Synthesis of quaternary carbon stereocenters by copper-catalyzed asymmetric allylic substitution of allyl phosphates with arylboronates

Article abstract of DOI:10.1021/jo500068p

A copper-catalyzed asymmetric allylic substitution of γ,γ- disubstituted allyl phosphates with arylboronates has been developed for the construction of quaternary stereocenters. High regio- and enantioselectivities have been achieved by employing a hydroxy-bearing chiral N-heterocyclic carbene ligand, and both E and Z substrates provide the same enantiomer as the major product. The mechanistic aspect of this catalysis has also been investigated to find that a 1:1 copper/ligand complex is most likely responsible for the present asymmetric catalysis, and the reaction proceeds with almost perfect 1,3-anti stereochemistry with respect to the allylic electrophile.

Full text of DOI:10.1021/jo500068p

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Synthesis of Quaternary Carbon Stereocenters by Copper-Catalyzed
Asymmetric Allylic Substitution of Allyl Phosphates with
Arylboronates
Momotaro Takeda,† Keishi Takatsu,† Ryo Shintani,*,†,‡ and Tamio Hayashi*,†,§,∥
†Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8502, Japan
‡Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku,
Tokyo 113-8656, Japan
§Institute of Materials Research and Engineering, A*STAR, 3 Research Link, Singapore 117602
∥Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543
S
* Supporting Information
ABSTRACT: A copper-catalyzed asymmetric allylic substitu-
tion of γ,γ-disubstituted allyl phosphates with arylboronates
has been developed for the construction of quaternary
stereocenters. High regio- and enantioselectivities have been
achieved by employing a hydroxy-bearing chiral N-heterocyclic
carbene ligand, and both E and Z substrates provide the same
enantiomer as the major product. The mechanistic aspect of
this catalysis has also been investigated to find that a 1:1
copper/ligand complex is most likely responsible for the
present asymmetric catalysis, and the reaction proceeds with
almost perfect 1,3-anti stereochemistry with respect to the allylic electrophile.
INTRODUCTION
RESULTS AND DISCUSSION
■
■
In 2010, Lalic and co-workers reported that a copper complex
coordinated with N-heterocyclic carbene (NHC) ligand IMes
(1,3-dimesitylimidazol-2-ylidene) could effectively catalyze the
allylic substitution of γ-monosubstituted allyl chlorides with
arylboronates with high γ-selectivity.12 When we initially
employed related NHC ligand salt L1 for a nonasymmetric
reaction of γ,γ-disubstituted allyl phosphate (E)-1a with 4-
methoxyphenylboronate 2a under the conditions shown in eq
1, an almost 1:1 mixture of γ-substitution product 3aa and α-
substitution product 4aa was obtained in 50% combined yield.
In contrast, the replacement of one of the methyl groups on L1
by hydroxy group (L2) led to a dramatic improvement of
regioselectivity, leading to exclusive formation of 3aa in 70%
yield under otherwise identical conditions. As a control
experiment, the use of L3 having methoxy group instead of
hydroxy group also provided compound 3aa as the major
product, but the regioselectivity became somewhat lower (3aa/
4aa = 90/10). These results clearly indicate the positive effect
of hydroxy group on the regioselectivity for the present allylic
substitution to construct a quaternary carbon stereocenter.13,14
Enantioselective construction of quaternary carbon stereo-
centers is a subject of great importance in modern asymmetric
catalysis.1 Among the various approaches to this end, copper-
catalyzed asymmetric allylic substitution with organometallic
reagents is one of the attractive methods through the formation
of a new carbon−carbon bond.2 Although various effective
protocols have been developed for the construction of tertiary
stereocenters by using γ-monosubstituted allylic electrophiles,3
only a limited number of publications have been made for the
construction of quaternary stereocenters. A pioneering work by
Hoveyda and co-workers employed dialkylzincs as the
nucleophile,4 and since then, alkylmetals based on zinc5 or
magnesium6 have been most widely utilized for the copper-
catalyzed construction of quaternary carbon stereocenters by
allylic substitution reactions. In contrast, the use of aryl
nucleophiles has been much less explored, and only
arylaluminum reagents had been successfully employed7−9
when we reported our preliminary results using air-stable, easily
handled arylboronic acid esters as the nucleophile for the first
time in 2011.10 After this report, allenyl- and alkenylboronates
were also utilized by Hoveyda and co-workers.11 In this paper,
we describe an overview of the copper-catalyzed asymmetric
allylic substitution of γ,γ-disubstituted allyl phosphates with
arylboronates to create quaternary carbon stereocenters with
high regio- and enantioselectivities.
́
Based on the results in eq 1 and the recent report by Crevisy,
Mauduit, and co-workers on the related asymmetric allylic
substitution with Grignard reagents using hydroxy-bearing
Received: January 11, 2014
Published: March 6, 2014
© 2014 American Chemical Society
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chiral NHCs,6c we turned our attention to the development of
its asymmetric variant by employing (S,S)-L415 and found that
3aa was obtained in 90% yield with 86% ee without the
formation of 4aa (eq 2).10 Changing the ligand substituent
ester 7 resulted in the formation of 3aa with significanty lower
enantioselectivity (77% ee) in 80% yield.
It is worth noting that the present reaction was best catalyzed
with diethyl phosphate as the leaving group, although chloride
could also be used as the leaving group, giving 3aa with
comparable yield and regioselectivity, albeit with slightly lower
enantioselectivity (eq 5). In contrast, much lower yield was
observed by using other leaving groups such as picolinate (35%
yield),19 methyl carbonate (26% yield), or benzoate (<1%
yield).
from 9-anthryl to 2,6-dimethylphenyl ((S,S)-L5)15 gave
somewhat improved enantioselectivity (91% ee), and the best
result was obtained with newly synthesized (S,S)-L6 having
pentamethylphenyl on the nitrogen (97% yield, 91% ee).16 The
absolute configuration of 3aa thus obtained was determined to
be S by comparing the value of its optical rotation with the
literature value.17 As was the case for the nonasymmetric
variant (eq 1), the presence of a hydroxy group in the ligand
substituent was found to be crucial for achieving high reactivity
and selectivity. Thus, the use of O-methylated ligand salt (S,S)-
L7 resulted in the formation of 3aa in lower yield of 79% with
68% ee, and the regioselectivity also became somewhat lower
(93/7). An even lower yield of 3aa with lower regio- and
enantioselectivities was observed by employing ligand salt
(S,S)-L8 with a bulkier cyclohexyl group on oxygen.
In the presence of (S,S)-L6, the effect of base was briefly
examined, and we found that the use of NaOH, which was
highly effective for the related copper-catalyzed asymmetric
allylic substitution with a silylboronate,18 showed much lower
reactivity, although the regio- and enantioselectivities were
identical to those with NaOMe (eq 3). When NaO-t-Bu was
used as the base instead, high yield and excellent regioselectivity
were observed, but the enantioselectivity of 3aa became slightly
lower (88% ee). The enantioselectivity was also affected by the
boronic ester portion of 4-methoxyphenylboronate, and
neopentyl glycol ester 2a gave the best result among those
tested (eq 4). Thus, 1,3-propanediol ester 5 or ethylene glycol
ester 6 gave a high yield of 3aa exclusively as well, but the
enantioselectivity was somewhat lower (88% ee), and pinacol
Under the conditions using (S,S)-L6 as the ligand precursor
and NaOMe as the base, various para- or meta-substituted
arylboronic acid neopentyl glycol esters 2a−g can efficiently
react with substrate (E)-1a with high regio- and enantiose-
lectivities (3/4 ≥ 90/10, 87−92% ee; Table 1, entries 1−7).
The reaction also smoothly proceeds with ortho-substituted
arylboronates such as 2-methoxyphenylboronate 2h, although
moderate regio- and enantioselectivities are observed (entry 8).
In addition to these simple aryl nucleophiles, 2-naphthylbor-
onate 2i, 1-methyl-5-indolylboronate 2j, and 3-thienylboronate
2k are also suitable nucleophiles to give the corresponding γ-
substitution products 3ai−ak in 85−93% yield with similar
efficiency (3/4 ≥ 97/3, 88−91% ee; entries 9−11).
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Table 1. Copper-Catalyzed Asymmetric Allylic Substitution
of (E)-1a with Arylboronates 2
Table 2. Copper-Catalyzed Asymmetric Allylic Substitution
of (E)-1 with Arylboronate 2a
a
b
Combined isolated yield of 3 and 4. Determined by 1H NMR.
c
Determined by chiral HPLC with hexane/2-propanol after converting
d
3 to alcohol 8 by a hydroboration−oxidation sequence. Determined
by chiral HPLC with hexane/2-propanol.
a
b
Combined isolated yield of 3 and 4. Determined by 1H NMR.
c
Determined by chiral HPLC with hexane/2-propanol after converting
d
3 to alcohol 8 by a hydroboration−oxidation sequence. The reaction
was conducted at 0.2 M concentration.
With regard to the scope of allyl phosphates, several (E)-3-
(hetero)aryl-2-butenyl diethyl phosphates 1b−f as well as (E)-
1a can be employed in the reaction with 4-methoxyphenylbor-
onate 2a, and γ-substitution products 3 are obtained almost
exclusively with relatively high enantioselectivity (3/4 ≥ 99/1,
83−91% ee; Table 2, entries 1−6).20 (E)-3-Alkyl-2-butenyl
diethyl phosphates 1g and 1h are also smoothly converted to γ-
substitution products 3ga and 3ha in high yield with perfect
regioselectivity, but the enantioselectivities become significantly
lower under the present reaction conditions (64−76% ee;
entries 7 and 8).21 In addition to (E)-3-substituted 2-butenyl
phosphates, exocyclic allyl phosphates 1i and 1j are also
successfully employed to give the corresponding γ-substitution
products 3ia and 3ja with a high level of enantioselectivity (eq
6; 91−92% ee).22 Furthermore, the reaction of bis(allyl
phosphate) (E,E)-9 gives double allylic substitution product
10 in 94% combined yield of chiral and meso isomers (ratio =
92/8) with 99% ee for the chiral isomer (eq 7).
In contrast to the (E)-substrates employed so far, the use of
(Z)-1a led to the formation of 3aa with lower enantioselectivity
(56% ee), and the absolute configuration of the major
enantiomer turned out to be the same as the one obtained
from (E)-1a (eq 8; see Table 2, entry 1, for comparison).23
Alkyl-substituted (Z)-1g also showed the same trend (see Table
2, entry 6 for comparison), indicating that the reacting
enantioface of the allyic substrates is primarily determined by
the γ-substituents in the present asymmetric catalysis.
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To probe the sterochemical course of the present catalysis
more in detail, we prepared enantioenriched monodeuterated
substrate (S)-(E)-1a-d (95% ee) and subjected it to the
reaction with 4-methoxyphenylboronate 2a as shown in eq 9.
Under these conditions, (S)-3aa-d was selectively obtained in
90% yield with 90% ee, and the Z/E ratio was 93/7. This result
can be explained by the 1,3-anti stereochemical course of this
overall SN′-type substitution reaction. Thus, if the reaction
proceeds with perfect 1,3-anti stereochemistry from (S)-(E)-1a-
d with 95% ee (er = 97.5/2.5) to (S)-3aa-d with 90% ee (er
=95/5), the Z/E ratio should be (97.5 × 0.95 + 2.5 × 0.05)/
(97.5 × 0.05 + 2.5 × 0.95) ≈ 93/7. The calculated Z/E ratio
matches very well with the observed one, indicating the present
catalysis proceeds with almost perfect 1,3-anti selectivity. This
1,3-anti stereochemistry was also confirmed by employing
(R,R)-L6, the opposite enantiomer of the ligand salt, for the
reaction of (S)-(E)-1a-d with 2a, which gave (R)-3aa-d in 96%
yield with 90% ee, and the Z/E ratio became 7/93 as expected
(eq 10). In addition, as shown in Figure 1, a linear correlation
Figure 1. Relationship between ee of L6 and ee of 3aa in the copper-
catalyzed asymmetric allylic substitution of (E)-1a with 2a.
Scheme 1. Possible Catalytic Cycle for the Cu/(S,S)-L6-
Catalyzed Allylic Substitution of 1a with 2a
between the ee of ligand salt L6 and the ee of product 3aa was
observed, indicating that a 1:1 copper/ligand complex is most
likely responsible for the present asymmetric catalysis.24
As demonstrated in eqs 1 and 2, the regioselectivity in the
present catalysis is highly dependent on the existence of the
hydroxy group in the ligand. In addition, as shown in eqs 2−4,
both the reactivity and the enantioselectivity are influenced by
the ligand substituent, metal alkoxide base, and the ester
portion of arylboronate nucleophile. Although further evidence
is still needed for conclusive elucidation of the reaction
mechanism, on the basis of these experimental data and the
result in Figure 1 as well as the literature precedents for the
mechanistic insights of the copper-catalyzed asymmetric allylic
substitutions,3h,11a a possible catalytic cycle for the reaction of
(E)-1a with 2a catalyzed by Cu/(S,S)-L6 in the presence of
NaOMe is shown in Scheme 1. At first, chelated 1:1 copper(I)/
NHC complex A is generated from CuCl and (S,S)-L6 in the
presence of NaOMe.25 Complex A then undergoes trans-
metalation with arylboronate to give arylcopper(I) B.12,15,26
Interaction of NaOMe with the pendant tricoordinated neutral
boron of intermediate B would form anionic borate-containing
intermediate C, which could undergo elimination of trialkox-
yborane to generate arylcuprate D.11a Subsequent oxidative
addition of allyl phosphate (E)-1a to D gives allyl(aryl)copper-
(III) E along with the formation of sodium diethyl phosphate.
Reductive elimination of E then provides the substitution
product and copper(I) complex A is regenerated. The
formation of E from B through C and D presumably
determines the regio- and stereoselectivities, and this scheme
can explain why these selectivities are dependent on the ligand
substituent,27 the boronic ester, and the base. Furthermore,
based on the 1,3-anti stereochemistry observed in eq 9, the
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1H), 5.14 (d, 3JHH = 7.1 Hz, 2H), 2.20 (s, 3H). 13C NMR (CDCl3): δ
165.2, 149.9, 148.2, 142.5, 140.7, 137.0, 128.3, 127.6, 126.9, 125.9,
125.2, 121.1, 63.1, 16.4. HRMS (ESI-TOF): calcd for C16H15NO2Na
(M + Na+) 276.0995, found 276.0992.
oxidative addition of (E)-1a to complex D could go through a
pathway illustrated in Figure 2 via a preferential coordination of
the γ-si face of (E)-1a with the anti geometry of the phosphate
group (X), although the precise mechanism of enantioinduc-
tion is still unclear.
(E)-3-Phenyl-2-butenyl Benzoate. Benzoyl chloride (665 μL,
5.72 mmol) was added dropwise to a solution of (E)-3-phenyl-2-
butenol (707 mg, 4.77 mmol) and Et3N (799 μL, 5.72 mmol) in
CH2Cl2 (10 mL) at 0 °C, and the mixture was stirred for 3 h at room
temperature. The reaction was quenched with 1 M HCl(aq), and this
was extracted with CH2Cl2. The organic layer was washed with
saturated NH4Cl(aq), dried over MgSO4, filtered, and concentrated
under vacuum. The residue was chromatographed on silica gel with
EtOAc/hexane = 1/50 to afford (E)-3-phenyl-2-butenyl benzoate as a
1
colorless oil (1.07 g, 4.24 mmol; 89% yield). H NMR (CDCl3): δ
3
3
8.08 (d, JHH = 8.3 Hz, 2H), 7.56 (t, JHH = 7.4 Hz, 1H), 7.47−7.42
(m, 4H), 7.34 (t, 3JHH = 7.7 Hz, 2H), 7.28 (t, 3JHH = 7.3 Hz, 1H), 6.04
Figure 2. Possible stereochemical course of the oxidative addition step
using (S)-(E)-1a-d in Scheme 1 (Ar = 4-MeOC6H4, X = OP(O)-
(OEt)2).
3
4
3
(tq, JHH = 6.9 Hz and JHH = 1.2 Hz, 1H), 5.05 (d, JHH = 6.8 Hz,
2H), 2.19 (s, 3H). 13C NMR (CDCl3): δ 166.7, 142.7, 140.4, 133.0,
130.4, 129.7, 128.43, 128.39, 127.6, 126.0, 121.5, 62.3, 16.4. HRMS
(ESI-TOF) calcd for C17H16O2Na (M + Na+) 275.1043, found
275.1041.
CONCLUSION
■
Diethyl (E)-3-(4-Trifluoromethylphenyl)-2-butenyl Phos-
phate ((E)-1c) (CAS no. 768392-44-5). Diisobutylaluminum
hydride (11.2 mL, 11.2 mmol; 1.0 M solution in hexane) was added
dropwise over 5 min to a solution of ethyl (E)-3-(4-trifluoromethyl-
phenyl)-2-butenoate (1.31 g, 5.07 mmol) in toluene (20 mL) at −78
°C. The mixture was stirred for 12 h while the temperature was
gradually raised to room temperature. The reaction was quenched with
1 M HCl(aq) at 0 °C, and the white precipitate was filtered off
through Celite with EtOAc. After extraction with EtOAc, the organic
layer was dried over MgSO4, filtered, and concentrated under vacuum.
The residue was chromatographed on silica gel with EtOAc/hexane =
1/2 to afford (E)-3-(4-trifluoromethylphenyl)-2-butenol (CAS
We have described that a Cu/NHC complex derived from
CuCl, and newly synthesized (S,S)-L6 can efficiently catalyze
the asymmetric allylic substitution of γ,γ-disubstituted allyl
phosphates with air-stable and easily handled arylboronates to
construct quaternary carbon stereocenters with high enantio-
selectivities. We have found that the pendant hydroxy group on
the chiral NHC ligand is essential for the induction of high
regio- and enantioselectivities, and the stereochemical course of
the reaction has also been monitored by employing a
deuterium-labeled substrate. Future studies will be directed
toward further expansion of the present catalysis as well as
more insight into the mechanistic aspect.
