Efficient Synthesis of 1,1'-Binaphthyl and 2,2'-Bi-o-tolyl-2,2'-bis(oxazoline)s and Preliminary Use for the Catalytic Asymmeric Allylic Oxidation of Cyclohexene

Full text of DOI:10.1021/jo9713619

J . Org. Chem. 1997, 62, 9365-9368
9365
Efficien t Syn th esis of 1,1′-Bin a p h th yl a n d
2,2′-Bi-o-tolyl-2,2′-bis(oxa zolin e)s a n d
P r elim in a r y Use for th e Ca ta lytic
Asym m etr ic Allylic Oxid a tion of
Cycloh exen e
Merritt B. Andrus,*,1 Davoud Asgari, and
J oseph A. Sclafani
F igu r e 1.
Purdue University, Department of Chemistry,
West Lafayette, Indiana 47907-1393
Sch em e 1
Received J uly 24, 1997
Chiral C2-symmetric bis(oxazoline)s have been suc-
cessfully employed as ligands with various metals in
numerous catalytic asymmetric processes. These include
cyclopropanation,2 aziridination,3 allylic substitution,4
hydrosilylation,5 imine additions,6 Diels-Alder,7 aldol,8
and Wacker-type cyclization9 reactions. In addition we
and Pfaltz have recently used bis(oxazoline) copper
complexes as catalysts for the asymmetric allylic oxida-
tion of simple olefins using tert-butyl perbenzoate.10
While the linker between the oxazolines in the past have
consisted of a methylene unit, derived from a malonyl
precursor, or a pyridyl unit, recently Corey reported the
synthesis of a unique biaryl-linked ligand, 1,1′-bis-o-tolyl-
2,2′-bis(oxazoline), for use in a highly selective intramo-
lecular copper-catalyzed cyclopropanation reaction lead-
ing to (-)-sirenin.11 This new catalyst was shown to
superior to a variety of known metal‚ligand combinations
including the standard methylene bis(oxazoline)s. The
synthesis of this new ligand required the use of a
preparative chiral HPLC separation on the racemic
bitolyl dicarboxylic acid precursor. The prohibitive cost
of this step and our desire to apply this new class of
ligands to the allylic oxidation reaction prompted the
effort to develop an efficient synthetic route to biarylbis-
(oxazoline)s that would not depend on a chiral separation
or a tedious resolution.12 To this end, new asymmetric
versions of the Ullman coupling reaction13 were applied
to produce two biarylbis(oxazoline)s, bi-o-tolyl diphenyl
1 and binaphthyl di-tert-butyl 2 (Figure 1).
Our route began with the efficient use of sodium
chlorite with added sodium phosphate and 2-methyl-
butene14 with 1-bromo-2-naphthaldehyde 311 to produce
the acid 4 in 94% yield (Scheme 1). Previous oxidations
reported using transition metal oxides are uniformly low
for this step.12,15 The next three operations were per-
formed without purification or isolation of the intermedi-
ates. Treatment of 4 with oxalyl chloride and catalytic
DMF produced the acid chloride that was then treated
with (S)-tert-leucinol and triethylamine to give the amide.
The crude material was then treated with the Burgess
reagent {[(methoxycarbonyl)sulfamoyl]triethylammonium
hydroxide} according to the conditions of Corey giving
oxazoline 5 in 89% overall yield.9b,11 Alternative proce-
dures using the dimesylate or the dichloride intermediate
were found to be lower yielding in this case.8,13a Coupling
with activated copper following the procedure of Meyers
was then performed to access bi-o-tolyl-bis(oxazoline) 2
in 77% isolated yield as a white solid (mp 109 °C, [R]D
-151).13a This compound was an intermediate on the
route to the enantiopure S-(-)-diacid dimethyl ester16 and
was not characterized previously. The coupling produced
only the S,S,S-atropisomer (>30:1) together with only a
small amount (<5%) of the reduced, debrominated byprod-
uct as reported earlier. When the oxazoline side chain
is changed from tert-butyl to the less sterically demand-
ing phenyl or isopropyl groups, the coupling selectivity
drops to 2:1 and 4:1.13a Recently Hayashi has reported
a route to binaphthyl bis(oxazoline)s that uses racemic
binaphthyl dicarboxylic acid and requires the separation
of diastereomeric amides prior to bis(oxazoline) forma-
tion.17
(1) New address: Brigham Young University, Department of Chem-
istry, Provo, UT 84602-5700. email: mbandrus@chemgate.byu.edu.
