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D. Didier, E. Schulz / Tetrahedron: Asymmetry 24 (2013) 769–775
ren-1-yl)butan-1-ol and the substrates used for the nitroaldol and
ene reactions were purchased and used as received. The synthesis
of ligand 218 and 4-(pyren-1-yl)butyl methanesulfonate 331 has
already been described. Activated charcoal, NORIT SA II was com-
mercially available from Acros Organics, the benzoylated dialysis
membrane was received from Sigma–Aldrich. Fullerene C60 and
carbon nanotubes (single walled) were purchased from Aldrich.
The HRMS analyses were performed with a MicroTOFq (quadru-
pole coupled with TOF analyzer).
125.7, 126.5, 127.0, 127.1, 127.4, 127.5, 128.4, 128.5, 128.6,
129.7, 130.9, 131.4, 136.9, 139.6, 141.9, 142.1, 168.6. HRMS (EI):
calcd for C42H37N2O2+: 601.2850, found: 601.2842. ½a 2D0
þ 99:4 (c
ꢃ
1.20, CHCl3).
4.4. Procedure for the Henry reaction with 2–Cu(OAc)2@char-
coal
Ligand 2 (33 mg, 0.055 mmol), dissolved in EtOH (2 mL) was
added to Cu(OAc)2ꢁH2O (10 mg, 0.05 mmol) and the blue–green
solution was stirred for 1 h at rt. Next, the mixture was directly
introduced into a tube containing charcoal (180 mg, NORIT SA II).
4.2. (3aR,3a0R,8aS,8a0S)-2,20-(5-(Pyren-1-yl)pentane-1,1-diyl)bis-
(8,8a-dihydro-3aHindeno[1,2-d]oxazole) 4
After 1 h of additional stirring, nitromethane (270
was introduced dropwise, followed by the addition of benzalde-
hyde (51 L, 0.5 mmol) and the mixture was stirred for the appro-
lL, 5.0 mmol)
In a dried Schlenk tube, TMEDA (114
lL, 0.76 mmol) and diiso-
propylamine (159 L, 1.14 mmol) were mixed in 3 mL of THF and
l
l
the solution was cooled to ꢀ20 °C. A lithium diisopropylamide
priate time at 20 °C. The suspension was then filtered after pentane
addition and the supported catalyst dried to be reengaged in the
following transformation. The solution containing products was
then evaporated in vacuum; the residue was purified by prepara-
tive thin layer chromatography (pentane/ether = 4:1) and analyzed
by HPLC for determination of the ee.
solution was then obtained by the slow addition of nBuLi
(605
lL, 1.6 M in hexane, 1.51 mmol) over 30 min at ꢀ20 °C. The
colorless solution was then allowed to stir at rt. After 1 h, the solu-
tion of LDA was transferred into a second Schlenk containing Box-1
(250 mg, 0.76 mmol) in 8 mL of THF and the mixture was stirred at
rt for 2 h. Mesylate 3 (293 mg, 0.83 mmol) in 4 mL of THF was then
added to the previous solution and the mixture was heated to 55 °C
and stirred for 24 h. Water was then added to the solution and the
aqueous layer was extracted with ethylacetate (3 ꢂ 15 mL). The
combined organic layers were washed with a saturated solution
of NH4Cl, dried over MgSO4, and then concentrated. The crude
product was purified on silica gel (cyclohexane/ethylacetate = 1:1)
to afford the pure product 4 as a yellow solid (124 mg, 28% yield).
1H NMR (360 MHz, CDCl3) d (ppm) 1.38–1.45 (m, 2H), 1.66–1.71
(m, 1H), 1.75–1.84 (m, 2H), 2.12–2.19 (m, 2H), 2.84 (dd, 2H,
J = 17.6 Hz and J = 5.4 Hz), 3.17–3.30 (m, 4H), 5.27–5.36 (m, 2H),
5.54–5.58 (m, 2H), 7.17–7.28 (m, 6H), 7.48–7.51 (m, 2H), 7.78 (d,
1H, J = 7.9 Hz), 7.98–8.20 (m, 8H). 13C NMR (90 MHz, CDCl3) d
(ppm) 23.0, 30.2, 31.4, 33.3, 35.2, 39.4, 71.8, 84.7, 123.5, 124.6,
124.8, 125.0, 125.1, 125.6, 125.7, 126.5, 127.1, 127.2, 127.4,
127.5, 128.5, 128.6, 129.7, 130.9, 131.4, 136.9, 139.6, 141.2,
141.9, 166.9. HRMS (EI): calcd for C41H35N2O2+: 587.2693, found:
587.2681.
