Access to 2′-substituted binaphthyl monoalcohols via complementary nickel-catalyzed kumada coupling reactions under mild conditions: Key role of a P,O ligand

Article abstract of DOI:10.1021/jo400349r

Two complementary Kumada coupling methods for the conversion of monotriflated 1,1′-binaphthalene-2,2′-diol (BINOL) into 2′-substituted binaphthyl monoalcohols under mild conditions are reported. A protocol using NiCl₂(dppe), in combination with

Full text of DOI:10.1021/jo400349r

Note
pubs.acs.org/joc
Access to 2′-Substituted Binaphthyl Monoalcohols via
Complementary Nickel-Catalyzed Kumada Coupling Reactions under
Mild Conditions: Key Role of a P,O Ligand
Sachin Handa, Yohan L. N. Mathota Arachchige, and LeGrande M. Slaughter*
Department of Chemistry, Oklahoma State University, Stillwater, Oklahoma 74078, United States
S
* Supporting Information
ABSTRACT: Two complementary Kumada coupling methods
for the conversion of monotriflated 1,1′-binaphthalene-2,2′-diol
(BINOL) into 2′-substituted binaphthyl monoalcohols under
mild conditions are reported. A protocol using NiCl2(dppe), in
combination with an improved preparation of the monotriflate, is
effective for 1,1′-binaphthalene-2-ols containing unsubstituted or
electron-poor aryl or benzyl 2′-substituents. An alternative
procedure, using a potentially hemilabile-bidentate phosphinan-
4-ol ligand, is superior for products containing neopentyl or electron-rich aryl 2′-substituents. The obtained binaphthyl alcohols
represent potentially useful synthons for chiral ligands and auxiliaries.
he 1,1′-binaphthyl moiety is a ubiquitious design element
T
in chiral auxiliaries and catalysts.1,2 For derivatives with
substituents at the 2- and 2′-positions, restricted rotation about
the 1,1′-bond prevents racemization,3 enforcing a sterically
pronounced, axially chiral conformation that can engender
highly asymmetric environments at metal-based or organo-
catalytic active sites.4 The vast majority of binaphthyl
derivatives used in asymmetric synthesis contain Lewis basic
substituents at both the 2- and 2′-positions.5 This is exemplified
by chiral diphosphine ligands such as 2,2′-bis-
(diphenylphosphino)-1,1′-binaphthyl (BINAP; 1),6 in which
chelation to a catalytic metal constrains the binaphthyl unit to a
rigid, C2-symmetric geometry and creates a static binding
pocket that is favorable for chiral induction.7 Monodentate
binaphthyl-based ligands are less developed8 but could provide
advantages when the metal is intrinsically low-coordinate or
forms underligated catalytic intermediates.9 Here, attention has
focused on ligand designs that tie the binaphthyl unit into
phosphite,10 phosphonite,11 or phosphoramidite12 structures
via P−O linkages at the 2,2′-positions, also rigidifying the chiral
backbone. Monodentate binaphthyl ligands with donor
substituents only at the 2-position are rare.13−19 The most
notable examples are the MOP family of monophosphines
(2),13−15 some of which have delivered high enantioselectivies
for certain palladium-catalyzed reactions14 despite the greater
conformational flexibility arising from the noncoordinated
second naphthyl ring. We have recently reported evidence
that this kind of flexibility can be advantageous in binaphthyl-
based monodentate carbene ligands, where it facilitates
noncovalent interactions of the 2′-substituent with the metal
active site that may contribute to highly enantioselective
catalysis.19
routes to 1,1′-binaphthalene-2-ols with electronically and
sterically diverse aryl and alkyl substituents at the 2′-position
(3). Only a few such binaphthyl monoalcohols are known,20−27
and no broadly applicable synthetic method for installing
nonheteroatom groups at the 2′-position of a binaphthyl unit
has been reported, in contrast to well-developed methods for
modification at the 3,3′-1,28 and 6,6′-positions.1 Most reported
alcohols of type 3 have been obtained by nickel-catalyzed
Kumada−Corriu coupling reactions29 of Grignard reagents with
derivatives of 1,1′-binaphthalene-2,2′-diol (BINOL: 4, Table
1), a widely used binaphthyl precursor that is readily available
in enantiomerically pure form.2 The 2′-phenyl-substituted
alcohol was prepared in two steps from BINOL, via the
monotriflate 5, using mild Kumada coupling conditions of 2
mol % NiCl2(dppe) catalyst [dppe = bis(diphenylphosphino)-
ethane] and 35 °C.20 A derivative with a bulky silyl substituent
at the para position of the 2′-phenyl group required slightly
more stringent conditions (5 mol % catalyst, 66 °C).21 One
example with an electron-deficient aryl substituent [R′ = 3,5-
(CF3)2C6H3] was synthesized similarly, but pretreatment of 5
with MeMgI prior to coupling was needed, and the yield was
modest (59%).22 Two variants of 3 with electronic-deficient 2′-
aryl groups were obtained by palladium-catalyzed Suzuki
Toward a goal of further exploring monodentate binaphthyl-
based ligands in asymmetric catalysis, we sought preparative
Received: February 15, 2013
Published: May 14, 2013
© 2013 American Chemical Society
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Note
iPr2NEt has been used previously to generate 5 in situ,22 but
not to prepare it as a pure material. Monotriflate 5 is isolated as
a crystalline solid in our optimized protocol, whereas the
literature procedure describes it as an oil.20
Table 1. Optimization of Reaction Conditions for Synthesis
of Monotriflated BINOL (5)
a
We examined the synthesis of p-methoxyphenyl-substituted
binaphthyl alcohol 3a as a test case for the identification of mild
Kumada coupling conditions. Although 3a has not been
previously reported, literature precedent indicates that similar
Kumada coupling reactions of binaphthyl triflates with aryl
Grignard reagents containing electron-donating groups typi-
cally require forcing conditions.15,24 Use of the standard
Kumada catalyst NiCl2(dppe) in 5 mol % at 25 °C with 2.2
equiv of aryl Grignard afforded 3a in only 25% yield after 20 h
(entry 1, Table 2). The related catalyst NiCl2(dppp) [dppp =
entry
base
Et3N
% yield 5
% yield 6
% recovered 4
1
2
3
4
5
65
69
89
60
62
10
10
<2
20
15
12
10
−
iPr2NH
iPr2NEt
pyridine
2,6-lutidine
18
17
a
Reactions were conducted with 2.0 g of 4.
