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B. H. Lipshutz et al. / Tetrahedron 60 (2004) 4443–4449
2H), 7.48–7.28 (m, 10H), 7.09–7.07 (m, 2H), 7.05 (d, J¼
2.4 Hz, 1H), 6.99 (dd, J¼8.8, 2.4 Hz, 1H), 6.93 (d, J¼
2.4 Hz, 1H), 6.86 (dd, J¼8.8, 2.4 Hz, 1H), 6.76 (dd, J¼8.8,
2.4 Hz, 1H), 6.70 (d, J¼2.4 Hz, 1H), 5.14 (s, 2H), 4.40 (s,
2H), 4.29–4.01 (m, 6H), 2.25–2.04 (m, 4H), 1.42 (s, 6H).
EIMS, m/z (rel int) 654(21), 653(47), 97(15), 91(100);
HREIMS, m/z calcd for C43H43NO5: 653.3141, found
653.3162.
108.7, 105.9, 105.4, 76.5, 76.4, 63.8, 63.7, 32.6, 27.3. EIMS,
m/z (rel int): 472(31), 471(100), 317(17), 97(15), 59(11),
43(31); HREIMS, m/z calcd for C29H29NO5: 471.2046,
found 471.2040.
4.1.13. Polymer supported (R)-cyclo-NOBIN (15). To a
5 mL CV was added (R)-cyclo-NOBIN (331 mg, 0.7 mmol).
THF (1.8 mL), H2O (1.8 mL), and conc. HCl (ca. 10 drops)
were added and the CV was fitted with a yellow-cap and
allowed to stir overnight. Upon completion by TLC (40%
EtOAc/hexanes; ca. 14.5 h), the reaction was poured into
sat. aq. NaHCO3 (ca. 10 mL) and extracted with EtOAc
(5£10 mL). The organic layer was collected and concen-
trated in vacuo followed by azeotropically drying with
toluene (3£20 mL) and high vacuum overnight. Poly-
styrene-1% cross-linked divinylbenzene supported alde-
hyde (505.8 mg, 1 mmol/g) and p-toluenesulfonic acid
monohydrate (26.9 mg, 0.14 mmol) were added as solids
followed by toluene (10 mL). The reaction was set up with a
Dean Stark trap and heated to 130–135 8C where it was
allowed to stir for 24 h. After cooling to rt, addition of sat.
aq. NaHCO3 (ca. 10 drops) and filtration through a Buchner
funnel with solvent washes (EtOAc, CH2Cl2, ether, THF,
H2O, EtOH; ca. 20 mL each) afforded polymer-bound
cyclo-NOBIN (new polymer weight¼632.9 mg corresponds
to 0.675 mmol/g), after drying under high vacuum over-
night; IR (KBr pellet) 3491, 3387, 3024, 2917, 2347, 1944,
4.1.11. 7-(-2-{5-[2-(7-Aminonaphthalen-2-yloxy)-ethyl]-
2,2-dimethyl-[1,3]dioxolan-4-yl}-ethoxy)-naphthalen-2-
ol (11). To a flame dried 100 mL RBF equipped with a
magnetic stir bar was added benzyl-[7-(2-{5-[2-(7-benzyl-
oxynaphthalen-2-yloxy)-ethyl]-2,2-dimethyl-[1,3]dioxolan-
4-yl}-ethoxy)-naphthalen-2-yl]-amine (3.17 g, 4.84 mmol)
and 10%-Pd/C (1.3 g, 1.21 mmol, 25 mol% Pd) as solids.
THF (50 mL) was added and the solution was purged well
with H2. The reaction flask was then equipped with a reflux
condenser and was warmed to 70 8C (bath temperature, not
reflux). Upon completion by TLC (52 h) the reaction was
cooled to room temperature and purged with Ar for 15 min.
The reaction was then filtered through a pad of Celite and
washed with copious amounts of EtOAc (ca. 250 mL total
volume of solvent). The solvent was then concentrated
in vacuo and azeotropically dried with toluene (25 mL)
followed by high vacuum overnight. The corresponding
aminonaphthol (2.24 g, 98%) was isolated as an off-white
solid. Rf¼0.39 (40% EtOAc/hexanes). 1H NMR (400 MHz,
CDCl3) d 8.55 (s, 1H), 7.66 (d, J¼8.8 Hz, 1H), 7.65 (d,
J¼9.2 Hz, 1H), 7.53 (d, J¼8.8 Hz, 1H), 7.51 (d, J¼8.8 Hz,
1H), 7.11 (m, 2H), 6.98–6.93 (m, 3H), 6.85 (app s, 1H),
6.82 (m, 1H), 6.79 (d, J¼2.4 Hz, 1H), 4.83 (s, 2H), 4.27–
4.04 (m, 6H), 2.23–2.04 (m, 4H), 1.37 (s, 6H). EIMS, m/z
(rel int): 473(10), 92(45), 91(100), 65(10), 56(14), 44(30),
43(27); HREIMS, m/z calcd for C29H31NO5: 473.2202,
found 473.2194.
1872, 1809, 1715, 1607, 1499, 1446, 1208, 1061, 756 cm21
.
Acknowledgements
We warmly thank the NIH (GM 40287) and AstraZeneca
(sabbatical leave for C.O.) for financial support. We are also
grateful to Mr. John Unger (UCSB) for outstanding
assistance with this project.
4.1.12. (R)-cyclo-NOBIN (12/13). To a flame dried 50 mL
RBF equipped with a magnetic stir bar was added CuCl2
(197.4 mg, 1.44 mmol, 4.0 equiv.) as a solid. The flask was
then charged with degassed MeOH (18 mL) and the green
solution was cooled to 0 8C. The flask was then charged
with racemic a-methylbenzylamine (0.74 mL, 5.76 mmol,
16.0 equiv.) and to the blue reaction mixture was then
quickly added 7-(-2-{5-[2-(7-aminonaphthalen-2-yloxy)-
ethyl]-2,2-dimethyl-[1,3]dioxolan-4-yl}-ethoxy)-naphthalen-
2-ol (11; 170 mg, 0.36 mmol) as a solid. Upon completion
by TLC (55 h) the reaction was poured into saturated
aqueous NH4Cl (50 mL) and extracted with EtOAc
(3£50 mL). The organic layer was dried over anhydrous
Na2SO4. Flash chromatography (200:1 silica/theoretical
yield (170 mg), 5% acetone/5% CH2Cl2/toluene, 1% NEt3
dope) afforded (124 mg, 73%) of the (R)-diastereomer as an
orange foam (106 mg) along with the minor isomer (18 mg).
1H NMR (major isomer; 400 MHz, CDCl3) d 7.80 (d,
J¼8.8 Hz, 1H), 7.75 (d, J¼8.8 Hz, 1H), 7.71 (d, J¼8.8 Hz,
1H), 7.67 (d, J¼8.8 Hz, 1H), 7.23 (d, J¼8.8 Hz, 1H), 7.0
(app d, J¼2.4 Hz, 1H), 6.97 (d, J¼8.8 Hz, 1H), 6.91 (dd,
J¼8.8, 2.3 Hz, 1H), 6.36 (d, J¼2.4 Hz, 1H), 6.25 (d, J¼
2.3 Hz, 1H), 5.71 (br s, 1H), 4.04–3.60 (m, 6H), 1.63–1.62
(m, 4H), 1.36 (s, 6H); 13C NMR (100 MHz, CDCl3) d 157.1,
156.8, 152.6, 143.6, 135.1, 134.3, 130.55, 130.50, 130.49,
130.4, 124.9, 123.9, 117.5, 116.5, 116.0, 115.9, 113.7,
References and notes
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