Enantioselective synthesis of (thiolan-2-yl)diphenylmethanol and its application in asymmetric, catalytic sulfur ylide-mediated epoxidation

Article abstract of DOI:10.1021/jo400648f

This work describes an expeditious and efficient preparation of enantiopure (thiolan-2-yl)diphenylmethanol (2) featuring a double nucleophilic substitution and Shi epoxidation as key steps. One of the applications of its benzyl ether derivative to asymmetric sulfur ylide-mediated epoxidation with up to 92% ee (14 examples) was also demonstrated herein.

Full text of DOI:10.1021/jo400648f

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Note
Enantioselective Synthesis of (Thiolan-2-yl)diphenylmethanol and Its
Application in Asymmetric, Catalytic Sulfur Ylide-Mediated Epoxidation
Hsin-Yi Wu, Chih-Wei Chang, and Rong-Jie Chein
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/jo400648f • Publication Date (Web): 02 May 2013
Downloaded from http://pubs.acs.org on May 7, 2013
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The Journal of Organic Chemistry
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Enantioselective Synthesis of
(Thiolan-2-yl)diphenylmethanol and Its Application in
Asymmetric, Catalytic Sulfur Ylide-Mediated
Epoxidation
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Hsin-Yi Wu†, Chih-Wei Chang‡, and Rong-Jie Chein‡, *
†Department of Chemistry, National Central University, Taoyuan, Taiwan 32001
‡Institute of Chemistry, Academia Sinica, Nankang, Taipei, Taiwan 11529
rjchein@chem.sinica.edu.tw
SYNOPSIS TOC :
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Abstract: This work describes an expeditious and efficient preparation of enantiopure
(thiolan-2-yl)diphenylmethanol (2) featuring a double nucleophilic substitution and Shi epoxidation as
key steps. One of the applications of its benzyl ether derivative to asymmetric sulfur ylide-mediated
epoxidation with up to 92% ee (14 examples) was also demonstrated herein.
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The parent diphenyl-2-pyrrolidinemethanol (1, ,-diphenyl prolinol) and its ether derivatives have
been proved as very useful ligands for a wide range of asymmetric transformations.1 1 was first reported
in 19342 and the interest of them were largely catalyzed by the work initiated by E. J. Corey on the
asymmetric reduction of ketones3 and the preparation of asymmetric super Lewis acid catalyst using
CBS catalyst and Bronsted acid for asymmetric Diels–Alder reaction.4 All these reactions mediated by 1
proceeded in high yields with excellent enantioselectivities. Subsequently, further contributions in 2005
based on organocatalyst with a similar motif, ,-diphenylprolinol ethers have also marked another
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milestone in practical applications of an enantioselective -sulfenylation of aldehydes,5 an
asymmetric Michael addition of aldehydes to nitroolefins,6 and a variety of C−C, C−N, C−F, and
C−Br bonds formation.7 Comparatively, the sulfur analog thiolanyl diphenylmethanol (2)8 possesses
different chemical character with stereo topology similar to 1, yet attracting least attention in the
synthetic community. Inspired by the particular reactivity of organic catalyst containing sulfur atom in
myriad of biochemical processes, chiral thioethers have become one of the major catalyst sources in
asymmetric transformations for accessing optically active natural products.9 For example, the use of
thiolanyl diphenylmethanol (2) for mediating enantioselective alkylation of aldehyde by diethylzinc
reagent is reported.10 Regrettably, the difficulty of preparation of 2 is attirbuted from using highly
toxic and expensive alkaloid Brucine for the optical resolution of the key intermediate
tetrahydro-2-thiophancarboxylic acid11 (Figure 1, upper panel). Therefore, it is desirable to develop a
more concise and accessible process to synthesize 2, which will have the further implications in the
organo- and organometallic catalysis. Herein we reported an efficient route to prepare compound 2 with