Table 2. Catalyst Optimization for Kumada Coupling of 5
with an Electron-Rich Aryl Grignard
a
coupling, but formation of the 2′-iodide was necessary in
addition to an alcohol protection step.23 The only reported
synthesis of a binaphthyl alcohol with an electron-rich 2′-aryl
substituent (R′ = 2-methoxyphenyl) used an arylzinc reagent
and harsh catalytic conditions, with 20 mol % NiCl2(dppe) and
extended reflux in THF.24 Similarly forcing conditions were
required for installation of electron-rich aryl groups at the 2′-
position of MOP-type ligands via Kumada coupling reactions of
2-(diphenylphosphino)-1,1′-binaphthyl-2′-triflate.15 Three 2′-
alkyl versions of 3 (R′ = Me, Et, iPr) have also been prepared
by Kumada coupling with NiCl2(dppe), but protection of the 2-
hydroxy group and extended heating at 60 °C were
necessary.25,26 The 2′-benzyl derivative has been obtained by
a three-step, noncatalytic route that is not applicable for
nonbenzylic 2′-groups.27
entry
catalyst
time (h)
% yield 3a
1
2
3
5 mol % NiCl2(dppe)
20
20
1
25
−
78
5 mol % NiCl2(dppp)
5 mol % anhyd NiCl2 + 10 mol % 7
a
Reactions were conducted with 100 mg of 5.
Herein we report two complementary procedures that
provide access to binaphthyl monoalcohols having a range of
2′-substituents via room temperature, nickel-catalyzed Kumada
couplings of monotriflated BINOL 5. An optimized version of
the literature protocol, involving NiCl2(dppe) catalyst and an
improved synthesis of 5, is effective for attachment of
unsubstituted or electron-deficient aryl or benzyl substituents
at the binaphthyl 2′-position. A new Kumada coupling
procedure, using a potentially hemilabile-bidentate phos-
phinan-4-ol ligand in combination with nickel, provides
superior yields for binaphthyl alcohols containing alkyl or
electron-rich aryl 2′-substituents. Monotriflate 5 represents a
challenging Kumada substrate due to the presence of a bulky
naphthyl substituent ortho to the reactive carbon−oxygen
bond,29 and it is notable that no catalyst systems other than
NiCl2(dppe) have been previously reported for cross-coupling
reactions of this useful chiral building block.
Our first goal was to identify conditions for synthesis of
monotriflated BINOL 5 using triflic anhydride, which is
significantly less expensive than the PhNTf2 used as a
sulfonating agent in the literature procedure.20 Several bases
were tested in reactions of (R)-BINOL with Tf2O, and most of
them afforded material contaminated with substantial amounts
of ditriflate 630 as well as unreacted BINOL (Table 1). The
ditriflate was difficult to remove chromatographically, and trace
amounts negatively impacted yields in subsequent catalytic
reactions. However, the use of iPr2NEt as a base led to isolation
of 5 in 89% yield with only traces of 6 present. The minor
ditriflate impurity in the optimized reaction is readily removed
by flash chromatography, affording very pure monotriflate 5
even when the reaction is conducted on a 12 g scale. Notably,
bis(diphenylphosphino)propane], which is known to provide
superior activities in some Kumada coupling reactions involving
electron-rich and/or hindered coupling partners,31 was even
less effective in this case, resulting in no detectable formation of
3a (entry 2). These disappointing results prompted us to
examine phosphinan-4-ol 7 as a ligand in the test reaction.
Ligand 7 and variants were recently shown by McNulty and co-
workers to be effective for the synthesis of electron-rich and
sterically hindered biaryls by palladium-catalyzed Suzuki−
Miyaura coupling.32,33 The use of phosphinan-4-ol ligands in
Ni-catalyzed coupling processes has not been previously
reported, but reports of room-temperature Kumada couplings
with nickel34−37 or palladium36,38−40 complexes of other
potentially bifunctional P,O-type ligands encouraged us to try
7. We were gratified to find that a catalyst system comprising 5
mol % NiCl2 in combination with 10 mol % 7 provided
binaphthyl alcohol 3a in 79% yield after 60 min at 25 °C (entry
3).
