated under reduced pressure. The crude residue
2
4
was purified by silica gel chromatography (20−30% acetone/hexanes)
mmol, 1.5 equiv), Ru(bpy)
Hantzsch ester 8 (88 mg, 0.35 mmol, 1.5 equiv), i-Pr
mg, 0.23 mmol, 1 equiv), and a magnetic stir bar under argon. After
sequential addition of THF (1.1 mL, sparged with Ar for 5 min),
3
(PF
6
)
2
(3 mg, 3.5 μmol, 0.015 equiv),
NEt·HBF (50
to provide an inseparable 3:1 mixture of C19 epimers of 21 (61 mg,
2
4
0
.11 mmol, 75%) as a colorless solid. Mixture of two epimers: R 0.53
f
1
(
30% acetone/hexanes); mp 72−74 °C; H NMR (500 MHz,
6
CDCl ): δ 7.37−7.27 (m, 5.7H), 7.25−7.21 (m, 1H), 5.49 (s, 1H),
CH
Cl
2
2
(1.1 mL, sparged with Ar for 5 min), and acceptor 24 (49
3
5
0
2
2
1
.25 (d, J = 1.8, 1H), 5.21 (d, J = 1.7, 0.3H), 5.10 (s, 0.3H), 5.04 (s,
.3H), 5.00 (s, 1H), 3.24−3.19 (m, 1.3H), 2.77 (d, J = 13.4, 1.3H),
.72 (d, J = 13.3, 0.3H), 2.51 (d, J = 13.3, 1H), 2.43−2.36 (m, 1.3H),
.25 (d, J = 14.5, 1.3H), 2.08−1.99 (m, 1.7H), 1.91−1.80 (m, 1.3H),
.80−1.69 (m, 1.7H), 1.67−1.54 (m, 7.7), 1.45−1.31 (m, 6.7H), 1.29
mg, 0.23 mmol, 1 equiv), the vial was capped and placed in the center
of a 30 cm loop of blue LEDs. The reaction mixture was stirred for 18
h, after which time it was diluted with Et O (30 mL) and transferred
2
to a separatory funnel. The ether layer was washed with aqueous 4 N
HCl (4 × 20 mL) and aqueous 2 N NaOH (3 × 20 mL) and dried
(
8
s, 1.3H), 1.26−1.19 (m, 2.3H), 1.18−1.02 (m, 14.7), 1.02−0.91 (m,
over MgSO . The organic layer was filtered and concentrated under
4
13
H), 0.90−0.77 (m, 15H), 0.70−0.64 (m, 2.7H); C NMR (125
reduced pressure. The crude residue was subjected to silica gel
chromatography (4% acetone/hexanes) to provide 25 (52 mg, 0.17
mmol, 72%, dr 8:2:1:1) as a colorless oil.
Preparation of Allylated Product 26 (eq 6). A 1-dram vial was
MHz, CDCl ): δ 200.5, 200.4, 170.7, 170.1, 147.3, 146.5, 144.1, 143.8,
3
6
1
5
3
2
28.4, 128.3, 128.1, 127.4, 127.2, 126.7, 126.5, 117.3, 117.2, 78.9, 61.8,
5.0, 55.0, 50.7, 47.4, 46.9, 45.5, 43.4, 43.3, 43.2, 42.4, 40.4, 39.3, 37.2,
6.2, 36.1, 35.2, 34.8, 34.0, 32.9, 32.8, 32.5, 32.3, 32.2, 30.8, 29.0, 28.7,
8.2, 27.4, 26.8, 26.5, 26.4, 23.5, 23.2, 22.7, 18.8, 17.6, 16.5, 15.7; IR
charged with N-(acyloxy)phthalimide 4 (75 mg, 0.26 mmol, 1 equiv),
Ru(bpy)
(PF )
(3 mg, 2.6 μmol, 0.01 equiv), and a magnetic stir bar
Cl (1.7 mL, sparged
with Ar for 5 min), acceptor 24 (84 mg, 0.39 mmol, 1.5 equiv), and i-
Pr NEt (100 μL, 0.57 mmol, 2.2 equiv), the vial was capped and
3
6 2
−1
(thin film): 3435, 2925, 2863, 1654, 1461, 1386, 1208, 1044 cm ;
under argon. After sequential addition of CH
2
2
+
6
HRMS-ESI (m/z) [M + Na] calculated for C H O Na 565.4022,
38
54
2
found 565.3996.
2
General Procedure for Coupling Reactions in the Absence
of a Photocatalyst (Tables 6 and 7). Preparation of 9. A 1-dram
vial was charged with N-(acyloxy)phthalimide 4 (75 mg, 0.26 mmol, 1
equiv), Hantzsch ester 8 (100 mg, 0.39 mmol, 1.5 equiv), and a
placed in the center of a 30 cm loop of blue LEDs. The reaction
mixture was stirred for 18 h, after which time it was diluted with Et O
(30 mL) and transferred to a separatory funnel. The ether layer was
washed with aqueous 4 N HCl (4 × 20 mL) and aqueous 2 N NaOH
(3 × 20 mL) and dried over MgSO . The organic layer was filtered and
concentrated under reduced pressure. The crude residue was subjected
2
magnetic stir bar under argon. After sequential addition of CH Cl2
2
4
(1.7 mL, sparged with Ar for 5 min), methyl vinyl ketone (33 μL, 0.39
mmol, 1.5 equiv), and i-Pr NEt (100 μL, 0.57 mmol, 2.2 equiv), the
to silica gel chromatography (4% acetone/hexanes) to provide 26 (19
mg, 0.10 mmol, 39%) as colorless oils.
2
6
vial was capped and placed in the center of a 30 cm loop of blue LEDs.
The reaction mixture was stirred for 18 h, after which time it was
concentrated under reduced pressure. The crude residue was purified
by silica gel chromatography (2.5% EtOAc/hexanes) to provide 9 (27
mg, 0.16 mmol, 61%) as a colorless oil. Characterization data obtained
Preparation of Allylated Product 26 (eq 7). A 1-dram vial was
charged with N-(acyloxy)phthalimide 4 (75 mg, 0.26 mmol, 1 equiv),
Ru(bpy) (PF ) (3 mg, 2.6 μmol, 0.01 equiv), Hantzsch ester 8 (100
3
6 2
mg, 0.39 mmol, 1.5 equiv), and a magnetic stir bar under argon. After
5
for 9 matched those previously reported.
sequential addition of CH Cl (1.7 mL, sparged with Ar for 5 min),
2
2
J
J. Org. Chem. XXXX, XXX, XXX−XXX