4.5. Tea-bag procedure for the Henry reaction with 2–
Cu(OAc)2@charcoal
Ligand 2 (33 mg, 0.055 mmol), dissolved in EtOH (2 mL) was
added to Cu(OAc)2ꢁH2O (10 mg, 0.05 mmol) and the blue–green
solution was stirred for 1 h at rt. Next, it was directly introduced
into a flask containing charcoal (180 mg, NORIT SA II). The solvents
were removed in vacuum and the resulting powder was enclosed
in a cellulosic membrane (1 cm3). Next, EtOH (10 mL) was added
and after 1 h of additional stirring, nitromethane (270
5.0 mmol) was introduced dropwise, followed by the addition of
benzaldehyde (51 L, 0.5 mmol) and the mixture was stirred for
lL,
l
the appropriate time at 20 °C. The supernatant was then directly
removed via a pipette and the supported catalyst was reengaged
in the following transformation. The solution containing products
was then evaporated in vacuum and the residue purified by pre-
parative thin layer chromatography (pentane/ether = 4:1) and ana-
lyzed by HPLC for the determination of the ee.
4.3. (3aR,3a’R,8aS,8a’S)-2,2’-(6-(Pyren-1-yl)hexane-2,2-diyl)bis-
(8,8a-dihydro-3aHindeno[1,2-d]oxazole) 5
4.6. (R)-(ꢀ)-2-Nitro-1-phenylethanol 6
In a dried Schlenk tube, TMEDA (86
propylamine (81 L, 0.59 mmol) were mixed in 1.5 mL of THF
and the solution was cooled to ꢀ20 °C. A lithium diisopropylamide
solution was then obtained by the slow addition of nBuLi (513 L,
1.6 M in hexane, 0.77 mmol) over 30 min at ꢀ20 °C. The colorless
solution was then allowed to stir at rt. After 1 h, the solution of
LDA was transferred into a second Schlenk containing Box-4
(250 mg, 0.43 mmol) in 8 mL of THF and the mixture was stirred
l
L, 0.59 mmol) and diiso-
1H NMR: (CDCl3, 250 MHz) d (ppm) 2.99 (br s, 1H), 4.53 (dd, 2H,
J = 13.3 Hz and J = 3.5 Hz), 4.64 (dd, 1H, J = 13.3 Hz and J = 9.3 Hz),
7.38–7.45 (m, 5H). 13C NMR: (CDCl3, 250 MHz) d (ppm) 71.1,
81.3, 126.1, 129.0, 129.1, 138.3. HPLC: IB (hexane/iPrOH = 9:1,
1.0 mL minꢀ1, 215 nm) tR (major) = 11.42 min, tS = 13.37 min.
l
l
4.7. Ene-reaction; immobilization of ligand-2 on charcoal
at RT for 2 h. Next, MeI (36
l
L, 0.59 mmol) was then added drop-
Ligand 2 (33 mg, 0.055 mmol) dissolved in DCM (2 mL) was
added to Cu(OTf)2 (18 mg, 0.05 mmol) and the blue–green solution
was stirred for 1 h at rt. Next, it was directly introduced into a tube
containing charcoal (180 mg, NORIT SA II). After 1 h of additional
wise to the previous solution and the mixture was heated to
55 °C and stirred for 24 h. Water was then added to the solution
and the aqueous layer was extracted with ethylacetate
(3 ꢂ 15 mL). The combined organic layers were washed with a sat-
urated solution of NH4Cl, dried over MgSO4, and then concentrated.
The crude product was purified on silica gel (cyclohexane/ethyl-
acetate = 1:1) to afford the pure product 5 as a yellow powder
(110 mg, 43% yield). 1H NMR (360 MHz, CDCl3) d (ppm) 1.29–
1.32 (m, 2H), 1.43 (s, 3H), 1.69–1.76 (m, 2H), 1.98–2.03 (m, 2H),
3.00 (dd, 2H, J = 178 Hz and J = 6.0 Hz), 3.08–3.23 (m, 2H), 3.30–
3.61 (m, 2H), 5.20–5.30 (m, 2H), 5.56 (t, 2H, J = 7.9 Hz), 7.23–7.34
(m, 4H), 7.50–7.58 (m, 2H), 7.75 (d, 1H, J = 8.0 Hz), 7.80–8.20 (m,
10H). 13C NMR (90 MHz, CDCl3) d(ppm) 20.8, 24.0, 31.7, 33.3,
35.9, 39.6, 42.1, 76.3, 83.0, 123.5, 124.6, 124.8, 125.1, 125.6,
stirring,
vious suspension and the homogeneous mixture was then stirred
for 10 additional minutes at 20 °C. Ethyl glyoxylate (510 L,
a-methylstyrene (65 lL, 0.5 mmol) was added to the pre-
l
2.5 mmol) was then introduced dropwise and the mixture was stir-
red for 12 h. The suspension was then filtered after pentane addi-
tion and the supported catalyst dried to be reengaged in the
following transformation, after the addition of DCM (2 mL). The
solution containing products was evaporated in vacuum, and the
residue was purified by preparative thin layer chromatography
(pentane/ether = 4:1) and analyzed by HPLC for determination of
the ee.