We next examined the effectiveness of the NiCl2/(7)2
catalyst system in room-temperature Kumada coupling
reactions of 5 with a range of Grignard reagents in comparison
with the standard NiCl2(dppe) catalyst. The results show that
the two catalyst systems are complementary (Table 3). In
couplings of aryl Grignard reagents with 5, the NiCl2/(7)2
system provides significantly better yields when electron-
donating methoxy or methyl groups are present (entries 1−
6), whereas NiCl2(dppe) is superior for unsubstituted or
electron-deficient aryl groups (entries 7−12). Notably, the P,O
ligand allowed formation of the known o-methoxyphenyl
derivative 3b in comparable yield to that previously reported
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Note
Table 3. Scope of 2′-Substituted Binaphthyl Alcohol Synthesis Using Complementary Kumada Coupling Methods
a
Reaction conditions: 100 mg of 5 (0.20 M in dry Et2O). Method A: 2.2 equiv of R′-MgBr (1.0 M in dry Et2O), 5 mol % NiCl2(dppe), rt. Method B:
b
2.2 equiv of R′-MgBr (1.0 M in dry Et2O), 5 mol % anhydrous NiCl2, 10 mol % 7, rt. Exists as a 50:50 mixture of two diastereomeric rotamers that
c
are interconverting on the 1H NMR time scale, consistent with published spectral data (ref 24). Obtained as a mixture of the two isomers that could
d
e
not be chromatographically separated. Combined yield, with isomeric ratio of 3h to 3i given. Binaphthalen-2-ol (ref 13) was also obtained in 32%
yield. Use of nPrMgBr resulted in an identical product ratio.
f
with NiCl2(dppe),24 but without the need for heating, high
catalyst loading, or conversion of the Grignard to an arylzinc
reagent (entry 4); by contrast, NiCl2(dppe) was much less
effective under the same conditions (entry 3). The NiCl2/(7)2
catalyst also gave significantly higher yields with alkyl Grignard
reagents, including one example without β-hydrogens (R′ =
neopentyl, entries 13, 14) and one with β-hydrogens (R′ = iPr,
entries 15, 16), although the yield was still modest (49%) in the
latter case. For R′ = iPr, a competing β-hydrogen elimination/
alkene reinsertion process resulted in a mixture of the iPr- and
nPr-substituted products with both catalysts. The high nPr:iPr
ratios obtained are in agreement with previous reports of facile
isomerization to the linear alkyl group in nickel-catalyzed
alkyl−aryl Kumada couplings.41 The coupling of 5 with benzyl
Grignard was the only case in which both catalysts gave good
yields of the desired product (entries 17, 18). However,
coupling reactions of 3,5-bis(trifluoromethyl)benzyl Grignard
exhibited catalyst-dependent differences in activity similar to
those seen for electron-deficient aryl Grignard reagents, with a
significantly higher yield obtained using the NiCl2(dppe)
catalyst (entries 19, 20). Finally, the use of highly pure 5 as a
precursor appeared to improve the performance of the catalyst
even when the standard NiCl2(dppe) system was employed.
For example, the synthesis of 3d (R′ = Ph, entry 7) used a
lower excess of Grignard reagent, and 3f [R′ = 3,5-
bis(CF3)2C6H3, entry 12] formed in higher yield without the
need to pretreat 5 with MeMgI, in comparison to literature
procedures using the same catalyst.20,22
The ability of related P,O-type ligands to promote room-
temperature Kumada-Corriu coupling reactions has been
attributed to enhancement of the oxidative addition rate of
the electrophile, either through formation of reactive anionic
M0 species upon deprotonation of ligand hydroxy groups38 or
through cooperative C−X activation involving O-bound Mg
ions.35,37,39 However, the electrophile (i.e., 5) is identical for all
reactions in this study, suggesting that other steps in the
catalytic cycle underlie the improved activities observed with
ligand 7. The NiII-bound binaphthyl ligand formed from 5 will
be highly electron-rich upon deprotonation of the 2-hydroxy
group by excess Grignard reagent, and C−C reductive
eliminations are known to be slow when two electron-rich
aryl ligands are involved.42 We hypothesize that 7 promotes
reductive elimination of electron-rich aryl groups by acting as a
hemilabile-bidentate ligand (Scheme 1). A chair−boat con-
formational change allows the oxygen of one ligand to bind
NiII, forming a 5-coordinate intermediate from which reductive
elimination may be faster.43 McNulty previously proposed that
7 stabilizes reactive Pd0 species through this type of
conformational flip.32,33 Retardation of the transmetalation
step due to bidentate binding and/or the stronger donicity of 7
may outweigh the improved reductive elimination rates in some
cases, potentially explaining why poorer results were obtained
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Note
133.3, 133.1, 131.8, 131.6, 129.3, 128.6, 128.4, 128.4, 127.7, 127.2,
126.6, 125.3, 124.3, 123.9, 119.9, 118.4 (q, J(C,F) = 319 Hz), 118.1,
112.2; HRMS (ESI-orbitrap) m/z calcd for C21H13F3O4SNa 441.0384
[M + Na]+, found 441.0386.
