Enantioselective α-Arylation of Primary Alcohols under Sequential One-Pot Catalysis

Article abstract of DOI:10.1021/acs.joc.1c00983

Secondary benzylic alcohols and diarylmethanols are common structural motifs of biologically active and medicinally relevant compounds. Here we report their enantioselective synthesis by α-arylation of primary aliphatic and benzylic alcohols under sequential catalysis integrating a Ru-catalyzed hydrogen transfer oxidation and a Ru-catalyzed nucleophilic addition. The method can be applied to various alcohols and aryl nucleophiles tolerating a range of functional groups, including secondary alcohols, ketones, alkenes, esters, NH amides, tertiary amines, aryl halides, and heterocycles.

Full text of DOI:10.1021/acs.joc.1c00983

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Note
Enantioselective α‑Arylation of Primary Alcohols under Sequential
One-Pot Catalysis
Bruno Lainer, Dawid Lichosyt,* Maiia Aleksandrova, and Paweł Dydio*
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ABSTRACT: Secondary benzylic alcohols and diarylmethanols are
common structural motifs of biologically active and medicinally
relevant compounds. Here we report their enantioselective synthesis
by α-arylation of primary aliphatic and benzylic alcohols under
sequential catalysis integrating a Ru-catalyzed hydrogen transfer
oxidation and a Ru-catalyzed nucleophilic addition. The method
can be applied to various alcohols and aryl nucleophiles tolerating a
range of functional groups, including secondary alcohols, ketones,
alkenes, esters, NH amides, tertiary amines, aryl halides, and
heterocycles.
Scheme 1. Synthesis of Secondary Benzylic Alcohols from
Simple Alcohols in the Context of This Work
econdary benzylic alcohols (SBAs) and diarylmethanols
(DAMs) constitute valuable synthetic intermediates and
S
prevalent structural motifs of numerous natural products and
bioactive compounds.1,2 Therefore, protocols for their stereo-
selective synthesis from various accessible starting materials
have attracted much attention over the years. Common
approaches include potent asymmetric (transfer) hydro-
genation of ketones1,3,4 or 1,2-addition of aryl nucleophiles
to aldehydes,5,6 which is particularly useful for fine-chemical
synthesis when such starting materials are available and do not
require additional synthetic steps.
Because aliphatic alcohols represent a class of abundant
starting materials, an increasing attention has been devoted to
developing methods for their valorization through selective C−
H bond functionalization.7−9 In the context of SBAs, an
elegant strategy for the enantioselective alkylation of α-C−H
bonds of primary benzylic alcohols with unsaturated hydro-
carbons (e.g., dienes and enynes) was devised by Krische and
co-workers (Scheme 1a).10,11 The methods of the arylation of
α-C−H bonds of aliphatic alcohols in the Minisci-type
reactions were also established12−17 (Scheme 1b). Unfortu-
nately, these methods lead to racemic products, leaving the
enantioselective α-C−H arylation of alcohols unexplored.
We have recently reported an enantioselective synthesis of
SBAs from unsaturated alcohols and aryl boronic acids under
sequential catalysis (Scheme 1c).18 The one-pot sequence of
an Ir-catalyzed isomerization of the starting material and a Ru-
catalyzed nucleophilic addition of an aryl boronic acid to the
aldehyde intermediate provided a convenient synthetic method
with a broad scope and functional group tolerance.
Received: April 27, 2021
Published: June 11, 2021
Intrigued by the prospect of employing a multicatalytic
sequential approach to the enantioselective synthesis of SBAs
from readily available primary alcohols, we considered utilizing
an intermolecular hydrogen transfer19 between the starting
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a
material and a sacrificial acceptor (in place of the intra-
molecular isomerization step) followed by a stereoselective 1,2-
addition step (Scheme 1d). Attractively, hydrogen transfer
catalysis enables selective oxidation of one of multiple alcohol
moieties in the presence of other functional groups, giving it
utility in the late-stage modifications of complex molecules.19,20
Here we report, established by the design described above, a
dual-catalytic method for the enantioselective α-arylation of
primary aliphatic or benzylic alcohols with aryl boronic acids as
nucleophiles. The protocol integrates a Ru-catalyzed hydrogen
transfer oxidation with an enantioselective Ru-catalyzed 1,2-
addition of an aryl nucleophile in a one-pot fashion to form
either secondary benzylic alcohols or chiral diarylmethanols in
an up to 99:1 enantiomeric ratio (er) and 88% yields (Scheme
1d).
Table 1. Reaction Development
The development of a multicatalytic system that executes
the envisioned sequential transformation required careful
balancing of the conditions to ensure compatibility between
the catalysts, reagents, and intermediates of the consecutive
steps.21−25 Special attention must be paid to the selection of
the catalysts, considering that any cross-reactivity or any ligand
scrambling is likely not only to decrease the required activity
but also to be detrimental for the overall stereoselectivity.26,27
The Ru catalyst containing me-bipam, a chiral phosphor-
amidite ligand developed by Yamamoto and Miyaura, proved
previously to be both highly enantioselective in the arylation of
aldehydes28,29 and compatible with a series of phosphine−Ru
complexes,18 which represent prospective hydrogen transfer
catalysts.19,20 Therefore, a Ru complex bearing me-bipam was
selected as a catalyst of choice for the 1,2-addition step, and
the main efforts for method development were focused on
identifying a phosphine-Ru-based hydrogen transfer catalyst
and a sacrificial hydrogen acceptor (HA). While typically used
in a large excess,19,20 a suitable hydrogen acceptor would be
preferably used in stoichiometric amounts, preventing
secondary oxidation reactions or any cross-reactivity in the
subsequent 1,2-addition step.
Extensive experimentation of the model reaction of 1-
hexanol 1a with phenylboronic acid 2a identified that
hydrogen transfer between the alcohol and N-ethylmaleimide
HA-1, used as a sacrificial hydrogen acceptor (1.1 equiv), in
the presence of the Ru complex bearing rac-binap (Ru-1) that
is followed by the 1,2-addition of the aryl nucleophile in the
presence of the Ru complex bearing (S,S)-me-bipam (Ru-2)
furnished product 3aa in 96:4 er (S:R) and 88% yield [80%
isolated yield (Table 1, entry 1)]. The reaction mixture
contained 10% of unreacted alcohol 1a, while all of the
aldehyde intermediate was converted, indicating the excellent
efficiency of Ru-2 in the second step. Control experiments
confirmed the role and the required reactivity of both
complexes. First, we observed that the stereoselectivity of the
product is not influenced by Ru-1 (entry 2), and the complex
with a racemic mixture of binap can be used. In addition, no
product was formed when Ru-2 was omitted (Table S1, entry
14), indicating that Ru-1 is completely inactive in the second
step of the reaction. Similarly, no product was formed when
Ru-1 was omitted and Ru-2 was employed in both steps,
indicating that Ru-2 is completely inactive in the oxidation
step, even for benzylic alcohols that are typically easily
dehydrogenated (Table S1, entry 15). In turn, reactions in
the presence of other ligands in place of binap, such as
xantphos, dpephos, or dppf, occurred in substantially lower
yields (≤39%), albeit high enantioselectivity was maintained
variations from the standard conditions
yield (%)
er
b
1
2
3
4
5
6
7
8
none
88 (80)
96:4
96:4
−
96:4
94:6
−
−
−
96:4
−
96:4
97:3
−
−
−
(R)- or (S)-binap used
xantphos instead of binap
dpephos instead of binap
dppf instead of binap
no NaOAc
90−91
5
39
20
<2
20
<2
50
<2
33
25 mol % NaOAc
Ru-3 instead of Ru-1
Ru-3 and 10 mol % TBACl (no Ru-1)
no HA-1
HA-2 instead of HA-1
HA-3 instead of HA-1
HA-4 instead of HA-1
HA-5 instead of HA-1
HA-6 instead of HA-1
9
10
11
12
13
14
15
32
<2
<2
<2
a
Standard conditions: 1a (0.25 mmol), HA-1 (1.1 equiv), Ru-1 (5
mol % Ru site, 2.5 mol % Ru dimer), NaOAc (5 mol %), toluene (1
mL), stirred for 5 h at 80 °C (step 1); then 2a (3 equiv), K2CO3 (1
equiv) in H2O (0.15 mL), (S,S)-Ru-2 (5 mol % Ru site, 2.5 mol % Ru
dimer) in toluene (1 mL) added and stirred for 6 h at 80 °C (step 2).
1
Yields determined by H NMR analysis with an internal standard;
enantiomeric ratios (er; S:R) determined by SFC analysis. For details,
b
see the Supporting Information. Yield of isolated material.
(entries 3−5), underscoring the robustness of catalyst Ru-2. It
is noteworthy that the presence of sodium acetate in a 1:1 ratio
per Ru site is key for the hydrogen transfer activity of Ru-1. No
reaction or substantially decreased activity was observed in its
absence or when the amount was 5-fold increased (entries 6
and 7). Similarly, no reaction was observed when Ru-3, an
analogue of Ru-1 bearing acetate ligands in place of chloride
anions, was used, but the reactivity of Ru-3 was partially
recovered in the presence of additives bearing chloride anions
(entries 8 and 9). These observations suggest that a mixed-
ligand Ru complex might be the active species;30,31 however,
further studies are required to verify this hypothesis. N-
Ethylmaleimide HA-1 proved to be by far the most efficient as
a sacrificial hydrogen acceptor among those tested. Up to 33%
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of 3aa was formed when diethyl maleate or fumarate was used
instead, and no reactions occurred with norbornadiene, ethyl
methacrylate, or acetone (entries 11−15). The lack of an inert
atmosphere, other solvents, or lower loadings of the catalysts
results in lower yields of the reaction (Table S1).
target products in 58−64% yields and with 97:3 stereo-
selectivity for the formation of the new stereogenic center
(racemic diol 1p was used; hence, product 3pa was formed as a
1:1 mixture of diastereomers with 97:3 er).
