A simple synthetic approach to 3,3′-diaryl BINOLs

Full text of DOI:10.1021/jo980959t

7536
J . Org. Chem. 1998, 63, 7536-7538
Sch em e 1
A Sim p le Syn th etic Ap p r oa ch to 3,3′-Dia r yl
BINOLs
Klaus B. Simonsen, Kurt V. Gothelf, and
Karl Anker J ørgensen*
Center for Metal Catalyzed Reactions, Department of
Chemistry, Aarhus University, DK-8000 Aarhus C, Denmark
Received May 20, 1998
In tr od u ction
Chiral auxiliaries and ligands with C2 symmetry, such
as binaphthyl1 and bis(oxazolidine)2 derivatives, have
been widely employed as ligands in catalytic asymmetric
Diels-Alder,3 ene,4 1,3-dipolar cycloaddition,5 and other
reactions.6 Although, chiral Lewis acid complexes of 3,3′-
disubstituted 1,1′-bi-2-naphthol 1 (BINOL) have been
used successfully for asymmetric induction in a variety
of reactions,7 general synthetic procedures to this impor-
tant class of ligands are scarce. In 1981 Cram et al.
synthesized two optical pure 3,3′-diaryl-substituted
BINOLs by a Grignard cross-coupling reaction of 3,3′-
dibromo-BINOL dimethyl ether and arylmagnesium
bromides employing dichlorobis(triphenylphosphine)-
nickel(II) as the catalyst.8 The 3,3′-diphenyl BINOL has
also been synthesized along with the 2-naphthyl deriva-
tive by a Suzuki cross-coupling reaction of the MOM-
protected 3,3′-dibromo BINOL and phenyl- and 2-naph-
thylboronic acids followed by standard deprotection.9,10
and efficient procedure to 3,3′-diaryl-substituted BINOLs
is needed. The approach for the synthesis of 3,3′-diaryl
BINOLs (R)-4 outlined in this paper presents an entry
that makes 3,3′-diaryl BINOLs easy to prepare by reac-
tion of the 3,3′-diboronic acid of BINOL ((R)-3) with
commercially available aromatic bromides by a Suzuki
cross-coupling reaction (Scheme 1).
Resu lts a n d Discu ssion
The reported Suzuki coupling reactions performed on
BINOLs all involve either 3,3′-diiodo or 3,3′-dibromo
BINOLs and an aromatic boronic acid.10,11 The attention
to this new approach is the introduction of two boronic
acid substituents in the 3,3′ position of BINOL. The key
diboronic acid (R)-3 is prepared by treatment of (R)-2,2′-
dimethoxy-1,1′-dinaphthyl ((R)-2) with n-BuLi (3.0 equiv)
and N,N,N′,N′-tetramethylethylenediamine (TMEDA, 3.0
equiv) in dry Et2O at room temperature for 3 h, generat-
ing the dilithiated compound, which reacts with B(OEt)3
at -78 °C. During acidic workup the borate was hydro-
lyzed to give the corresponding diboronic acid (R)-3 in
87% isolated yield after recrystallization. It should be
noted that this reaction has been carried out on a 6 g
scale without any difficulties.
Compound (R)-3 and the appropriate aromatic bromide
were refluxed for 24 h in 1,4-dioxane containing Ba(OH)2,
H2O, and a catalytic amount of Pd(PPh3)4. Standard
acidic workup gave the bis-coupled product 3,3′-diaryl-
2,2′-dimethoxy-1,1′-dinaphthyl as a yellow semicrystal-
line oil. Demethylation was carried out on the crude
material using BBr3 in CH2Cl2 for 18 h. Chromato-
graphic purification on silica gel afforded (R)-3,3′-diaryl
BINOLs (R)-4a -e as white crystalline compounds in
overall good yields. The results are presented in Table
1.