Scheme 1
1-Cyclohexyl-2,2,6,6-tetramethylphosphinan-4-ol (7). Neat
cyclohexylphosphine (1.0 g, 7.2 mmol) and freshly distilled 2,6-
dimethylhepta-2,5-dien-4-one (phorone, 0.84 g, 7.2 mmol) were added
to a sealable reaction vessel under argon counterflow. The vessel was
sealed, and the reaction mixture was heated at 130 °C for 8 h. The
reaction mixture was then cooled to room temperature, and the
intermediate 1-cyclohexyl-2,2,6,6-tetramethylphosphinan-4-one47
(0.80 g, 44% yield, air-sensitive waxy solid) was obtained by vacuum
with 7 versus dppe when electron-poor Grignard reagents were
employed.44
1
distillation (120 °C, 10 mtorr) under rigorous exclusion of air: H
The complementary Kumada coupling protocols presented
herein expand the number of accessible 2′-substituted
binaphthyl alcohols while also improving upon existing routes
to these chiral synthons. Both procedures use inexpensive
nickel as a catalyst but avoid the high catalyst loadings,24 larger
excesses of Grignard reagent,20 or alcohol protection
steps23,25,26 used in some reported syntheses. The mild catalytic
conditions preclude high temperatures that could lead to loss of
enantiomeric purity. Ligand 7, which improves access to
variants of 3 with alkyl or electron-rich aryl 2′-substituents, is
easily prepared in two steps from commercial materials,
although it requires air-sensitive handling; detailed synthetic
procedures and characterization data are provided below, as
these are not available in the original report of 7.32 The
syntheses of all alcohols except 3b and 3h/3i, including five
previously unreported compounds (3a,c,e,g,k), were scaled up
to 1−4 g with no appreciable loss of yield (see the
Experimental Section). These binaphthyl monoalcohols
represent potential synthons for a range of new monodentate
chiral ligands and auxiliaries, since the hydroxyl group or its
sulfonated derivatives can be readily converted into a variety of
donor functionalities including phosphines,6 amines,45 and
carbenes.19
NMR (400 MHz, CD2Cl2) δ 2.56 (dd, J = 12, 3.4 Hz, 2H), 2.13 (dd, J
= 17, 12 Hz, 2H), 1.98−1.91 (m, 2H), 1.88−1.76 (m, 3H), 1.70−1.64
(m, 1H), 1.48−1.36 (m, 2H), 1.34−1.22 (m, 3H), 1.22 (d, J(P,H) = 16
Hz, 6H), 1.17 (d, J(P,H) = 4.0 Hz, 6H). For the next step, dry THF (20
mL) was transferred to a two-neck flask, and LiAlH4 (180 mg, 4.72
mmol) was added under argon counterflow. The resulting slurry was
stirred for 5 min at 0 °C, and a solution of the phosphinan-4-one
intermediate (0.60 g, 2.4 mmol) in 5.0 mL of THF was slowly added.
The reaction mixture was stirred for 30 min at 25 °C and then for a
further 1 h at 50 °C. After complete consumption of the starting
material as judged by disappearance of the carbonyl IR stretch at 1723
cm−1, the reaction mixture was cooled to 0 °C, quenched with 1.0 mL
of degassed water, and stirred for 30 min at 25 °C. The mixture was
then filtered through a glass frit under argon, and the solvent was
removed in vacuo. The crude product was recrystallized from dry
hexanes to afford 7 as a white, air-sensitive solid (0.20 g, 33%): mp =
55−57 °C (decomp, under N2); 1H NMR (400 MHz, CDCl3) δ 4.07
(m, 1H), 3.21 (br s, 1H), 2.23−2.10 (m, 3H), 1.95−1.71 (m, 6H),
1.60−1.48 (m, 2H), 1.32 (d, J(P,H) = 11 Hz, 6H), 1.30−1.18 (m, 4H),
1.26 (d, J(P,H) = 13 Hz, 6H); 13C NMR (101 MHz, CDCl3) δ 63.7 (d,
J(C,P) = 4.4 Hz), 48.9, 39.0 (d, J(C,P) = 56 Hz), 35.4 (d, J(C,P) = 54 Hz),
27.8 (d, J(C,P) = 2.2 Hz), 27.7, 27.6, 26.5, 26.4; 31P NMR (101 MHz,
CDCl3) δ 29.8; HRMS (ESI-orbitrap) m/z calcd for C15H30OP
257.2034 [M + H]+, found 257.2028.
General Procedure for Grignard Reagent Preparation.
Magnesium turnings were activated by washing with 1.0 M HNO3,
water, and acetone, followed by drying in vacuo, and 1.5 equiv (relative
to R′-Br) were placed in a two-neck flask fitted with a reflux
condenser. Dry Et2O (10 mL per mmol of R′-Br) was transferred into
the flask by vacuum distillation. Half of the R′-Br was introduced
slowly with stirring, and the reaction mixture was heated at reflux in a
48 °C oil bath until initiation of the reaction (time specific to R′-Br).
After initiation, the remaining R′-Br was added dropwise, and the
mixture was stirred for an additional 30 min to 2 h (time specific to R′-
Br). After cooling, the Grignard solution was used immediately in a
Kumada coupling reaction.
General Procedure for Kumada Coupling (Method A). To a
stirred solution of 5 in dry Et2O (6.0 mL per mmol of 5) were added
NiCl2(dppe) (5.0 mol %) and freshly prepared Grignard reagent (2.2
equiv) under argon counterflow. The reaction mixture was stirred at
25 °C until 5 had been completely consumed as judged by TLC (30−
120 min; see Table 3). The reaction mixture was then quenched with
saturated aqueous NH4Cl and extracted with Et2O and water. The
organic layer was dried over Na2SO4 and concentrated under reduced
pressure to obtain the crude product, which was purified by flash
chromatography.