1
273377-09-6) as a colorless oil (973 mg, 4.50 mmol: 89% yield). H
NMR (CDCl3): δ 7.58 (d, 3JHH = 8.3 Hz, 2H), 7.50 (d, 3JHH = 8.4 Hz,
3
4
3
2H), 6.03 (tq, JHH = 6.5 Hz and JHH = 1.3 Hz, 1H), 4.39 (d, JHH
=
EXPERIMENTAL SECTION
4
■
6.5 Hz, 2H), 2.09 (d, JHH = 1.2 Hz, 3H), 1.45 (bs, 1H).
General Methods. All air- and moisture-sensitive manipulations
were carried out with standard Schlenk techniques under nitrogen or
in a glovebox under argon. CH2Cl2, THF, toluene, and Et2O were
purified by passing through neutral alumina columns under nitrogen.
1,2-Dichloroethane was distilled over CaH2 under nitrogen. Et3N and
pyridine were distilled over KOH under nitrogen. CuCl was washed
with HCl(aq) and dried under vacuum prior to use. NaOH was
ground into a powder and dried under vacuum prior to use. (E)-1a,10
(E)-1b,18 (E)-1e,18 (E)-1g,18 (E)-1h,9b (Z)-1g,18 (E)-3-phenyl-2-
butenol,28 ethyl (E)-3-(4-trifluoromethylphenyl)-2-butenoate,29 (E)-3-
(3-methylphenyl)-2-butenol,30 (Z)-3-phenyl-2-butenol,30 (S)-(E)-1-
deuterio-3-phenyl-2-butenol,31 (E)-1-chloro-3-phenyl-2-butene,32
methyl (E)-3-phenyl-2-buten-1-yl carbonate,33 (S,S)-L4,15 (S,S)-L5,15
ethyl 2,6-dimethylphenyloxamate,15 and 2,3,4,5,6-pentamethylaniline34
were synthesized following the literature procedures. Arylboronates
2a−k and 5−7 were synthesized by esterification of the corresponding
arylboronic acids with diols.26a,35 All other commercial chemicals and
solvents were used as received.
4-Dimethylaminopyridine (55.5 mg, 0.455 mmol) and Et3N (380
μL, 2.73 mmol) were added to a solution of (E)-3-(4-trifluorome-
thylphenyl)-2-butenol (541 mg, 2.50 mmol) in CH2Cl2 (15 mL), and
the resulting solution was cooled to 0 °C. Diethyl chlorophosphate
(327 μL, 2.27 mmol) was added dropwise, and the mixture was stirred
for 20 h at room temperature. The reaction was quenched with H2O,
and this was extracted with EtOAc. The organic layer was washed with
saturated NH4Cl(aq), dried over MgSO4, filtered, and concentrated
under vacuum. The residue was passed through a pad of alumina with
EtOAc and then purified by GPC with CHCl31to afford (E)-1c as a
colorless oil (629 mg, 1.79 mmol; 71% yield). H NMR (CDCl3): δ
7.59 (d, 3JHH = 8.3 Hz, 2H), 7.49 (d, 3JHH = 8.2 Hz, 2H), 6.00 (tq, 3JHH
4
3
3
= 6.8 Hz and JHH = 1.2 Hz, 1H), 4.77 (t, JHH = JHP = 7.6 Hz, 2H),
4.14 (dq, 3JHP = 7.8 Hz and 3JHH = 7.1 Hz, 4H), 2.12 (s, 3H), 1.35 (td,
3JHH = 7.1 Hz and 4JHP = 0.9 Hz, 6H). 13C NMR (CDCl3): δ 146.0 (q,
5JCF = 1.0 Hz), 139.0, 129.6 (q, 2JCF = 32.6 Hz), 126.2, 125.3 (q, 3JCF
=
1
3
3.6 Hz), 124.2 (q, JCF = 272 Hz), 124.1 (d, JCP = 6.7 Hz), 64.1 (d,
2JCP = 5.7 Hz), 63.9 (d, 2JCP = 6.2 Hz), 16.2 (d, 3JCP = 6.7 Hz). HRMS
(E)-3-Phenyl-2-butenyl Picolinate. N,N′-Dicyclohexylcarbodii-
mide (1.34 g, 6.50 mmol) and 4-dimethylaminopyridine (305 mg, 2.50
mmol) were added to a suspension of picolic acid (739 mg, 6.00
mmol) in CH2Cl2 (15 mL) at 0 °C, and the mixture was stirred for 30
min at 0 °C. (E)-3-Phenyl-2-butenol (741 mg, 5.00 mmol) in CH2Cl2
(10 mL) was added, and the mixture was stirred for 5 h at 0 °C. The
precipitate that formed was filtered through Celite with Et2O, and the
resulting solution was concentrated under vacuum. The residue was
chromatographed on silica gel with hexane/EtOAc = 1/1 to afford
(E)-3-phenyl-2-butenyl picolinate as a yellow oil (1.19 g, 4.70 mmol;
94% yield). 1H NMR (CDCl3): δ 8.77 (ddd, 3JHH = 4.6 Hz, 4JHH = 1.7
Hz, and 5JHH = 1.0 Hz, 1H), 8.16 (d, 3JHH = 7.8 Hz, 1H), 7.85 (td, 3JHH
= 7.8 Hz and 4JHH = 1.7 Hz, 1H), 7.48 (ddd, 3JHH = 7.6 and 4.7 Hz and
(ESI-TOF): calcd for C15H20O4F3PNa (M + Na+) 375.0944, found
375.0939.
Diethyl (E)-3-(3-Methylphenyl)-2-butenyl Phosphate ((E)-
1d). This was synthesized from (E)-3-(3-methylphenyl)-2-butenol,
following the procedure for compound (E)-1c. Colorless oil. 62% yield
1
(1.43 g). H NMR (CDCl3): δ 7.25−7.18 (m, 3H), 7.12−7.08 (m,
1H), 5.93 (tq, 3JHH = 6.9 Hz, 4JHH = 1.3 Hz, 1H), 4.76 (t, 3JHH = 3JHP
=
3
3
7.7 Hz, 2H), 4.13 (quint, JHH3 = JHP = 7.3 Hz, 4H), 2.36 (s, 3H),
4
2.11−2.08 (m, 3H), 1.34 (td, JHH = 7.1 Hz and JHP = 0.9 Hz, 6H).
4
13C NMR (CDCl3): δ 142.5 140.6 (d, JCP = 1.0 Hz), 137.9, 128.5,
3
2
128.3, 126.7, 123.1, 121.8 (d, JCP = 6.7 Hz), 64.4 (d, JCP = 5.2 Hz),
2
3
63.8 (d, JCP = 6.2 Hz), 21.5, 16.3, 16.2 (d, JCP = 6.7 Hz). HRMS
(ESI-TOF) calcd for C15H23O4PNa (M + Na+) 321.1226, found
321.1221.
3
4JHH = 1.0 Hz, 1H), 7.45−7.41 (m, 2H), 7.32 (t, JHH = 7.5 Hz, 2H),
7.26 (t, 3JHH = 7.3 Hz, 1H), 6.07 (tq, 3JHH = 7.0 Hz and 4JHH = 1.3 Hz,
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Diethyl (E)-3-(3-Thienyl)-2-butenyl Phosphate ((E)-1f). Trieth-
yl phosphonoacetate (4.40 mL, 22.0 mmol) was added to a suspension
of NaH (840 mg, 21.0 mmol; 60 wt % in mineral oil) in THF (25 mL)
at 0 °C, and the mixture was stirred for 1 h at 0 °C. 3-Acetylthiophene
(2.52 g, 20.0 mmol) was then added with additional THF (5 mL), and
the resulting mixture was stirred for 24 h at room temperature. The
reaction was quenched with H2O at 0 °C, and this was extracted with
EtOAc. The organic layer was washed with saturated NaCl(aq), dried
over MgSO4, filtered, and concentrated under vacuum. The residue
was chromatographed on silica gel with EtOAc/hexane = 1/60→1/30
to afford ethyl (E)-3-(3-thienyl)-2-butenoate (CAS no. 65121-25-7) as
added with additional THF (10 mL), and the resulting mixture was
stirred for 48 h at room temperature. The reaction was quenched with
H2O at 0 °C and extracted with EtOAc. The organic layer was washed
with saturated NaCl(aq), dried over MgSO4, filtered, and concentrated
under vacuum. The residue was chromatographed on silica gel with
EtOAc/hexane = 1/30→1/20, and the solid thus obtained was washed
with cold pentane to afford diethyl (2E,2′E)-3,3′-(1,4-phenylene)bis-
1
(2-butenoate) as a white solid (2.15 g, 7.09 mmol; 47% yield). H
4
NMR (CDCl3): δ 7.48 (s, 4H), 6.16 (q, JHH = 1.2 Hz, 2H), 4.22 (q,
3JHH = 7.1 Hz, 4H), 2.58 (d, 4JHH = 1.2 Hz, 6H), 1.32 (t, 3JHH = 7.1 Hz,
6H).
1
a colorless oil (2.41 g, 12.2 mmol; 61% yield). H NMR (CDCl3): δ
Diisobutylaluminum hydride (34.0 mL, 34.0 mmol; 1.0 M solution
in hexane) was added dropwise over 15 min to a solution of diethyl
(2E,2′E)-3,3′-(1,4-phenylene)bis(2-butenoate) (2.15 g, 7.09 mmol) in
toluene (20 mL) at −78 °C, and the mixture was stirred for 24 h at
room temperature. The reaction was quenched with 1 M HCl(aq) at 0
°C, and the white precipitate was filtered off through Celite with
EtOAc. After extraction with EtOAc, the organic layer was dried over
MgSO4, filtered, and concentrated under vacuum. The residue was
passed through a pad of silica gel with EtOAc/hexane = 1/1, and the
solid thus obtained was washed with Et2O to afford (2E,2′E)-3,3′-(1,4-
phenylene)bis(2-buten-1-ol) as a white solid (1.03 g, 4.71 mmol; 66%
yield). 1H NMR (CDCl3): δ 7.38 (s, 4H), 6.01 (t, 3JHH = 6.7 Hz, 2H),
7.48 (dd, 4JHH = 2.7 and 1.6 Hz, 1H), 7.32 (dd, 3JHH = 5.1 Hz and 4JHH
3
4
= 2.7 Hz, 1H), 7.30 (dd, JHH = 5.2 Hz and JHH = 1.7 Hz, 1H), 6.22
(q, 4JHH = 1.2 Hz, 1H), 4.21 (q, 3JHH = 7.1 Hz, 2H), 2.57 (d, 4JHH = 1.2
Hz, 3H), 1.32 (t, JHH = 7.1 Hz, 3H).
3
(E)-1f was synthesized from ethyl (E)-3-(3-thienyl)-2-butenoate,
following the procedure for compound (E)-1c. Pale brown oil. 60%
1
3
yield over two steps (1.05 g). H NMR (CDCl3): δ 7.28 (dd, JHH
=
5.1 Hz and 4JHH = 2.8 Hz, 1H), 7.25 (dd, 3JHH = 5.1 Hz and 4JHH = 1.4
Hz, 1H), 7.23 (d, 4JHH = 2.8 and 1.4 Hz, 1H), 6.05 (tq, 3JHH = 7.1 Hz
and 4JHH = 1.2 Hz, 1H), 4.76 (tq, 3JHH = 3JHP = 7.7 Hz and 5JHH = 0.5
3
3
Hz, 2H), 4.12 (dq, JHP = 7.7 Hz and JHH = 7.4 Hz, 4H), 2.11−2.08
(m, 3H), 1.34 (td, JHH = 7.1 Hz and JHP = 0.8 Hz, 6H). 13C NMR
(CDCl3): δ 143.6, 135.1, 125.8, 125.1, 121.0, 120.4 (d, 3JCP = 6.7 Hz),
64.1 (d, 2JCP = 5.7 Hz), 63.8 (d, 2JCP = 5.7 Hz), 16.2 (d, 3JCP = 6.7 Hz),
15.9. HRMS (ESI-TOF): calcd for C12H19O4PSNa (M + Na+)
313.0634, found 313.0628.
3
4
3
4.37 (t, JHH = 5.9 Hz, 4H), 2.09 (s, 6H), 1.35 (bs, 2H).
4-Dimethylaminopyridine (83.0 mg, 0.682 mmol) and Et3N (570
μL, 4.09 mmol) were added to a solution of (2E,2′E)-3,3′-(1,4-
phenylene)bis(2-buten-1-ol) (372 mg, 1.71 mmol) in CH2Cl2 (10
mL) and the resulting solution was cooled to 0 °C. Diethyl
chlorophosphate (588 μL, 4.09 mmol) was added dropwise, and the
mixture was stirred for 16 h at room temperature. The reaction was
quenched with H2O, and this was extracted with CH2Cl2. The organic
layer was washed with saturated NH4Cl(aq), dried over MgSO4,
filtered, and concentrated under vacuum. The residue was passed
through a pad of alumina with EtOAc and then purified by GPC with
CHCl3 to afford (E,E)-9 as a colorless oil (710 mg, 1.45 mmol; 85%
yield). 1H NMR (CDCl3): δ 7.38 (s, 4H), 5.97 (t, 3JHH = 6.8 Hz, 2H),
Diethyl (Z)-3-Phenyl-2-butenyl phosphate ((Z)-1a) (CAS
853658-20-5). This was synthesized from (Z)-3-phenyl-2-butenol,
following the procedure for compound (E)-1c. Colorless oil. 94% yield
(1.16 g). 1H NMR (CDCl3): δ 7.34 (t, 3JHH = 7.3 Hz, 2H), 7.30−7.26
3
4
(m, 1H), 7.19−7.15 (m, 2H), 5.71 (tq, JHH = 7.1 Hz and JHH = 1.4
Hz, 1H), 4.46 (t, 3JHH = 3JHP = 7.4 Hz, 2H), 4.07 (quint, 3JHH = 3JHP
=
7.2 Hz, 4H), 2.11 (s, 3H), 1.30 (td, JHH = 7.1 Hz and 4JHP = 1.4 Hz,
6H), 13C NMR (CDCl3): δ 143.0, 140.3, 128.4, 127.8, 127.6, 121.8 (d,
3
3JCP = 7.2 Hz), 65.1 (d, JCP = 5.2 Hz), 63.7 (d, JCP = 6.2 Hz), 25.5,
2
2
3
3
3
3
4.76 (t, JHH = JHP = 7.7 Hz, 4H), 4.13 (quint, JHH = JHP = 7.3 Hz,
3
8H), 2.10 (s, 6H), 1.34 (t, 3JHH = 7.1 Hz, 12H). 13C NMR (CDCl3): δ
141.6, 139.8, 125.8, 121.9 (d, JCP = 6.7 Hz), 64.3 (d, JCP = 5.2 Hz),
16.2 (d, JCP = 6.7 Hz).
3
2
Diethyl (E)-2-(3,4-Dihydronaphthalen-1(2H)-ylidene)ethyl
Phosphate ((E)-1i). This was synthesized from 1-tetralone, following
the procedure for compound (E)-1f. Colorless oil. 12% yield over
three steps (1.10 g). For storage, it is kept in a freezer under inert
2
3
63.8 (d, JCP = 5.7 Hz), 16.1 (d, JCP = 6.2 Hz), 16.0. HRMS (ESI-
TOF): calcd for C22H36O8P2Na (M + Na+) 513.1778, found 513.1780.
Diethyl (S)-(E)-1-Deuterio-3-phenyl-2-butenyl Phosphate
((S)-(E)-1a-d). This was synthesized from (S)-(E)-1-deuterio-3-
phenyl-2-butenol (95% ee) following the procedure for compound
1
atmosphere to prevent decomposition. H NMR (CDCl3): δ 7.62−
7.57 (m, 1H), 7.20−7.13 (m, 2H), 7.13−7.07 (m, 1H), 6.15 (t, 3JHH
=
3
3
(E)-1c. Colorless oil. 72% yield (285 mg). [α]30 −0.9 (c 2.00,
7.0 Hz, 1H), 4.78 (t, J = 7.6 Hz, 2H), 4.13 (quint, J = 7.3 Hz, 4H),
D
3
3
1
2.79 (t, JHH = 6.2 Hz, 2H), 2.59−2.53 (m, 2H), 1.85 (quint, JHH
=
CHCl3). H NMR (CDCl3): δ 7.42−7.38 (m, 2H), 7.36−7.31 (m,
6.3 Hz, 2H), 1.34 (td, 3JHH = 7.1 Hz and 4JHP = 0.9 Hz, 6H). 13C NMR
(CDCl3): δ 139.5, 138.0, 134.7, 128.9, 127.7, 126.1, 124.1, 117.5 (d,
2H), 7.30−7.25 (m, 1H), 5.94 (d, 3JHH = 6.8 Hz, 1H), 4.74 (t, 3J = 7.6
Hz, 1H), 4.17−4.09 (m, 4H), 2.13−2.09 (m, 3H), 1.344 (t, 3JHH = 7.1
3JCP = 6.7 Hz), 64.1 (d, JCP = 5.7 Hz), 63.7 (d, JCP = 5.7 Hz), 30.2,
2
2
Hz, 3H), 1.342 (t, JHH = 7.1 Hz, 3H). 13C NMR (CDCl3): δ 142.5,
3
3
3
1
26.6, 22.9, 16.1 (d, JCP = 6.7 Hz). HRMS (ESI-TOF): calcd for
140.6, 128.4, 127.7, 125.9, 121.9 (d, JCP = 6.7 Hz), 64.1 (td, JCD
=
C16H23O4PNa (M + Na+) 333.1226, found 333.1222.