(2) Denmark, S. E.; Stavenger, R. A.; Faucher, A.-M.; Edwards, J .
P. J . Org. Chem. 1997, 62, 3375. Bedekar, A. V.; Koroleva, E. B.;
Andersson, P. G. J . Org. Chem. 1997, 62, 2518. Pfaltz, A. Acc. Chem.
Res. 1993, 26, 339. Lowenthal, R. E.; Masamune, S. Tetrahedron Lett.
1991, 32, 7373-7376. Evans, D. A.; Woerpel, K. A.; Hinman, M. M.;
Faul, M. M. J . Am. Chem. Soc. 1991, 113, 726.
(3) Hansen, K. B.; Finney, N. S.; J acobsen, E. N. Angew. Chem., Int
Ed. Engl. 1995, 34, 676. Evans, D. A.; Faul, M. M.; Bilodeau, M. T. J .
Am. Chem. Soc. 1994, 116, 2742.
(4) Leutenegger, U.; Umbricht, G.; Fahrni, C.; von Matt, P.; Pfaltz,
A. Tetrahedron 1992, 48, 2143.
(5) Nishiyama, H,; Yamaguchi, S.; Kondo, M.; Itoh, K. J . Org. Chem.
1992, 57, 4306.
(6) Denmark, S. E.; Nakajima, N.; Nicaise, O. J .-C.; Faucher, A.-
M.; Edwards, J . P. J . Org. Chem. 1995, 60, 4884.
(7) (a) Evans, D. A.; Shaughnessy, E. A.; Barnes, D. M. Tetrahedron
Lett. 1997, 38, 3193. Evans, D. A.; Murry, J . A.; von Matt, P.; Norcross,
R. D.; Miller, S. J . Angew. Chem., Int. Ed. Engl. 1995, 34, 798. (b)
Corey, E. J .; Ishihara, K. Tetrahedron Lett. 1992, 33, 6807. (c)
J ohannsen, M.; J orgensen, K. A. Tetrahedron 1996, 52, 7321.
(8) Evans, D. A.; Murry, J . A.; Kozlowski, M. C. J . Am. Chem. Soc.
1996, 118, 5814.
(9) Uozumi, Y.; Kato, K.; Hayashi, T. J . Am. Chem. Soc. 1997, 119,
5063.
(10) (a) Andrus, M. B.; Chen, X. Tetrahedron 1997, in press. (b)
Andrus, M. B.; Argade, A. B.; Chen, X.; Pamment, M. G. Tetrahedron
Lett. 1995, 36, 2945. (c) Gokhale, A. S.; Minidis, A. B. E.; Pfaltz, A.
Tetrahedron Lett. 1995, 36, 1831.
(11) Gant, T. G.; Noe, M. C.; Corey, E. J . Tetrahedron Lett. 1995,
36, 8745.
(12) Hall, D. M.; Turner, E. E. J . Chem. Soc. 1955, 1242. Weber,
E.; Csoregh, I.; Stensland, B.; Czugler, M. J . Am. Chem. Soc. 1984,
106, 3297.
(13) (a) Nelson, T. D.; Meyers, A. I. J . Org. Chem. 1994, 59, 2655.
(b) Lipshutz, B. H.; Kayser, F.; Liu, Z.-P. Angew. Chem., Int. Ed. Engl.
1994, 33, 1842.