General Procedure for Kumada Coupling (Method B). To a
solution of 5 in dry Et2O (6.0 mL per mmol of 5) were added
anhydrous NiCl2 (5.0 mol %) and 7 (10 mol %) under argon
counterflow. The mixture was stirred at 25 °C for 15 min, and a small
portion (∼5% of 2.2 equiv total) of freshly prepared Grignard reagent
was introduced. After appearance of a deep brown color (5−10 min),
the remaining Grignard was added. Stirring was continued until 5 had
been completely consumed as judged by TLC (30−120 min; see Table
3). The reaction mixture was then quenched with saturated aqueous
NH4Cl and extracted with Et2O and water. The organic layer was dried
EXPERIMENTAL SECTION
■
General Experimental Methods. Manipulations were performed
under dry nitrogen in oven-dried glassware using freshly distilled dry
solvents unless otherwise noted. (R)-BINOL 4 (>99%) was purchased
from Chem-Impex International, Inc., and checked for optical purity
prior to reaction. NiCl2 (anhydrous, >99%) was purchased from
Strem. NiCl2(dppe) was synthesized in iPrOH/MeOH using a
literature procedure.46 Preparative flash column chromatography was
performed on silica gel 60 (230−400 mesh) using solvent mixtures
that gave optimal separations by TLC (specified below). For
development of chiral HPLC separation conditions used for
confirmation of enantiomeric purity, racemic samples of 3a−k were
prepared from commercial rac-BINOL using the methods reported in
Table 3.
(R)-2′-Trifluoromethanesulfonyl-[1,1′-binaphthalene]-2-ol
(5). A three-neck flask was fitted with two dropping funnels, which
contained solutions of Tf2O (5.90 mL, 34.9 mmol) in 50 mL of
CH2Cl2 and iPr2NEt (6.10 mL, 34.9 mL) in 49 mL of CH2Cl2,
respectively. A solution of (R)-BINOL 4 (10.0 g, 34.9 mmol) in
CH2Cl2 (350 mL) was added to the flask. The flask was cooled to 0
°C, and the solutions of Tf2O and iPr2NEt were slowly added together
over a period of 30 min. The reaction mixture was slowly warmed to
25 °C and then stirred for an additional 9 h. After complete
consumption of 4, the mixture was diluted with 150 mL of CH2Cl2
and then sequentially washed with cold 1.0 N HCl and 0.5 N
NaHCO3. The organic layer was dried over Na2SO4, and the solvent
was removed under vacuum. The oily crude product was purified by
flash chromatography to yield a white solid (12.1 g, 89%). Optical
rotation and 1H NMR data were in agreement with published values:20
23
Rf 0.50 (2:3 CH2Cl2/hexanes); mp = 38−39 °C; [α]D = +12.7 (c =
4.0, CHCl3); 13C NMR (101 MHz, CDCl3) δ 151.9, 146.3, 133.4,
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Note
over Na2SO4 and concentrated under reduced pressure to obtain the
crude product, which was purified by flash chromatography.
(d, J = 8.4 Hz, 1H), 4.77 (s, 1H); 13C NMR (101 MHz, CDCl3) δ
151.1, 144.6, 140.2, 134.1, 133.6, 133.2, 130.3, 129.8, 129.1, 129.0,
129.0 (q, J(C,F) = 32 Hz), 128.8, 128.4, 128.3, 128.1, 127.6, 126.9,
126.9, 126.5, 124.8, 124.7 (q, J(C,F) = 3.7 Hz), 124.2 (q, J(C,F) = 272
Hz), 123.5, 117.3, 117.2; 19F NMR (376 MHz, CDCl3) δ −63.5. Anal.
Calcd for C27H17F3O: C, 78.25; H, 4.14%. Found: C, 78.08; H, 4.31%.
(R)-2′-[3,5-Bis(trifluoromethyl)phenyl]-[1,1′-binaphthalen]-
2-ol (3f). Method A (Grignard preparation: initiation 10 min, reaction
time 40 min): Rf 0.61 (2:3 CH2Cl2/hexanes); 3.2 g, 92%; white solid,
(R)-2′-(4-Methoxyphenyl)-[1,1′-binaphthalen]-2-ol (3a).
Method B (Grignard preparation: initiation 45 min, reaction time
120 min): Rf 0.52 (2:3 CH2Cl2/hexanes); 2.7 g, 79%; white solid, mp
24
= 78−79 °C, [α]D = +67.2 (c = 0.5, THF); er 0.2(S):99.8(R),
determined by chiral HPLC (Chiralpak IC column, 4.6 × 250 mm, 5
μm particle size, 25 °C, hexanes/iPrOH 95:5, pressure = 3.4 MPa, flow
1
rate 1.0 mL min−1, tR(S) = 5.7 min, tR(R) = 7.0 min); H NMR (400
24
mp = 96−97 °C, [α]D = −17.0 (c = 0.5, THF); er 0.2(S):99.8(R),
MHz, CDCl3) δ 8.07 (d, J = 8.8 Hz, 1H), 7.97 (d, J = 8.4 Hz, 1H),
7.80 (d, J = 8.4 Hz, 1H), 7.79 (d, J = 9.2 Hz, 1H), 7.70 (d, J = 8.8 Hz,
1H), 7.49 (ddd, J = 8.1, 6.7, 1.6 Hz, 1H), 7.33−7.25 (m, 3H), 7.22
(ddd, J = 8.1, 6.8, 1.2 Hz, 1H), 7.15 (d, J = 9.2 Hz, 1H), 7.09 (d, J =
8.8 Hz, 1H), 7.06 (m, 2H), 6.60 (m, 2H), 4.82 (s, 1H), 3.67 (s, 3H);
13C NMR (101 MHz, CDCl3) δ 158.6, 151.0, 141.2, 134.34, 133.4,
133.3, 133.2, 129.9 (2C), 129.5, 128.9, 128.8, 128.3, 128.3, 128.2,
127.2, 126.7, 126.4, 126.4, 125.2, 123.3, 118.0, 117.4, 113.3, 55.2. Anal.