22.7 Hz and 2JCP = 5.7 Hz), 63.8 (d, 2JCP = 6.1 Hz), 16.3, 16.2 (d, 3JCP
= 6.7 Hz). HRMS (ESI-TOF): calcd for C14H20DO4PNa (M + Na+)
308.1132, found 308.1131.
Diethyl (E)-2-(Chroman-4-ylidene)ethyl Phosphate ((E)-1j).
This was synthesized from 4-chromanone, following the procedure for
compound (E)-1f. Yellow oil. 27% yield over three steps (873 mg).
For storage, it is kept in a freezer under inert atmosphere to prevent
decomposition. 1H NMR (CDCl3): δ 7.55 (dd, 3JHH = 8.0 Hz and 4JHH
1,3-Bis(2,6-dimethylphenyl)imidazolinium Hexafluorophos-
phate (L1). Oxalyl chloride (430 μL, 5.00 mmol) in CH2Cl2 (5 mL)
was added dropwise to a solution of 2,6-dimethylaniline (1.33 g, 11.0
mmol) and pyridine (967 μL, 12.0 mmol) in CH2Cl2 (20 mL) at 0 °C,
and the resulting solution was stirred for 12 h at room temperature.
The reaction mixture was diluted with CH2Cl2 and washed
successively with 1 M HCl(aq) and saturated NaHCO3(aq). The
organic layer was dried over MgSO4, filtered, and concentrated under
vacuum. The resulting solid was washed with hexane and dried under
vacuum to afford N,N′-bis(2,6-dimethylphenyl)oxalamide (CAS
91325-47-2) as a white solid (1.45 g, 4.90 mmol; 98% yield). 1H
NMR (CDCl3): δ 8.86(bs, 2H),7.20−7.15 (m, 2H), 7.15−7.11 (m,
4H), 2.29 (s, 12H). 13C NMR (DMSO-d6): δ 158.9, 135.1, 134.2,
127.8, 127.0, 18.0.
3
4
= 1.6 Hz, 1H), 7.18 (ddd, JHH = 8.1 and 7.3 Hz and JHH = 1.6 Hz,
3
4
1H), 6.93−6.88 (m, 1H), 6.85 (dd, JHH = 8.1 Hz and JHH = 1.1 Hz,
3
3
3
1H), 6.20 (t, JHH = 7.2 Hz, 1H), 4.75 (dd, JHP = 8.8 Hz and JHH
=
7.3 Hz, 2H), 4.22 (t, 3JHH = 5.8 Hz, 2H), 4.12 (quint, 3J = 7.3 Hz, 4H),
3
4
2.77−2.71 (m, 2H), 1.34 (td, JHH = 7.1 Hz and JHH = 0.9 Hz, 6H).
13C NMR (CDCl3): δ 155.2, 134.2, 129.9, 124.3, 121.5, 121.0, 117.7,
115.4 (d, 3JCP = 6.2 Hz), 65.9, 63.9 (d, JCP = 5.7 Hz), 63.4 (d, JCP
=
2
2
3
5.2 Hz), 25.9, 16.2 (d, JCP = 6.7 Hz). HRMS (ESI-TOF): calcd for
C15H21O5PNa (M + Na+) 335.1019, found 335.1013.
Tetraethyl (2E,2′E)-1,4-Phenylenebis(2-butene-3,1-diyl) Bis-
(phosphate) ((E,E)-9). Triethyl phosphonacetate (7.74 mL, 39.0
mmol) was added to a suspension of NaH (1.44 g, 36.0 mmol; 60 wt
% in mineral oil) in THF (40 mL) at 0 °C, and the mixture was stirred
for 1 h at 0 °C. 1,4-Diacetylbenzene (2.43 g, 20.0 mmol) was then
LiAlH4 (744 mg, 19.6 mmol) was added to a solution of N,N′-
bis(2,6-dimethylphenyl) oxalamide (1.45 g, 4.90 mmol) in THF (25
mL) at 0 °C, and the mixture was stirred for 48 h at 70 °C. The
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Featured Article
reaction was diluted with Et2O at 0 °C and slowly quenched with H2O.
The resulting suspension was filtered through Celite with THF, and
the solution was concentrated under vacuum. The residue was
chromatographed on silica gel with EtOAc/hexane = 1/5 to afford
N,N′-bis(2,6-dimethylphenyl)ethane-1,2-diamine (CAS 72991-60-7)
as a colorless oil (494 mg, 1.85 mmol; 38% yield). 1H NMR (CDCl3):
δ 7.01(d, JHH = 7.3 Hz, 4H), 6.84 (t, JHH = 7.5 Hz, 2H), 3.39 (bs,
2H), 3.22 (s, 4H), 2.32 (s, 12H). 13C NMR (CDCl3): δ 146.0, 129.6,
129.0, 122.2, 49.0, 18.7.
52.4, 52.3, 17.7, 17.6. HRMS (ESI-TOF): calcd for C18H21N2O (M −
−
PF6 ) 281.1648, found 281.1648.
1-(2,6-Dimethylphenyl)-3-(2-methoxy-6-methylphenyl)-
imidazolinium Hexafluorophosphate (L3). Trimethylsilyldiazo-
methane (2.00 mL, 4.00 mmol; 2.0 M solution in Et2O) was added
dropwise to a solution of compound L2 (213 mg, 0.500 mmol) and
HBF4(aq) (80.0 μL, 0.500 mmol; 42 wt %) in CH2Cl2 (10 mL) at 0
°C. The reaction mixture was stirred for 15 min at 0 °C, and it was
poured into H2O. After extraction with CH2Cl2, the organic layer was
dried over MgSO4, filtered, and concentrated under vacuum. The
residue was washed with CHCl3 to afford compound L3 as a white
3
3
HCl (2.22 mL, 2.22 mmol; 1.0 M solution in Et2O) was added to a
solution of N,N′-bis(2,6-dimethylphenyl)ethane-1,2-diamine (494 mg,
1.85 mmol) in Et2O (20 mL), and the mixture was stirred for 15 min
at room temperature. The precipitate was collected by filtration and
washed with Et2O/hexane to afford a white solid. Toluene (10 mL)
and trimethyl orthoformate (1.01 mL, 9.25 mmol) were successively
added to this solid, and the mixture was stirred for 16 h at 90 °C. After
being cooled to room temperature, the resulting precipitate was
collected by filtration and washed with Et2O. The solid thus obtained
was then suspended in H2O (10 mL) and MeOH (10 mL), and KPF6
(682 mg, 3.70 mmol) was added. The mixture was stirred for 2 h at
room temperature, and this was diluted with H2O. After extraction
with CH2Cl2, the organic layer was concentrated under vacuum. The
residue was chromatographed on silica gel with CH2Cl2/EtOAc = 10/
1, and the solid thus obtained was triturated with CH2Cl2 and washed
with CHCl3 to afford compound L1 as a white solid (490 mg, 1.15
1
solid (176 mg, 0.40 mmol; 80% yield). H NMR (acetone-d6): δ 8.86
(s, 1H), 7.44 (t, 3JHH = 8.1 Hz, 1H), 7.38 (t, 3JHH = 7.4 Hz, 1H), 7.31
(d, 3JHH = 7.3 Hz, 2H), 7.13 (d, 3JHH = 8.1 Hz, 1H), 7.03 (d, 3JHH = 7.8
Hz, 1H), 4.77−4.64 (m, 4H), 3.99 (s, 3H), 2.51 (s, 9H). 13C NMR
(acetone-d6): δ 162.5, 156.1, 138.0, 136.9, 134.3, 132.0, 131.2, 130.1,
124.3, 123.8, 110.9, 56.9, 52.5, 52.4, 17.6, 17.5. HRMS (ESI-TOF):
−
calcd for C19H23N2O (M−PF6 ) 295.1805, found 295.1806.
1-((1S,2S)-2-Hydroxyindan-1-yl)-3-pentamethylphenylimi-
dazolinium Hexafluorophosphate ((S,S)-L6). Ethyl chloroglyox-
ylate (1.09 mL, 9.77 mmol) was added dropwise to a solution of
2,3,4,5,6-pentamethylaniline (1.75 g, 10.8 mmol) and pyridine (1.02
mL, 12.7 mmol) in CH2Cl2 (11 mL) at 0 °C, and the resulting
solution was stirred for 18 h at room temperature. The reaction
mixture was diluted with EtOAc and washed successively with 1 M
HCl(aq) and saturated NaHCO3(aq). The organic layer was dried
over MgSO4, filtered, and concentrated under vacuum. The resulting
solid was washed with hexane and dried under vacuum to afford ethyl
2,3,4,5,6-pentamethylphenyloxamate as a white solid (1.90 g, 7.24
1
mmol; 62% yield). H NMR (acetone-d6): δ 8.96 (s, 1H), 7.39 (dd,
3JHH = 8.3 and 6.8 Hz, 2H), 7.34−7.29 (m, 4H), 4.80 (s, 4H), 2.53 (s,
12H). 13C NMR (acetone-d6): δ 161.2, 136.9, 134.3, 131.3, 130.2,
−
52.3, 17.8. HRMS (ESI-TOF): calcd for C19H23N2 (M − PF6 )
mmol; 74% yield). 1H NMR (CDCl3): δ 8.41 (bs, 1H), 4.43 (q, 3JHH
=
=
279.1856, found 279.1855.
3
7.1 Hz, 2H), 2.23 (s, 3H), 2.22 (s, 6H), 2.15 (s, 6H), 1.45 (t, JHH
1-(2,6-Dimethylphenyl)-3-(2-hydroxy-6-methylphenyl)-
imidazolinium Hexafluorophosphate (L2). A solution of ethyl
2,6-dimethylphenyloxamate (1.11 g, 5.00 mmol), 2-amino-m-cresol
(616 mg, 5.00 mmol), and 4-(dimethylamino)pyridine (30.5 mg, 0.25
mmol) in CH2Cl2 (25 mL) was refluxed for 48 h. After the solution
was cooled to room temperature, the solvent was removed under
vacuum and the residue was chromatographed on silica gel with
CHCl3/EtOAc = 20/1 to afford N-(2,6-dimethylphenyl)-N′-(2-
hydroxy-6-methylphenyl)oxalamide as a white solid (1.02 g, 3.43
mmol; 69% yield). 1H NMR (CDCl3): δ 9.50 (bs, 1H), 8.81 (bs, 1H),
7.1 Hz, 3H). 13C NMR (CDCl3): δ 162.5, 156.1, 138.0, 136.9, 134.3,
132.0, 131.2, 130.1, 124.3, 123.8, 110.9, 56.9, 52.5, 52.4, 17.6, 17.5.
HRMS (ESI-TOF): calcd for C15H21NO3Na (M + Na+) 286.1414,
found 286.1412.
A solution of ethyl 2,3,4,5,6-pentamethylphenyloxamate (1.05 g,
4.00 mmol) and (1S,2S)-trans-1-amino-2-indanol (597 mg, 4.00
mmol) in CH2Cl2 (20 mL) was refluxed for 60 h. After the solution
was cooled to room temperature, the solvent was removed under
vacuum and the residue was chromatographed on silica gel with
CHCl3/EtOAc/hexane = 4/2/1 to afford N-(2,3,4,5,6-pentamethyl-
8.19 (s, 1H), 7.22−7.17 (m, 1H), 7.17−7.10 (m, 3H), 6.97 (d, 3JHH
=
3
8.2 Hz, 1H), 6.83 (d, JHH = 7.6 Hz, 1H), 2.37 (s, 3H), 2.29 (s, 6H).
13C NMR (CDCl3): δ 158.4, 157.2, 150.2, 135.1, 132.0, 131.4, 128.6,
128.5, 128.3, 122.9, 122.7, 118.6, 18.6, 18.1.
phenyl)-N′-((1S,2S)-2-hydroxy-1-indanyl)oxalamide as a white solid
1
(861 mg, 2.35 mmol; 59% yield). [α]20 +8.4 (c 1.00, CHCl3). H
D
3
NMR (CDCl3): δ 8.81 (bs, 1H), 7.94 (d, JHH = 5.8 Hz, 1H), 7.33−
7.23 (m, 4H), 5.24 (t, 3JHH = 6.2 Hz, 1H), 4.58 (td, 3JHH = 7.7 and 6.2
LiAlH4 (357 mg, 9.40 mmol) was added to a solution of N-(2,6-
dimethylphenyl)-N′-(2-hydroxy-6-methylphenyl)oxalamide (1.02 g,
3.43 mmol) in THF (15 mL) at 0 °C, and the mixture was stirred
for 12 h at 70 °C. The reaction was diluted with Et2O at 0 °C and
slowly quenched with H2O. The resulting suspension was filtered
through Celite with THF, and the solution was concentrated under
vacuum. Et2O (20 mL) and HCl (5.15 mL, 5.15 mmol; 1.0 M solution
in Et2O) were added to the residue, and the mixture was stirred for 15
min at room temperature. The precipitate was collected by filtration
and washed with Et2O/hexane to afford a brown solid. Toluene (25
mL) and trimethyl orthoformate (1.88 mL, 17.2 mmol) were
successively added to this solid, and the mixture was stirred for 18 h
at 90 °C. After being cooled to room temperature, the resulting
precipitate was collected by filtration and washed with Et2O. The solid
thus obtained was suspended in H2O (10 mL) and MeOH (10 mL),
and KPF6 (1.26 g, 6.86 mmol) was added. The mixture was stirred for
2 h at room temperature, and this was diluted with H2O. After
extraction with CH2Cl2, the organic layer was concentrated under
vacuum. The residue was chromatographed on silica gel with CH2Cl2/
EtOAc = 10/1, and the solid thus obtained was triturated with CH2Cl2
and washed with CHCl3 to afford compound L2 as a white solid (540
2
3
Hz, 1H), 3.80 (bs, 1H), 3.37 (dd, JHH = 15.7 Hz and JHH = 7.6 Hz,
2
3
1H), 3.00 (dd, JHH = 15.7 Hz and JHH = 7.8 Hz, 1H), 2.24 (s, 3H),
2.23 (s, 6H), 2.17 (s, 6H). 13C NMR (CDCl3): δ 161.7, 158.1, 140.4,
138.3, 135.3, 133.4, 130.5, 129.7, 129.1, 127.6, 125.4, 123.7, 80.8, 64.0,
38.8, 17.0, 16.8, 15.7. HRMS (ESI-TOF): calcd for C22H26N2O3Na (M
+ Na+) 389.1836, found 389.1833.
LiAlH4 (357 mg, 9.40 mmol) was added to a solution of N-
(2,3,4,5,6-pentamethylphenyl)-N′-((1S,2S)-2-hydroxy-1-indanyl)-
oxalamide (861 mg, 2.35 mmol) in THF (10 mL) at 0 °C, and the
mixture was stirred for 16 h at 70 °C. The reaction was diluted with
Et2O at 0 °C and slowly quenched with H2O. The resulting suspension
was filtered through Celite with THF, and the solution was
concentrated under vacuum. Et2O (40 mL) and HCl (2.05 mL, 2.05
mmol; 1.0 M solution in Et2O) were added to the residue, and the
mixture was stirred for 15 min at room temperature. The precipitate
was collected by filtration and washed with Et2O/hexane to afford a
brown solid. Toluene (15 mL) and trimethyl orthoformate (1.12 mL,
10.3 mmol) were successively added to this solid, and the mixture was
stirred for 17 h at 90 °C. After being cooled to room temperature, the
resulting precipitate was collected by filtration and washed with Et2O.
The solid thus obtained was suspended in H2O (40 mL), and KPF6
(757 mg, 4.11 mmol) was added. The mixture was stirred for 2 h at
room temperature, and this was diluted with H2O. After extraction
with CH2Cl2, the organic layer was concentrated under vacuum. The
residue was chromatographed on silica gel with CH2Cl2/acetone = 4/
1
mg, 1.27 mmol; 73% yield). H NMR (acetone-d6): δ 8.87 (s, 1H),
3
7.38 (dd, JHH = 8.3 and 6.7 Hz, 1H), 7.32−7.25 (m, 3H), 6.99 (d,
3JHH = 8.2 Hz, 1H), 6.92 (d, 3JHH = 7.7 Hz, 1H), 4.72 (s, 4H), 2.87 (bs,
1H), 2.494 (s, 6H), 2.490 (s, 3H). 13C NMR (acetone-d6): δ 162.3,
154.0, 137.8, 136.9, 134.3, 131.8, 131.2, 130.1, 123.4, 123.0, 115.0,
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1, and the solid thus obtained was triturated with CH2Cl2 and washed
6H), 2.11−1.92 (m, 2H), 1.92−1.83 (m, 1H), 1.83−1.69 (m, 2H),
1.62−1.51 (m, 1H). 13C NMR (CDCl3): δ 160.2, 160.1, 158.54,
158.53, 140.6, 140.3, 139.4, 139.3, 135.1, 133.3, 131.2, 131.0, 130.5,
129.9, 128.8, 128.7, 128.2, 127.9, 127.3, 125.2, 124.7, 124.6, 84.04,
84.00, 72.6, 72.5, 61.2, 61.0, 38.2, 37.8, 29.2, 29.0, 25.30, 25.26, 19.32,
19.29, 16.9, 16.8, 15.62, 15.60.
with CHCl3 to afford compound (S,S)-L6 as a white solid (736 mg,
1.49 mmol; 73% yield). [α]20 +40.8 (c 1.00, acetone). 1H NMR
D
3
(acetone-d6): δ 8.77 (s, 1H), 7.49 (d, JHH = 7.1 Hz, 1H), 7.41−7.32
3
3
(m, 3H), 5,40 (d, JHH = 6.6 Hz, 1H), 5.00 (d, JHH = 5.2 Hz, 1H),
4.91−4.84 (m, 1H), 4.55−4.30 (m, 4H), 3.37 (dd, 2JHH = 15.8 Hz and
3JHH = 7.2 Hz, 1H), 2.93 (dd, 2JHH = 15.9 Hz and 3JHH = 7.3 Hz, 1H),
2.33 (s, 3H), 2.30 (s, 3H), 2.27 (s, 3H), 2.25 (s, 6H). 13C NMR
(acetone-d6): δ 160.0, 141.7, 138.2, 136.1, 135.0, 132.2, 131.93,
131.87, 130.4, 128.3, 126.5, 125.4, 76.2, 71.4, 52.7, 47.1, 39.2, 17.0,
A mixture of palladium on carbon (41.7 mg, 39.2 μmol; 10 wt %
Pd) and N-((1S,2S)-2-(2-cyclohexen-1-yloxy)-1-indanyl)-N′-
(2,3,4,5,6-pentamethylphenyl)oxalamide (584 mg, 1.31 mmol) in
EtOH (10 mL) and CH2Cl2 (10 mL) was stirred for 12 h at room
temperature under H2 (1 atm). The catalyst was filtered off through
Celite with CH2Cl2, and the solvent was removed under vacuum. The
residue was chromatographed on silica gel with hexane/EtOAc = 3/1
to afford N-((1S,2S)-2-cyclohexyloxy-1-indanyl)-N′-(2,3,4,5,6-pentam-
−
16.7, 15.5, 15.4. HRMS (ESI-TOF): calcd for C23H29N2O (M − PF6 )
349.2274, found 349.2269.