(14) Kraus, G. A.; Taschner, M. J . Org. Chem. 1980, 45, 1175.
Lindgren, O.; Nilsson, T. Acta Chem. Scand. 1973, 27, 888.
(15) Kim, J .-I.; Schuster, G. B. J . Am. Chem. Soc. 1992, 114, 9309.
(16) Oi, S.; Matsuzaka, Y.; Yamashita, J .; Miyano, S. Bull. Chem.
Soc. J pn. 1989, 62, 956.
(17) Uozumi, Y.; Kyota, H.; Kishi, E.; Kitayama, K.; Hayashi, T.
Tetrahedron: Asymmetry 1996, 7, 1603.
S0022-3263(97)01361-3 CCC: $14.00 © 1997 American Chemical Society

9366 J . Org. Chem., Vol. 62, No. 26, 1997
Notes
F igu r e 2.
Sch em e 2
The recent work of van Koten with the isolation and
characterization of well defined arylcopper-copper bro-
mide aggregates can now be used to suggest a model for
the origin of the selectivity for the asymmetric intermo-
lecular Ullman process.18 Unlike previous mechanisms
that have suggested a diarylcopper(III) intermediate,19
the bis-diamine X-ray structures indicate a diaryl-Cipso
-
bonded copper(I) structure with additional copper halide
forming a ring of either 6 or 8 atoms depending on the
stoichiometry of the added copper. Applying this copper-
(I) aggregate intermediate to the asymmetric binaphthyl
coupling, the selectivity then appears to be controlled by
the interaction of the flanking tert-butyl groups with the
bridged bromine ligands (Figure 2). The transition state
leading to the observed S,S,S isomer is formed avoiding
this interaction. This is achieved by aligning the forming
biaryl carbon-carbon bond in a parallel orientation to
the flanking tert-butyl groups. This pseudo-diaxial align-
ment of the tert-butyl groups in the transition state will
avoid nonbonded interactions with the copper-bromide
aggregate. The alternative equatorial alignment, leading
to the S,R,S isomer, forcing the tert-butyl groups out
toward the copper-halide aggregate would be a higher
energy process.
Due to the decreased selectivity for the intermolecular
Ullman when other ligands besides tert-butyl are used,
a more flexible route to access alternatively substituted
diaryl bis(oxazoline)s was investigated using an intramo-
lecular variant. Diol 6, readily obtained using a Sharp-
less asymmetric dihydroxylation reaction with AD-mix-R
reagent on trans-stilbene,20 was converted to diether 7
(Scheme 2). Treatment with tert-butyllithium followed
by the addition of copper(I) cyanide and dry oxygen at
-78 °C, following the conditions of Lipshutz, gave the
di-o-tolyl intermediate 8 in 63% yield as a single isomer.13b
The original substrate used to establish this process was
the analogous dinaphthyl diether. The selectivity can be
explained by examining the energies of the diastereo-
meric S,S,S and S,R,R ground state structures. The
observed S,S,S isomer is shown by MM2 representations
to be favored by ∼1 kcal (Figure 3).21 Placement of the
two phenyl groups in equatorial positions in a chair-twist
chair transition state is preferred leading to 8. Alterna-
tive diaxial arrangement of the phenyls lead to the
opposite atropisomer. The copper intermediate leading
to biaryl formation, prior to oxygen exposure, is envi-
sioned to be a six-membered diaryl Cipso-copper(I)-Li2-
(CN) cyclic aggregate, as determined by ab initio calcu-
lation22 analogous to the copper(I) bromide structure
discussed above. The synthesis was completed by hy-
drogenation, oxidation with TPAP to the dialdehyde,23
and treatment with sodium chlorite giving the intermedi-
ate S-diacid 9 in 85% combined yield (Scheme 2). Treat-
ment with oxalyl chloride, S-phenylglycinol, followed by
the Burgess reagent, then gave the desired bis(oxazoline)
target 1 in high overall yield. The main advantage of
the intramolecular Ullman route to the diacid intermedi-
ate is flexibility, allowing for either enantiomeric form
depending on the AD reaction and the incorporation of
various amino alcohols at the final stage of the synthesis.