The scope of aryl boronic acids for the devised method
reflects the previously disclosed reactivity of Ru-2,18,29
indicating no noticeable effect of the Ru-1 catalyst on the
1,2-addition step. Specifically, a range of aryl boronic acid
derivatives bearing either electron-donating or electron-with-
drawing substituents in the para or meta position of the aryl
ring reacted to deliver the target products with 91:9−97:3 er
and 54−81% yields of isolated material. Noteworthy are
previously undisclosed examples of benzofuran 2h and
triphenylamine derivatives 2i that reacted to form the products
with 96:4−91:9 er and 59−80% yields. Reactions for aryl
boronic acids bearing either a strongly electron-withdrawing
group or steric hindrance in the ortho position, such as 2d or
2f, respectively, furnished the products in modest yields,
indicating the limitations of the protocol imposed by the
inherent limitations of Ru-2;18 no additional limitations related
to the presence of Ru-1 were encountered in the 1,2-addition
step.
The hydrogen transfer activity of Ru-1 was found to be
selective toward primary aliphatic alcohols over secondary
alcohols, creating the attractive possibility for α-functionaliza-
tion of primary alcohol moieties in the presence of other
alcohol functions. Specifically, the competition experiments
between linear 1a and a series of branched aliphatic alcohols
1b−e revealed 7:1 kinetic selectivity for the reaction of primary
1a over (α-branched) secondary 1b and nearly no selectivity
over other primary alcohols, β-branched 1c and 1d or γ-
branched 1e (Scheme 2). In sharp contrast, primary benzylic
alcohol 1f reacted selectively over primary aliphatic alcohol 1a
(6:1 ratio), revealing the highest reactivity of 1f among
alcohols 1a−f.
Scheme 2. Competition Experiments Revealing the
Selectivity of the Hydrogen Transfer from Varied Alcohols
a
by Ru-1
Lastly, intrigued by the high reactivity of benzylic alcohol 1f
in hydrogen transfer reactivity mediated by Ru-2, we evaluated
the established protocol toward enantioselective α-arylation of
benzylic alcohols to form diarylmethanols (DAMs), which are
known to exhibit potent biological and medicinal properties.2
Pleasingly, 1f reacted with electron-rich 2j or electron-deficient
2k aryl boronic acids under standard conditions to form chiral
DAMs with >97:3 er and 66−78% yields of isolated material.
In addition, electron-deficient benzyl alcohols 1q and 1r and
electron-rich 3-furanmethanol 1s reacted with 2a to form the
target products with >96:4 er and 27−70% yields of isolated
material.
In conclusion, the disclosed dual-catalytic protocol enables
the formal enantioselective arylation of the α-C−H bond of
primary aliphatic and benzylic alcohols with varied aryl boronic
acids. Importantly, the method tolerates starting materials and
nucleophilic reagents bearing a range of common functional
groups, including secondary alcohols and ketones. The one-pot
strategy offers advantages over tedious and wasteful stepwise
approaches,32−35 especially for sequences occurring through
the aldehyde intermediates that are often prone to side
reactions. In a greater perspective, the study demonstrates that
sequential catalysis complements current strategies for the
functionalization of strong C−H bonds that require enforcing
conditions with limited applicability in fine-chemical synthesis
or those that are burdened with limited control of chemo-,
regio-, or stereoselectivity.
a
Reactions under the standard conditions of step 1 described in
footnote a of Table 1; conversions were determined by GC-FID
analysis with dodecane as an internal standard. For details, see the
Supporting Information.
The established dual-Ru/Ru-catalytic protocol is easily
scalable, broadly applicable, and tolerant to many common
functional groups (Scheme 3). A range of primary aliphatic
alcohols were converted to SBAs with 93:7−98:2 er and 44−
82% yields of isolated material. Reactions for alcohol 1a on
standard (0.25 mmol) and larger (1.75 mmol) scales furnished
product 3aa with the same selectivity (96:4 er) and similar
yields (80−84%). Besides 1a, unsaturated 1g aliphatic alcohol,
β,β-disubstituted alcohol 1h, and ethanol β-substituted with a
cyclohexyl group (1i) or an aryl group (1j) reacted to form the
target products. Starting materials bearing common functional
groups, such as a carboxylic ester 1k, a tertiary amide 1l, or an
NH-containing amide 1m, are tolerated. Alcohols containing
free NH amines or terminal alkynes as well as (homo)allylic
alcohols are not compatible (Figure S2), due to either side
reactions or no conversion in the presence of Ru-1. However,
the reaction for alcohol-bearing N-phthalimide-protected
amine 1n furnished the target product. Most noteworthy are
reactions of primary alcohols bearing a ketone 1o or a
secondary alcohol 1o function, which were not hampered by
either competitive 1,2-addition or oxidation but formed the
EXPERIMENTAL SECTION
■
General Information. Unless stated otherwise, all reactions and
manipulations were conducted on a laboratory bench or in a well-
ventilated fume hood in air with reagent grade solvents. Reactions
under an inert gas atmosphere were carried out in oven-dried
glassware in a nitrogen-filled glovebox or by standard Schlenk
techniques under nitrogen. Unless noted otherwise, all reagents and
solvents were purchased from commercial suppliers and used without
further purification. (S,S)-BIPAM was prepared according to the
literature procedure.36,37 Ru(p-cymene)(OAc)2 was prepared accord-
ing to the literature procedure.38 For experiments under an inert gas
atmosphere, dry solvents like dichloromethane (DCM), tetrahydro-
furan (THF), toluene, hexane, diethyl ether (Et2O), dioxane,
acetonitrile, and 1,4-xylene were purchased from commercial suppliers
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Scheme 3. Scope of the Enantioselective Synthesis of Secondary Benzylic Alcohols and Diarylmethanols from Primary
a
Alcohols
a
For reaction conditions, see footnote a of Table 1; yields correspond to the isolated material. For details, see the Supporting Information.
b
c
d
e
Reaction conducted on a 1.75 mmol scale. Double loading of Ru-2 (10 mol % Ru). With alcohol 1 (0.20 mmol), 2 (0.60 mmol). With alcohol
f
g
h
1
1 (0.13 mmol), 2 (0.39 mmol). Racemic diol 1o was used as the starting material. At 90 °C in step 2. Yield determined by H NMR analysis
using an internal standard. Sixteen hours in step 1.
i
and used as received. Water was degassed by being purged with
nitrogen for 30 min. Column chromatography was carried out with
the aid of a CombiFlash EZ Prep Chromatography System with
integrated ELSD using RediSep Rf (Gold) Silica Gel Disposable Flash
columns. TLC visualization was carried out with ultraviolet light (254
nm), followed by staining with a 1% aqueous KMnO4 solution. NMR
spectra were acquired on the 400 or 500 MHz Bruker instrument at
the Institute of Science and Supramolecular Engineering (ISIS),
University of Strasbourg. NMR spectra were processed using
MestReNova version 14.2. Chemical shifts are reported in parts per
million and referenced to residual solvent peaks or tetramethylsilane
(TMS). Coupling constants are reported in hertz. SFC analysis was
conducted using an Agilent SFC 1260 Infinity II instrument
connected to Agilent MSD XT mass spectrometry equipment. Chiral
SFC separation was achieved using Chiralpak SFC {100 mm × 3 mm
[inside diameter (ID)] × 3 μm} columns. GC-FID analysis was
performed either on a Shimadzu GC-2010 Plus instrument equipped
with a SH-Rxi-5MS column [25 m × 0.20 mm (ID) × 0.33 μm film]
connected to a FID detector or on a ThermoFisher TRACE 1300
instrument equipped with a HP-5 column [25 m × 0.20 mm (ID) ×
0.33 μm film] for achiral analysis or with an CP-Chiralsil-Dex CB
column (30 m × 0.25 mm × 0.25 μm film) for chiral analysis,
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connected to a FID detector. GC-MS analysis was performed on a
Shimadzu QP2020 (EI) instrument equipped with a SH-Rxi-5MS
column [25 m × 0.20 mm (ID) × 0.33 μm film]. GC and NMR yields
were calculated using 1,3,5-trimethoxybenzene or dodecane as the
internal standard. GC yields were corrected for response factors for all
compounds. Optical rotations were measured on a PerkinElmer
Precisely/model-341 polarimeter operating at the sodium D line with
a 100 mm path length cell. Electrospray ionization high-resolution
mass spectra (ESI-HRMS) were recorded on a ThermoFisher
Ultimate3000 instrument with a Scientific Vanquish Flex UHPLC
instrument with a ThermoFisher Orbitrap: Exactive Plus with Extend
Mass Range: Source HESI II (at ISIS).
resealed with the screw cap, removed from the glovebox, and placed
in a preheated heating block at 60 °C, and the contents were allowed
to stir for 6 h at 800 rpm. The reaction mixture was allowed to cool to
room temperature. The mixture was diluted with DCM (50 mL),
followed by the addition of Celite (5 g). The volatiles were removed
under reduced pressure. The solid residue was subjected to flash
column chromatography on silica gel (12 g), conducted with the aid
of a CombiFlash EZ Pack instrument using a mixture of petroleum
ether and ethyl acetate (typically with a gradient from 100:0 to 85:15)
as the eluent. The fractions containing the product (based on TLC
and/or GC analysis) were combined, and the solvent was evaporated,
yielding the product.
Starting Materials. Starting materials 1a−j and 1q−s were
purchased from common chemical suppliers and used without further
purification. Other starting materials were prepared and characterized
as described below.
Isopropyl 6-Hydroxyhexanoate (1k). Compound 1k was prepared
from caprolactone and isopropanol according to the literature
procedure.9 The NMR data match those of the reported molecule.9
1H NMR (500 MHz, CDCl3): δ 4.94 (hept, J = 6.3 Hz, 1H), 3.58 (t, J
= 6.5 Hz, 2H), 2.21 (t, J = 7.5 Hz, 2H), 1.63−1.48 (m, 4H), 1.43−
1.24 (m, 3H), 1.16 (d, J = 6.2 Hz, 6H).