The main drawback in the above reactions is the in
situ preparation of the Grignard compounds and the
accessibility of the boronic acid derivatives. Thus, to
screen a given reaction with a variety of 3,3′-diaryl-
substituted BINOLs for asymmetric induction, a versatile
(1) Rosini, C.; Franzani, L.; Raffaelli, A.; Salvadori, P. Synthesis
1992, 503.
(2) (a) Ghosh, A. K.; Mathivanan, P.; Cappiello, J . Tetrahedron:
Asymmetry 1998, 9, 1. (b) Pfaltz, A. Acc. Chem. Res. 1993, 23, 339. (c)
Pfaltz, A. Acta Chem. Scand. 1996, 50, 189.
(3) Kagan, H. B.; Riant, O. Chem. Rev. 1992, 92, 1007. For
application in catalytic asymmetric hetero Diels-Alder reactions,
see: Tietze, L. F.; Kettschau, G. Stereoselective Heterocyclic Synthesis
II; Metz, P., Ed.; Springer-Verlag: Berlin, 1997; Vol. 189, pp 1-120.
(4) Mikami, K.; Shimizu, M. Chem. Rev. 1992, 92, 1021.
(5) Gothelf, K. V.; J ørgensen, K. A. Chem. Rev. 1998, 98, 863.
(6) See e.g.: Narasaka, K. Synthesis 1991, 1.
(7) See e.g.: (a) Maruoka, K.; Itoh, T.; Shirasaka, T.; Yamamoto,
H. J . Am. Chem. Soc. 1988, 110, 310. (b) Kelly, T. R.; Whiting, A.;
Chandrakumar, N.S. J . Am. Chem. Soc. 1986, 108, 3510. (c) Chapuis,
C.; J urczak, J . Helv. Chim. Acta 1987, 70, 436. (d) Maruoka, K.;
Hoshino, Y.; Shirasaka, T.; Yamamoto, H. Tetrahedron Lett. 1988, 29,
3967.
(8) Lingenfelter, D. S.; Helgeson, R. G.; Cram, D. J . J . Org. Chem.
1981, 46, 393.
(9) For application of Suzuki coupling, see e.g.: (a) Watanabe, T.;
Miyaura, N.; Suzuki, A. Synlett 1992, 207. (b) Miyaura, N.; Suzuki,
A. Chem. Rev. 1995, 95, 5, 2457.
(10) Cox, P. J .; Wang, W.; Snieckus, V. Tetrahedron Lett. 1992, 33,
2253.
The (R)-3,3′-diaryl BINOLs (R)-4a -e were pure by 1H
and 13C NMR spectroscopy after chromatography and can
be used as ligands without further purification. It
appears from Table 1 that the (R)-3,3′-diaryl BINOLs (R)-
4a ,c-e are formed in good yields (entries 1, 3-5). The
3,3′-bis(2,6-dimethylphenyl) BINOL (R)-4b is formed in
lower yield compared with the use of the other aromatic
(11) (a) Huang, W.-S.; Hu, Q.-S.; Pu, L. J . Org. Chem. 1998, 63, 1364.
(b) Ishihare, K.; Yamamoto, H. J . Am. Chem. Soc. 1994, 116, 1561. (c)
Maruoka, K.; Murase, N.; Yamamoto, H. J . Org. Chem. 1993, 58, 2938.