an optically pure form in gram scale. We also examined the use of 2 to conduct the catalytic and
asymmetric epoxidations based on benzaldehydes with benzyl bromide.12
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Figure 1. Synthesis of enantiopure (thiolan-2-yl)diphenylmethanol (2)
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As depicted in Figure 1 (lower panel), we anticipated that deployment of double nucleophilic
substitution by sulfide dianion at asymmetric 2,2-diphenyl-3-propyloxirane bearing a leaving group at
the terminal carbon atom would be a viable way to thiophane 2. More importantly, the chirality of the
oxirane will be fully transferred. Based on this rationale, commercially available 5-bromovaleric acid (4)
was selected and the corresponding acid chloride was reacted with phenylmagnesium bromide to afford
diphenylalcohol 5 (Scheme 1 in Supporting Information). In the presence of PTSA in hot toluene
solution, compound 5 was readily converted to diphenylethylene 6 in 82% yield. With considerable
optimization, we were pleased to find that Shi epoxidation protocol13 is suitable protocol for making
epoxide product 7 in high yield (96%) with excellent (96%) ee. As expected, when epoxide 7 was
subjected to a suspension of Na2S treatment in ethanol solution (an ultrasonicator bath), bromide was
substituted by sulfide dianion followed by second internal nucleophilic attack of sulfide on epoxide ring
to form the cyclized compound ((S)-(−)-Thiolan-2-yl)diphenylmethanol (2) in 86% yield without the
loss of ee. The ee of 2 was further improved to >99% by the recrystallization of 2 in hot hexane solution.
The absolute configuration of 2 was confirmed by single-crystal X-ray diffraction. Vice versa, its
optical isomer (R)-(+)-2 could also be synthesized through the similar way with the exception that the
Shi pyranose catalyst prepared from L-fructose was used in this synthetic route. It is important to note
that these procedures are reliable and could be easily carried out in multigram scale.14
With 2 in hand, we were posed to study its application in the asymmetric sulfur ylide-mediated
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epoxidations. Thiolane 2 (50 mol %), benzyl bromide (2 equiv) and benzaldehyde (1 equiv) were mixed
together at room temperature in the basic medium.12f Through the in situ formation of sulfonium salt
and then the corresponding ylide, trans and cis stilbene oxides were obtained in a ratio of 4:1.
Unfortunately, 0 % ee was observed for the trans isomer accompanied with the decomposition of
catalyst 2. To preserve active species 2 in the catalytic cycle for the asymmetric induction, methyl ether
2a, trimethylsilyl (TMS) ether 2b and benzyl ether 2c were synthesized and subjected to the same
reaction condition. To our delight, benzyl ether 2c (Table 1, entry 4) showed the best enantioselectivity
(84% ee) with lower catalyst loading (20 mol %, Table 1, entry 5), while still keeping good selectivity
in trans/cis ratio.
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Table 1. Catalyst screening for asymmetric epoxidation
entry catalyst time yield trans/cisa eeb
(equiv)
1
2
2(0.5)
24 h 23%
79/21
77/23
0
2a(0.5) 48 h 82%
2b(0.5) 12 h 61%
2c(0.5) 36 h 89%
2c(0.2) 48 h 72%
2c(0.1) 48 h 57%
83%
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6
74/26
78/22
75/25
73/27
67%
84%
84%
82%
aTrans/cis ratio was determined by 1H NMR. bee
of trans product was determined by HPLC
analysis with a Chiralcel OD column.
Encouraged by the outcome using benzyl ether 2c as sulfur ylide source, we next examined for the
optimized condition for this transformation. As shown in Table 2, all aprotic solvents (entries 2, 3, 7, 8,
and 9) mediated the reaction with higher diastereoselectivity but lower enantioselectivity. In contrast,
protic solvents (entries 1, 4, and 10) showed reversed effect in selectivity. Combining acetonitrile and
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t-butanol as solution (entry 6) did not seem any beneficial effect on the stereoselectivity of the reaction.