N-Cyclohexyl-6-hydroxyhexanamide (1l). Compound 1l was
prepared from cyclohexylamine and caprolactone according to the
literature procedure.9 The NMR data match those of the reported
molecule.9 1H NMR (500 MHz, CDCl3): δ 5.20 (bs, 1H), 3.76−3.64
(m, 1H), 3.59 (t, J = 6.5 Hz, 2H), 2.08 (t, J = 7.5 Hz, 2H), 1.88−1.80
(m, 2H), 1.68−1.47 (m, 8H), 1.41−1.27 (m, 4H), 1.14−0.94 (m,
3H).
6-Hydroxy-1-(piperidin-1-yl)hexan-1-one (1m). Compound 1m
was prepared from piperidine and caprolactone according to the
literature procedure.9 The NMR data match those of the reported
molecule.9 1H NMR (400 MHz, CDCl3): δ 3.63−3.56 (m, 2H),
3.51−3.45 (m, 2H), 3.35−3.29 (m, 2H), 2.26 (t, J = 7.5 Hz, 2H),
1.64−1.42 (m, 11H), 1.40−1.30 (m, 2H).
rac-Octadecane-1,12-diol (1p). Compound 1p was prepared
according to the literature procedure from rac-12-hydroxystearic
acid.9 The NMR data match those of the reported molecule.9 1H
NMR (400 MHz, CDCl3): δ 3.65 (t, J = 6.6 Hz, 2H), 3.62−3.56 (m,
1H), 1.67−1.51 (m, 2H), 1.51−1.20 (m, 30H), 1.00−0.82 (m, 3H).
18-Hydroxyoctadecan-7-one (1o). Compound 1o was prepared
from 1p according to the literature procedure.9 The NMR data match
those of the reported molecule.9 1H NMR (500 MHz, CDCl3): δ 3.57
(t, J = 6.7 Hz, 2H), 2.31 (t, J = 7.4 Hz, 4H), 1.68−1.35 (m, 9H),
1.35−1.07 (m, 18H), 0.94−0.66 (m, 3H).
2-(5-Hydroxypentyl)isoindoline-1,3-dione (1n). Compound 1n
was prepared from phthalic anhydride and 5-aminopentan-1-ol
according to the literature procedure.39 The NMR data match
those of the reported molecule.39 1H NMR (400 MHz, CDCl3): δ
7.77 (dd, J = 5.4, 3.1 Hz, 2H), 7.64 (dd, J = 5.5, 3.1 Hz, 2H), 3.63 (t, J
= 7.2 Hz, 2H), 3.57 (t, J = 6.5 Hz, 2H), 1.72−1.60 (m, 2H), 1.60−
1.50 (m, 2H), 1.43−1.30 (m, 3H).
General Procedure for α-Arylation of Alcohols. In a nitrogen-
filled glovebox, a solution of Ru-1 and sodium acetate was prepared
by allowing [Ru(p-cymene)Cl2]2 (0.025 equiv, 0.0063 mmol, 3.8 mg),
rac-binap (0.05 equiv, 0.013 mmol, 7.8 mg), and sodium acetate
(0.05 equiv, 0.013 mmol, 1.0 mg) to stir in toluene (1 mL) at 80 °C
for 1 h. Next, a 4 mL screw cap vial equipped with a stirring bar was
charged with N-ethylmaleimide (34.4 mg, 1.1 equiv, 0.275 mmol), the
solution of Ru-1 and sodium acetate, and an alcohol (1 equiv, 0.25
mmol). The vial was then sealed with a Teflon-lined screw cap and
placed in a preheated heating block at 80 °C, and the contents were
allowed to stir for 5 h at 800 rpm. {In the meantime, a solution of Ru-
2 was prepared by allowing [Ru(p-cymene)Cl2]2 (0.025 equiv, 0.0063
mmol, 3.8 mg) and me-bipam (0.055 equiv, 0.0138 mmol, 10.5 mg)
to stir in toluene (1 mL) for 0.5 h at room temperature. Also, a
solution of K3CO3 (1 equiv, 0.25 mmol, 34.5 mg) in water (150 μL)
was prepared.} Upon cooling to room temperature, the vial was
opened, and the solution of Ru-2, the solution of K3CO3, and an aryl
boronic acid (3 equiv, 0.75 mmol) were added. The vial was then
Characterization of Products. (S)-1-Phenylhexan-1-ol (3aa).
Compound 3aa was prepared according to the general procedure with
(S,S)-me-bipam by reaction of hexan-1-ol (0.25 mmol, 31.4 μL) with
phenyl boronic acid (0.75 mmol, 91.4 mg) and isolated by column
chromatography (silica gel, petroleum ether/ethyl acetate from 100:0
to 85:15) to give a volatile colorless oil in 80% yield (35.6 mg). The
analytical data are consistent with those previously reported.18 1H
NMR (500 MHz, CDCl3): δ 7.39−7.32 (m, 4H), 7.32−7.23 (m, 1H),
4.67 (dd, J = 7.6, 5.8 Hz, 1H), 1.86−1.65 (m, 3H), 1.49−1.35 (m,
1H), 1.34−1.28 (m, 5H), 0.96−0.81 (m, 3H). 13C{1H} NMR (126
MHz, CDCl3): δ 145.0, 128.5, 127.5, 125.9, 74.8, 39.1, 31.8, 25.6,
22.6, 14.1. HRMS (ESI+-Orbitrap) calcd for C12H17: m/z 161.1325
[M + H − H2O]+, found m/z 161.1327. SFC (Chiralpak IG-3, 3:97
iPrOH:CO2, flow rate of 1.2 mL/min, λ = 210 nm): tR = 3.18 min
23
[major, (S)-3aa], 3.51 min [minor, (R)-3aa]. Specific rotation: [α]D
−28.8° (c 0.98, CHCl3) for an enantiomerically enriched sample of
96:4 er. The absolute configuration was determined by comparison of
the sign and the value of the optical rotation with those reported in
20
the literature for the opposite enantiomer [[α]D +31.6° (c 1.0,
CHCl3), 96:4].18 For scale-up, compound 3aa was also prepared on a
1.75 mmol scale according to the general procedure with (S,S)-me-
bipam by reaction of hexan-1-ol (1.75 mmol, 219.6 μL) with phenyl
boronic acid (5.25 mmol, 640.1 mg) and isolated by column
chromatography (silica gel, petroleum ether/ethyl acetate from 100:0
to 85:15) to give a volatile colorless oil in 84% yield (262.4 mg) with
the same NMR data and 96:4 er.
(S)-1-Phenylhex-5-en-1-ol (3ga). Compound 3ga was prepared
according to the general procedure with (S,S)-me-bipam by reaction
of hexen-1-ol (0.25 mmol, 30.0 μL) with phenyl boronic acid (0.75
mmol, 91.4 mg) and isolated by column chromatography (silica gel,
petroleum ether to petroleum ether/ethyl acetate 85:15) to give a
volatile colorless oil in 79% yield (35.0 mg). The analytical data are
consistent with those previously reported.40 1H NMR (500 MHz,
CDCl3): δ 7.36−7.31 (m, 4H), 7.31−7.24 (m, 1H), 5.84−5.72 (m,
1H), 5.03−4.91 (m, 2H), 4.68 (dd, J = 7.6, 5.7 Hz, 1H), 2.14−2.03
(m, 2H), 1.89−1.67 (m, 3H), 1.62−1.47 (m, 1H), 1.45−1.33 (m,
1H). 13C{1H} NMR (126 MHz, CDCl3): δ 144.8, 138.6, 128.5, 127.6,
125.9, 114.7, 74.6, 38.5, 33.6, 25.1. HRMS (ESI+-Orbitrap) calcd for
C12H15: m/z 159.1168 [M + H − H2O]+, found m/z 159.1172. SFC
(Chiralpak IG-3, 5:95 iPrOH:CO2, flow rate of 1.2 mL/min, λ = 210
nm): tR = 2.44 min [major, (S)-3ga], 2.65 min [minor, (R)-3ga].
23
Specific rotation: [α]D −41.2° (c 1.0, CHCl3) for an enantiomeri-
cally enriched sample of 98:2 er. The absolute configuration was
determined by comparison of the sign and the value of the optical
rotation with those reported in the literature for the opposite
40
20
enantiomer [[α]D +38.0° (c 1.1, CHCl3), 92:8].
(S)-2-Methyl-1-phenylpropan-1-ol (3ha). Compound 3ha was
prepared according to the general procedure with (S,S)-me-bipam by
reaction of 2-methylpropan-1-ol (0.25 mmol, 23.1 μL) with phenyl
boronic acid (0.75 mmol, 91.4 mg) and isolated by column
chromatography (silica gel, n-pentane to dichloromethane) to give a
volatile colorless oil in 80% yield (35.0 mg). The analytical data are
consistent with those previously reported.41 1H NMR (500 MHz,
CDCl3): δ 7.37−7.30 (m, 4H), 7.29−7.27 (m, 1H), 4.37 (d, J = 6.9
Hz, 1H), 1.96 (dq, J = 13.4, 6.7 Hz, 1H), 1.78 (bs, 1H), 1.01 (d, J =
6.7 Hz, 3H), 0.80 (d, J = 6.8 Hz, 3H). 13C NMR (126 MHz, CDCl3):
δ 143.6, 128.2, 127.5, 126.6, 80.1, 35.3, 19.0, 18.3. HRMS (ESI+-
Orbitrap) calcd for C10H13: m/z 133.1012 [M + H − H2O]+, found
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m/z 133.1019. SFC (Chiralpak IG-3, 2.5:97.5 iPrOH:CO2, flow rate
of 1.2 mL/min, λ = 210 nm): tR = 3.44 min [major, (S)-3ha], 3.19
min [minor, (R)-3ha]. Specific rotation: [α]D23 −39.4° (c 0.97, Et2O)
for an enantiomerically enriched sample of 96:4 er. The absolute
configuration was determined by comparison of the sign and the value
of the optical rotation with those reported in the literature for the
to give a greenish oil in 51% yield (28.3 mg). H NMR (500 MHz,
CDCl3): δ 7.36−7.31 (m, 4H), 7.30−7.26 (m, 1H), 4.70 (dd, J = 8.0,
5.5 Hz, 1H), 3.52 (t, J = 5.5 Hz, 2H), 3.36 (t, J = 5.4 Hz, 2H), 2.29 (t,
J = 7.5 Hz, 2H), 2.20 (s, 1H), 1.90−1.58 (m, 6H), 1.56−1.42 (m,
5H), 1.41−1.27 (m, 1H). 13C{1H} NMR (126 MHz, CDCl3): δ
171.3, 145.0, 128.4, 127.4, 125.9, 74.1, 46.7, 42.7, 38.9, 33.2, 26.5,
25.7, 25.6, 25.0, 24.6. HRMS (ESI+-Orbitrap) calcd for C17H24NO:
m/z 258.1852 [M + H − H2O]+, found m/z 258.1857. SFC
(Chiralpak IA-3, 13:87 iPrOH:CO2, flow rate of 1.2 mL/min, λ = 210
nm): tR = 6.79 min [major, (S)-3la], 7.15 min [minor, (R)-3la].