S0022-3263(98)00959-1 CCC: $15.00 © 1998 American Chemical Society
Published on Web 09/30/1998

Notes
Ta ble 1. Resu lts for th e Cou p lin g of Dibor on ic Acid
BINOL (R)-3 w ith Va r iou s Ar om a tic Br om id es Ca ta lyzed
by P d (P P h 3)4 a n d F ollow ed by Dem eth yla tion Lea d in g to
(R)-3,3′-Dia r yl BINOLs (R)-4a -e
J . Org. Chem., Vol. 63, No. 21, 1998 7537
bottomed flask equipped with a N2-inlet were placed dry Et2O
(300 mL) and TMEDA (6.3 g, 54 mmol). To this solution was
added 1.6 M n-BuLi in hexane (35 mL, 56 mmol). The solution
was stirred for 30 min at room temperature, solid (R)-2 (5.9 g,
19 mmol) was added in one portion, and the reaction mixture
was stirred for 3 h. The resulting light brown suspension was
cooled to -78 °C, and B(OEt)3 (17.1 g, 117 mmol) was added via
syringe over a period of 10 min. The solution was allowed to
warm to room temperature and was left stirring overnight. The
reaction mixture was cooled to 0 °C, 1 M HCl (150 mL) was
added, and the reaction mixture was stirred for 2 h. The phases
were separated, and the organic phase was washed twice with
1 M HCl (100 mL) and saturated aqueous NaCl (100 mL) and
dried over Na2SO4. The solvent was removed under reduced
pressure, and the resulting white solid was recrystallized from
toluene to give (R)-3 (6.53 g, 87%) as white crystals: mp >250
°C; [R]D ) -153.4° (c ) 1, CHCl3). 1H NMR (acetone-d6): δ 3.41
(s, 6H), 7.11 (dd, J ) 8.1, 1.1 Hz, 2H), 7.34 (td, J ) 7.5, 1.2 Hz,
2H), 7.46 (td, J ) 7.4, 1.2 Hz, 2H), 8.05 (d br, J ) 7.1 Hz, 2H),
8.56 (s, 2H). 13C (acetone-d6): δ 61.8, 124.2, 125.7, 126.3, 128.2,
129.7, 131.4, 136.6, 139.1, 161.2. MS(PDMS) m/z: 402 (M+),
calcd for C22H20B2O6 402.0.
a
Overall yield.
Gen er a l P r oced u r e for th e Su zu k i Cr oss-Cou p lin g Re-
a ction . In a 50 mL two-necked flask equipped with a condenser
were placed (R)-3 (0.75 g, 1,9 mmol), Ba(OH)2‚8H2O (1.74 g, 5.5
mmol), and Pd(PPh3)4 (0.116 g, 0.1 mmol), and the flask was
evacuated and filled with N2 three times. 1,4-Dioxane (12 mL),
H2O (4 mL), and the appropriate bromoarene (6.0 mmol) were
added. The reaction mixture was refluxed for 24 h under N2
and cooled to room temperature. The dioxane was removed, and
the resulting phase was redissolved in CH2Cl2 (75 mL), washed
with 1 M HCl (2 × 50 mL) and saturated aqueous NaCl (75 mL),
and dried over Na2SO4. The solvent was removed to give the
crude product as a yellow semicrystalline oil. The crude product
was dissolved in dry CH2Cl2 (75 mL) and cooled to 0 °C, BBr3 (1
mL) was added over a period of 10 min, and the reaction mixture
was stirred for 18 h at room temperature. The pale yellow
solution was cooled to 0 °C, and H2O (150 mL) was carefully
added. The phases were separated, and the organic phase was
washed with H2O (2 × 100 mL) and saturated aqueous NaCl
(100 mL), dried over Na2SO4, and concentrated. The resulting
yellow solid was chromatographed on silica to give (R)-4 as white
crystalline solids.
bromides (entry 2). The reason for the lower yield by use
of 2,6-dimethylphenyl bromide via the coupling reaction
is probably due to steric reasons, and the main (by-)-
product formed is the mono-arylated BINOL (R)-5.
Furthermore, we have also tried to use heteroaromatic
bromides, such as 2-bromopyridine and 2-bromothiophene,
for the preparation of (R)-3,3′-bis(heteroaryl) BINOLs.
However, the present approach gives only the BINOLs
in low yields.
(R)-3,3′-Dip h en yl-2,2′-d ih yd r oxy-1,1′-d in a p h th yl ((R)-4a ).