As an initial investigation, 1 was used with copper(I)
as a ligand (10 mol %) in the catalytic asymmetric allylic
oxidation of cyclohexene (5 equiv) (Scheme 3). The new,
more reactive oxidant, tert-butyl p-nitroperbenzoate was
used as the limiting reagent.10a After reacting at -20
°C for 5 d in acetonitrile, the S-benzoate ester was
isolated in 76% yield and 73% ee,24 demonstrating
increased reactivity in addition to improved selectivity
over the previously reported use of a S,S-methylene-
linked phenylglycine-derived bis(oxazoline) ligand.10b
Exp er im en ta l Section
Gen er a l P r oced u r es. Unless otherwise specified, materials
were used as obtained from commercial sources. THF and ethyl
(18) J assen, M. D.; Corsten, M. A.; Spek, A. L.; Grove, D. M.; van
Koten, G. Organometallics 1996, 15, 2810.
(19) Ziegler, F. E.; Chliwer, I.; Fowler, K. W.; Kanfer, S. J .; Kuo, S.
J .; Sinha, N. D. J . Am. Chem. Soc. 1980, 102, 790.
(20) Crispino, G. A.; J eong, K.-S.; Kolb, H. C.; Wang, Z.-M.; Xu, D.;
Sharpless, K. B. J . Org. Chem. 1993, 58, 3785.
(21) MM2 force field with modified parameters neglecting π-overlap
by the C-C biaryl bond.
(22) Snyder, J . P.; Spangler, D. P.; Behling, J . R.; Rossiter, B. E. J .
Org. Chem. 1994, 59, 2665.
(23) Griffith, W. P.; Ley, S. V. Aldrichim. Acta 1990, 23, 13.
(24) The selectivity was determined by integration of the 1H NMR
(500 MHz) signal for the ortho-protons of the benzoate using the chiral
shift reagent Eu(hfc)3 compared to the spectra of the racemic material.

Notes
J . Org. Chem., Vol. 62, No. 26, 1997 9367
F igu r e 3.
CH2Cl2. The CH2Cl2 layer was dried with MgSO4, and solvent
was removed by rotary evaporator and high vacuum. The crude
residue was then dissolved in THF (50 mL) and Burgess reagent
[(methoxycarbonyl)sulfamoyl]triethylammonium hydroxide (1.9
g, 7.96 mmol) was added. The solution was allowed to stir under
N2 overnight at ambient temperature. The solvent was then
removed by rotary evaporation to afford a yellow oil. Purification
using radial chromatography (5-30% EtOAc/hexane) produced
Sch em e 3
(2.29 g, 89%) of a light yellow solid: mp 65-67 °C. [R]23
)
D
-55.1° (c ) 3.06, CH2Cl2); 1H NMR (CDCl3, 200 MHz) δ 8.40 (2
H, d, J ) 8 Hz), 7.82-7.78 (m, 2H), 7.65-7.50 (m, 3H), 4.39
(dd, 10 Hz, 8.2 Hz, 1H), 4.31 (t, 8.4 Hz, 1H), 4.16 (dd, 10.0 Hz,
8 Hz, 1 Hz), 1.04 (s, 9H); 13C (CDCl3, 50 MHz) δ 164.3, 135.3,
132.8, 129.3, 128.7, 128.7, 128.40, 128.2, 128.2, 127.4, 123.6, 77.3,
69.7, 34.5, 26.6; IR (KBr, cm-1) 3051, 2864, 1659, 1472, 1239,
1104.
ether were distilled prior to use from sodium benzophenone
ketyl. Methylene chloride and amine reagents were distilled
from calcium hydride. Column chromatography was performed
on silica gel 60 (230-400 mesh) eluting with distilled hexanes
and ethyl acetate. TLC was performed using silica gel 60 F254
plates with visualization by UV irradiation and standard stain-
ing. 1H (200 MHz) and 13C (50 MHz) NMR spectra were
(S,S,S)-1,1′-Bin a p h th yl-2,2′-ter t-Bu tylbis(oxa zolin e) (2).