41
25
opposite enantiomer [[α]D +39.3° (c 1.25, Et2O), 94:6].
(S)-2-Cyclohexyl-1-phenylethan-1-ol (3ia). Compound 3ia was
prepared according to the general procedure with (S,S)-me-bipam by
reaction of 2-cyclohexylethan-1-ol (0.25 mmol, 34.9 μL) with phenyl
boronic acid (0.75 mmol, 91.4 mg) and isolated by column
chromatography (silica gel, petroleum ether to petroleum ether/
ethyl acetate 85:15) to give a white amorphous solid in 82% yield
(42.0 mg). The analytical data are consistent with those previously
reported.42 1H NMR (500 MHz, CDCl3): δ 7.37−7.31 (m, 4H),
7.31−7.24 (m, 1H), 4.79 (dd, J = 8.8, 5.1 Hz, 1H), 1.86−1.75 (m,
1H), 1.78−1.48 (m, 7H), 1.46−1.34 (m, 1H), 1.30−1.09 (m, 3H),
1.03−0.86 (m, 2H). 13C{1H} NMR (126 MHz, CDCl3): δ 145.4,
128.5, 127.5, 125.8, 72.1, 47.1, 34.3, 34.0, 32.9, 26.6, 26.3, 26.2.
HRMS (ESI+-Orbitrap) calcd for C14H19: m/z 187.1481 [M + H −
H2O]+, found m/z 187.1438. SFC (Chiralpak IA-3, 5:95 iPrOH:CO2,
flow rate of 1.2 mL/min, λ = 210 nm): tR = 4.15 min [major, (S)-3ia],
23
Specific rotation: [α]D −12.6° (c 1.02, CHCl3) for an enantiomeri-
cally enriched sample of 98:2 er. The absolute configuration was
determined by analogy to compound (S)-3aa.
(S)-N-Cyclohexyl-6-hydroxy-6-phenylhexanamide (3ma). Com-
pound 3ma was prepared according to the general procedure with
(S,S)-me-bipam, except the loading of Ru-2 was doubled, by reaction
of N-cyclohexyl-6-hydroxyhexamide (1m, 0.25 mmol, 53.3 mg) with
phenyl boronic acid (0.75 mmol, 91.4 mg) and isolated by column
chromatography (silica gel, petroleum ether to ethyl acetate) to give a
1
greenish amorphous solid in 55% yield (39.6 mg). H NMR (500
MHz, CDCl3): δ 7.38−7.31 (m, 4H), 7.31−7.23 (m, 1H), 5.24 (d, J =
8.3 Hz, 1H), 4.68 (dd, J = 7.7, 5.6 Hz, 1H), 3.88−3.59 (m, 1H),
2.18−2.06 (m, 2H), 2.04−1.52 (m, 11H), 1.52−1.28 (m, 3H), 1.21−
0.87 (m, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ 171.9, 144.8,
128.5, 127.5, 125.9, 74.3, 48.1, 38.7, 36.9, 33.3, 25.6, 25.5, 25.4, 24.9.
HRMS (ESI+-Orbitrap) calcd for C18H26NO: m/z 272.2009 [M + H
− H2O]+, found m/z 272.2011. SFC (Chiralpak IC-3, 20:80
iPrOH:CO2, flow rate of 1.2 mL/min, λ = 210 nm): tR = 6.69 min
[major, (S)-3ma], 8.15 min [minor, (R)-3ma]. Specific rotation:
[α]D23 −16.8° (c 1.0, CHCl3) for an enantiomerically enriched sample
of 96:4 er. The absolute configuration was determined by analogy to
compound (S)-3aa.
(S)-2-(5-Hydroxy-5-phenylpentyl)isoindoline-1,3-dione (3na).
Compound 3na was prepared according to the general procedure
with (S,S)-me-bipam, except the loading of Ru-2 was doubled, by
reaction of 2-(5-hydroxypentyl)isoindoline-1,3-dione (1n, 0.25 mmol,
58.3 mg) with phenyl boronic acid (0.75 mmol, 91.4 mg) and isolated
by column chromatography (silica gel, petroleum ether to ethyl
acetate) to give a greenish amorphous solid in 49% yield (37.7 mg).
1H NMR (500 MHz, CDCl3): δ 7.87−7.79 (m, 2H), 7.75−7.66 (m,
2H), 7.39−7.29 (m, 4H), 7.29−7.21 (m, 1H), 4.76−4.59 (m, 1H),
3.76−3.58 (m, 2H), 2.02−1.63 (m, 5H), 1.59−1.29 (m, 2H).
13C{1H} NMR (126 MHz, CDCl3): δ 168.5, 144.7, 133.9, 132.1,
128.5, 127.5, 125.8, 123.2, 74.3, 38.5, 37.8, 28.4, 23.1. HRMS (ESI+-
Orbitrap) calcd for C19H18NO2: m/z 292.1332 [M + H − H2O]+,
found m/z 292.1333. SFC (Chiralpak IC-3, 10:90 iPrOH:CO2, flow
rate of 1.2 mL/min, λ = 210 nm): tR = 6.73 min [major, (S)-3na],
23
4.85 min [minor, (R)-3ia]. Specific rotation: [α]D −21.7° (c 1.0,
CHCl3) for an enantiomerically enriched sample of 95:5 er. The
absolute configuration was determined by analogy to compound (S)-
3aa.
(S)-2-(4-Methoxyphenyl)-1-phenylethan-1-ol (3ja). Compound
3ja was prepared according to the general procedure with (S,S)-me-
bipam by reaction of 2-(4-methoxyphenyl)ethan-1-ol (0.25 mmol,
34.6 μL) with phenyl boronic acid (0.75 mmol, 91.4 mg) and isolated
by column chromatography (silica gel, petroleum ether to petroleum
ether/ethyl acetate 85:15) to give a white solid in 44% yield (25.3
mg). The analytical data are consistent with those previously
reported.43 1H NMR (500 MHz, CDCl3): δ 7.38−7.33 (m, 4H),
7.31−7.27 (m, 1H), 7.14−7.08 (m, 2H), 6.88−6.81 (m, 2H), 4.86
(dd, J = 8.5, 4.8 Hz, 1H), 3.80 (s, 3H), 3.03−2.89 (m, 2H), 1.63−
1.46 (br, 1H). 13C{1H} NMR (126 MHz, CDCl3): δ 158.4, 143.9,
130.5, 130.0, 128.4, 127.6, 125.9, 114.0, 75.4, 55.3, 45.2. HRMS
(ESI+-Orbitrap) calcd for C15H15O: m/z 211.1117 [M + H − H2O]+,
found m/z 211.1119. SFC (Chiralpak IH-3, 5:95 iPrOH:CO2, flow
rate of 1.2 mL/min, λ = 210 nm): tR = 5.96 min [major, (S)-3ja], 7.47
min [minor, (R)-3ja]. Specific rotation: [α]D23 −2.8° (c 0.87, CHCl3)
for an enantiomerically enriched sample of 93:7 er. The absolute
configuration was determined by comparison of the sign and the value
of the optical rotation with those reported in the literature for the
43
22
opposite enantiomer [[α]D +3.8° (c 1.4, CHCl3), 94:6].
(S)-Isopropyl 6-Hydroxy-6-phenylhexanoate (3ka). Compound
3ka was prepared according to the general procedure with (S,S)-me-
bipam by reaction of isopropyl 6-hydroxyhexanoate (1k, 0.25 mmol,
43.6 mg) with phenyl boronic acid (0.75 mmol, 91.4 mg) and isolated
by column chromatography (silica gel, petroleum ether to petroleum
ether/ethyl acetate 85:25) to give a white, amorphous solid in 66%
yield (41.1 mg). 1H NMR (500 MHz, CDCl3): δ 7.37−7.32 (m, 4H),
7.31−7.27 (m, 1H), 4.98 (hept, J = 6.3 Hz, 1H), 4.68 (dd, J = 7.6, 5.7
Hz, 1H), 2.25 (t, J = 7.5 Hz, 2H), 1.93−1.78 (m, 1H), 1.73−1.53 (m,
4H), 1.51−1.39 (m, 2H), 1.28−1.17 (m, 6H). 13C{1H} NMR (126
MHz, CDCl3): δ 173.4, 144.8, 128.6, 127.7, 126.0, 74.5, 67.6, 38.8,
34.7, 25.4, 25.0, 22.0. HRMS (ESI+-Orbitrap) calcd for C15H22O2: m/
z 233.1536 [M + H − H2O]+, found m/z 233.1541. SFC (Chiralpak
IC-3, 5:95 iPrOH:CO2, flow rate of 1.2 mL/min, λ = 210 nm): tR =
6.55 min [major, (S)-3ka], 7.24 min [minor, (R)-3ka]. Specific
23
7.13 min [minor, (R)-3na]. Specific rotation: [α]D −14.5° (c 1.0,
CHCl3) for an enantiomerically enriched sample of 97:3 er. The
absolute configuration was determined by analogy to compound (S)-
3aa.