1-((1R,2R)-2-Hydroxyindan-1-yl)-3-pentamethylphenylimi-
dazolinium Hexafluorophosphate ((R,R)-L6). This was synthe-
sized from (1R,2R)-trans-1-amino-2-indanol and ethyl 2,6- dimethyl-
phenyloxamate, following the procedure for compound (S,S)-L6.
White solid. 46% yield (313 mg). [α]20 −40.1 (c 0.50, acetone).
1-((1S,2S)-2-Methoxyindan-1-yl)-D3-pentamethylphenylimi-
dazolinium Hexafluorophosphate ((S,S)-L7). Trimethylsilyldiazo-
methane (0.60 mL, 1.20 mmol; 2.0 M solution in Et2O) was added
dropwise to a solution of compound (S,S)-L6 (74.2 mg, 0.150 mmol)
and HBF4(aq) (24.0 μL, 0.150 mmol; 42 wt %) in CH2Cl2 (5 mL) at 0
°C. The reaction mixture was stirred for 15 min at 0 °C, and it was
poured into H2O. After extraction with CH2Cl2, the organic layer was
concentrated under vacuum. The resulting solid was suspended in
MeOH/H2O (25 mL; 4/1), and KPF6 (28.2 mg, 0.150 mmol) was
added. The mixture was stirred for 1 h at room temperature, and this
was diluted with H2O. After extraction with CH2Cl2, the organic layer
was dried over MgSO4, filtered, and concentrated under vacuum. The
residue was chromatographed on silica gel with acetone/CH2Cl2 = 1/
10, and the resulting solid was dissolved in CH2Cl2 and triturated with
hexane. The precipitate that formed was collected by filtration and
dried under vacuum to afford compound (S,S)-L7 as a white solid
(65.4 mg, 0.129 mmol; 85% yield). [α]20D +27.6 (c 0.72, acetone). 1H
NMR (acetone-d6): δ 8.77 (s, 1H), 7.53 (d, 3JHH = 7.1 Hz, 1H), 7.44−
7.32 (m, 3H), 5.52 (d, 3JHH = 6.0 Hz, 1H), 4.61−4.55 (m, 1H), 4.55−
ethylphenyl)-oxalamide as a white solid (470 mg, 1.05 mmol; 80%
1
yield). [α]25 +30.4 (c 1.00, CHCl3). H NMR (CDCl3): δ 8.85 (bs,
D
1H), 7.68 (d, 3JHH = 9.1 Hz, 1H), 7.30−7.19 (m, 4H), 5.38 (dd, 3JHH
8.8 and 5.6 Hz, 1H), 4.30 (q, JHH = 6.2 Hz, 1H), 3.54 (tt, JHH = 9.1
=
3
3
2
3
and 4.0 Hz, 1H), 3.30 (dd, JHH = 16.0 Hz and JHH = 7.2 Hz, 1H),
2.93 (dd, 2JHH = 16.0 Hz and 3JHH = 5.9 Hz, 1H), 2.24 (s, 3H), 2.23 (s,
6H), 2.17 (s, 6H), 1.98−1.88 (m, 2H), 1.80−1.70 (m, 2H), 1.57−1.50
(m, 1H), 1.40−1.16 (m, 5H). 13C NMR (CDCl3): δ 160.2, 158.6,
140.5, 139.4, 135.2, 133.4, 130.5, 129.9, 128.8, 127.3, 125.2, 124.6,
83.7, 61.1, 38.0, 32.9, 32.8, 25.9, 24.3, 17.0, 16.9, 15.6. HRMS (ESI-
TOF): calcd for C28H36N2O3Na (M + Na+) 471.2618, found
471.2618.
N-((1S,2S)-2-Cyclohexyloxy-1-indanyl)-N′-(2,3,4,5,6-
pentamethylphenyl)oxalamide was converted to (S,S)-L8 following the
procedure for compound (S,S)-L6. The final purification was
performed by silica gel chromatography with hexane/EtOAc = 1/1,
and the solid thus obtained was washed with Et2O to afford compound
(S,S)-L8 as a pale brown solid (272 mg, 0.472 mmol; 45% yield).
1
[α]25 +212 (c 1.20, CHCl3). H NMR (CDCl3): δ 7.70 (s, 1H),
D
7.40−7.35 (m, 1H), 7.33−7.26 (m, 2H), 7.25−7.20 (m, 1H), 5.23 (d,
3
3JHH = 6.5 Hz, 1H), 4.49 (q, JHH = 6.8 Hz, 1H), 4.31−4.18 (m, 4H),
3.56−3.46 (m, 1H), 3.35 (dd, 2JHH = 15.6 Hz and 3JHH = 7.1 Hz, 1H),
2.86 (dd, 2JHH = 15.8 Hz and 3JHH = 6.7 Hz, 1H), 2.24 (s, 3H), 2.23 (s,
3H), 2.22 (s, 3H), 2.21 (s, 6H), 1.98−1.86 (m, 2H), 1.79−1.67 (m,
2H), 1.59−1.50 (m, 1H), 1.39−1.14 (m, 5H). 13C NMR (CDCl3): δ
157.6, 140.4, 137.9, 134.7, 134.5, 133.8, 131.1, 130.6, 130.5, 129.9,
128.0, 125.8, 124.8, 80.2, 77.5, 69.4, 52.0, 46.2, 37.3, 33.3, 32.5, 25.7,
24.0, 17.0, 16.8, 16.7, 15.3, 15.2. HRMS (ESI-TOF): calcd for
2
3
4.30 (m, 4H), 3.54 (s, 3H), 3.50 (dd, JHH = 15.9 Hz and JHH = 7.1
2
3
Hz, 1H), 2.92 (dd, JHH = 16.0 Hz and JHH = 6.6 Hz, 1H), 2.32 (s,
3H), 2.29 (s, 3H), 2.27 (s, 3H), 2.25 (s, 6H). 13C NMR (acetone-d6):
δ 160.1, 141.6, 138.2, 135.7, 135.04, 135.03, 132.2, 131.9, 131.8, 130.6,
128.5, 126.7, 125.6, 84.8, 69.3, 57.7, 52.8, 47.2, 36.6, 17.0, 16.74, 16.71,
−
15.5, 15.4. HRMS (ESI-TOF): calcd for C24H31N2O (M − PF6 )
−
363.2431, found 363.2426.
C29H39N2O (M − PF6 ) 431.3057, found 431.3061.
1-((1S,2S)-2-Cyclohexyloxyindan-1-yl)-3-pentamethylpheny-
limidazolinium Hexafluorophosphate ((S,S)-L8). 3-Bromocyclo-
hexene (524 μL, 4.53 mmol) was added to a suspension of N-
(2,3,4,5,6-pentamethylphenyl)-N′-((1S,2S)-2-hydroxy-1-indanyl)-
oxalamide (632 mg, 2.27 mmol) and silver oxide (1.04 g, 4.53 mmol)
in 1,2-dichloroethane (30 mL) at room temperature. The mixture was
stirred for 24 h at 80 °C while 3-bromocyclohexene (262 μL, 2.27
mmol) and silver oxide (502 mg, 2.27 mmol) were added after 8 and
16 h. After the mixture was cooled to room temperature, the
precipitate was filtered off through Celite with CH2Cl2 and
concentrated under vacuum. The residue (starting oxalamide/product
oxalamide ∼3.5/1) was chromatographed on silica gel with CHCl3 and
then with CHCl3/EtOAc = 10/1 to afford N-((1S,2S)-2-(2-cyclo-
hexen-1-yloxy)-1-indanyl)-N′-(2,3,4,5,6-pentamethylphenyl)oxalamide
as a yellow solid after washing with Et2O/pentane (218 mg, 0.488
mmol; 21% yield), and N-(2,3,4,5,6-pentamethylphenyl)-N′-((1S,2S)-
2-hydroxy-1-indanyl)oxalamide was recovered as a yellow solid. This
process was repeated two more times with the recovered starting
material to afford N-((1S,2S)-2-(2-cyclohexen-1-yloxy)-1-indanyl)-N′-
(2,3,4,5,6-pentamethylphenyl)oxalamide in 58% overall yield (584 mg,
General Procedure for Tables 1 and 2 and eqs 8−10. A
solution of CuCl (1.5 mg, 15 μmol), (S,S)-L6 (8.2 mg, 17 μmol), and
NaOMe (32.4 mg, 0.600 mmol) in THF (0.40 mL) was stirred for 15
min at room temperature. Organoboronate 2 (0.600 mmol) was
added, and the mixture was stirred for 5 min at room temperature.
Allyl phosphate 1 (0.300 mmol) was then added with additional THF
(0.20 mL), and the resulting mixture was stirred for 40 h at 30 °C.
After dilution with EtOAc, the reaction mixture was passed through a
pad of silica gel with EtOAc, and the solvent was removed under
vacuum. The residue was purified by silica gel preparative TLC with
EtOAc/hexane to afford compounds 3 and 4. Further purification by
GPC with CHCl3 was carried out when necessary.
For ee analysis, compound 3 was converted to the corresponding
alcohol 8 through a hydroboration−oxidation sequence: BH3·SMe2
(0.15 mL, 0.30 mmol; 2.0 M solution in THF) was added to a solution
of compound 3 in THF (1.0 mL) at 0 °C, and the mixture was stirred
for 1 h at room temperature. NaOH(aq) (1 M, 0.45 mL) and 30 wt %
H2O2(aq) (61 μL, 0.600 mmol) were successively added at 0 °C, and
the resulting mixture was stirred for 1 h at room temperature. The
reaction was quenched with saturated NaCl(aq) and extracted with
Et2O. The organic layer was dried over MgSO4, filtered, and
concentrated under vacuum. The residue was purified by silica gel
preparative TLC with EtOAc/hexane to afford compound 8.
1.31 mmol; 1/1 mixture of diastereomers). [α]25 +69.2 (c 1.00,
D
1
CHCl3). H NMR (CDCl3): δ 8.85 (bs, 1H), 7.73−7.64 (m, 1H),
7.30−7.20 (m, 4H), 5.91−5.83 (m, 1H), 5.83−5.77 (m, 1H), 5.41 (t,
3JHH = 5.8 Hz, 0.5H), 5.39 (t, JHH = 5.6 Hz, 0.5H), 4.37−4.31 (m,
3
((S)-3-(4-Methoxyphenyl)-3-phenyl-1-butene ((S)-3aa))
2
1H), 4.25−4.19 (m, 0.5H), 4.17−4.11 (m, 0.5H), 3.34 (dd, JHH
=
=
(Table 1, Entry 1) (CAS 1301717-33-8 for (S)). Colorless oil.
16.0 Hz and 3JHH = 6.8 Hz, 0.5H), 3.33 (dd, 2JHH = 15.6 Hz and 3JHH
97% yield (69.0 mg, 3aa/4aa > 99/1). [α]30 −12.1 (c 0.94, CHCl3).
D
6.8 Hz, 0.5H), 3.02−2.92 (m, 1H), 2.24 (s, 3H), 2.23 (s, 6H), 2.17 (s,
The absolute configuration was determined by comparison of the
2361
dx.doi.org/10.1021/jo500068p | J. Org. Chem. 2014, 79, 2354−2367

The Journal of Organic Chemistry
Featured Article
optical rotation with the literature value.17 1H NMR (CDCl3): δ 7.29
(S)-3-(4-Methoxycarbonylphenyl)-3-phenyl-1-butanol ((S)-
8ad). Colorless oil. 51% yield (36.3 mg). The ee was determined
on a Daicel Chiralpak AS-H column with hexane/2-propanol = 80/20,
flow = 0.8 mL/min. Retention times: 15.4 min (major enantiomer),
3
3
(t, JHH = 7.7 Hz, 2H), 7.24−7.18 (m, 3H), 7.13 (d, JHH = 8.6 Hz,
3
3
2H), 6.83 (d, JHH = 8.6 Hz, 2H), 6.39 (dd, JHH = 17.3 and 10.6 Hz,
1H), 5.18 (d, 3JHH = 10.5 Hz, 1H), 4.91 (d, 3JHH = 17.3 Hz, 1H), 3.80
(s, 3H), 1.78 (s, 3H). 13C NMR (CDCl3): δ 157.9, 148.5, 146.9, 140.4,
129.0, 128.1, 127.9, 126.1, 113.4, 112.9, 55.4, 49.7, 27.5.
21.2 min (minor enantiomer). 87% ee. [α]30 +1.1 (c 1.08, CHCl3).
D
1H NMR (CDCl3): δ 7.94 (d, 3JHH = 8.4 Hz, 2H), 7.31−7.25 (m, 4H),
7.22−7.16 (m, 3H), 3.90 (s, 3H), 3.52 (t, 3JHH = 7.4 Hz, 2H), 2.48 (dt,
(S)-3-(4-Methoxyphenyl)-3-phenyl-1-butanol ((S)-8aa) (CAS
1334512-30-9 for (S)). Colorless oil. 53% yield (39.4 mg). The ee
was determined on a Daicel Chiralcel OD-H column with hexane/2-
propanol = 90/10, flow = 1.0 mL/min. Retention times: 9.0 min
2
2JHH = 13.4 Hz and 3JHH = 7.4 Hz, 1H), 2.45 (dt, JHH = 13.3 Hz and
3JHH = 7.3 Hz, 1H), 1.69 (s, 3H), 1.54 (bs, 1H). 13C NMR (CDCl3): δ
167.1, 154.9, 148.4, 129.6, 128.4, 128.0, 127.3, 127.2, 126.3, 60.0, 52.1,
45.6, 44.1, 28.1. HRMS (ESI-TOF): calcd for C18H20O3Na (M + Na+)
307.1299, found 307.1305.
(major enantiomer), 13.1 min (minor enantiomer). 91% ee. [α]30
D
−3.2 (c 0.92, C6H6). 1H NMR (CDCl3): δ 7.27 (t, 3JHH = 7.6 Hz, 2H),
3
3
7.22−7.15 (m, 3H), 7.12 (d, JHH = 8.9 Hz, 2H), 6.82 (d, JHH = 8.9
Hz, 2H), 3.79 (s, 3H), 3.53 (t, 3JHH = 7.3 Hz, 2H), 2.42 (t, 3JHH = 7.3
Hz, 2H), 1.65 (s, 3H), 1.07 (bs, 1H). 13C NMR (CDCl3): δ 157.7,
149.6, 141.4, 128.3, 128.2, 127.2, 126.0, 113.6, 60.3, 55.3, 44.6, 44.4,
28.4.
((S)-3-(3-Methoxyphenyl)-3-phenyl-1-butene ((S)-3ae))
(Table 1, Entry 5). Colorless oil. 96% yield (68.6 mg, 3ae/4ae >
99/1). [α]25 +1.7 (c 1.29, CHCl3). The absolute configuration was
D
assigned by analogy with Table 1, entry 1. 1H NMR (CDCl3): δ 7.30−
7.25 (m, 2H), 7.24−7.17 (m, 4H), 6.81−6.78 (m, 2H), 6.75 (dd, 3JHH
4
3
= 8.2 Hz and JHH = 2.3 Hz, 1H), 6.39 (dd, JHH = 17.3 and 10.6 Hz,
1H), 5.19 (d, 3JHH = 10.6 Hz, 1H), 4.93 (d, 3JHH = 17.3 Hz, 1H), 3.76
(s, 3H), 1.78 (s, 3H). 13C NMR (CDCl3): δ 159.5, 150.0, 148.1, 146.5,
129.0, 128.1, 127.9, 126.1, 120.6, 114.5, 113.2, 110.8, 55.2, 50.3, 27.2.
HRMS (APCI-TOF): calcd for C17H19O (M + H+) 239.1430, found
239.1428.
((S)-3-(4-Methylphenyl)-3-phenyl-1-butene ((S)-3ab)) (Table
1, Entry 2). Colorless oil. 87% yield (58.2 mg, 3ab/4ab > 99/1).