Naphthyloxazoline bromide 5 (100 mg, 0.31 mmol) was azeo-
troped three times with benzene (5 mL) in a 10 mL roundbottom
flask. To this were added activated Cu (0.5 g, 7.9 mmol) and
dry freshly distilled pyridine (3 mL). The mixture was heated
to reflux and allowed to react overnight. Upon cooling, the
pyridine was removed by rotary evaporation and high vacuum.
The residue was treated with CH2Cl2, and the copper was filtered
through glass wool. The CH2Cl2 solution was treated with 20%
NH4OH (50 mL) and saturated aqueous NH4Cl (10 mL) several
times until loss of blue color from the aqueous layer. The organic
layer was then dried with MgSO4 and solvent was removed. The
residue was then dissolved in EtOAc and filtered through a 2.5
cm plug of silica eluting with EtOAc. Solvent was removed, and
the product was separated using radial chromatography (1 mm
rotor, 5-50% EtOAc/hexane). The product was pumped under
high vacuum to afford a white foam which solidified upon
recorded on
a QE-300 instrument. Optical rotations were
measured at 589 nm. Melting points are uncorrected. Mass
spectral analyses were performed in the chemistry department
at Purdue University.
1-Br om o-2-n a p th oic Acid (4). To a mixture of 1-bromo-2-
napthaldehyde 3 (3.0 g, 12.7 mmol) and tert-butyl alcohol (200
mL) was added 2-methyl-2-butene (10 mL). A 100 mL aqueous
solution of NaClO2 (10 g, 116.4 mmol) and NaH2PO4‚H2O (12.1
g, 87.8 mmol) was added dropwise over a period of 20 min. This
resulted in a clear solution which was allowed to stir overnight
at rt. The tert-butyl alcohol was removed by rotary evaporation
and the mixture was treated with 50 mL of H2O and washed
with two 50 mL portions of hexane. The aqueous layer was then
acidified to pH 1 and extracted (3×) with 50 mL of ether. The
organic extracts were combined, and solvent was removed by
rotary evaporation to afford the acid 4 (2.99 g, 94% yield) as a
white solid: mp 185-187 °C; 1H NMR (CDCl3, 200 MHz) δ 8.52
(d, J ) 8 Hz, 1 H), 7.87 (d, J ) 8 Hz, 1 H), 7.70-7.63 (m, 4 H);
13C (CDCl3, 50 MHz) δ 172.3, 136.2, 134.2, 133.0, 129.5, 129.1,
128.7, 128.4, 126.9, 124.7; IR (KBr) 2944 (b) 1696, 1662.
Na p h th yloxa zolin e Br om id e (5). To 50 mL of CH2Cl2 was
added 1-bromo-2-napthoic acid 4 (2.0 g, 7.96 mmol). The mixture
was allowed to stir for 10 min. Oxalyl chloride (2.83 mL, 31.9
mmol) was added dropwise followed by three drops of DMF. The
mixture turned clear and was allowed to stir overnight at
ambient temperature under N2. The solvent was removed by
rotary evaporator, and the residue was pumped under high
vacuum for 10 min. The solid was treated with CH2Cl2 (100
mL), and the solution was cooled to -10 °C. In a separate flask
were combined (S)-tert-butyl leucinol25 (1.03 g, 8.76 mmol),
triethylamine (7 mL), and CH2Cl2 (50 mL) which were also
cooled to -10 °C. The acid chloride solution was next added
dropwise by cannula into the flask containing the leucinol, and
the solution was allowed to warm to rt. After stirring overnight
under N2, the solvent was removed, and the solid was treated
with a saturated solution of brine (50 mL) and extracted with
standing under vacuum (60 mg, 77%): mp 109-113 °C; [R]23
D
) -150.8 (c 0.65, CHCl3); 1H NMR (CDCl3, 500 MHz): δ 8.13 (2
H, d, J ) 8 Hz), 7.93 (2 H, d, J ) 8.5 Hz), 7.88 (2 H, d, J ) 8.0
Hz), 7.44 (2 H, t, J ) 7.5 Hz), 7.19 ( 2 H, t, J ) 7 Hz), 7.13 ( 2
H, d, J ) 8.5 Hz), 3.6-3.78 (6H, m), 0.49 (18H, s); 13C (CDCl3,
50 MHz): d 163.9, 134.7, 133.6, 128.1, 127.8, 127.7, 127.1, 126.6,
126.1, 76.5, 68.6, 34.0, 25.9; IR (KBr, cm-1) 3051, 1649, 1473,
1234, 1109; HRMS: Calcd for C34H36N2O2: 504.2777. Found:
504.2782.