(S)-18-Hydroxy-18-phenyloctadecan-7-one (3oa). Compound
3oa was prepared according to the general procedure with (S,S)-
me-bipam by reaction of 18-hydroxyhexadecan-7-one (1o, 0.13
mmol, 37.0 mg) with phenyl boronic acid (0.39 mmol, 47.6 mg) and
isolated by column chromatography (silica gel, petroleum ether to
petroleum ether/ethyl acetate 85:25) to give a white amorphous solid
1
in 58% yield (27.1 mg). H NMR (500 MHz, CDCl3): δ 7.38−7.31
(m, 4H), 7.30−7.27 (m, 1H), 4.66 (dd, J = 7.6, 5.8 Hz, 1H), 2.37 (td,
J = 7.5, 2.4 Hz, 4H), 2.04−1.62 (m, 2H), 1.67−1.52 (m, 4H), 1.47−
1.37 (m, 1H), 1.34−1.10 (m, 20H), 0.95−0.72 (m, 3H). 13C{1H}
NMR (126 MHz, CDCl3): δ 211.9, 145.0, 128.4, 127.5, 125.9, 74.7,
42.8, 42.8, 39.1, 31.6, 29.5, 29.5, 29.5, 29.4, 29.4, 29.3, 29.0, 25.8,
23.9, 23.9, 22.5, 14.1. HRMS (ESI+-Orbitrap) calcd for C24H39O: m/z
343.2995 [M + H − H2O]+, found m/z 343.2998. SFC (Chiralpak
IA-3, 8.5:91.5 iPrOH:CO2, flow rate of 1.2 mL/min, λ = 210 nm): tR
= 6.41 min [major, (S)-3oa], 6.01 min [minor, (R)-3oa]. Specific
23
rotation: [α]D −19.6° (c 1.02, CHCl3) for an enantiomerically
enriched sample of 95:5 er. The absolute configuration was
determined by analogy to compound (S)-3aa.
Hydroxy-6-phenyl-1-(piperidin-1-yl)hexan-1-one (3la). Com-
pound 3la was prepared according to the general procedure with
(S,S)-me-bipam, except the loading of Ru-2 was doubled, by reaction
of 6-hydroxy-1-(piperidin-1-yl)hexan-1-one (1l, 0.20 mmol, 39.8 mg)
with phenyl boronic acid (0.60 mmol, 73.2 mg) and isolated by
column chromatography (silica gel, petroleum ether to ethyl acetate)
24
rotation: [α]D −12.0° (c 0.99, CHCl3) for an enantiomerically
enriched sample of 97:3 er. The absolute configuration was
determined by analogy to compound (S)-3aa.
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(1S,12R/S)-1-Phenyloctadecane-1,12-diol (3pa). Compound 3pa
was prepared according to the general procedure with (S,S)-me-
bipam by reaction of rac-octadecane-1,12-diol (rac-1p, 0.25 mmol,
71.6 mg) with phenyl boronic acid (0.75 mmol, 91.4 mg) and isolated
by column chromatography (silica gel, petroleum ether to petroleum
ether/ethyl acetate 85:25) to give a white amorphous solid in 64%
yield (58.0 mg). The isolated material contains both diastereomers
the literature for the opposite enantiomer [[α]D +29.3° (c 1.03,
CHCl3), 96:4 er].18
(S)-1-(3-Methylphenyl)hexan-1-ol (3ae). Compound 3ae was
prepared according to the general procedure with (S,S)-me-bipam
by reaction of hexan-1-ol (0.25 mmol, 31.4 μL) with 3-methylphenyl
boronic acid (0.75 mmol, 109.5 mg) and isolated by column
chromatography (silica gel, petroleum ether to petroleum ether/ethyl
acetate 85:15) to give a volatile colorless oil in 67% yield (32.4 mg).
The analytical data are consistent with those previously reported.18
1H NMR (500 MHz, CDCl3): δ 7.16 (t, J = 7.6 Hz, 1H), 7.11−6.88
(m, 3H), 4.56 (dd, J = 7.6, 5.7 Hz, 1H), 2.29 (s, 3H), 1.80−1.44 (m,
3H), 1.41−1.31 (m, 1H), 1.28−1.14 (m, 5H), 0.84−0.77 (m, 3H).
13C{1H} NMR (126 MHz, CDCl3): δ 145.0, 138.1, 128.3, 128.2,
126.6, 123.0, 74.8, 39.1, 31.8, 25.6, 22.6, 21.5, 14.1. HRMS (ESI+-
Orbitrap) calcd for C13H19: m/z 175.1481 [M + H − H2O]+, found
m/z 175.1486. SFC (Chiralpak ID-3, 5:95 iPrOH:CO2, flow rate of
1.2 mL/min, λ = 210 nm): tR = 1.72 min [major, (S)-3ae], 1.47 min
1
that cannot be distinguished by H and 13C NMR spectroscopy. The
diastereomeric ratio, which reflects the stereoselectivity of the
formation of the new stereogenic center, was determined by SFC
analysis for the diester of the p-nitrobenzoic acid derivative of 3pa
[3pa′, 1-phenyloctadecane-1,12-diylbis(4-nitrobenzoate)], which was
prepared following a literature procedure.44 1H NMR (500 MHz,
CDCl3): δ 7.38−7.32 (m, 4H), 7.31−7.26 (m, 1H), 4.66 (dd, J = 7.6,
5.8 Hz, 1H), 3.62−3.54 (m, 1H), 2.01−1.63 (m, 2H), 1.55−1.36 (m,
7H), 1.36−1.17 (m, 23H), 0.97−0.77 (m, 3H). 13C{1H} NMR (126
MHz, CDCl3): δ 145.0, 128.4, 127.5, 125.9, 74.7, 72.1, 39.1, 37.5,
37.5, 31.9, 29.7, 29.6, 29.6, 29.6, 29.5, 29.5, 29.4, 25.8, 25.7, 25.6,
22.6, 14.1. HRMS (ESI+-Orbitrap) calcd for C24H41O: m/z 327.3046
[M + H − H2O]+, found m/z 327.3046. SFC of diester derivative
(Chiralpak IA-3, 20:80 iPrOH:CO2, flow rate of 1.2 mL/min, λ = 254
nm): tR = 2.44 min [major, (S)-3pa′], 2.65 min [minor, (R)-3pa′].
24
[minor, (R)-3ae]. Specific rotation: [α]D −17.2° (c 0.91, CHCl3)
for an enantiomerically enriched sample of 91:9 er. The absolute
configuration was determined by comparison of the sign and the value
of the optical rotation with those reported in the literature for the
opposite enantiomer [[α]D +19.6° (c 0.32, CHCl3), 97:3].18
20
24
(S)-1-(Naphthalen-2-yl)hexan-1-ol (3ag). Compound 3ag was
prepared according to the general procedure with (S,S)-me-bipam by
reaction of hexan-1-ol (0.25 mmol, 31.4 μL) with 2-naphthyl boronic
acid (0.75 mmol, 129.0 mg) and isolated by column chromatography
(silica gel, petroleum ether to petroleum ether/ethyl acetate 85:15) to
give a white amorphous solid in 81% yield (46.0 mg). The analytical
data are consistent with those previously reported.18 1H NMR (500
MHz, CDCl3): δ 7.92−7.66 (m, 4H), 7.52−7.42 (m, 3H), 4.84 (dd, J
= 7.4, 5.9 Hz, 1H), 1.94−1.75 (m, 3H), 1.59−1.37 (m, 1H), 1.37−
1.29 (m, 5H), 0.96−0.82 (m, 3H). 13C{1H} NMR (126 MHz,
CDCl3): δ 142.3, 133.3, 133.0, 128.3, 127.9, 127.7, 126.1, 125.8,
124.6, 124.1, 74.8, 39.0, 31.8, 25.5, 22.6, 14.1. HRMS (ESI+-Orbitrap)
calcd for C16H19: m/z 211.1481 [M + H − H2O]+, found m/z
211.1488. SFC (Chiralpak ID-3, 5:95 iPrOH:CO2, flow rate of 1.2
mL/min, λ = 210 nm): tR = 4.05 min [major, (S)-3ag], 3.85 min
[minor, (R)-3ag]. Specific rotation: [α]D23 −23.9° (c 1.0, CHCl3) for
an enantiomerically enriched sample of 97:3 er. The absolute
configuration was determined by comparison of the sign and the
value of the optical rotation with those reported in the literature for
Specific rotation: [α]D −14.1° (c 1.01, CHCl3) for a sample
containing a 97:3 mixture of (1S,12R/S)-3pa and (1R,12R/S)-3pa.
The absolute configuration of the newly formed stereocenter was
determined by analogy to compound (S)-3aa.
(S)-1-([1,1′-Biphenyl]-4-yl)hexan-1-ol (3ab). Compound 3ab was
prepared according to the general procedure with (S,S)-me-bipam,
except the reaction mixture was heated to 90 °C during the
hydroarylation step instead of 60 °C, by reaction of hexan-1-ol (0.25
mmol, 31.4 μL) with 2 4-biphenylboronic acid (0.75 mmol, 148.5
mg) and isolated by column chromatography (silica gel, petroleum
ether to petroleum ether/ethyl acetate 85:15) to give a white
amorphous solid in 54% yield (32.4 mg). The analytical data are
consistent with those previously reported.18 1H NMR (500 MHz,
CDCl3): δ 7.68−7.53 (m, 4H), 7.51−7.40 (m, 4H), 7.39−7.31 (m,
1H), 4.72 (t, J = 6.7 Hz, 1H), 1.91−1.67 (m, 3H), 1.46 (m, 1H),
1.37−1.22 (m, 5H), 0.88 (m, 3H). 13C{1H} NMR (126 MHz,
CDCl3): δ 144.0, 140.9, 140.4, 128.8, 127.3, 127.2, 127.1, 126.4, 74.5,
39.1, 31.8, 25.6, 22.6, 14.1. HRMS (ESI+-Orbitrap) calcd for C18H21:
m/z 237.1638 [M + H − H2O]+, found m/z 237.1637. SFC
(Chiralpak IG-3, 10:90 iPrOH:CO2, flow rate of 1.2 mL/min, λ = 210
nm): tR = 4.52 min [major, (S)-3ab], 5.65 min [minor, (R)-3ab].