determined by chiral HPLC (Phenomenex Lux Cellulose-1 column,
4.6 × 250 mm, 3 μm particle size, 25 °C, hexanes/EtOH 97:3,
pressure = 5.8 MPa, flow rate 1.0 mL min−1, tR(S) = 9.9 min, tR(R) =
1
9.3 min); H AND 13C NMR data were in agreement with published
values;22 19F NMR (376 MHz, CDCl3) δ −64.1. Anal. Calcd for
C28H16F6O: C, 69.71; H, 3.34%. Found: C, 69.61; H, 3.42%.
(S)-2′-Neopentyl-[1,1′-binaphthalen]-2-ol (3g). Method B
(Grignard preparation: initiation 10 min, reaction time 60 min): Rf
0.48 (2:3 CH2Cl2/hexanes); 2.3 g, 82%; white solid, mp = 75−76 °C,
1
Calcd for C27H20O2·0.1(C6H14) (solvent content by H NMR; not
removable under a vacuum): C, 86.09; H, 5.60%. Found: C, 85.85; H,
5.99%.
25
[α]D = +86.0 (c = 0.15, THF; α observed to fluctuate at higher
concentrations); er 99.7(S):0.3(R), determined by chiral HPLC
(Phenomenex Lux Cellulose-1 column, 4.6 × 250 mm, 3 μm particle
size, 25 °C, hexanes/iPrOH 95:5, pressure = 4.0 MPa, flow rate 0.7 mL
min−1, tR(S) = 7.6 min, tR(R) = 8.5 min); 1H NMR (400 MHz,
CDCl3) δ 7.94 (d, J = 8.4 Hz, 1H), 7.92 (d, J = 8.4 Hz, 2H), 7.87 (d, J
= 8.0 Hz, 1H), 7.63 (d, J = 8.4 Hz, 1H), 7.47 (ddd, J = 7.8, 6.4, 1.2 Hz,
1H), 7.34 (d, J = 8.8 Hz, 1H), 7.34−7.20 (m, 4H), 7.04 (d, J = 8.4 Hz,
1H), 4.84 (s, 1H), 2.49 (AB, J = 13 Hz, 2C = 32 Hz, 2H),48 0.76 (s,
9H); 13C NMR (101 MHz, CDCl3) δ 151.2, 139.7, 133.9, 133.0,
132.8, 130.3, 130.1, 129.9, 129.2, 128.3, 128.2 (2C), 126.9, 126.6,
126.2, 125.9, 125.5, 123.4, 118.0, 117.5, 47.0, 33.0, 30.3. Anal. Calcd
for C25H24O: C, 88.20; H, 7.11%. Found: C, 88.36; H, 7.44%.
(S)-2′-Isopropyl-[1,1′-binaphthalen]-2-ol (3h, minor, 29%)
and (S)-2′-Propyl-[1,1′-binaphthalen]-2-ol (3i, major, 71%).
Method B (used commercial Grignard reagent: iPrMgBr, 0.5 M in
(R)-2′-(2-Methoxyphenyl)-[1,1′-binaphthalen]-2-ol (3b).
Method B (Grignard preparation: initiation 45 min, reaction time 50
min): Rf 0.51 (2:3 CH2Cl2/hexanes); 0.23 g, 61%; white solid, mp =
24
78−79 °C, [α]D = +17.0 (c = 0.5, THF); er 0.1(S):99.9(R),
determined by chiral HPLC (Phenomenex Lux Cellulose-1 column,
4.6 × 250 mm, 3 μm particle size, 25 °C, hexanes/iPrOH 99:1,
pressure = 5.7 MPa, flow rate 1.0 mL min−1, tR(S) = 11.4 min, tR(R) =
12.5 min); Optical rotation and 1H NMR data were in agreement with
published values;24 HRMS (ESI-orbitrap) m/z calcd for C27H20O2Na
399.1361 [M + Na]+, found 399.1372.