Among the protic solvents we screened, t-butanol provided the best ee with decent trans/cis ratio, yet
the reaction proceeded slowly, as 3/4 of benzaldehyde left untouched after a day. We were pleased to
find that LiOTf additive significantly accelerated the reaction rate (entries 11-13). In fact, trace amount
of water with catalytic LiOTf assisted the completion of the reaction within 24 hours without having
any adverse effect on stereoselectivity (entry 14).15
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Table 2. Optimization of the 2c mediated asymmetric epoxidation.
entry
1
solvent
tBuOH/H2O (9/1)
additive (equiv)
none
time
48 h
yielda trans/cisb
ee of
72 %
85 %
5 %
75/25
90/10
91/9
84 %
2
3
MeCN
THF
none
none
48 h
24 h
24 h
24 h
24 h
24 h
24 h
24 h
24 h
24 h
24 h
19 h
24 h
24 h
75 %
71 %
84 %
80 %
78 %
75 %
74 %
73 %
86 %
86 %
87 %
85 %
86 %
85 %
4
MeOH/H2O (1/1)
EtOH
none
48 %
5 %
75/25
67/33
87/13
90/10
89/11
92/8
5
none
6
MeCN/ tBuOH (15/1)
DCE
none
52 %
30 %
1 %
7
none
8
toluene
none
9
CH2Cl2
none
54 %
27 %
47 %
51 %
75 %
92 %
95 %
10
11
12
13
14
15
tBuOH
none
78/22
78/22
77/23
75/25
77/23
tBuOH
LiOTf (0.2)
LiOTf (0.5)
LiOTf (1)
LiOTf (0.2), H2O (5)
LiOTf (1), H2O (5)
tBuOH
tBuOH
tBuOH
tBuOH
71/29
b
aGC yield, using 2,6-di-tert-butyl-4-methylphenol as an internal standard. Trans/cis ratio was
1
c
determined by H NMR. ee of trans product was determined by HPLC analysis with a Chiralcel
OD column.
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The scope of this asymmetric epoxidation process was then assessed through variation of the
aldehyde components under the optimized condition. We first examined the electronic effect on the
reactivity of aldehyde toward stilbene oxide (Table 3). Benzaldehydes bearing an electron-withdrawing
group such as CF3 (entry 2), Cl (entry 3), and F (entry 4) at para position afforded the corresponding
trans-stilbene oxides 9, 10, and 11 in good yields with good to excellent enantiocontrol. On the other
hand, benzyl bromide was converted slowly into trans-oxide 12, 13, and 15 when it reacted with
benzaldehydes bearing one (entries 14, 15) or two (entry 17) electron-donating groups. Ortho
substitution deteriorated the enantioselectivity (entries 7, 11, 12) and diastereoselectivity (entry 7),
albeit with good yield. Finally, 2-naphthaldehyde (entry 13) and cinnamaldehyde (entry 14) gave
epoxides 20 and 21 in good stereocontrol manner.
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Table 3. The substrate scope of catalytic sulfur ylide-mediated epoxidation.
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To provide a mechanistic rationale for the high asymmetric induction observed in epoxidation
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2
involving sulfide 2c, the catalytic cycle is proposed in Figure 2. The sulfide is initially transformed to
sulfonium salts 22, which then subsequently turned into the corresponding ylide 23 under basic
condition. In this juncture, the ylide can adopt either conformations 23a or 23b in which the filled
orbital on the ylide carbons is perpendicular to the lone pair electron on sulfur.12c,16 Intermediate 23b
should be favored as the phenyl group is located away from the bulky substituent  to sulfur. In addition,
minimization of steric energy is achieved with the phenyl group pointing at equatorial position. As a
result, the orientation of the bulky substituent in 23a would block the Si face of the ylide carbon,
forcing the Re face addition of aldehyde to give the (R,R)-epoxide.
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Figure 2. Thiolane catalyzed asymmetric epoxidation (arrows may be considered equilibria).
In conclusion,
a
new and efficient method for the synthesis of enantiopure
(thiolan-2-yl)diphenylmethanol (2) and its application in asymmetric sulfide-catalyzed epoxidation are
reported. These chiral thioethers have high potential for other asymmetric organocatalysis and are good
donor ligands17 for the development of chiral organometallic catalysts.