18
20
the opposite enantiomer [[α]D +27.8° (c 1.43, CHCl3), 98:2].
(S)-1-(Benzofuran-5-yl)hexan-1-ol (3ah). Compound 3ah was
prepared according to the general procedure with (S,S)-me-bipam by
reaction of hexan-1-ol (0.25 mmol, 31.4 μL) with benzofuran-5-yl
boronic acid (0.75 mmol, 121.5 mg) and isolated by column
chromatography (silica gel, petroleum ether to petroleum ether/ethyl
acetate 85:15) to give a white amorphous solid in 59% yield (32.4
23
Specific rotation: [α]D −17.7° (c 1.0, CHCl3) for an enantiomeri-
cally enriched sample of 92:8 er. The absolute configuration was
determined by comparison of the sign and the value of the optical
rotation with those reported in the literature for the opposite
18
20
enantiomer [[α]D +23.4° (c 0.94, CHCl3), 95:5].
1
mg). H NMR (500 MHz, CDCl3): δ 7.63 (d, J = 2.2 Hz, 1H), 7.58
(S)-1-(4-Fluorophenyl)hexan-1-ol (3ac). Compound 3ac was
prepared according to the general procedure with (S,S)-me-bipam
by reaction of hexan-1-ol (0.25 mmol, 31.4 μL) with 4-fluorophenyl
boronic acid (0.75 mmol, 104.9 mg) and isolated by column
chromatography (silica gel, petroleum ether to petroleum ether/ethyl
acetate 85:15) to give a white amorphous solid in 77% yield (37.9
mg). The analytical data are consistent with those previously
reported.18 1H NMR (500 MHz, CDCl3): δ 7.38−7.28 (m, 2H),
7.07−6.98 (m, 2H), 4.65 (dd, J = 7.5, 5.9 Hz, 1H), 1.87−1.73 (m,
2H), 1.71−1.59 (m, 1H), 1.47−1.35 (m, 1H), 1.29 (dt, J = 7.0, 3.7
Hz, 5H), 0.92−0.82 (m, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ
162.1 (d, J = 245.1 Hz), 140.6 (d, J = 3.1 Hz), 127.5 (d, J = 8.0 Hz),
115.2 (d, J = 21.3 Hz), 74.1 (d, J = 0.7 Hz), 39.2 (d, J = 0.8 Hz), 31.7,
25.5, 22.6, 14.0. 19F NMR (471 MHz, CDCl3): δ −115.25, −−115.34
(m). HRMS (ESI+-Orbitrap) calcd for C12H16F: m/z 179.1231 [M +
H − H2O]+, found m/z 179.1230. SFC (Chiralpak IG-3, 5:95
iPrOH:CO2, flow rate of 1.2 mL/min, λ = 210 nm): tR = 1.83 min
(d, J = 1.8 Hz, 1H), 7.47 (d, J = 8.4 Hz, 1H), 7.29 (dd, J = 8.5, 1.8 Hz,
1H), 6.76 (dd, J = 2.2, 1.0 Hz, 1H), 4.76 (dd, J = 7.5, 6.0 Hz, 1H),
1.97−1.67 (m, 3H), 1.49−1.36 (m, 1H), 1.36−1.22 (m, 5H), 0.94−
0.83 (m, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ 154.5, 145.4,
139.7, 127.4, 122.5, 118.5, 111.3, 106.6, 74.9, 39.4, 31.8, 25.6, 22.6,
14.1. HRMS (ESI+-Orbitrap) calcd for C14H17O: m/z 201.1274 [M +
H − H2O]+, found m/z 201.1275. SFC (Chiralpak IC-3, 5:95
iPrOH:CO2, flow rate of 1.2 mL/min, λ = 210 nm): tR = 4.28 min
[major, (S)-3ah], 3.86 min [minor, (R)-3ah]. Specific rotation:
23
[α]D −24.0° (c 0.99, CHCl3) for an enantiomerically enriched
sample of 96:4 er. The absolute configuration was determined by
analogy to compound (S)-3aa.
(S)-1-[4-(Diphenylamino)phenyl]hexan-1-ol (3ai). Compound
3ai was prepared according to the general procedure with (S,S)-me-
bipam by reaction of hexan-1-ol (0.25 mmol, 31.4 μL) with 4-
(diphenylamino)phenyl boronic acid (0.75 mmol, 216.9 mg) and
isolated by column chromatography (silica gel, petroleum ether to
petroleum ether/ethyl acetate 85:15) to give a red oil in 80% yield
23
[major, (S)-3ac], 2.03 min [minor, (R)-3ac]. Specific rotation: [α]D
1
−26.6° (c 0.98, CHCl3) for an enantiomerically enriched sample of
96:4 er. The absolute configuration was determined by comparison of
the sign and the value of the optical rotation with those reported in
(69.2 mg). H NMR (500 MHz, CDCl3): δ 7.26−7.18 (m, 6H),
7.10−7.04 (m, 6H), 7.03−6.93 (m, 2H), 4.65−4.58 (m, 1H), 1.89−
1.76 (m, 1H), 1.74 (d, J = 3.3 Hz, 1H), 1.73−1.64 (m, 1H), 1.48−
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Note
1.40 (m, 1H), 1.39−1.24 (m, 5H), 0.94−0.82 (m, 3H). 13C{1H}
NMR (126 MHz, CDCl3): δ 147.8, 147.2, 139.1, 129.2, 126.9, 124.2,
123.9, 122.7, 74.4, 38.9, 31.8, 25.7, 22.6, 14.1. HRMS (ESI+-Orbitrap)
calcd for C24H26N: m/z 328.2060 [M + H − H2O]+, found m/z
328.2066. SFC-MS (Chiralpak IG-3, 15:85 iPrOH:CO2, flow rate of
1.2 mL/min, m/z = 345, 346, and 368 ([M]+, [M+H]+, and [M
+H]+, respectively)) tR = 2.48 min (major, (S)-3ai), 2.27 min
(minor, (R)-3ai). Specific rotation: [α]D23 −36.8° (c 0.95, CHCl3) for
an enantiomerically enriched sample of 91:9 er. The absolute
configuration was determined by analogy to compound (S)-3aa.
(S)-(4-Methoxyphenyl)phenylmethanol (3fj). Compound 3fj was
prepared according to the general procedure with (S,S)-me-bipam by
reaction of benzyl alcohol (0.25 mmol, 25.7 μL) with 4-
methoxyphenyl boronic acid (0.75 mmol, 114.0 mg) and isolated
by column chromatography (silica gel, petroleum ether to petroleum
ether/ethyl acetate 85:15) to give a colorless oil in 78% yield (41.8
mg). The analytical data are consistent with those previously
reported.28 1H NMR (500 MHz, CDCl3): δ 7.41−7.31 (m, 4H),
7.31−7.21 (m, 3H), 6.90−6.82 (m, 2H), 5.82 (s, 1H), 3.79 (s, 3H),
2.16 (d, J = 8.4 Hz, 1H). 13C{1H} NMR (126 MHz, CDCl3): δ 159.1,
144.0, 136.2, 128.5, 127.9, 127.5, 126.4, 113.9, 75.8, 55.3. HRMS
(ESI+-Orbitrap) calcd for C14H13O: m/z 197.0961 [M + H − H2O]+,
found m/z 197.0966. SFC (Chiralpak IC-3, 5:95 iPrOH:CO2, flow
rate of 1.2 mL/min, λ = 210 nm): tR = 8.41 min [major, (S)-3fj], 7.66
(R)-(4-Bromophenyl)phenylmethanol (3ra). Compound 3ra was
prepared according to the general procedure with (S,S)-me-bipam by
reaction of 4-bromophenylmethanol (0.25 mmol, 46.5 mg) with
phenyl boronic acid (0.75 mmol, 91.4 mg) and isolated by column
chromatography (silica gel, petroleum ether to petroleum ether/ethyl
acetate 85:15) to give a white amorphous solid in 70% yield (46.0
mg). The analytical data are consistent with those previously
reported.28 1H NMR (500 MHz, CDCl3): δ 7.49−7.43 (m, 2H),
7.38−7.31 (m, 4H), 7.30−7.25 (m, 3H), 5.81 (d, J = 3.3 Hz, 1H),
2.19 (d, J = 3.5 Hz, 1H). 13C{1H} NMR (126 MHz, CDCl3): δ 143.4,
142.7, 131.6, 128.7, 128.2, 127.9, 126.5, 121.4, 75.7. HRMS (ESI+-
Orbitrap) calcd for C13H10Br: m/z 244.9960 [M + H − H2O]+, found
m/z 244.9965. SFC (Chiralpak IC-3, 5:95 iPrOH:CO2, flow rate of
1.2 mL/min, λ = 210 nm): tR = 5.15 min [major, (R)-3ra], 5.62 min
[minor, (S)-3ra]. Specific rotation: [α]D23 −15.5° (c 0.98, CHCl3) for
an enantiomerically enriched sample of 97:3 er. The absolute
configuration was determined by comparison of the sign and the
value of the optical rotation with those reported in the literature for
28
22
the opposite enantiomer [[α]D +18.2° (c 0.3, CHCl3), 96:4 er].