[α]25D −5.5 (c 1.06, CHCl3). The absolute configuration was assigned
by analogy with Table 1, entry 1. 1H NMR (CDCl3): δ 7.30−7.25 (m,
3
2H), 7.23−7.17 (m, 3H), 7.12−7.06 (m, 4H), 6.39 (dd, JHH = 17.4
3
2
and 10.6 Hz, 1H), 5.17 (dd, JHH = 10.6 Hz and JHH = 1.2 Hz, 1H),
4.91 (dd, 3JHH = 17.3 Hz and 2JHH = 1.2 Hz, 1H), 2.32 (s, 3H), 1.77 (s,
3H). 13C NMR (CDCl3): δ 148.5, 146.8, 145.3, 135.6, 128.9, 128.1,
127.9, 127.8, 126.0, 113.0, 50.0, 27.3, 21.1. HRMS (APCI-TOF): calcd
for C17H19 (M + H+) 223.1481, found 223.1487.
(S)-3-(3-Methoxyphenyl)-3-phenyl-1-butanol ((S)-8ae). Col-
orless oil. 48% yield (34.9 mg). The ee was determined on a Daicel
Chiralpak AS-H column with hexane/2-propanol = 80/20, flow = 0.8
mL/min. Retention times: 19.3 min (minor enantiomer), 22.7 min
1
(major enantiomer). 91% ee. [α]20 −3.9 (c 1.24, CHCl3). H NMR
(S)-3-(4-Methylphenyl)-3-phenyl-1-butanol ((S)-8ab). Color-
less oil. 34% yield (21.2 mg). The ee was determined on a Daicel
Chiralpak AS-H column with hexane/2-propanol = 90/10, flow = 0.8
D
(CDCl3): δ 7.30−7.24 (m, 2H), 7.23−7.16 (m, 4H), 6.80−6.76 (m,
2H), 6.75−6.71 (m, 1H), 3.76 (s, 3H), 3.57−3.49 (m, 2H), 2.43 (t,
3JHH = 7.3 Hz, 2H), 1.66 (s, 3H), 1.02 (bs, 1H). 13C NMR (CDCl3): δ
mL/min. Retention times: 19.6 min (minor enantiomer), 22.6 min
1
(major enantiomer). 87% ee. [α]25 +0.8 (c 1.06, CHCl3). H NMR
159.5, 151.0, 149.1, 129.2, 128.3, 127.1, 126.0, 119.9, 113.9, 110.6,
60.2, 55.2, 45.2, 44.2 28.2. HRMS (ESI-TOF): calcd for C17H20O2Na
(M + Na+) 279.1356, found 279.1354.
D
3
(CDCl3): δ 7.27 (t, JHH = 7.1 Hz, 2H), 7.23−7.19 (m, 2H), 7.17 (t,
3JHH = 7.2 Hz, 1H), 7.13−7.05 (m, 4H), 3.54 (t, JHH = 7.3 Hz, 2H),
3
2.43 (t, 3JHH = 7.3 Hz, 2H), 2.31 (s, 3H), 1.66 (s, 3H), 0.99 (bs, 1H).
13C NMR (CDCl3): δ 149.5, 146.3, 135.5, 129.0, 128.2, 127.2, 127.1,
((S)-3-(3-Methylphenyl)-3-phenyl-1-butene ((S)-3af)) (Table
1, Entry 6) (CAS 1334512−28−5 for (S)). Colorless oil. 92% yield
(61.3 mg, 3af/4af = 99/1). [α]30 +4.2 (c 0.91, C6H6). The absolute
D
126.0, 60.3, 44.9, 44.3, 28.3, 21.0. HRMS (ESI-TOF) calcd for
configuration was assigned by analogy with Table 1, entry 1. 1H NMR
(CDCl3): δ 7.31−7.26 (m, 2H), 7.24−7.16 (m, 4H), 7.06−6.99 (m,
3H), 6.41 (dd, 3JHH = 17.3 and 10.6 Hz, 1H), 5.19 (dd, 3JHH = 10.6 Hz
C17H20ONa (M + Na+) 263.1406, found 263.1406.
((S)-3-(4-Chlorophenyl)-3-phenyl-1-butene ((S)-3ac)) (Table
1, Entry 3) (CAS 1334512-27-4 for (S)). Colorless oil. 84% yield
2
3
2
and JHH = 1.2 Hz, 1H), 4.93 (dd, JHH = 17.5 Hz and JHH = 1.1 Hz,
1H), 2.32 (s, 3H), 1.79 (s, 3H). 13C NMR (CDCl3): δ 148.4, 148.3,
146.8, 137.6, 128.6, 128.1, 128.02, 127.95, 126.9, 126.1, 125.1, 113.0,
50.2, 27.2, 21.8.
(61.4 mg, 3ac/4ac = 96/4). [α]30 −12.1 (c 1.01, CHCl3). The
D
1
absolute configuration was assigned analogy with Table 1, entry 1. H
NMR (CDCl3): δ 7.30 (t, 3JHH = 7.5 Hz, 2H), 7.25 (d, 3JHH = 8.8 Hz,
2H), 7.24−7.18 (m, 3H), 7.15 (d, 3JHH = 8.7 Hz, 2H), 6.37 (dd, 3JHH
=
(S)-3-(3-Methylphenyl)-3-phenyl-1-butanol ((S)-8af) (CAS
1334512-32-1 for (S)). Colorless oil. 52% yield (34.5 mg). The ee
was determined on a Daicel Chiralcel OJ-H column with hexane/2-
propanol = 90/10, flow = 0.8 mL/min. Retention times: 11.9 min
3
2
17.3 and 10.6 Hz, 1H), 5.21 (dd, JHH = 10.6 Hz and JHH = 1.1 Hz,
3
2
1H), 4.92 (dd, JHH = 17.3 Hz and JHH = 1.1 Hz, 1H), 1.78 (s, 3H).
13C NMR (CDCl3): δ 147.7, 146.8, 146.2, 132.0, 129.4, 128.3, 128.2,
(minor enantiomer), 13.7 min (major enantiomer). 92% ee. [α]30
127.8, 126.3, 113.6, 50.0, 27.3.
D
+1.1 (c 0.98, C6H6). 1H NMR (CDCl3): δ 7.28 (t, 3JHH = 7.7 Hz, 2H),
7.24−7.17 (m, 3H), 7.16 (d, 3JHH = 7.5 Hz, 1H), 7.04−6.98 (m, 3H),
3.53 (t, 3JHH = 7.3 Hz, 2H), 2.44 (t, 3JHH = 7.3 Hz, 2H), 2.31 (s, 3H),
1.66 (s, 3H), 1.33 (bs, 1H). 13C NMR (CDCl3): δ 148.4, 148.3, 146.8,
137.6, 128.6, 128.1, 128.02, 127.95, 126.9, 126.1, 125.1, 113.0, 50.2,
27.2, 21.8.
(S)-3-(4-Chlorophenyl)-3-phenyl-1-butanol ((S)-8ac) (CAS
1334512-31-0 for (S)). Colorless oil. 55% yield (36.4 mg). The
ee was determined on a Daicel Chiralcel OD-H column with hexane/
2-propanol = 95/5, flow = 0.8 mL/min. Retention times: 14.9 min
(major enantiomer), 20.4 min (minor enantiomer). 89% ee. [α]30
D
+2.9 (c 0.84, C6H6). 1H NMR (CDCl3): δ 7.28 (t, 3JHH = 7.5 Hz, 2H),
3
3
7.24 (d, JHH = 8.7 Hz, 2H), 7.22−7.16 (m, 3H), 7.13 (d, JHH = 8.6
((S)-3-(3-Chlorophenyl)-3-phenyl-1-butene ((S)-3ag)) (Table
1, Entry 7). Colorless oil. 83% yield (60.2 mg, 3ag/4ag = 97/3).
[α]25D −1.1 (c 1.04, CHCl3). The absolute configuration was assigned
3
2
Hz, 2H), 3.51 (t, JHH = 7.4 Hz, 2H), 2.44 (dt, JHH = 13.3 Hz and
3JHH = 7.2 Hz, 1H), 2.40 (dt, 2JHH = 13.2 Hz and 3JHH = 7.2 Hz, 1H),
1.65 (s, 3H), 1.05 (bs, 1H). 13C NMR (CDCl3): δ 148.7, 148.0, 131.8,
128.7, 128.39, 128.36, 127.2, 126.3, 60.1, 45.0, 44.2, 28.2.
by analogy with Table 1, entry 1. 1H NMR (CDCl3): δ 7.30 (t, 3JHH
7.5 Hz, 2H), 7.24−7.16 (m, 6H), 7.10−7.05 (m, 1H), 6.36 (dd, 3JHH
=
=
=
3
3
((S)-3-(4-Methoxycarbonylphenyl)-3-phenyl-1-butene ((S)-
17.3 and 10.6 Hz, 1H), 5.22 (d, JHH = 10.5 Hz, 1H), 4.93 (d, JHH
17.3 Hz, 1H), 1.78 (s, 3H). 13C NMR (CDCl3): δ 150.5, 147.5, 145.9,
134.1, 129.4, 128.3, 128.1, 127.8, 126.40, 126.36, 126.3, 113.8, 50.3,
27.2. HRMS (APCI-TOF): calcd for C16H15Cl (M + ) 242.0857, found
242.0862.
3ad)) (Table 1, Entry 4) (CAS 527744-57-6 for racemate).
Colorless oil. 88% yield (70.5 mg, 3ad/4ad = 96/4). [α]30 −8.0 (c
D
1.16, CHCl3). The absolute configuration was assigned by analogy
1
3
with Table 1, entry 1. H NMR (CDCl3): δ 7.94 (d, JHH3 = 8.3 Hz,
2H), 7.31−7.26 (m, 4H), 7.24−7.16 (m, 3H), 6.39 (dd, JHH = 17.3
(S)-3-(3-Chlorophenyl)-3-phenyl-1-butanol ((S)-8ag). Color-
less oil. 42% yield (27.3 mg). The ee was determined on a Daicel
Chiralcel OD-H column with hexane/2-propanol = 90/10, flow = 0.7
3
3
and 10.6 Hz, 1H), 5.22 (d, JHH = 10.6 Hz, 1H), 4.92 (d, JHH = 17.3
Hz, 1H), 3.90 (s, 3H), 1.80 (s, 3H). 13C NMR (CDCl3): δ 167.1,
153.7, 147.5, 145.9, 129.5, 128.3, 128.1, 128.0, 127.8, 126.4, 113.8,
52.1, 50.5, 27.1.
mL/min. Retention times: 26.9 min (major enantiomer), 29.1 min
1
(minor enantiomer). 89% ee. [α]20 +0.8 (c 1.01, CHCl3). H NMR
D
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Featured Article
3
(CDCl3): δ 7.29 (t, JHH = 7.6 Hz, 2H), 7.23−7.14 (m, 6H), 7.06 (d,
(S)-3-(1-Methyl-5-indolyl)-3-phenyl-1-butanol ((S)-8aj). Col-
orless oil. 78% yield (54.5 mg). The ee was determined on a Daicel
Chiralcel OD-H column with hexane/2-propanol = 80/20, flow = 0.8
mL/min. Retention times: 17.9 min (major enantiomer), 41.8 min
(minor enantiomer). 88% ee. [α]20D −16.3 (c 1.05, CHCl3). 1H NMR
(CDCl3): δ 7.58 (d, 4JHH = 1.6 Hz, 1H), 7.28−7.22 (m, 4H), 7.20 (d,
3JHH = 7.6 Hz, 1H), 3.55−3.47 (m, 2H), 2.44 (dt, 2JHH = 13.2 Hz and
3JHH = 7.2 Hz, 1H), 2.40 (dt, 2JHH = 13.3 Hz and 3JHH = 7.3 Hz, 1H),
1.66 (s, 3H), 1.08 (bs, 1H). 13C NMR (CDCl3): δ 151.7, 148.4, 134.2,
129.5, 128.4, 127.4, 127.1, 126.31, 126.25, 125.6, 60.0, 45.3, 44.0, 28.1.
HRMS (ESI-TOF): calcd for C16H17ClONa (M + Na+) 283.0860,
found 283.0858.
3
3JHH = 8.7 Hz, 1H), 7.19−7.14 (m, 1H), 7.03 (d, JHH = 3.0 Hz, 1H),
3
4
3
((S)-3-(2-Methoxyphenyl)-3-phenyl-1-butene ((S)-3ah))
(Table 1, Entry 8). Colorless oil. 94% yield (67.4 mg, 3ah/4ah =
87/13). [α]20D −12.5 (c 1.37, CHCl3). The absolute configuration was
6.97 (dd, JHH = 8.6 Hz and JHH = 1.9 Hz, 1H), 6.44 (dd, JHH = 3.0
4
Hz and JHH = 0.7 Hz, 1H), 3.76 (s, 3H), 3.62−3.52 (m, 2H), 2.58−
2.46 (m, 2H), 1.73 (s, 3H), 0.95 (bs, 1H). 13C NMR (CDCl3): δ
150.6, 140.0, 135.1, 129.1, 128.2, 128.1, 127.3, 125.7, 122.2, 118.7,
109.1, 101.2, 60.5, 45.1, 44.7, 32.9, 28.8. HRMS (ESI-TOF): calcd for
C19H21NONa (M + Na+) 302.1515, found 302.1513.
1
assigned by analogy with Table 1, entry 1. H NMR (CDCl3): δ 7.41
(dd, 3JHH = 7.8 Hz and 4JHH = 1.7 Hz, 1H), 7.28−7.18 (m, 3H), 7.15−
3
4
7.10 (m, 3H), 6.98 (td, JHH = 7.5 Hz and JHH = 1.1 Hz, 1H), 6.84
(dd, 3JHH = 8.0 Hz and 4JHH = 1.0 Hz, 1H), 6.62 (dd, 3JHH = 17.4 and
((S)-3-Phenyl-3-(3-thienyl)-1-butene ((S)-3ak)) (Table 1, Entry
3
2
10.6 Hz, 1H), 5.14 (dd, JHH = 10.7 Hz and JHH = 1.0 Hz, 1H), 4.99
11) (CAS 1259553-77-9 for (S)). Colorless oil. 85% yield (52.9 mg,
3
2
3ak/4ak = 97/3). [α]25 −15.9 (c 0.89, C6H6). The absolute
(dd, JHH = 17.5 Hz and JHH = 1.0 Hz, 1H), 3.37 (s, 3H), 1.79 (s,
3H). 13C NMR (CDCl3): δ 157.8, 149.4, 145.7, 136.5, 128.0, 127.9,
127.8, 126.2, 125.3, 120.6, 113.0, 112.4, 55.3, 49.0, 26.0. HRMS
(APCI-TOF): calcd for C17H19O (M + H+) 239.1430, found
239.1426.
D
configuration was assigned by analogy with Table 1, entry 1. 1H NMR
3
4
(CDCl3): δ 7.31−7.26 (m, 2H), 7.25 (dd, JHH = 5.1 Hz and JHH
=
4
2.9 Hz, 1H), 7.23−7.18 (m, 3H), 6.96 (dd, JHH = 3.0 and 1.3 Hz,
1H), 6.84 (dd, 3JHH = 5.0 Hz and 4JHH = 1.3 Hz, 1H), 6.36 (dd, 3JHH
=
3
2
(S)-3-(2-Methoxyphenyl)-3-phenyl-1-butanol ((S)-8ah). Col-
orless oil. 52% yield (38.0 mg). The ee was determined on a Daicel
Chiralpak AD-H column with hexane/2-propanol = 90/10, flow = 0.8
mL/min. Retention times: 9.9 min (minor enantiomer), 12.0 min
(major enantiomer). 75% ee. [α]25D −22.2 (c 0.96, CHCl3). 1H NMR
17.3 and 10.5 Hz, 1H), 5.17 (dd, JHH = 10.5 Hz and JHH = 1.1 Hz,
3
2
1H), 4.92 (dd, JHH = 17.3 Hz and JHH = 1.1 Hz, 1H), 1.79 (s, 3H).
13C NMR (CDCl3): δ 149.1, 147.6, 146.1, 128.19, 128.18, 127.5,
126.3, 125.3, 120.9, 113.1, 48.3, 27.6. HRMS (APCI-TOF): calcd for
C14H15S (M + H+) 215.0889, found 215.0884.
3
4
(CDCl3): δ 7.43 (dd, JHH = 7.7 Hz and JHH = 1.4 Hz, 1H), 7.28−
(S)-3-Phenyl-3-(3-thienyl)-1-butanol ((S)-8ak). Colorless oil.
44% yield (26.0 mg). The ee was determined on two Daicel Chiralcel
OD-H columns with hexane/2-propanol = 90/10, flow = 0.8 mL/min.
Retention times: 25.6 min (major enantiomer), 29.6 min (minor
enantiomer). 88% ee. [α]25D +5.5 (c 0.98, CHCl3). 1H NMR (CDCl3):
δ 7.28 (t, 3JHH = 7.7 Hz, 2H), 7.24−7.21 (m, 3H), 7.21−7.16 (m, 1H),
7.05−7.03 (m, 1H), 6.79−6.76 (m, 1H), 3.62−3.52 (m, 2H), 2.44 (dt,
7.18 (m, 3H), 7.16−7.09 (m, 3H), 6.99 (td, 3JHH = 7.5 Hz and 4JHH
=
3
0.6 Hz, 1H), 6.80 (d, JHH = 7.7 Hz, 1H), 3.57−3.48 (m, 1H), 3.48−
3.40 (m, 1H), 3.31 (s, 3H), 2.79 (ddd, 2JHH = 13.0 Hz and 3JHH = 8.6
and 6.1 Hz, 1H), 2.31 (ddd, 2JHH = 13.1 Hz and 3JHH = 8.4 and 5.7 Hz,
1H), 1.66 (s, 3H), 1.01 (bs, 1H). 13C NMR (CDCl3): δ 158.3, 151.1,
136.8, 128.3, 128.1, 127.7, 125.9, 125.4, 120.8, 113.3, 60.9, 55.6, 44.3,
42.3, 28.5. HRMS (ESI-TOF): calcd for C17H20O2Na (M + Na+)
279.1356, found 279.1355.