Experimental Section
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5-Bromo-1,1-diphenylpentan-1-ol (5): To a stirred solution of 5-bromovaleric acid (4) (9 g, 50 mmol)
in CH2Cl2 (15 mL) at room temperature was slowly added thionyl chloride (7.2 mL, 99 mmol) in a
period of 10 min through a dropping funnel. DMF (few drops) was added to the reaction mixture, which
was then heated to reflux for 2 h. The reaction mixture was concentrated in vacuo (to remove excess
SOCl2 and DMF) and the resulting acid chloride was directly used for the following Grignard reaction.
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To a solution of magnesium powder (1.7 g, 73 mmol) and a small piece of iodine in THF (50 mL) was
added phenyl bromide (1 mL, 9.5 mmol) at room temperature. After the color of iodine disappeared, the
rest of phenyl bromide (6.9 mL, 65.5 mmol)) was slowly added by a syringe pump in a period of 1 h.
The mixture was stirred for another 30 min after the exothermic reaction was ceased. When magnesium
disappeared, the mixture was stirred for another 1 h, and 5-bromopentanoyl chloride (4.95 g, 25 mmol)
o
in dry THF (15 mL) was added dropwise to the above mixture at 0 C. After stirring for 12 h at room
o
temperature, the reaction mixture was quenched with sat. NH4Cl (10 mL) at 0 C, and extracted with
EtOAc (30 mL x 3). The combined organic layers were washed with sat. NaHCO3 (20 mL x 2) and
brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column
chromatography (EtOAc-hexanes, 1:9) to give 5-bromo-1,1-diphenylpentan-1-ol as a colorless oil (5.4 g,
1
68 % yield). IR (neat) 3472, 3058, 2948, 2867, 1493, 1446, 1263, 1059, 963, 753, 700 cm−1; H NMR
(400 MHz, CDCl3) δ 7.48-7.26 (10H, m), 3.36 (2H, t, J = 7.0 Hz), 2.42 (1H, s), 2.35-2.31 (2H, m), 1.91
(2H, dt, J = 14.5, 7.1 Hz), 1.52-1.44 (2H, m); 13C NMR (100 MHz, CDCl3) δ 146.7, 128.0, 126.7, 125.9,
77.9, 40.8, 33.3, 32.9, 22.4; HRMS (ESI+, TOF) calcd. for C17H19BrO [(M+H-H2O)+] 301.0602, found
301.0592.
5,5-Diphenyl-4-pentenyl bromide (6): A stirred solution of 5-bromo-1,1-diphenylpentan-1-ol (5) (5.1
o
g, 16 mmol) and p-TsOH (255 mg, 1.5 mmol) in toluene (63 mL) was heated to 70 C for 3 h. After
cooling down to room temperature, the reaction mixture was diluted with DI water (10 mL), extracted
with EtOAc (10 mL x 3), dried over Na2SO4, and concentrated in vacuo. The residue was purified by
flash column chromatography (EtOAc-hexanes, 3:97) to give 5,5-diphenyl-4-pentenyl bromide as a
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colorless oil (4.2 g, 82 % yield). IR (neat) 3054, 2959, 1633, 1243, 759, 699 cm−1; 1H NMR (400 MHz,
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CDCl3) δ 7.39-7.16 (10H, m), 6.04 (1H, t, J = 7.4 Hz), 3.37 (2H, t, J = 6.9 Hz), 2.26 (2H, dd, J = 14.7,
4
5
6
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7.4 Hz), 2.03-1.95 (2H, m); C NMR (100 MHz, CDCl3) δ 143.0, 142.4, 139.8, 129.8, 128.2, 128.1,
127.5, 127.2, 127.0, 33.1, 33.0, 28.4; HRMS (FAB+, magnetic sector) calcd. for C17H17Br (M+)
300.0514, found 300.0518.