(R)-Furan-3-yl(phenyl)methanol (3sa). Compound 3sa was
prepared according to the general procedure with (S,S)-me-bipam,
except that during the oxidation step the reaction mixture was stirred
for 16 h, by reaction of furan-3-ylmethanol (0.25 mmol, 21.6 μL) with
phenyl boronic acid (0.75 mmol, 91.4 mg) and isolated by column
chromatography (silica gel, petroleum ether to petroleum ether/ethyl
acetate 85:15) to give a white amorphous solid in 27% yield (11.8
mg). The analytical data are consistent with those previously
reported.2 1H NMR (500 MHz, CDCl3): δ 7.45−7.34 (m, 5H),
7.34−7.28 (m, 2H), 6.34 (d, J = 1.8 Hz, 1H), 5.78 (s, 1H), 2.16 (s,
1H). 13C{1H} NMR (126 MHz, CDCl3): δ 143.5, 143.0, 139.8, 128.9,
128.6, 127.9, 126.4, 109.2, 69.5. HRMS (ESI+-Orbitrap):calcd for
C11H9O: m/z 157.0648 [M + H − H2O]+, found m/z 157.0651. SFC
(Chiralpak IC-3, 2.5:97.5 iPrOH:CO2, flow rate of 1.2 mL/min, λ =
210 nm): tR = 4.26 min [major, (R)-3sa], 4.82 min [minor, (S)-3sa].
23
min [minor, (R)-3fj]. Specific rotation: [α]D −11.3° (c 0.99,
CHCl3) for an enantiomerically enriched sample of 99:1 er. The
absolute configuration was determined by comparison of the sign and
the value of the optical rotation with those reported in the literature
28
22
[[α]D −14.8° (c 0.81, CHCl3), 96:4 er].
(S)-(3-Chlorophenyl)phenylmethanol (3fk). Compound 3fk was
prepared according to the general procedure with (S,S)-me-bipam by
reaction of benzyl alcohol (0.25 mmol, 25.7 μL) with 3-chlorophenyl
boronic acid (0.75 mmol, 117.3 mg) and isolated by column
chromatography (silica gel, petroleum ether to petroleum ether/ethyl
acetate 85:15) to give a colorless oil in 66% yield (36.4 mg). The
analytical data are consistent with those previously reported.28 1H
NMR (500 MHz, CDCl3): δ 7.31 (d, J = 2.0 Hz, 1H), 7.29−7.23 (m,
4H), 7.19 (ddd, J = 8.2, 4.1, 1.8 Hz, 1H), 7.17−7.07 (m, 3H), 5.71 (d,
J = 3.2 Hz, 1H), 2.13 (d, J = 3.4 Hz, 1H). 13C{1H} NMR (126 MHz,
CDCl3): δ 145.7, 143.2, 134.4, 129.8, 128.7, 128.0, 127.7, 126.6,
126.6, 124.6, 75.7. HRMS (ESI+-Orbitrap) calcd for C13H10Cl: m/z
201.0466 [M + H − H2O]+, found m/z 201.0469. SFC (Chiralpak IB-
3, 5:95 iPrOH:CO2, flow rate of 1.2 mL/min, λ = 210 nm): tR = 7.38
min [major, (S)-3fk], 6.76 min [minor, (R)-3fk]. Specific rotation:
[α]D23 +33.0° (c 1.0, CHCl3) for an enantiomerically enriched sample
of 97::3 er. The absolute configuration was determined by comparison
of the sign and the value of the optical rotation with those reported in
24
Specific rotation: [α]D −3.4° (c 0.49, CHCl3) for an enantiomeri-
cally enriched sample of 99:1 er. The absolute configuration was
determined by comparison of the sign and the value of the optical
20
rotation with those reported in the literature [[α]D −2.7° (c 0.833
CHCl3), 97:3 er].2
Competition Experiments. In a nitrogen-filled glovebox, a
solution of Ru-1 and sodium acetate was prepared by allowing [Ru(p-
cymene)Cl2]2 (0.025 equiv, 0.0063 mmol, 3.8 mg), rac-binap (0.05
equiv, 0.013 mmol, 7.8 mg), and sodium acetate (0.05 equiv, 0.013
mmol, 1.0 mg) to stir in toluene (1 mL) at 80 °C for 1 h. Next, a 4
mL screw cap vial equipped with a stirring bar was charged with N-
ethylmaleimide (31.3.4 mg, 1.0 equiv, 0.25 mmol), the solution of Ru-
1 and sodium acetate, 1-hexanol (1 equiv, 0.25 mmol, 31.3 μL), and
the competing alcohol (1 equiv, 0.25 mmol). The vial was then sealed
with a Teflon-lined screw cap, removed from the glovebox, and placed
in a preheated heating block at 80 °C, and the contents were allowed
to stir for 5 h at 800 rpm. After that, the reaction mixture was cooled,
a known amount of dodecane was added, and the reaction mixture
was analyzed by GC-FID. GC conversions were corrected for
response factors for all compounds (see the section III of the
Supporting Information).
28
22
the literature [[α]D +33.1° (c 0.37, CHCl3), 98:2 er].
(R)-[3,5-Bis(trifluoromethyl)phenyl]phenylmethanol (3qa). Com-
pound 3qa was prepared according to the general procedure with
(S,S)-me-bipam by reaction of 3,5-bis(trifluoromethyl)-
phenylmethanol (0.25 mmol, 61.0 mg) with phenyl boronic acid
(0.75 mmol, 91.4 mg) and isolated by column chromatography (silica
gel, petroleum ether to petroleum ether/ethyl acetate 85:15) to give a
white amorphous solid in 42% yield (33.9 mg). The analytical data are
consistent with those previously reported.45 1H NMR (500 MHz,
CDCl3): δ 7.87 (s, 2H), 7.78 (s, 1H), 7.43−7.31 (m, 5H), 5.94 (d, J =
3.1 Hz, 1H), 2.37 (d, J = 3.2 Hz, 1H). 13C{1H} NMR (126 MHz,
CDCl3): δ 146.1, 142.4, 131.7 (q, J = 33.3 Hz), 129.1, 128.7, 126.7,
126.5 (m), 123.3 (d, J = 272.7 Hz), 121.8−121.1 (m), 75.3. 19F NMR
(471 MHz, CDCl3): δ −62.79. HRMS (ESI+-Orbitrap) calcd for
C15H9F6: m/z 303.0603 [M + H − H2O]+, found m/z 303.0610. SFC
(Chiralpak IB-3, 0.5:99.5 iPrOH:CO2, flow rate of 1.2 mL/min, λ =
210 nm): tR = 5.45 min [major, (R)-3qa], 4.98 min [minor, (S)-3qa].
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c00983.
■
sı
Experimental details and analytical data (PDF)
AUTHOR INFORMATION
Corresponding Authors
■
24
Specific rotation: [α]D −34.1° (c 0.84, CHCl3) for an enantiomeri-
Dawid Lichosyt − University of Strasbourg, CNRS, ISIS UMR
7006, 67000 Strasbourg, France; Present
cally enriched sample of 96:4 er. The absolute configuration was
determined by comparison of the sign and the value of the optical
20
Address: Biological and Chemical Research Centre,
rotation with those reported in the literature [[α]D −38.6° (c 0.80,
CHCl3), 90:10 er].45
Faculty of Chemistry, University of Warsaw, Zwirki
̇
9260
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Note
Abstraction through Induced Bond Polarization: Direct α-Arylation of
Alcohols through Photoredox, HAT, and Nickel Catalysis. Angew.
Chem., Int. Ed. 2018, 57 (19), 5369−5373.
i Wigury Street 101, 02-089 Warsaw, Poland;
Email: dlichosyt@gmail.com
Paweł Dydio − University of Strasbourg, CNRS, ISIS UMR
7006, 67000 Strasbourg, France; orcid.org/0000-0001-
5095-4943; Email: dydio@unistra.fr
(14) Niu, L.; Liu, J.; Liang, X.-A.; Wang, S.; Lei, A. Visible Light-
Induced Direct α C−H Functionalization of Alcohols. Nat. Commun.
2019, 10 (1), 467 DOI: 10.1038/s41467-019-08413-9.
(15) Aoki, K.; Yonekura, K.; Ikeda, Y.; Ueno, R.; Shirakawa, E.
Direct Α-Arylation of Alcohols with Aryl Halides through a Radical
Chain Mechanism. Adv. Synth. Catal. 2020, 362 (11), 2200−2204.
(16) He, T.; Yu, L.; Zhang, L.; Wang, L.; Wang, M. Direct C2-
Alkylation of Azoles with Alcohols and Ethers through Dehydrogen-
ative Cross-Coupling under Metal-Free Conditions. Org. Lett. 2011,
13 (19), 5016−5019.
Authors
Bruno Lainer − University of Strasbourg, CNRS, ISIS UMR
7006, 67000 Strasbourg, France
Maiia Aleksandrova − University of Strasbourg, CNRS, ISIS
UMR 7006, 67000 Strasbourg, France
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c00983
(17) Correia, C. A.; Yang, L.; Li, C.-J. Palladium-Catalyzed Minisci
Reaction with Simple Alcohols. Org. Lett. 2011, 13 (17), 4581−4583.
(18) Casnati, A.; Lichosyt, D.; Lainer, B.; Veth, L.; Dydio, P.
Multicatalytic Approach to One-Pot Stereoselective Synthesis of
Secondary Benzylic Alcohols. Org. Lett. 2021, 23 (9), 3502−3506.
(19) Wang, D.; Astruc, D. The Golden Age of Transfer
Hydrogenation. Chem. Rev. 2015, 115 (13), 6621−6686.
(20) Hill, C. K.; Hartwig, J. F. Site-Selective Oxidation, Amination
and Epimerization Reactions of Complex Polyols Enabled by Transfer
Hydrogenation. Nat. Chem. 2017, 9 (12), 1213−1221.
(21) Martínez, S.; Veth, L.; Lainer, B.; Dydio, P. Challenges and
Opportunities in Multicatalysis. ACS Catal. 2021, 11, 3891−3915.
(22) Sancheti, S. P.; Urvashi; Shah, M. P.; Patil, N. T. Ternary
Catalysis: A Stepping Stone toward Multicatalysis. ACS Catal. 2020,
10 (5), 3462−3489.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The authors acknowledge funding from the European Research
Council (ERC StG No. 804106) and the French National
Research Agency (ANR IdEx, ANR LabEx, “Chemistry of
Complex Systems”, and the fellowships for B.L. and M.A.
under Contract 17-EURE-0016).