2-Br om o-1-((2-((2-b r om o-3-m e t h ylb e n zyl)oxy)-1,2-d i-
p h en yleth oxy)m eth yl)-3-m eth ylben zen e (7). Sodium hy-
dride (1.86 g, 77.5 mmol) was placed in a flame-dried round
bottom flask (250 mL) containing THF (50 mL) and (S,S)-
stilbenediol 6 (1.66 g, 7.75 mmol). The mixture was stirred for
30 min at rt. Then, 2-bromo-3-(bromomethyl)toluene (4.5 g,
17.05 mmol) in THF (50 mL) was slowly cannulated into the
reaction flask containing the diol 6 and sodium hydride. The
mixture was then refluxed overnight and benzylamine (2 or 3
drops) was added to the reaction flask and allowed to reflux for
an additional 2 h. The flask was then cooled to rt and carefully
quenched with methanol (10 mL), extracted with ethyl acetate
(3 × 40 mL), washed with cold water (30 mL), HCl solution
(10%), and again with cold water (40 mL), and dried over MgSO4.
After evaporation of the solvent, the pure product 7 was obtained
1
(4.65 g, 93% yield): mp 78-80 °C; H NMR (200 MHz, CDCl3):
δ 7.46 (d, 2H), 7.32-6.92 (m, 14H), 4.73 (s, 2H), 4.52 (d, 4H),
2.35 (s, 6H); 13C NMR (50 MHz, CDCl3): δ 138.92, 138.72,
138.43, 129.86, 128.63, 128.43, 128.30, 128.15, 127.33, 126.67,
(25) McKennon, M. J .; Meyers, A. I.; Drauz, K.; Schwarm, M. J . Org.
Chem. 1993, 58, 3568.

9368 J . Org. Chem., Vol. 62, No. 26, 1997
Notes
125.06, 86.21, 71.53, 23.85; IR (neat): 3061, 2916, 1332, 1109,
1088 cm-1; [R]D +44.85 (c 1.2, CHCl3).