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(R)-(+)-3-(3-Bromopropyl)-2,2-diphenyloxirane (7): A combined solution of 5,5-diphenyl-4-pentenyl
bromide (6) (2.4 g, 8.0 mmol) in CH3CN/DMM (1:2, v/v, 60 mL), and Na2B4O7·10H2O (1.5 g, 4.0
mmol), tetrabutylammonium hydrogen sulfate (108 mg, 0.32 mmol) and Shi catalyst (1.03 g, 4.0 mmol)
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in a buffer solution (4 x 10-4 M aqueous Na2(EDTA), 40 mL) was cooled to -5 C with mechanical
stirring in an ice bath. A solution of Oxone (12.28 g, 20 mmol) in aqueous Na2(EDTA) (4 x 10-4 M, 50
mL) and a solution of K2CO3 (12.3 g, 89.2 mmol) in DI water (50 mL) were added dropwise through
two separate addition funnels respectively over a period of 3 h at -5 oC. Upon completion of the addition,
the reaction was stirred for another 1 h at the same temperature. After diluted with DI water (100 mL),
the resulting mixture was extracted with hexanes (100 mL x 2), dried over Na2SO4, and concentrated to
afford the crude product which was purified by flash column chromatography (EtOAc-hexanes, 1:40 to
1:25) to afford (R)-(+)-3-(3-bromopropyl)-2,2-diphenyloxirane as a colorless oil. (2.41 g, 95 % yield, 96
% ee). [α]D28 = +37.0 (c 1.0, CHCl3); IR (neat) 3059, 3028, 2963, 2853, 1494, 1277, 762, 699 cm−1; 1H
NMR (400 MHz, CDCl3) δ 7.40-7.23 (10H, m), 3.44-3.30 (3H, m), 2.13-1.94 (2H, m), 1.69 (1H, ddd, J
13
= 14.0, 9.8, 5.3 Hz), 1.33 (1H, m); C NMR (100 MHz, CDCl3) δ 140.7, 137.2, 128.2, 128.1, 127.9,
127.8, 127.6, 126.9, 66.1, 65.4, 32.9, 29.6, 28.2; HRMS (FAB+, magnetic sector) calcd. for C17H18BrO
[(M+H)+] 317.0534, found 317.0541; enantioselectivity was determined by HPLC analysis
(Chiralcel-OJ, 1.0 mL/min, 220 nm, hexanes/i-PrOH 4/1); retention time: 19.4 min (enantiomer) and
35.8 min (major).
1,2:4,5-Di-O-isopropylidene-D-erythro-2,3-hexodiuro-2,6-pyranose (Shi catalyst):13 To a stirred
solution of D-fructose (3.68 g, 20.5 mmol) and 2,2- dimethoxypropane (1.48 mL, 12 mmol) in acetone
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(74 mL) at 0 oC was slowly added perchloric acid (70 %, 860 uL) dropwise. After stirring for 6 h at 0 oC,
the reaction mixture was quenched with 28 % NH4OH (2 mL) at 0 oC (adjust to pH 7-8). Upon removal
of acetone, the residue was diluted with DI water (50 mL) and CH2Cl2 (50 mL). The aqueous layer was
extracted with CH2Cl2 (10 mL x 2). The combined organic layers were washed with brine, dried over
Na2SO4, and concentrated to get the crude product which was recrystallized from hexanes-CH2Cl2 (4:1
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v/v) to give 1,2;4,5-di-O-isopropylidene-β-D-fructopyranose as white needles. (2.1 g, 40 %). H NMR
(400 MHz, CDCl3) δ 4.19 (1H, ddd, J = 5.8, 2.5, 0.7 Hz), 4.16 (1H, d, J = 8.8 Hz), 4.13-4.08 (2H, m),
4.00-3.95 (2H, m), 3.65 (1H, dd, J = 8.2, 6.9 Hz), 1.99 (1H, d, J = 8.2 Hz), 1.51 (3H, s), 1.49 (3H, s),
1.42 (3H, s), 1.35 (3H, s).