2
2JHH = 13.7 Hz and 3JHH = 7.1 Hz, 1H), 2.39 (dt, JHH = 13.4 Hz and
3JHH = 6.8 Hz, 1H), 1.68 (s, 3H), 1.50 (bs, 1H). 13C NMR (CDCl3): δ
((S)-3-(2-Naphthyl)-3-phenyl-1-butene ((S)-3ai)) (Table 1,
Entry 9) (CAS 1334512-29-6 for (S)). Colorless oil. 93% yield
(72.3 mg, 3ai/4ai > 99/1). [α]30D +5.1 (c 1.06, CHCl3). The absolute
150.6, 148.4, 128.3, 127.8, 126.7, 126.2, 125.6, 119.9, 60.2, 44.6, 43.4,
28.1. HRMS (ESI-TOF): calcd for C14H16OSNa (M + Na+) 255.0814,
found 255.0811.
1
configuration was assigned analogy with Table 1, entry 1. H NMR
(CDCl3): δ 7.82−7.77 (m, 2H), 7.75 (d, 4JHH = 0.9 Hz, 1H), 7.72 (d,
3JHH = 8.6 Hz, 1H), 7.49−7.42 (m, 2H), 7.31−7.19 (m, 6H), 6.51 (dd,
3JHH = 17.3 and 10.6 Hz, 1H), 5.24 (dd, 3JHH = 10.6 Hz and 2JHH =1.0
((R)-3-(4-Chlorophenyl)-3-(4-methoxyphenyl)-1-butene ((R)-
3ba)) (Table 2, Entry 2). Colorless oil. 90% yield (75.3 mg, 3ba/4ba
> 99/1). [α]25 −1.1 (c 1.35, C6H6). The absolute configuration was
D
1
assigned by analogy with Table 1, entry 1. H NMR (CDCl3): δ 7.23
3
2
Hz, 1H), 4.98 (dd, JHH = 17.3 Hz and JHH = 1.0 Hz, 1H), 1.89 (s,
3H). 13C NMR (CDCl3): δ 148.1, 146.4, 145.7, 133.4, 132.1, 128.23,
128.16, 128.0, 127.7, 127.6, 127.2, 126.2, 126.1, 125.8, 125.6, 113.5,
50.5, 27.2.
(d, 3JHH = 8.7 Hz, 2H), 7.13 (d, 3JHH = 8.7 Hz, 2H), 7.10 (d, 3JHH = 8.9
3
3
Hz, 2H), 6.82 (d, JHH = 8.8 Hz, 2H), 6.33 (dd, JHH = 17.3 and 10.6
3
2
Hz, 1H), 5.17 (dd, JHH = 10.6 Hz and JHH = 1.0 Hz, 1H), 4.88 (dd,
3JHH = 17.3 Hz and 2JHH = 0.9 Hz, 1H), 3.79 (s, 3H), 1.74 (s, 3H). 13
C
(S)-3-(2-Naphthyl)-3-phenyl-1-butanol ((S)-8ai) (CAS
1334512-31-0 for (S)). Colorless oil. 56% yield (43.3 mg). The ee
was determined on a Daicel Chiralcel OD-H column with hexane/2-
propanol = 90/10, flow = 1.0 mL/min. Retention times: 12.8 min
NMR (CDCl3): δ 158.0, 147.1, 146.4, 139.7, 131.9, 129.4, 128.9,
128.2, 113.6, 113.4, 55.4, 49.4, 27.5. HRMS (APCI-TOF): calcd for
C17H18ClO (M + H+) 273.1041, found 273.1044.
(R)-3-(4-Chlorophenyl)-3-(4-methoxyphenyl)-1-butanol ((R)-
8ba). Colorless oil. 56% yield (36.4 mg). The ee was determined on a
Daicel Chiralcel OD-H column with hexane/2-propanol = 90/10, flow
(major enantiomer), 19.4 min (minor enantiomer). 91% ee. [α]30
D
1
3
−1.7 (c 0.90, CHCl3). H NMR (CDCl3): δ 7.85 (d, JHH = 7.9 Hz,
1H), 7.83 (d, 4JHH = 1.7 Hz, 1H), 7.80 (d, 3JHH = 7.5 Hz, 1H), 7.72 (d,
3JHH = 8.7 Hz, 1H), 7.53−7.45 (m, 2H), 7.32−7.24 (m, 4H), 7.24−
7.17 (m, 2H), 3.62−3.51 (m, 2H), 2.63−2.52 (m, 2H), 1.79 (s, 3H)
1.40 (s, 1H). 13C NMR (CDCl3): δ 149.1, 146.5, 133.3, 132.0, 128.3,
128.1, 128.0, 127.6, 127.3, 126.9, 126.2, 126.1, 125.8, 124.6, 60.3, 45.4,
44.0, 28.1.
= 1.0 mL/min. Retention times: 11.9 min (major enantiomer), 15.8
1
min (minor enantiomer). 84% ee. [α]30 −2.0 (c 1.05, CHCl3). H
D
NMR (CDCl3): δ 7.23 (d, 3JHH = 8.8 Hz, 2H), 7.13 (d, 3JHH = 8.6 Hz,
2H), 7.09 (d, 3JHH = 8.9 Hz, 2H), 6.82 (d, 3JHH = 8.9 Hz, 2H), 3.79 (s,
3
3H), 3.51 (t, JHH = 7.3 Hz, 2H), 2.44−2.33 (m, 2H), 1.62 (s, 3H),
1.06 (bs, 1H). 13C NMR (CDCl3): δ 157.9, 148.3, 140.7, 131.7, 128.6,
128.3, 128.2, 113.7, 60.1, 55.3, 44.33, 44.31, 28.4. HRMS (ESI-TOF):
calcd for C17H19ClO2Na (M + Na+) 313.0966, found 313.0973.
((S)-3-(4-Methoxyphenyl)-3-(4-trifluoromethylphenyl)-1-bu-
tene ((S)-3ca)) (Table 2, Entry 3). Colorless oil. 94% yield (86.0 mg,
((S)-3-(1-Methyl-5-indolyl)-3-phenyl-1-butene ((S)-3aj))
(Table 1, Entry 10). The reaction was conducted in 1.5 mL of
THF (instead of 0.60 mL). Colorless oil. 89% yield (69.8 mg, 3aj/4aj
= 99/1). [α]20D −5.2 (c 1.05, CHCl3). The absolute configuration was
1
assigned by analogy with Table 1, entry 1. H NMR (CDCl3): δ 7.54
3ca/4ca > 99/1). [α]20 −3.7 (c 1.00, CHCl3). The absolute
4
3
D
(d, JHH = 1.7 Hz, 1H), 7.30−7.24 (m, 4H), 7.22 (d, JHH3 = 8.5 Hz,
configuration was assigned by analogy with Table 1, entry 1. 1H NMR
1H), 7.21−7.17 (m, 1H), 7.05−7.01 (m, 2H), 6.51 (dd, JHH = 17.4
(CDCl3): δ 7.52 (d, 3JHH = 8.3 Hz, 2H), 7.32 (d, 3JHH = 8.3 Hz, 2H),
3
3
and 10.6 Hz, 1H), 6.44 (d, JHH = 3.1 Hz, 1H), 5.18 (dd, JHH = 10.5
3
3
2
3
2
7.10 (d, JHH = 8.9 Hz, 2H), 6.84 (d, JHH = 8.8 Hz, 2H), 6.35 (dd,
Hz and JHH = 1.2 Hz, 1H), 4.94 (dd, JHH = 17.3 Hz and JHH = 1.1
Hz, 1H), 3.77 (s, 3H), 1.86 (s, 3H). 13C NMR (CDCl3): δ 149.3,
147.5, 139.3, 135.3, 129.0, 128.2, 128.04, 128.01, 125.8, 122.6, 119.6,
112.6, 108.9, 101.2, 50.2, 32.9, 27.7. HRMS (ESI-TOF): calcd for
C19H19NNa (M + Na+) 284.1410, found 284.1407.
3JHH = 17.3 and 10.6 Hz, 1H), 5.21 (d, JHH = 10.5 Hz, 1H), 4.91 (d,
3
3JHH = 17.5 Hz, 1H), 3.80 (s 3H), 1.78 (s, 3H). 13C NMR (CDCl3): δ
2
158.2, 152.7, 146.1, 139.4, 128.9, 128.4 (q, JCF = 32.6 Hz), 128.3,
125.1 (q, JCF = 4.1 Hz), 124.5 (q, JCF = 272 Hz), 113.71, 113.70,
3
1
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Featured Article
3
55.3, 49.8, 27.4. HRMS (APCI-TOF): calcd for C18H17OF3 (M +
306.1226, found 306.1228.
)
1H), 4.91 (d, JHH = 17.3 Hz, 1H), 3.80 (s, 3H), 1.77 (s, 3H). 13C
NMR (CDCl3): δ 158.0, 149.3, 146.3, 139.7, 128.5, 128.2, 125.3,
120.7, 113.5, 112.9, 55.3, 47.6, 27.7. HRMS (APCI-TOF): calcd for
C15H17OS (M + H+) 245.0995, found 245.0992.
(S)-3-(4-Methoxyphenyl)-3-(4-trifluoromethylphenyl)-1-bu-
tanol ((S)-8ca). Colorless oil. 57% yield (52.3 mg). The ee was
determined on a Daicel Chiralcel OD-H column with hexane/2-
propanol = 90/10, flow = 1.0 mL/min. Retention times: 10.4 min
(R)-3-(4-Methoxyphenyl)-3-(3-thienyl)-1-butanol ((R)-8fa).
Colorless oil. 52% yield (29.6 mg). The ee was determined on a
Daicel Chiralcel OD-H column with hexane/2-propanol = 90/10, flow
(major enantiomer), 14.6 min (minor enantiomer). 86% ee. [α]25
D
1
3
−5.0 (c 0.87, CHCl3). H NMR (CDCl3): δ 7.52 (d, JHH = 8.2 Hz,
= 1.0 mL/min. Retention times: 11.4 min (major enantiomer), 15.5
2H), 7.31 (d, 3JHH = 8.4 Hz, 2H), 7.10 (d, 3JHH = 8.7 Hz, 2H), 6.83 (d,
1
min (minor enantiomer). 89% ee. [α]25 −6.2 (c 1.07, CHCl3). H
D
3JHH = 8.8 Hz, 2H), 3.79 (s, 3H), 3.52 (t, JHH = 7.3 Hz, 2H), 2.48−
3
4
3
NMR (CDCl3): δ 7.22 (dd, JHH = 5.0 Hz and JHH = 2.9 Hz, 1H),
2.38 (m, 2H), 1.66 (s, 3H), 1.07 (bs, 1H). 13C NMR (CDCl3): δ
3
3
7.14 (d, JHH = 8.6 Hz, 2H), 7.03−7.00 (m, 1H), 6.82 (d, JHH = 8.5
Hz, 2H), 6.78 (dd, 3JHH = 5.0 Hz and 4JHH = 1.2 Hz, 1H), 3.78 (s, 3H),
3.60−3.53 (m, 2H), 2.44−2.32 (m, 2H), 1.65 (s, 3H), 1.05 (bs, 1H).
13C NMR (CDCl3): δ 157.9, 151.0, 140.5, 127.7, 125.6, 119.7, 113.6,
5
2
158.0, 154.0 (q, JCF = 1.4 Hz), 140.2, 128.24 (q, JCF = 32.6 Hz),
3
1
128.23, 127.5, 125.2 (q, JCF = 3.8 Hz), 124.4 (q, JCF = 272 Hz),
113.8, 60.0, 55.3, 44.8, 44.2, 28.2. HRMS (ESI-TOF): calcd for
C18H19O2F3Na (M + Na+) 347.1229, found 347.1228.
60.2, 55.3, 44.7, 42.8, 28.2. HRMS (ESI-TOF): calcd for C15H18O2SNa
((R)-3-(4-Methoxyphenyl)-3-(3-methylphenyl)-1-butene ((R)-
(M + Na+) 285.0920, found 285.0917.
3da)) (Table 2, Entry 4). Colorless oil. 81% yield (65.8 mg, 3da/4da
> 99/1). [α]20 −13.5 (c 1.25, CHCl3). The absolute configuration
((R)-3-(4-Methoxyphenyl)-3-methyl-5-phenyl-1-pentene
((R)-3ga)) (Table 2, Entry 7). Colorless oil. 98% yield (78.2 mg, 3ga/
4ga > 99/1). [α]20D −7.7 (c 0.91, CHCl3). The absolute configuration
D
1
was assigned by analogy with Table 1, entry 1. H NMR (CDCl3): δ
3
3
7.17 (t, JHH = 7.6 Hz, 1H), 7.12 (d, JHH = 8.9 Hz, 2H), 7.05−7.03
1
3
was assigned by analogy with Table 1, entry 1. H NMR (CDCl3): δ
(m, 1H), 7.03−6.98 (m, 2H), 6.82 (d, JHH = 8.9 Hz, 2H), 6.38 (dd,
7.28 (d, 3JHH = 8.9 Hz, 2H), 7.26 (t, 3JHH = 7.6 Hz, 2H), 7.16 (t, 3JHH
3JHH = 17.3 and 10.6 Hz, 1H), 5.16 (dd, 3JHH = 10.6 Hz and 2JHH = 1.1
3
3
3
2
= 7.2 Hz, 1H), 7.14 (d, JHH = 7.8 Hz, 2H), 6.88 (d, JHH = 8.9 Hz,
Hz, 1H), 4.90 (dd, JHH = 17.3 Hz and JHH = 1.1 Hz, 1H), 3.80 (s
3H), 2.31 (s, 3H), 1.76 (s, 3H). 13C NMR (CDCl3): δ 157.8, 148.5,
147.0, 140.5, 137.6, 129.0, 128.6, 128.0, 126.8, 125.0, 113.4, 112.8,
55.3, 49.5, 27.4, 21.7. HRMS (APCI-TOF): calcd for C18H21O (M +
H+) 253.1587, found 253.1587.
2H), 6.08 (dd, 3JHH = 17.4 and 10.7 Hz, 1H), 5.13 (d, 3JHH = 10.7 Hz,
3
2
1H), 5.08 (d, JHH = 17.5 Hz, 1H), 3.81 (s, 3H), 2.50 (ddd, JHH
=
3
2
13.3 Hz and JHH = 12.5 and 5.0 Hz, 1H), 2.42 (ddd, JHH = 13.3 Hz
and 3JHH = 12.7 and 5.0 Hz, 1H), 2.09 (ddd, 2JHH = 13.1 Hz and 3JHH
= 12.7 and 4.9 Hz, 1H), 2.00 (ddd, 2JHH = 13.3 Hz and 3JHH = 12.6 Hz,
1H), 1.44 (s, 3H). 13C NMR (CDCl3): δ 157.8, 147.1, 143.2, 139.3,
128.5, 128.4, 127.8, 125.8, 113.7 111.9, 55.3, 44.0, 43.5, 31.3, 25.3.
HRMS (APCI-TOF): calcd for C19H23O (M + H+) 267.1743, found
267.1744.
(R)-3-(4-Methoxyphenyl)-3-(3-methylphenyl)-1-butanol ((R)-
8da). Colorless oil. 53% yield (35.0 mg). The ee was determined on a
Daicel Chiralcel OD-H column with hexane/2-propanol = 90/10, flow
= 1.0 mL/min. Retention times: 8.5 min (major enantiomer), 12.3 min
1
(minor enantiomer). 83% ee. [α]25 +3.9 (c 1.16, C6H6). H NMR
D
3
3
(CDCl3): δ 7.16 (t, JHH = 7.6 Hz, 1H), 7.12 (d, JHH = 9.0 Hz, 2H),
7.03−6.97 (m, 3H), 6.81 (d, JHH = 8.9 Hz, 2H), 3.79 (s, 3H), 3.57−
(R)-3-(4-Methoxyphenyl)-3-methyl-5-phenyl-1-pentanol
((R)-8ga). Colorless oil. 62% yield (52.0 mg). The ee was determined
on a Daicel Chiralcel OD-H column with hexane/2-propanol = 90/10,
flow = 1.0 mL/min. Retention times: 13.3 min (major enantiomer),
19.6 min (minor enantiomer). 64% ee. [α]25D −21.2 (c 1.16, CHCl3).
3
3.49 (m, 2H), 2.45−2.36 (m, 2H), 2.30 (s, 3H), 1.63 (s, 3H), 1.01 (bs,
1H). 13C NMR (CDCl3): δ 157.7, 149.5, 141.5, 137.7, 128.2, 128.1,
127.9, 126.7, 124.3, 113.5, 60.3, 55.3, 44.4, 28.4, 21.8. HRMS (ESI-
TOF): calcd for C18H22O2Na (M + Na+) 293.1512, found 293.1513.