colorless after 3 h. Then solvent and volatiles were removed
under reduced pressure, the residue was dissolved in water (15
mL), and extracted with n-hexanes (2 × 20 mL). The water layer
was acidified to pH 3 with HCl and extracted with ethyl acetate
(3 × 50 mL), washed with cold water (30 mL), saturated
NaHCO3 (aq), and cold water again. The organic layer was dried
over MgSO4, and evaporation of the solvent afforded yellow solid
Dieth er 8. Copper(I) cyanide (0.65 g, 7.3 mmol) was placed
in
a flame-dried two-necked round bottom flask (500 mL)
equipped with two rubber septa and a stirring bar. The flask
was again gently dried with a heat gun under vacuum and
allowed to cool to rt under N2. THF (125 mL) was added and
the mixture cooled to -78 °C. In another 250 mL round bottom
flask, compound 7 (4.15 g, 7.16 mmol) was dissolved in THF (110
mL) and cooled to -78 °C, and tert-butyllithium (1.5 M, 28.6
mmol) was slowly added, giving an orange solution. The reaction
mixture was stirred for 1 h at this temperature, and this solution
of the dilithium compound was cannulated to the flask contain-
ing CuCN at -78 °C. The mixture was then warmed to -40
°C, and a yellow solution was obtained. The reaction mixture
was then recooled to -78 °C. The N2 flow was then stopped,
and dry O2 (passed through a trap at -78 °C) was bubbled into
the reaction mixture for 2 h where upon the solution turned to
a dark color. The mixture was allowed to warm to 0 °C, and
the flow of O2 was continued for an additional 1 h. The reaction
mixture was then quenched with methanol (5 mL) and saturated
aqueous NaHSO3. The reaction was then allowed to warm to
rt, poured into a solution of 10% NH4OH in NH4Cl (15 mL),
stirred for 0.5 h, extracted with ethyl acetate (3 × 80 mL), and
added over MgSO4. After evaporation of the solvent, the crude
yellow product obtained was purified by column chromatography
(1-3% ethyl acetate/hexane) to obtain a white solid-oil product
8 (1.9 g, 63% yield): 1H NMR (200 MHz, CDCl3): δ 7.65-6.76
(m, 16H), 4.62-4.46 (m, 3H), 4.45-4.23 (m, 3H), 2.28 (3H, s),
1.85 (3H, s); 13C NMR (50 MHz, CDCl3) δ 139.86, 139.04, 138.84,
137.01, 129.90, 128.46, 128.29, 128.11, 128.05, 127.85, 127.61,
87.56, 70.40, 20.71; IR (KBr): 3062, 2913, 1329, 1100 cm-1; [R]D
-15.41 (c 1.85, CHCl3).
(S)-2,2′-Bis(h ydr oxym eth yl)-6,6′-dim eth ylbiph en yl. Com-
pound 8 (1.9 g, 4.52 mmol) was dissolved in a round bottom flask
(50 mL) containing methanol (25 mL). Then a catalytic amount
of Pd/C (10%, 5 mg) was added to the reaction flask, and H2
was slowly bubbled into the flask for 1 d with stirring. The
mixture was filtered and evaporation of the solvent afforded a
yellow solid product. A white solid product was obtained after
purification by column chromatography (0.95 g, 87% yield): mp
116-118 °C; 1H NMR (200 MHz, CDCl3): δ 7.43-7.13 (m, 6H),
4.32 (d, 2H), 4.11 (d, 2H), 2.46 (s, 1H), 1.83 (s, 6H); 13C NMR
(50 MHz, CDCl3): δ 130.44, 128.64, 128.41, 128.0, 62.19, 20.48;
IR (KBr): 3383, 3050, 2988, 1420, 1264 cm-1; [R]D ) -30.0 (c
0.4, chloroform).
(S)-3,3′-Dim eth yl-2,2′-bip h en yl-1,1′-d ica r boxylic Acid (9).
The above diol intermediate (0.70 g, 2.89 mmol) was placed in a
flame-dried round bottom flask (100 mL) equipped with a
magnetic stirring bar. Methylene chloride (25 mL), molecular
sieves (4 Å, 2.89 g), and NMO (1.02 g, 8.71 mmol) were added
to the reaction flask and allowed to stir for 5 min. TPAP (0.11
g, 0.29 mmol) was then added to the reaction mixture and the
reaction stirred for 15 min at rt. The reaction mixture was then
passed through silica gel using ethyl acetate (150 mL), and
evaporation of the solvent afforded a white solid of dialdehyde
intermediate (0.65 g, 94% yield). This aldehyde (0.57 g, 2.40
mmol) was then dissolved in a round bottom flask (250 mL)
containing tert-butyl alcohol (55 mL) and 2-methyl-2-butene
(13.5 mL). A solution of sodium chlorite (2.52 g, 26.4 mmol) and
sodium dihydrogen phosphate (2.52 g, 21.6 mmol) in water (21
mL) was slowly added to the reaction mixture. The pale yellow
reaction mixture was stirred overnight, and the solution turned
1
product diacid 9 (0.63 g, 97% yield): mp 187-190 °C; H NMR
(200 MHz, CDCl3): δ 9.56 (s, 2H), 7.86 (d, 2H), 7.57-7.11 (m,
4H), 1.83 (s, 6H); 13C NMR (50 MHz, CDCl3): δ 172.96, 142.52,
136.82, 135.15, 129.39, 128.20, 127.35, 20.48; IR (KBr) δ 3445,
3051, 2978, 1701, 1415, 1264, 1186, 1156 cm-1; [R]D (c 1.0,
chloroform).