(R)-2′-(p-Tolyl)-[1,1′-binaphthalen]-2-ol (3c). Method B
(Grignard preparation: initiation 40 min, reaction time 90 min): Rf
0.31 (2:3 EtOAc/hexanes); 3.9 g, 90%; white solid, mp = 92−93 °C,
[α]D25 = +56.6 (c = 0.5, THF); er 0.2(S):99.8(R), determined by chiral
HPLC (Phenomenex Lux Cellulose-1 column, 4.6 × 250 mm, 3 μm
particle size, 25 °C, hexanes/iPrOH 98:2, pressure = 2.8 MPa, flow
THF): Rf 0.44 (2:3 CH2Cl2/hexanes; both isomers eluted together);
25
1
rate 0.5 mL min−1, tR(S) = 6.8 min, tR(R) = 7.5 min); H NMR (400
0.37 g, 45% (3h/3i 29:71); white solid, mp = 78−79 °C, [α]D
=
−82.0 (c = 0.1, CH2Cl2); er (3h) 99.8(S):0.2(R), er (3i) >99.9-
(S):0.1(R), determined by chiral HPLC (Chiralpak IC column, 4.6 ×
250 mm, 5 μm particle size, 25 °C, hexanes/iPrOH 99:1, pressure =
3.4 MPa, flow rate 1.0 mL min−1, tR[(S)-3h] = 6.1 min, tR[(R)-3h] =
MHz, CDCl3) δ 8.07 (d, J = 8.8 Hz, 1H), 7.97 (d, J = 8.0 Hz, 1H),
7.79 (d, J = 8.8 Hz, 2H), 7.70 (d, J = 8.8 Hz, 1H), 7.50 (ddd, J = 8.3,
6.6, 1.6 Hz, 1H), 7.33−7.25 (m, 3H), 7.23 (ddd, J = 8.3, 6.6, 1.6 Hz,
1H), 7.15 (d, J = 8.8 Hz, 1H), 7.10 (d, J = 8.4 Hz, 1H), 7.03 (m, 2H),
6.87 (m, 2H), 4.83 (s, 1H), 2.18 (s, 3H); 13C NMR (101 MHz,
CDCl3) δ 151.0, 141.6, 138.0, 136.8, 134.4, 133.3, 133.3, 129.9, 129.5,
128.9, 128.8, 128.6 (2C), 128.4, 128.3, 128.2, 127.2, 126.7, 126.5,
126.4, 125.2, 123.3, 118.0, 117.3, 21.2. Anal. Calcd for C27H20O: C,
89.97; H, 5.59%. Found: C, 89.89; H, 5.91%.
1
5.2 min, tR[(S)-3i] = 5.8 min, tR[(R)-3i] = 5.6 min); H NMR (400
MHz, CDCl3) δ 8.03 (d, J = 8.4 Hz, 1H minor), 7.98 (d, J = 8.4 Hz,
1H major), 7.94−7.90 (m, 2H major + minor), 7.88 (d, J = 8.4 Hz, 1H
major + minor), 7.69 (d, J = 8.8 Hz, 1H minor), 7.59 (d, J = 8.4 Hz,
1H major), 7.47−7.42 (m, 1H major + minor), 7.37−7.21 (m, 4H
major + minor), 7.20−7.14 (m, 1H major + minor), 7.02−6.98 (m,
1H major + minor), 4.76 (br s, 1H major), 4.75 (br s, 1H minor), 2.74
(septet, J = 6.8 Hz, 1H minor), 2.41 (m, 2H major), 1.48 (m, 2H
major), 1.19 (d, J = 6.8 Hz, 3H minor), 1.07 (d, J = 6.8 Hz, 3H
minor), 0.73 (t, J = 7.6 Hz, 3H major); 13C NMR (101 MHz, CDCl3)
δ 151.2, 151.1, 147.8, 142.0, 134.1, 133.4, 133.2, 132.7, 129.9, 129.8,
129.3, 129.2, 129.2, 128.2, 128.2, 127.1, 127.0, 126.9, 126.7, 126.1,
125.9, 125.8, 124.9, 124.4, 123.6, 123.5, 117.6, 117.4, 36.0, 31.1, 25.4,
24.2, 23.9, 22.8; HRMS (ESI-orbitrap) m/z calcd for C23H20ONa
335.1412 [M + Na]+, found 335.1454. Anal. Calcd for C23H20O: C,
88.43; H, 6.45%. Found: C, 88.51; H, 6.59%.
(R)-2′-Phenyl-[1,1′-binaphthalen]-2-ol (3d). Method A
(Grignard preparation: initiation 20 min, reaction time 60 min): Rf
0.58 (2:3 CH2Cl2/hexanes); 1.9 g, 80%; white solid, mp = 174−175
25
°C; [α]D = +26.1 (c = 0.5, CH2Cl2); er 0.2(S):99.8(R), determined
by chiral HPLC (Chiralpak IC column, 4.6 × 250 mm, 5 μm particle
size, 25 °C, hexanes/iPrOH 95:5, pressure = 3.4 MPa, flow rate 1.0 mL
min−1, tR(S) = 4.6 min, tR(R) = 5.1 min); Melting point, optical
rotation, and 1H NMR data were in agreement with published
values;20 13C NMR (101 MHz, CDCl3) δ 151.1, 141.8, 141.0, 134.4,
133.4, 133.3, 130.1, 129.6, 128.9, 128.8 (2C), 128.7, 128.4, 128.3,
127.9, 127.4, 127.2, 126.8, 126.6, 126.5, 125.2, 123.4, 117.9, 117.4.
Anal. Calcd for C26H18O: C, 90.14; H, 5.24%. Found: C, 90.21; H,
5.41%.