((R)-3-(4-Methoxyphenyl)-3-(2-naphthyl)-1-butene ((R)-3ea))
(Table 2, Entry 5). Colorless oil. 95% yield (82.3 mg, 3ea/4ea > 99/
1H NMR (CDCl3): δ 7.28 (d, 3JHH = 8.8 Hz, 2H), 7.24 (t, JHH = 7.7
3
3
Hz, 2H), 7.15 (t, JHH = 7.3 Hz, 1H), 7.11−7.06 (m, 2H), 6.89 (d,
3JHH = 8.9 Hz, 2H), 3.81 (s, 3H), 3.64−3.53 (m, 1H), 3.53−3.44 (m,
1). [α]25 −12.0 (c 1.25, CHCl3). The absolute configuration was
1H), 2.46 (td, JHH = 13.0 Hz and 3JHH = 5.0 Hz, 1H), 2.25 (td, JHH
=
D
assigned by analogy with Table 1, entry 1. 1H NMR (CDCl3): δ 7.81−
7.77 (m, 2H), 7.74−7.70 (m, 2H), 7.48−7.41 (m, 2H), 7.26 (dd, 3JHH
= 8.5 Hz and 4JHH = 1.7 Hz, 1H), 7.15 (d, 3JHH = 8.7 Hz, 2H), 6.83 (d,
3
13.0 Hz and JHH = 4.4 Hz, 1H), 2.12−1.97 (m, 2H), 1.92−1.81 (m,
2H), 1.41 (s, 3H), 0.96 (bs, 1H). 13C NMR (CDCl3): δ 157.7, 143.0,
138.8, 128.42, 128.36, 127.3, 125.7, 113.8, 59.8, 55.3, 46.2, 46.1, 39.5,
30.7, 24.2. HRMS (ESI-TOF): calcd for C19H24O2Na (M + Na+)
307.1669, found 307.1663.
3
3JHH = 8.7 Hz, 2H), 6.48 (dd, JHH = 17.4 and 10.6 Hz, 1H), 5.22 (d,
3JHH = 10.6 Hz, 1H), 4.95 (d, 3JHH = 17.3 Hz, 1H), 3.80 (s, 3H), 1.86
(s, 3H). 13C NMR (CDCl3): δ 157.9, 146.7, 145.9, 140.1, 133.3, 132.0,
129.0, 128.1, 127.7, 127.5, 127.2, 126.0, 125.7, 125.6, 113.5, 113.3,
55.3, 49.8, 27.4. HRMS (APCI-TOF): calcd for C21H21O (M + H+)
289.1587, found 289.1592.
((S)-3-Cyclohexyl-3-(4-methoxyphenyl)-1-butene ((S)-3ha))
(Table 2, Entry 8). Colorless oil. 91% yield (66.4 mg, 3ha/4ha >
99/1). The ee was determined on two Daicel Chiralcel OJ-H columns
with hexane/2-propanol = 97/3, flow = 0.7 mL/min. Retention times:
15.0 min (major enantiomer), 22.9 min (minor enantiomer). 76% ee.
(R)-3-(4-Methoxyphenyl)-3-(2-naphthyl)-1-butanol ((R)-8ea).
Colorless oil. 63% yield (55.4 mg). The ee was determined on a Daicel
Chiralpak AS-H column with hexane/2-propanol =80/20, flow =0.9
[α]20 −41.8 (c 1.12, CHCl3). The absolute configuration was
D
1
assigned by analogy with Table 1, entry 1. H NMR (CDCl3): δ 7.22
mL/min. Retention times: 22.1 min (minor enantiomer), 27.7 min
3
1
(d, 3JHH = 8.8 Hz, 2H), 6.84 (d, JHH = 8.8 Hz, 2H), 6.15 (dd, 3JHH
=
=
(major enantiomer). 85% ee. [α]20 +0.8 (c 1.01, CHCl3). H NMR
D
3
3
(CDCl3): δ 7.82 (d, 3JHH = 7.9 Hz, 1H), 7.81−7.75 (m, 2H), 7.70 (d,
17.5 and 10.9 Hz, 1H), 5.12 (d, JHH = 10.8 Hz, 1H), 5.00 (d, JHH
3JHH = 8.7 Hz, 1H), 7.51−7.42 (m, 2H), 7.18 (d, JHH = 8.6 Hz, 1H),
3
17.5 Hz, 1H), 3.79 (s, 3H), 1.76−1.59 (m, 5H), 1.51−1.43 (m, 1H),
1.31 (s, 3H), 1.25−1.01 (m, 3H), 1.00−0.84 (m, 2H). 13C NMR
(CDCl3): δ 157.5, 145.8, 140.3, 127.8, 113.4, 112.6, 55.3, 47.5, 46.8,
28.3, 28.0, 27.4, 27.3, 26.9, 21.1. HRMS (APCI-TOF): calcd for
C17H25O (M + H+) 245.1900, found 245.1897.
7.15 (d, 3JHH = 8.7 Hz, 2H), 6.82 (d, 3JHH = 8.7 Hz, 2H), 3.79 (s, 3H),
3.62−3.51 (m, 2H), 2.59−2.48 (m, 2H), 1.75 (s, 3H), 1.10 (bs, 1H).
13C NMR (CDCl3): δ 157.8, 146.8, 141.2, 133.3, 131.9, 128.3, 128.1,
127.9, 127.5, 126.8, 126.1, 125.8, 124.5, 113.6, 60.3, 55.3, 44.7, 44.1,
28.2. HRMS (ESI-TOF): calcd for C21H22O2Na (M + Na+) 329.1512,
found 329.1512.
Equation 8 ((S)-3aa: R = Ph) (CAS 1301717-33-8 for (S)).
Colorless oil. 75% yield (53.8 mg, 3aa/4aa = 98/2). [α]30 −6.2 (c
D
1.18, CHCl3). The absolute configuration was determined by
comparison of the optical rotation with the literature value.17
(S)-8aa (CAS 1334512-30-9 for (S)). Colorless oil. 65% yield
(37.4 mg). The ee was determined on a Daicel Chiralcel OD-H
column with hexane/2-propanol = 90/10, flow = 1.0 mL/min.
Retention times: 8.7 min (major enantiomer), 12.7 min (minor
((R)-3-(4-Methoxyphenyl)-3-(3-thienyl)-1-butene ((R)-3fa))
(Table 2, Entry 6). Colorless oil. 72% yield (52.9 mg, 3fa/4fa =
99/1). [α]25 +10.5 (c 1.04, CHCl3). The absolute configuration was
D
1
assigned by analogy with Table 1, entry 1. H NMR (CDCl3): δ 7.25
3
4
3
(dd, JHH = 5.0 Hz and JHH = 2.9 Hz, 1H), 7.14 (d, JHH = 8.8 Hz,
2H), 6.97−6.94 (m, 1H), 6.86−6.83 (m, 1H), 6.83 (d, 3JHH = 8.9 Hz,
2H), 6.35 (dd, 3JHH = 17.3 and 10.5 Hz, 1H), 5.15 (d, 3JHH = 10.5 Hz,
enantiomer). 56% ee. [α]25 −1.6 (c 0.95, C6H6).
D
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Featured Article
3
Equation 8 ((R)-3ga: R = CH2CH2Ph). Colorless oil. 94% yield
(d, 3JHH = 7.5 Hz, 1H), 6.80 (d, JHH = 8.9 Hz, 2H), 6.26 (dd, 3JHH
=
3
2
(75.3 mg, 3ga/4ga > 99/1). [α]25 −6.8 (c 1.40, CHCl3). The
17.4 and 10.6 Hz, 1H), 5.28 (dd, JHH = 10.5 Hz and JHH = 1.3 Hz,
D
3
2
absolute configuration was assigned by analogy with Table 1, entry 1.
(R)-8ga. Colorless oil. 29% yield (23.2 mg). The ee was determined
on a Daicel Chiralcel OD-H column with hexane/2-propanol = 90/10,
flow = 1.0 mL/min. Retention times: 13.0 min (major enantiomer),
19.3 min (minor enantiomer). 40% ee. [α]25D −26.9 (c 1.02, CHCl3).
Equation 9 ((S)-(Z)-3aa-d). Colorless oil. 90% yield (64.9 mg,
1H), 4.76 (dd, JHH = 17.3 Hz and JHH = 1.3 Hz, 1H), 3.78 (s, 3H),
2.90−2.78 (m, 2H), 2.17 (ddd, 2JHH = 13.4 Hz and 3JHH = 9.5 and 2.9
2
3
Hz, 1H), 2.06 (ddd, JHH = 13.3 Hz and JHH = 7.9 and 2.9 Hz, 1H),
1.86−1.76 (m, 1H), 1.73−1.63 (m, 1H). 13C NMR (CDCl3): δ 157.8,
146.7, 141.1, 140.8, 137.6, 130.9, 129.6, 129.2, 126.1, 125.4, 115.5,
113.3, 55.3, 50.5, 37.9, 30.0, 19.4. HRMS (APCI-TOF): calcd for
C19H21O (M + H+) 265.1587, found 265.1581.
3aa/4aa > 99/1, Z/E = 93/7). [α]30 −11.6 (c 1.08, CHCl3). The
D
absolute configuration was assigned by analogy with Table 1, entry 1.
1H NMR (CDCl3): δ 7.30−7.25 (m, 2H), 7.23−7.16 (m, 3H), 7.12 (d,
(R)-2-(1-(4-Methoxyphenyl)-1,2,3,4-tetrahydronaphthalen-
1-yl)ethanol ((R)-8ia). Colorless oil. 31% yield (22.3 mg). The ee
was determined on a Daicel Chiralpak AD-H column with hexane/2-
propanol = 90/10, flow = 1.0 mL/min. Retention times: 11.9 min
3
3
3JHH = 8.9 Hz, 2H), 6.82 (d, JHH = 8.8 Hz, 2H), 6.37 (d, JHH = 10.5
3
3
Hz, 1H), 5.15 (d, JHH = 10.6 Hz, 0.93H), 4.88 (d, JHH = 17.3 Hz,
(major enantiomer), 17.5 min (minor enantiomer). 91% ee. [α]20
0.07H), 3.79 (s, 3H), 1.77 (s, 3H). 13C NMR (CDCl3): δ 157.9, 148.5,
D
+13.9 (c 1.11, CHCl3). 1H NMR (CDCl3): δ 7.17−7.08 (m, 4H), 6.96
1
146.8, 140.3, 129.0, 128.1, 127.9, 126.0, 113.5, 112.7 (t, JCD = 23.8
3
3
(d, JHH = 8.8 Hz, 2H), 6.77 (d, JHH = 8.8 Hz, 2H), 3.76 (s, 3H),
3.71−3.62 (m, 1H), 3.61−3.52 (m, 1H), 2.84−2.71 (m, 2H), 2.52−
2.41 (m, 2H), 2.08−1.96 (m, 2H), 1.75−1.67 (m, 1H), 1.62−1.52 (m,
1H), 1.12 (bs, 1H). 13C NMR (CDCl3): δ 157.5, 143.0, 141.1, 138.3,
129.5, 129.1, 128.5, 126.1, 125.9, 113.3, 60.5, 55.3, 44.7, 44.4, 37.9,
30.2, 19.2. HRMS (ESI-TOF): calcd for C19H22O2Na (M + Na+)
305.1512, found 305.1511.
Hz), 55.3, 49.6, 27.5. HRMS (APCI-TOF): calcd for C17H18DO (M +
H+) 240.1493, found 240.1489.
(S)-8aa-d. Colorless oil. 53% yield (36.8 mg). The ee was
determined on a Daicel Chiralcel OD-H column with hexane/2-
propanol = 90/10, flow = 1.0 mL/min. Retention times: 8.6 min
(major enantiomer), 13.0 min (minor enantiomer). 90% ee. [α]30
D
−3.1 (c 0.88, C6H6). 1H NMR (CDCl3): δ 7.27 (t, 3JHH = 7.7 Hz, 2H),
3
3
(R)-4-Ethenyl-4-(4-methoxyphenyl)chromane ((R)-3ja: X =
O). Colorless oil. 90% yield (72.8 mg, 3ja/4ja = 99/1). [α]25D +12.5 (c
1.02, CHCl3). The absolute configuration was assigned by analogy
with Table 1, entry 1. 1H NMR (CDCl3): δ 7.14 (ddd, 3JHH = 8.4 and
7.2 Hz and 4JHH = 1.7 Hz, 1H), 7.10 (d, 3JHH = 8.6 Hz, 2H), 6.90 (dd,
7.22−7.15 (m, 3H), 7.12 (d, JHH = 8.8 Hz, 2H), 6.81 (d, JHH = 8.8
3
Hz, 2H), 3.79 (s, 3H), 3.55−3.48 (m, 1H), 2.41 (d, JHH = 7.3 Hz,
2H), 1.65 (s, 3H), 1.02 (bs, 1H). 13C NMR (CDCl3): δ 157.7, 149.6,
141.4, 128.3, 128.2, 127.2, 126.0, 113.6, 59.9 (t, 1JCD = 21.7 Hz), 55.3,
44.6, 44.3, 28.4. HRMS (ESI-TOF): calcd for C17H19DO2Na (M +
Na+) 280.1418, found 280.1414.
3JHH = 7.8 Hz and JHH = 1.7 Hz, 1H), 6.85 (dd, JHH = 8.3 Hz and
4
3
4JHH = 1.1 Hz, 1H), 6.82 (d, JHH = 8.6 Hz, 2H), 6.83−6.80 (m, 1H),
3
Equation 10 ((R)-(E)-3aa-d). Colorless oil. 96% yield (68.9 mg,
6.23 (dd, 3JHH = 17.3 and 10.5 Hz, 1H), 5.36 (dd, 3JHH = 10.6 Hz and
2JHH = 0.9 Hz, 1H), 4.86 (dd, 3JHH = 17.3 Hz and 2JHH = 0.8 Hz, 1H),
4.18 (ddd, 2JHH = 10.9 Hz and 3JHH = 7.8 and 3.0 Hz, 1H), 4.03 (ddd,
3aa/4aa > 99/1, Z/E = 7/93). [α]20 +11.3 (c 1.02, CHCl3). The
D
absolute configuration was assigned by analogy with Table 1, entry 1.
1H NMR (CDCl3): δ 7.31−7.24 (m, 2H), 7.24−7.17 (m, 3H), 7.13 (d,
2JHH = 11.0 Hz and JHH = 7.4 and 2.9 Hz, 1H), 3.79 (s, 3H), 2.38
3
3
3
3JHH = 8.7 Hz, 2H), 6.82 (d, JHH = 8.7 Hz, 2H), 6.38 (d, JHH = 17.5
(ddd, 2JHH = 13.9 Hz and 3JHH = 7.7 and 2.9 Hz, 1H), 2.20 (ddd, 2JHH
3
3
Hz, 1H), 5.15 (d, JHH = 10.6 Hz, 0.07H), 4.89 (d, JHH = 17.3 Hz,
= 13.9 Hz and JHH = 7.5 and 2.9 Hz, 1H). 13C NMR (CDCl3): δ
3
0.93H), 3.79 (s, 3H), 1.77 (s, 3H). 13C NMR (CDCl3): δ 157.9, 148.5,
1
158.1, 154.8, 145.3, 138.6, 131.0, 129.6, 128.1, 126.3, 120.0, 117.0,
116.7, 113.5, 63.0, 55.3, 47.0, 36.1. HRMS (APCI-TOF): calcd for
C18H19O2 (M + H+) 267.1380, found 267.1375.
146.8, 140.3, 128.9, 128.1, 127.9, 126.0, 113.5, 112.6 (t, JCD = 24.0
Hz), 55.3, 49.6, 27.4. HRMS (APCI-TOF): calcd for C17H18DO (M +
H+) 240.1493, found 240.1489.
(S)-2-(4-(4-Methoxyphenyl)chroman-4-yl)ethanol ((S)-8ja).
Colorless oil. 56% yield (43.4 mg). The ee was determined on a
Daicel Chiralpak AD-H column with hexane/2-propanol = 80/20, flow
= 0.8 mL/min. Retention times: 9.8 min (major enantiomer), 11.1 min
(minor enantiomer). 92% ee. [α]25D −11.0 (c 0.97, CHCl3). 1H NMR
(R)-8aa-d. Colorless oil. 58% yield (43.2 mg). The ee was
determined on a Daicel Chiralcel OD-H column with hexane/2-
propanol =90/10, flow =1.0 mL/min. Retention times: 9.1 min (minor
enantiomer), 13.1 min (major enantiomer). 90% ee. [α]30 +2.4 (c
D
0.90, C6H6).
3
3
(CDCl3): δ 7.17 (t, JHH = 7.6 Hz, 1H), 7.11 (d, JHH = 7.7 Hz, 1H),
Procedure for Equation 6. A solution of CuCl (1.5 mg, 15
μmol), (S,S)-L6 (8.2 mg, 17 μmol), and NaOMe (32.4 mg, 0.600
mmol) in THF (0.40 mL) was stirred for 15 min at room temperature.
Compound 2a (132.0 mg, 0.600 mmol) was added, and the mixture
was stirred for 5 min at room temperature. Allyl phosphate 1 (0.300
mmol) was then added with additional THF (0.20 mL), and the
resuting mixture was stirred for 20 h at 60 °C. After dilution with
EtOAc, the reaction mixture was passed through a pad of silica gel with
EtOAc, and the solvent was removed under vacuum. The residue was
purified by silica gel preparative TLC with EtOAc/hexane to afford
compounds 3 and 4.
7.04 (d, 3JHH = 8.6 Hz, 2H), 6.90 (t, 3JHH = 7.5 Hz, 1H), 6.87 (d, 3JHH
3
2
= 8.1 Hz, 1H), 6.81 (d, JHH = 8.8 Hz, 2H), 4.14 (dt, JHH = 11.0 Hz
3
3
and JHH = 3.9 Hz, 1H), 3.84 (td, JHH = 11.1 Hz and JHH = 1.8 Hz,
1H), 3.77 (s, 3H), 3.72−3.64 (m, 1H), 3,64−3.57 (m, 1H), 2.53−2.41
(m, 2H), 2.38 (ddd, 2JHH = 13.9 Hz and 3JHH = 11.1 and 3.4 Hz, 1H),
2.08 (ddd, JHH = 13.9 Hz and JHH = 3.3 and 2.3 Hz, 1H), 1.23 (bs,
1H). 13C NMR (CDCl3): δ 157.9, 155.4, 141.3, 129.2, 128.5, 128.1,
126.1, 120.4, 117.5, 113.6, 62.8, 60.0, 55.3, 43.3, 41.6, 35.8. HRMS
(ESI-TOF): calcd for C18H20O3Na (M + Na+) 307.1305, found
307.1302.