(S,S,S)-2,2′-Bi-o-tolyl-1,1′-d ip h en ylbis(oxa zolin e) (1). Di-
acid 9 (0.35 g, 1.3 mmol) was placed in a flame-dried round
bottom flask (100 mL). Methylene chloride (25 mL) was then
added to the reaction flask. Oxalyl chloride (1.64 g, 13.0 mmol)
was added dropwise followed by two drops of DMF. The reaction
mixture was stirred for 8 h at rt under N2. The solvent was
then removed under reduced pressure, and yellow oil diacid
chloride was isolated (0.40 g, 88% yield). Without delay, a
solution of this intermediate (0.40 g, 1.30 mmol) in methylene
chloride (15 mL) was cooled to -40 °C. In a separate flask, a
mixture of (S)-phenylglycinol (0.36 g, 2.6 mmol) and triethyl-
amine (1 mL) in methylene chloride (15 mL) was cooled to -40
°C. The diacid chloride solution was then added dropwise by
cannula into the flask containing phenylglycinol, and the solu-
tion was allowed to warm after 30 min with stirring overnight
under N2. The solvent was removed, and the solid obtained was
treated with saturated solution of brine (10 mL) and extracted
with methylene chloride. The organic layer was dried over
MgSO4, and the solvent was removed under reduced pressure
to obtain the crude residue. This was then dissolved in THF
(10 mL) and Burgess Reagent (0.63 g, 2.65 mmol) was added to
the solution. The solution was allowed to stir under N2 overnight
at rt. The solvent was then removed under reduced pressure
to obtain a crude yellow residue. Purification using radial
chromatography (1 mm rotor, 5-35% ethyl acetate/hexane)
produced a white oil-solid product (0.40 g, 65% yield): 1H NMR
(CDCl3, 200 MHz) δ 7.83 (d, 2H, J ) 8 Hz), 7.52-7.13 (m, 10H),
7.12-6.91 (m, 4H), 5.13 (t, 2H, J ) 8.5 Hz), 4.38 (t, 2H, J ) 8.5
Hz), 3.85 (t, 2H, J ) 8.5 Hz), 1.98 (s, 6H); 13C NMR (50 MHz,
CDCl3): δ 163.2, 141.9, 140.1, 138.9, 136.5, 128.9, 128.1, 127.9,
127.5, 77.5, 70.3, 20.5; IR (neat): 3061, 2967, 2895, 1949, 1882,
1804, 1643, 1487, 1451, 1347, 1150 cm-1; HRMS: Calcd for
C
32H28O2N2: 473.2229. Found: 473.2209. [R]D ) +26.2 (c 4.20,
CHCl3).
Ack n ow led gm en t. We are grateful to the National
Science Foundation and Purdue Research Foundation
for funding. We also thank Mr. Xi Chen for assistance
with the allylic oxidation reaction and Arlene Rothwell
for mass spectroscopy.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra for the intermediates and biaryl bis(oxazoline)s 1 and
2 (16 pages). This material is contained in libraries on
microfiche, immediately follows this article in the microfilm
version of the journal, and can be ordered from the ACS; see
any current masthead page for ordering information.
J O9713619