REFERENCES
■
(1) Seo, C. S. G.; Morris, R. H. Catalytic Homogeneous Asymmetric
Hydrogenation: Successes and Opportunities. Organometallics 2019,
38 (1), 47−65.
(2) Salvi, L.; Kim, J. G.; Walsh, P. J. Practical Catalytic Asymmetric
Synthesis of Diaryl-, Aryl Heteroaryl-, and Diheteroarylmethanols. J.
Am. Chem. Soc. 2009, 131 (34), 12483−12493.
(23) Lohr, T. L.; Marks, T. J. Orthogonal Tandem Catalysis. Nat.
Chem. 2015, 7 (6), 477−482.
(24) Patil, N. T.; Shinde, V. S.; Gajula, B. A One-Pot Catalysis: The
Strategic Classification with Some Recent Examples. Org. Biomol.
Chem. 2012, 10 (2), 211−224.
(25) Fogg, D. E.; dos Santos, E. N. Tandem Catalysis: A Taxonomy
and Illustrative Review. Coord. Chem. Rev. 2004, 248 (21−24), 2365−
2379.
(3) Noyori, R. Facts Are the Enemy of Truth-Reflections on
Serendipitous Discovery and Unforeseen Developments in Asym-
metric Catalysis. Angew. Chem., Int. Ed. 2013, 52 (1), 79−92.
(4) Noyori, R.; Ohkuma, T. Asymmetric Catalysis by Architectural
and Functional Molecular Engineering: Practical Chemo- and
Stereoselective Hydrogenation of Ketones. Angew. Chem., Int. Ed.
2001, 40 (1), 40−73.
(26) Romiti, F.; del Pozo, J.; Paioti, P. H. S.; Gonsales, S. A.; Li, X.;
Hartrampf, F. W. W.; Hoveyda, A. H. Different Strategies for
Designing Dual-Catalytic Enantioselective Processes: From Fully
Cooperative to Non-Cooperative Systems. J. Am. Chem. Soc. 2019,
141 (45), 17952−17961.
(27) Pellissier, H. Recent Developments in Enantioselective
Multicatalyzed Tandem Reactions. Adv. Synth. Catal. 2020, 362
(12), 2289−2325.
(28) Yamamoto, Y.; Kurihara, K.; Miyaura, N. Me-Bipam for
Enantioselective Ruthenium(II)-Catalyzed Arylation of Aldehydes
with Arylboronic Acids. Angew. Chem., Int. Ed. 2009, 48 (24), 4414−
4416.
(29) Yamamoto, Y.; Shirai, T.; Watanabe, M.; Kurihara, K.; Miyaura,
N. Ru/Me-BIPAM-Catalyzed Asymmetric Addition of Arylboronic
Acids to Aliphatic Aldehydes and α-Ketoesters. Molecules 2011, 16
(6), 5020−5034.
(30) Chaplin, A. B.; Dyson, P. J. Reactivity and Catalytic Activity of
a Robust Ruthenium(II)−Triphos Complex. Inorg. Chem. 2008, 47
(1), 381−390.
(31) Huang, Z.; Wang, Y.; Leng, X.; Huang, Z. An Amine-Assisted
Ionic Monohydride Mechanism Enables Selective Alkyne Cis
-Semihydrogenation with Ethanol: From Elementary Steps to
Catalysis. J. Am. Chem. Soc. 2021, 143 (12), 4824−4836.
(32) Hayashi, Y. Pot Economy and One-Pot Synthesis. Chem. Sci.
2016, 7 (2), 866−880.
(33) Ambrosini, L. M.; Lambert, T. H. Multicatalysis: Advancing
Synthetic Efficiency and Inspiring Discovery. ChemCatChem 2010, 2
(11), 1373−1380.
(5) Tian, P.; Dong, H.-Q.; Lin, G.-Q. Rhodium-Catalyzed
Asymmetric Arylation. ACS Catal. 2012, 2 (1), 95−119.
(6) Defieber, C.; Grutzmacher, H.; Carreira, E. M. Chiral Olefins as
̈
Steering Ligands in Asymmetric Catalysis. Angew. Chem., Int. Ed.
2008, 47 (24), 4482−4502.
(7) Mo, F.; Tabor, J. R.; Dong, G. Alcohols or Masked Alcohols as
Directing Groups for C−H Bond Functionalization. Chem. Lett. 2014,
43 (3), 264−271.
(8) Nguyen, K. D.; Park, B. Y.; Luong, T.; Sato, H.; Garza, V. J.;
Krische, M. J. Metal-Catalyzed Reductive Coupling of Olefin-Derived
Nucleophiles: Reinventing Carbonyl Addition. Science 2016, 354
(6310), aah5133.
(9) Lichosyt, D.; Zhang, Y.; Hurej, K.; Dydio, P. Dual-Catalytic
Transition Metal Systems for Functionalization of Unreactive Sites of
Molecules. Nat. Catal. 2019, 2 (2), 114−122.
(10) Zbieg, J. R.; Yamaguchi, E.; McInturff, E. L.; Krische, M. J.
Enantioselective C-H Crotylation of Primary Alcohols via Hydro-
hydroxyalkylation of Butadiene. Science 2012, 336 (6079), 324−327.
(11) Kim, S. W.; Zhang, W.; Krische, M. J. Catalytic Enantioselective
Carbonyl Allylation and Propargylation via Alcohol-Mediated Hydro-
gen Transfer: Merging the Chemistry of Grignard and Sabatier. Acc.
Chem. Res. 2017, 50 (9), 2371−2380.
(12) Guo, S.; Kumar, P. S.; Yang, M. Recent Advances of Oxidative
Radical Cross-Coupling Reactions: Direct α-C(Sp 3)-H Bond
Functionalization of Ethers and Alcohols. Adv. Synth. Catal. 2017,
359 (1), 2−25.
(13) Twilton, J.; Christensen, M.; DiRocco, D. A.; Ruck, R. T.;
Davies, I. W.; MacMillan, D. W. C. Selective Hydrogen Atom
(34) Ramachary, D. B.; Jain, S. Sequential One-Pot Combination of
Multi-Component and Multi-Catalysis Cascade Reactions: An
Emerging Technology in Organic Synthesis. Org. Biomol. Chem.
2011, 9 (5), 1277−1300.
9261
https://doi.org/10.1021/acs.joc.1c00983
J. Org. Chem. 2021, 86, 9253−9262

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
(35) Yadav, R. N.; Srivastava, A. K.; Banik, B. K. One-Pot Strategy: A
Highly Economical Tool in Organic Synthesis and Medicinal
Chemistry. In Green Approaches in Medicinal Chemistry for Sustainable
Drug Design; Elsevier, 2020; pp 353−425.
(36) Matsunaga, S.; Das, J.; Roels, J.; Vogl, E. M.; Yamamoto, N.;
Iida, T.; Yamaguchi, K.; Shibasaki, M. Catalytic Enantioselective m
Eso -Epoxide Ring Opening Reaction with Phenolic Oxygen
Nucleophile Promoted by Gallium Heterobimetallic Multifunctional
Complexes. J. Am. Chem. Soc. 2000, 122 (10), 2252−2260.
(37) Kurihara, K.; Sugishita, N.; Oshita, K.; Piao, D.; Yamamoto, Y.;
Miyaura, N. Enantioselective 1,4-Addition of Arylboronic Acids to
α,β-Unsaturated Carbonyl Compounds Catalyzed by Rhodium(I)-
Chiral Phosphoramidite Complexes. J. Organomet. Chem. 2007, 692
(1−3), 428−435.
(38) Lo, V. K.-Y.; Guo, Z.; Choi, M. K.-W.; Yu, W.-Y.; Huang, J.-S.;
Che, C.-M. Highly Selective Intramolecular Carbene Insertion into
Primary C−H Bond of α-Diazoacetamides Mediated by a (p
-Cymene)Ruthenium(II) Carboxylate Complex. J. Am. Chem. Soc.
2012, 134 (18), 7588−7591.
(39) Allegretti, P. A.; Ferreira, E. M. Vicinal Bisheterocyclizations of
Alkynes via Nucleophilic Interception of a Catalytic Platinum
Carbene. J. Am. Chem. Soc. 2013, 135 (46), 17266−17269.
(40) Harris, M. R.; Konev, M. O.; Jarvo, E. R. Enantiospecific
Intramolecular Heck Reactions of Secondary Benzylic Ethers. J. Am.
Chem. Soc. 2014, 136 (22), 7825−7828.
(41) Hayes, A. M.; Morris, D. J.; Clarkson, G. J.; Wills, M. A Class of
Ruthenium(II) Catalyst for Asymmetric Transfer Hydrogenations of
Ketones. J. Am. Chem. Soc. 2005, 127 (20), 7318−7319.
(42) Lovinger, G. J.; Morken, J. P. Ni-Catalyzed Enantioselective
3
Conjunctive Coupling with C(Sp ) Electrophiles: A Radical-Ionic
Mechanistic Dichotomy. J. Am. Chem. Soc. 2017, 139 (48), 17293−
17296.
(43) Cao, W.; Tan, D.; Lee, R.; Tan, C.-H. Enantioselective 1,2-
Anionotropic Rearrangement of Acylsilane through a Bisguanidinium
Silicate Ion Pair. J. Am. Chem. Soc. 2018, 140 (5), 1952−1955.
(44) Williams, D. R.; Heidebrecht, R. W. Total Synthesis of (+)-4,5-
Deoxyneodolabelline. J. Am. Chem. Soc. 2003, 125 (7), 1843−1850.
(45) Barsamian, A. L.; Wu, Z.; Blakemore, P. R. Enantioselective
Synthesis of α-Phenyl- and α-(Dimethylphenylsilyl)Alkylboronic
Esters by Ligand Mediated Stereoinductive Reagent-Controlled
Homologation Using Configurationally Labile Carbenoids. Org.
Biomol. Chem. 2015, 13 (12), 3781−3786.
9262
https://doi.org/10.1021/acs.joc.1c00983
J. Org. Chem. 2021, 86, 9253−9262