(S)-2′-Benzyl-[1,1′-binaphthalen]-2-ol (3j). Method B
(Grignard preparation: initiation 12 min, reaction time 60 min): Rf
0.41 (2:3 CH2Cl2/hexanes); 2.6 g, 85%; white solid, mp = 138−139
°C; [α]D25 = +130.0 (c = 0.4, THF); er 99.9(S):0.1(R), determined by
chiral HPLC (Phenomenex Lux Cellulose-1 column, 4.6 × 250 mm, 3
μm particle size, 25 °C, hexanes/iPrOH 95:5, pressure = 4.0 MPa, flow
(R)-2′-[4-(Trifluoromethyl)phenyl]-[1,1′-binaphthalen]-2-ol
(3e). Method A (Grignard preparation: initiation 35 min, reaction
time 60 min): Rf 0.56 (2:3 CH2Cl2/hexanes); 1.2 g, 50%; white solid,
24
mp = 146−147 °C, [α]D = +21.5 (c = 0.5, CH2Cl2); er
1
rate 0.7 mL min−1, tR(S) = 12.7 min, tR(R) = 11.9 min); H and 13C
0.1(S):99.9(R), determined by chiral HPLC (Chiralpak IC column,
4.6 × 250 mm, 5 μm particle size, 25 °C, hexanes/iPrOH 95:5,
pressure = 1.7 MPa, flow rate 0.5 mL min−1, tR(S) = 8.4 min, tR(R) =
NMR data were in agreement with published values;27 melting point
and optical rotation were not previously reported. Anal. Calcd for
C27H20O: C, 89.97; H, 5.59%. Found: C, 89.68; H, 5.72%.
1
9.5 min); H NMR (400 MHz, CDCl3) δ 8.12 (d, J = 8.4 Hz, 1H),
8.01 (d, J = 8.4 Hz, 1H), 7.80 (d, J = 9.2 Hz, 1H), 7.79 (d, J = 7.2 Hz,
1H), 7.67 (d, J = 8.4 Hz, 1H), 7.55 (ddd, J = 8.2, 6.6, 1.6 Hz, 1H),
7.38−7.27 (m, 5H), 7.26−7.20 (m, 3H), 7.14 (d, J = 8.8 Hz, 1H), 7.06
(S)-2′-[3,5-Bis(trifluoromethyl)benzyl]-[1,1′-binaphthalen]-
2-ol (3k). Method A (Grignard preparation: initiation 15 min, reaction
time 40 min): Rf 0.61 (1:1 CH2Cl2/hexanes); 1.0 g, 49%; viscous oil;
5698
dx.doi.org/10.1021/jo400349r | J. Org. Chem. 2013, 78, 5694−5699

The Journal of Organic Chemistry
Note
24
[α]D = −117.2 (c = 0.5, CH2Cl2); er 99.8(S):0.2(R), determined by
(18) Ficks, A.; Martinez-Botella, I.; Stewart, B.; Harrington, R. W.;
Clegg, W.; Higham, L. J. Chem. Commun. 2011, 47, 8274−8276.
(19) Handa, S.; Slaughter, L. M. Angew. Chem., Int. Ed. 2012, 51,
2912−2915.
chiral HPLC (Phenomenex Lux Cellulose-1 column, 4.6 × 250 mm, 3
μm particle size, 25 °C, hexanes/EtOH 99:1, pressure = 5.8 MPa, flow
rate 1.0 mL min−1, tR(S) = 19.2 min, tR(R) = 21.4 min); H NMR
1
(400 MHz, CD2Cl2) δ 8.07 (d, J = 8.4 Hz, 1H), 7.98 (d, J = 8.4 Hz,
1H), 7.92 (d, J = 8.8 Hz, 1H), 7.83 (d, J = 8.4 Hz, 1H), 7.64 (d, J = 8.4
Hz, 1H), 7.53−7.48 (m, 2H), 7.34−7.21 (m, 4H), 7.17 (s, 2H), 7.09
(ddd, J = 8.4, 6.9, 1.3 Hz, 1H), 6.73 (d, J = 8.4 Hz, 1H), 4.74 (s, 1H),
3.95 (AB, J = 15 Hz, 2C = 18 Hz, 2H);48 13C NMR (101 MHz,
CD2Cl2) δ 151.4, 143.1, 138.6, 133.8, 133.6, 133.6, 131.2 (q, J(C,F) = 33
Hz), 130.8, 130.6, 130.1, 129.4, 129.1, 128.9, 128.7, 128.6, 127.5,
127.2, 126.7, 125.9, 124.5, 123.8, 123.7 (q, J(C,F) = 273 Hz), 120.2
(septet, J(C,F) = 3.7 Hz), 111.7, 117.1, 40.4; 19F NMR (376 MHz,
CDCl3) δ −63.9. HRMS (ESI-orbitrap) m/z calcd for C29H18F6O
497.1340 [M + H]+, found 497.1349.
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ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C NMR spectra of newly characterized compounds;
1H NMR spectra of known compounds synthesized by new
routes; chiral HPLC chromatograms. This material is available
free of charge via the Internet at http://pubs.acs.org.
(29) For a relevant review of nickel-catalyzed coupling reactions, see:
Rosen, B. M.; Quasdorf, K. W.; Wilson, D. A.; Zhang, N.; Resmerita,
A.-M.; Garg, N. K.; Percec, V. Chem. Rev. 2011, 111, 1346−1416.
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5599−5601.
AUTHOR INFORMATION
Corresponding Author
*E-mail: lms@chem.okstate.edu.
Notes
■
(33) Ullah, E.; McNulty, J.; Larichev, V.; Robertson, A. J. Eur. J. Org.
Chem. 2010, 6824−6830.
The authors declare no competing financial interest.
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(35) Yoshikai, N.; Mashima, H.; Nakamura, E. J. Am. Chem. Soc.
2005, 127, 17978−17979.
ACKNOWLEDGMENTS
■
We thank the National Science Foundation (CHE-1214066)
for financial support of this work.
(36) Wolf, C.; Xu, H. J. Org. Chem. 2008, 73, 162−167.
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