Chromatography (silica, hexane:EtOAc 19:1, Rf ) 0.4): yield
By reversing the reactants in the Suzuki coupling, we
have been able to make a series of chiral (R)-3,3-diaryl
BINOLs (R)-(4) in overall good yields in a two-step
reaction starting from the 3,3′-diboronic acid BINOL
(R)-3 dimethyl ether and the appropriate aromatic bro-
mide. Compound (R)-3 represents a late common inter-
mediate to several enantiopure 3,3′-disubstituted BINOLs
in large batches employing standard reactions.
73%; mp 202-204 °C (CH2Cl2/hexane, lit.8 197-198 °C); [R]D
)
69.1° (c ) 1, CHCl3). 1H NMR (CDCl3): δ 5.36 (s, 2H), 7.25-
7.52 (m, 12 H), 7.45 (m, 4H), 7.93 (d, J ) 7.7 Hz, 2H), 8.03 (s,
2H). 13C (CDCl3): δ 112.4, 124.3, 124.4, 127.4, 127.8, 128.5,
128.5, 129.5, 129.6, 130.7, 131.4, 133.0, 137.5, 150.2. MS(PDMS)
m/z: 438.7 (M+), calcd for C32H20O2 438.5.
(R)-3,3′-Bis(2,6-d im et h ylp h en yl)-2,2′-d ih yd r oxy-1,1′-d i-
n a p h th yl ((R)-4b). Chromatography (silica, CH2Cl2:hexanes
1:1, Rf ) 0.3): yield 22%; mp 153-156 °C; [R]D ) 46.3° (c ) 1,
CHCl3). 1H NMR (CDCl3): δ 2.14 (s, 6), 2.22 (s, 6H), 5.01 (s,
2H), 7.15-7.54 (m, 14 H), 7.78 (s, 2H), 7.91 (d, J ) 8.7 Hz,
2H).13C (CDCl3): δ 20.6, 20.7, 113.0, 124.0, 124.5, 127.0, 127.6,
127.7, 128.1, 128.3, 129.5, 130.5, 133.4, 136.0, 137.2, 137.3, 149.9.
MS(PDMS) m/z: 494.6 (M+), calcd for C36H30O2 494.6.
Exp er im en ta l Section
Gen er a l Meth od s. The 1H and 13C NMR spectra were
recorded at 300 and 75 MHz, respectively. The chemical shifts
are reported in ppm downfield with respect to tetramethylsilane
(TMS). Plasma desorption mass spectrometry (PDMS) was
recorded on a Bio-Ion 20K time-of-flight instrument on the basis
of 500 000 fission events. Optical rotations were measured on
a Perkin-Elmer 241 polarimeter. Et2O and 1,4-dioxane were
distilled from sodium and benzophenone prior to use. TMEDA
was distilled form CaH2 and stored over molecular sieves (4 Å).
Ma ter ia ls. (R)-BINOL was prepared by resolution of rac-
BINOL (Aldrich) employing N-benzylcinchonidinium chloride
(Aldrich)12 and converted to 2,2′-dimethoxy-1,1′-dinaphthyl ((R)-
2) according to the literature.8 B(OEt)3 (Aldrich) was distilled
prior to use. Pd(PPh3)4 and the aromatic bromides were
purchased from Aldrich and used without further purification.
(R)-3,3′-Bis(dih ydr oxybor an e)-2,2′-dim eth oxy-1,1′din aph -
th yl ((R)-3). In a 500 mL flame-dried three-necked round-
(R)-3-(2,6-Dim et h ylp h en yl)-2,2′-d ih yd r oxy-1,1′-d in a p h -
th yl ((R)-5). Chromatography (silica, CH2Cl2:hexanes 1:1, Rf
) 0.15) gave (R)-5 as a semicrystalline solid: yield 48%; [R]D
)
91.3° (c ) 1, CHCl3). 1H NMR (CDCl3): δ 2.17 (s, 6H), 2.18 (s,
6H), 5.03 (br. s, 2H), 7.15-7.45 (m, 10 H), 7.83 (s, 1H), 7.92 (d,
J ) 8.4 Hz, 2H), 8.00 (d, J ) 8.7 Hz, 1H). 13C (CDCl3): δ 20.6,
20.8, 111.6, 112.4, 117.7, 123.8, 124.2, 124.4, 127.2, 127.3, 127.7,
128.2, 128.4, 128.5, 129.5, 129.6, 129.6, 131.0, 131.1, 133.3, 133.5,
135.8, 137.1, 137.3, 150.4, 152.2. MS(PDMS) m/z: 390.3 (M+),
calcd for C28H22O2 390.0.