2
3
Procedure for Equation 7. A solution of CuCl (1.5 mg, 15
μmol), (S,S)-L6 (8.2 mg, 17 μmol), and NaOMe (48.6 mg, 0.900
mmol) in THF (0.40 mL) was stirred for 15 min at room temperature.
Compound 2a (198 mg, 0.900 mmol) and THF (0.20 mL) were
added, and the mixture was stirred for 5 min at room temperature.
(E,E)-9 (147 mg, 0.300 mmol) was then added with additional THF
(0.30 mL), and the resuting mixture was stirred for 60 h at 30 °C.
After dilution with EtOAc, the reaction mixture was passed through a
pad of silica gel with EtOAc, and the solvent was removed under
vacuum. The residue was purified by silica gel preparative TLC with
EtOAc/hexane = 1/20 to afford 1,4-bis(2-(4-methoxyphenyl)-3-buten-
2-yl)benzene 10 as a colorless oil (113 mg, 0.283 mmol; 94% yield,
For ee analysis, compound 3 was converted to the corresponding
alcohol 8 through a hydroboration−oxidation sequence: BH3·SMe2
(0.15 mL, 0.30 mmol; 2.0 M solution in THF) was added to a solution
of compound 3 in THF (1.0 mL) at 0 °C, and the mixture was stirred
for 1 h at room temperature. NaOH(aq) (1 M, 0.45 mL) and 30 wt %
H2O2(aq) (61 μL, 0.600 mmol) were successively added at 0 °C, and
the resulting mixture was stirred for 1 h at room temperature. The
reaction was quenched with saturated NaCl(aq) and extracted with
Et2O. The organic layer was dried over MgSO4, filtered, and
concentrated under vacuum. The residue was purified by silica gel
preparative TLC with EtOAc/hexane to afford compound 8.
(R)-1-Ethenyl-1-(4-methoxyphenyl)-1,2,3,4-tetrahydronaph-
thalene ((R)-3ia: X = CH2). Colorless oil. 83% yield (67.8 mg, 3ia/4ia
> 99/1). [α]25D +33.9 (c 0.90, CHCl3). The absolute configuration was
assigned by analogy with Table 1, entry 1. 1H NMR (CDCl3): δ 7.15−
regioselectivity: >99/1). [α]30 +5.4 (c 2.00, CHCl3). The absolute
D
configuration was assigned by analogy with Table 1, entry 1. 1H NMR
(CDCl3): δ 7.13 (d, 3JHH = 8.9 Hz, 4H), 7.10 (s, 4H), 6.82 (d, 3JHH
8.8 Hz, 4H), 6.36 (dd, 3JHH = 17.3 and 10.5 Hz, 2H), 5.15 (dd, 3JHH
=
=
3
7.10 (m, 2H), 7.07 (d, JHH = 8.9 Hz, 2H), 7.07−7.04 (m, 1H), 6.93
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Featured Article
10.6 Hz and 2JHH = 0.9 Hz, 2H), 4.89 (dd, 3JHH = 17.3 Hz and 2JHH
=
(f) Giannerini, M.; Fananas
Soc. 2012, 134, 4108. (g) Hornillos, V.; Perez, M.; Fananas-Mastral,
́ ́
̃
́
-Mastral, M.; Feringa, B. L. J. Am. Chem.
̃
1.0 Hz, 2H), 3.79 (s, 6H), 1.75 (s, 6H). 13C NMR (CDCl3): δ 157.8,
147.1, 145.9, 140.4, 129.0, 127.4, 113.4, 112.8, 55.3, 49.3, 27.4. HRMS
(APCI-TOF): calcd for C28H31O2 (M + H+) 399.2319, found
399.2318.
M.; Feringa, B. L. J. Am. Chem. Soc. 2013, 135, 2140. (h) Yoshikai, N.;
Miura, K.; Nakamura, E. Adv. Synth. Catal. 2009, 351, 1014. (i) Lee,
Y.; Akiyama, K.; Gillingham, D. G.; Brown, M. K.; Hoveyda, A. H. J.
Am. Chem. Soc. 2008, 130, 446. (j) Akiyama, K.; Gao, F.; Hoveyda, A.
H. Angew. Chem., Int. Ed. 2010, 49, 419. (k) Shido, Y.; Yoshida, M.;
Tanabe, M.; Ohmiya, H.; Sawamura, M. J. Am. Chem. Soc. 2012, 134,
18573.
For ee and diastereoselectivity analyses, compound 10 was
converted to 3,3′-(1,4-phenylene)bis(3-(4-methoxyphenyl)butanol)
11 through a hydroboration−oxidation sequence: BH3·SMe2 (0.30
mL, 0.60 mmol; 2.0 M solution in THF) was added to a solution of
compound 10 (113 mg, 0.283 mmol) in THF (1.0 mL) at 0 °C, and
the mixture was stirred for 1 h at room temperature. NaOH(aq) (1 M,
0.60 mL) and 30 wt % H2O2(aq) (82 μL, 0.80 mmol) were
successively added at 0 °C, and the resulting mixture was stirred for 1
h at room temperature. The reaction was quenched with saturated
NaCl(aq) and extracted with Et2O. The organic layer was dried over
MgSO4, filtered, and concentrated under vacuum. The residue was
purified by silica gel preparative TLC with EtOAc/hexane = 1/1 to
afford compound 11 as a colorless oil (61.6 mg, 0.142 mmol; 50%
yield). The ee and diastereoselectivity were determined on a Daicel
Chiralcel OD-H column with hexane/2-propanol = 80/20, flow = 1.0
mL/min. Retention times: 16.2 min (major enantiomer), 21.6 min
[meso isomer], and 28.7 min (minor enantiomer). 99% ee, chiral/
meso = 92/8. [α]25D −2.0 (c 1.02, CHCl3). 1H NMR (CDCl3): δ 7.11
(d, 3JHH = 8.8 Hz, 4H), 7.09 (s, 4H), 6.81 (d, 3JHH = 8.8 Hz, 4H), 3.78
(s, 6H), 3.55−3.46 (m, 4H), 2.38 (t, 3JHH = 7.3 Hz, 4H), 1.62 (s, 6H),
1.03 (bs, 2H). 13C NMR (CDCl3): δ 157.7, 146.9, 141.3, 128.2, 126.8,
113.5, 60.3, 55.3, 44.4, 44.2, 28.3. HRMS (ESI-TOF): calcd for
C28H34O4Na (M + Na+) 457.2349, found 457.2354.
(4) Luchaco-Cullis, C. A.; Mizutani, H.; Murphy, K. E.; Hoveyda, A.
H. Angew. Chem., Int. Ed. 2001, 40, 1456.
(5) (a) Kacprzynski, M. A.; Hoveyda, A. H. J. Am. Chem. Soc. 2004,
126, 10676. (b) Larsen, A. O.; Leu, W.; Oberhuber, C. N.; Campbell, J.
E.; Hoveyda, A. H. J. Am. Chem. Soc. 2004, 126, 11130. (c) Van
Veldhuizen, J. J.; Campbell, J. E.; Giudici, R. E.; Hoveyda, A. H. J. Am.
Chem. Soc. 2005, 127, 6877.
(6) (a) Falciola, C. A.; Tissot-Croset, K.; Reyneri, H.; Alexakis, A.
Adv. Synth. Catal. 2008, 350, 1090. (b) Falciola, C. A.; Alexakis, A.
Chem.Eur. J. 2008, 14, 10615. (c) Magrez, M.; Guen, Y. L.; Basle,
́
O.; Crev
́
isy, C.; Mauduit, M. Chem.Eur. J. 2013, 19, 1199.
(7) Gao, F.; Lee, Y.; Mandai, K.; Hoveyda, A. H. Angew. Chem., Int.
Ed. 2010, 49, 8370.
(8) Diarylzinc reagents have been used for the synthesis of
tetrasubstituted enantioenriched allylsilanes: Kacprzynski, M. A.;
May, T. L.; Kazane, S. A.; Hoveyda, A. H. Angew. Chem., Int. Ed.
2007, 46, 4554.
(9) Alkenyl- and alkynylaluminum reagents have also been utilized:
(a) Gao, F.; McGrath, K. P.; Lee, Y.; Hoveyda, A. H. J. Am. Chem. Soc.
2010, 132, 14315. (b) Dabrowski, J. A.; Gao, F.; Hoveyda, A. H. J. Am.
Chem. Soc. 2011, 133, 4778.
(10) Shintani, R.; Takatsu, K.; Takeda, M.; Hayashi, T. Angew. Chem.,
Int. Ed. 2011, 50, 8656.
(11) (a) Jung, B.; Hoveyda, A. H. J. Am. Chem. Soc. 2012, 134, 1490.
(b) Gao, F.; Carr, J. L.; Hoveyda, A. H. Angew. Chem., Int. Ed. 2012,
51, 6613.
ASSOCIATED CONTENT
■
S
* Supporting Information
HPLC data for asymmetric reactions, X-ray crystal structure of
1
compound (S,S)-L6, and H and 13C NMR spectra of new
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
(12) Whittaker, A. M.; Rucker, R. P.; Lalic, G. Org. Lett. 2010, 12,
3216.
AUTHOR INFORMATION
Corresponding Authors
*E-mail: shintani@chembio.t.u-tokyo.ac.jp.
*E-amil: tamioh@imre.a-star.edu.sg.
■
(13) For examples of hydroxy-bearing chiral NHCs for copper-
catalyzed allylic substitutions, see: (a) Jennequin, T.; Wencel-Delord,
J.; Rix, D.; Daubignard, J.; Crevisy, C.; Mauduit, M. Synlett 2010, 1661.
́
(b) Reference 3i. (c) Reference 6c. (d) Reference 8. (e) Reference
10. See also refs 3j, 9b, and 11 for sulfonate-bearing NHCs.
Notes
(14) Hydroxy-bearing chiral NHCs are known to be effective ligands
for copper-catalyzed asymmetric conjugate additions as well:
The authors declare no competing financial interest.
́
(a) Wencel, J.; Mauduit, M.; Henon, H.; Kehrli, S.; Alexakis, A.
ACKNOWLEDGMENTS
■
Aldrichimica Acta 2009, 42, 42. (b) Clavier, H.; Coutable, L.;
Guillemin, J.-C.; Mauduit, M. Tetrahedron: Asymmetry 2005, 16, 921.
(c) Clavier, H.; Coutable, L.; Toupet, L.; Guillemin, J.-C.; Mauduit, M.
J. Organomet. Chem. 2005, 690, 5237.
Support has been provided in part by a Grant-in-Aid for Young
Scientists (B), the Ministry of Education, Culture, Sports,
Science and Technology, Japan. M.T. thanks JSPS for a
fellowship.
(15) Takatsu, K.; Shintani, R.; Hayashi, T. Angew. Chem., Int. Ed.
2011, 50, 5548.
REFERENCES
(16) Incomplete conversion of (E)-1a was observed when the
reaction was stopped after 20 h (93% conversion) or conducted with
1.2 equiv of 2a and NaOMe (69% conversion).
(17) Sonawane, R. P.; Jheengut, V.; Rabalakos, C.; Larouche-
Gauthier, R.; Scott, H. K.; Aggarwal, V. K. Angew. Chem., Int. Ed. 2011,
50, 3760.
■
(1) For reviews, see: (a) Hong, A. Y.; Stoltz, B. M. Eur. J. Org. Chem.
2013, 2745. (b) Das, J. P.; Marek, I. Chem. Commun. 2011, 47, 4593.
(c) Hawner, C.; Alexakis, A. Chem. Commun. 2010, 46, 7295. (d) Bella,
M.; Gasperi, T. Synthesis 2009, 1583. (e) Trost, B. M.; Jiang, C.
Synthesis 2006, 369. (f) Christoffers, J.; Baro, A. Adv. Synth. Catal.
2005, 347, 1473.
(2) For reviews, see: (a) Falciola, C. A.; Alexakis, A. Eur. J. Org. Chem.
2008, 3765. (b) Geurts, K.; Fletcher, S. P.; van Zijl, A. W.; Minnard, A.
J.; Feringa, B. L. Pure Appl. Chem. 2008, 80, 1025. (c) Alexakis, A.;
(18) Takeda, M.; Shintani, R.; Hayashi, T. J. Org. Chem. 2013, 78,
5007.
(19) (a) Kawashima, H.; Kaneko, Y.; Sakai, M.; Kobayashi, Y.
Chem.Eur. J. 2014, 20, 272. (b) Feng, C.; Kaneko, Y.; Kobayashi, Y.
Tetrahedron Lett. 2013, 54, 4629. (c) Feng, C.; Kobayashi, Y. J. Org.
Chem. 2013, 78, 3755.
(20) Substrates 1 bearing an electron-rich aryl group (e.g., R = 4-
MeOC6H4) could not be employed due to their thermal instability.
(21) We currently do not have a good explanation for the ee
difference between γ-aryl substrates and γ-alkyl substrates.
(22) For a related copper-free asymmetric allylic substitution, see:
Grassi, D.; Alexakis, A. Angew. Chem., Int. Ed. 2013, 52, 13642.
̀ ́
Backvall, J. E.; Pamies, O.; Dieguez, M. Chem. Rev. 2008, 108, 2796.
̈
See also: (d) Yoshikai, N.; Nakamura, E. Chem. Rev. 2012, 112, 2339.
(3) For selected recent examples, see: (a) Falciola, C. A.; Alexakis, A.
Angew. Chem., Int. Ed. 2007, 46, 2619. (b) Li, H.; Alexakis, A. Angew.
Chem., Int. Ed. 2012, 51, 1055. (c) Langlois, J.-B.; Emery, D.; Mareda,
J.; Alexakis, A. Chem. Sci. 2012, 3, 1062. (d) Carosi, L.; Hall, D. G.
Angew. Chem., Int. Ed. 2007, 46, 5913. (e) Selim, K. B.; Matsumoto, Y.;
Yamada, K.; Tomioka, K. Angew. Chem., Int. Ed. 2009, 48, 8733.
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(23) For similar observations in copper-catalyzed asymmetric allylic
substitutions, see: (a) Park, J. K.; Lackey, H. H.; Ondrusek, B. A.;
McQuade, D. T. J. Am. Chem. Soc. 2011, 133, 2410. (b) Delvos, L. B.;
Vyas, D. J.; Oestreich, M. Angew. Chem., Int. Ed. 2013, 52, 4650. (c)
Reference 3k.
(24) For reviews on nonlinear effects, see: (a) Satyanarayana, T.;
Abraham, S.; Kagan, H. B. Angew. Chem., Int. Ed. 2009, 48, 456.
(b) Girard, C.; Kagan, H. B. Angew. Chem., Int. Ed. 1998, 37, 2922.
(25) See ref 13a for a related silver complex.
(26) (a) Ohishi, T.; Nishiura, M.; Hou, Z. Angew. Chem., Int. Ed.
2008, 47, 5792. (b) Shintani, R.; Takatsu, K.; Hayashi, T. Chem.
Commun. 2010, 46, 6822.
(27) The higher regioselectivity with ligand salt L3 compared with
L1 in eq 1 could be attributed to the coordination ability of the
methoxy group to the copper center, which provides a similar effect as
hydroxy-bearing ligand salt L2.
(28) Tummatorn, J.; Ruchirawat, S.; Ploypradith, P. Chem.Eur. J.
2010, 16, 1445.
(29) Deng, J.; Duan, Z.-C.; Huang, J.-D.; Hu, X.-P.; Wang, D.-Y.; Yu,
S.-B.; Xu, X.-F.; Zheng, Z. Org. Lett. 2007, 9, 4825.
(30) Guzman-Martinez, A.; Hoveyda, A. H. J. Am. Chem. Soc. 2010,
132, 10634.
(31) Tanaka, K.; Fu, G. C. J. Org. Chem. 2001, 66, 8177.
(32) Pinna, G. A.; Cignarella, G.; Ruiu, S.; Loriga, G.; Murineddu, G.;
Villa, S.; Grella, G. E.; Cossu, G.; Fratta, W. Bioorg. Med. Chem. 2003,
11, 4015.
(33) Matsubara, R.; Jamison, T. F. J. Am. Chem. Soc. 2010, 132, 6880.
(34) Wu, C.; Decker, E. R.; Blok, N.; Bui, H.; Chen, Q.; Raju, B.;
Bourgoyne, A. R.; Knowles, V.; Biediger, R. J.; Market, R. V.; Lin, S.;
́
Dupre, B.; Kogan, T. P.; Holland, G. W.; Brock, T. A.; Dixon, A. F. J.
Med. Chem. 1999, 42, 4485.
(35) (a) Chaumeil, H.; Signorella, S.; Le Drian, C. Tetrahedron 2000,
56, 9655. (b) Wong, K.-T.; Chien, Y.-Y.; Liao, Y.-L.; Lin, C.-C.; Chou,
M.-Y.; Leung, M. J. Org. Chem. 2002, 67, 1041. (c) Ukai, K.; Aoki, M.;
Takaya, J.; Iwasawa, N. J. Am. Chem. Soc. 2006, 128, 8706.
2367
dx.doi.org/10.1021/jo500068p | J. Org. Chem. 2014, 79, 2354−2367