(R)-3,3′-Bis(3,5-d im et h ylp h en yl)-2,2′-d ih yd r oxy-1,1′-d i-
n a p h th yl ((R)-4c). Chromatography (silica, hexane:EtOAc 19:
1, Rf ) 0.4): yield 65%; mp >250 °C; [R]D ) 75.6° (c ) 1, CHCl3).
1H NMR (CDCl3): δ 2.55 (s, 6H), 2.63 (s, 6H), 4.43 (s, 2H), 7.15-
7.45 (m, 10H), 8.04 (d, J ) 8.2 Hz, 2H). 8.16 (s, 2H), 8.80 (s,
2H). 13C (CDCl3): δ 22,1, 22.9, 120.3, 120.8, 123.2, 123.8, 124.2,
125.6, 126.3, 128.5, 129.5, 131.2, 133.4, 141.3, 141.5, 146.2, 146.9.
MS(PDMS) m/z: 494.6 (M+), calcd for C36H30O2 494.6.
(12) Cai, D.; Hughes, D. L.; Verhoeven, T. R.; Reider, P. J . Tetra-
hedron Lett. 1995, 36, 7991.

7538 J . Org. Chem., Vol. 63, No. 21, 1998
Notes
(R)-3,3′-Bis(4-b ip h en yl)-2,2′-d ih yd r oxy-1,1′-d in a p h t h yl
124.4, 124.4, 126.3, 126.3, 127.5, 127.7, 128.0, 128.2, 128.5, 129.6,
130.7, 131.7, 132.8, 133.1, 133.5, 135.0, 150.3. MS(PDMS) m/z:
539.0 (M+), calcd for C40H26O2 538.6.
((R)-4d ). Chromatography (silica, CH2Cl2:hexane 1:1, Rf
)
0.3): yield 68%; mp 220-222 °C; [R]D ) -70.3° (c ) 1, CHCl3).
1H NMR (CDCl3): δ 5.43 (s, 2H), 7.29-7.54 (m, 12 H), 7.69 (d,
J ) 7.1 Hz, 4H), 7.75 (d, J ) 8.2 Hz, 4H), 7.86 (d, J ) 8.8 Hz,
4H), 7.97 (d, J ) 7.8 Hz, 2H), 8.11 (s, 2H).13C (CDCl3): δ 112.4,
124.3, 124.5, 127.2, 127.3, 127.5, 128.5, 128.9, 129.6, 130.1, 130.3,
131.5, 133.0, 136.5, 140.6, 140.8, 150.3. MS(PDMS) m/z: 590.8
(M+), calcd for C44H30O2 590.7.
Ack n ow led gm en t. This work was made possible by
a grant from The Danish National Science Foundation.
Su p p or tin g In for m a tion Ava ila ble: Copies of NMR
spectra (14 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.
(R)-3,3′-Bis(2-n a p h t h yl)-2,2′-d ih yd r oxy-1,1′-d in a p h t h yl
((R)-4e). Chromatography (silica, CH2Cl2:hexane 1:1, Rf
)
0.4): yield 70%; mp 248-249 °C; [R]D ) -40.2° (c ) 1, CHCl3).
1H NMR (CDCl3): δ 5.50 (s, 2H), 7.31-7.62 (m, 10 H), 7.88-
7.97 (m, 10 H), 8.16 (s, 2H), 8.24 (s, 2H).13C (CDCl3): δ 112.5,
J O980959T