To a stirred solution of 1,2;4,5-di-O-isopropylidene-β-D-fructopyranose (3.9 g, 15 mmol) and powdered
3 Å molecular sieves (37 g, activated at 180-200 oC under high vacuum) in CH2Cl2 (112 mL) was added
PCC (8.76 g, 40.5 mmol) portionwise over 30 min. After stirring for 3 h under nitrogen, the reaction
mixture was filtered through Celite-cotton-silica gel and washed carefully with ether-hexanes (2:1, 400
mL).
The
filtrate
was
concentrated
to
afford
1
1,2;4,5-Di-O-isopropylidene-D-erythro-2,3-hexodiuro-2,6-pyranose as white needles (3.76 g, 97 %). H
NMR (400 MHz, CDCl3) δ 4.70 (1H, d, J = 5.6 Hz), 4.59 (1H, d, J = 9.5 Hz), 4.52 (1H, dd, J = 5.6, 1.5
Hz), 4.36 (1H, dd, J = 13.5, 2.2 Hz), 4. 09 (1H, d, J = 13.5 Hz), 3.97 (1H, d, J = 9.5 Hz), 1.53 (3H, s),
1.44 (3H, s), 1.37 (6H, s).
((S)-(−)-Thiolan-2-yl)diphenylmethanol
(2):
A
mixture
of
the
(R)-(+)-3-(3-bromopropyl)-2,2-diphenyloxirane (7) (3.06 g, 9.7 mmol) and Na2S·9H2O (4.64 g, 19.3
o
mmol) in 95 % ethanol (33 mL) was sonicated at 10~25 C for 34 h (conversion is monitored by the
1
crude H NMR). Upon removal of ethanol, the crude residue was diluted with DI water (40 mL) and
CH2Cl2 (40 mL). The aqueous layer was extracted with CH2Cl2 (25 mL x 2). The combined organic
layers were washed with brine, dried over Na2SO4, and concentrated to afford the crude product which
was purified by flash column chromatography (EtOAc-hexanes, 1:99 to 1:20) to afford
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((S)-(-)-thiolan-2-yl)diphenylmethanol as a white solid. (2.24 g, 86 % yield, 93 % ee). The solid
((S)-(-)-thiolan-2-yl)diphenylmethanol was recrystallized from hexanes to give white needles with >99
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6
o
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% ee. m.p. 72-75 C; [α]D = -120.4 (c 1.0, CHCl3); IR (neat) 3471, 3056, 2934, 1596, 1491, 1447,
1353, 1167, 754, 701 cm−1; H NMR (400 MHz, CDCl3) δ 7.54-7.51 (2H, m), 7.44-7.41 (2H, m),
7
8
1
9
7.30-7.22 (4H, m), 7.21-7.12 (2H, m), 4.66 (1H, dd, J = 8.4, 6.8 Hz), 3.53 (1H, s), 2.86-2.83 (2H, m),
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2.16 (1H, m), 1.87-1.73 (2H, m), 1.62 (1H, m); C NMR (100 MHz, CDCl3) δ 148.0, 145.0, 128.2,
128.0, 127.1, 126.5, 126.1, 125.4, 77.9, 59.5, 33.4, 31.7; HRMS (FAB+, magnetic sector) calcd. for
C17H19OS [(M+H)+] 271.1157, found 271.1150; enantioselectivity was determined by HPLC analysis
(Chiralpak-AD, 1.0 mL/min, 220 nm, hexanes/i-PrOH 19/1); retention time: 6.0 min (enantiomer) and
8.5 min (major).
(S)-(+)-2-(Methoxydiphenylmethyl)tetrahydrothiophene (2a): To
a
stirred solution of
o
((S)-(-)-thiolan-2-yl)diphenylmethanol (2) (135 mg, 0.5 mmol) in DMF (2 mL) at 0 C was added
sodium hydride (40 mg, 1.0 mmol). The reaction mixture was warmed to room temperature and stirred
for 1 h. Methyl iodide (37 uL, 0.6 mmol) was then slowly added to the reaction mixture. After 2 h
o
stirring at room temperature, the reaction mixture was quenched with sat. NH4Cl (1 mL) at 0 C,
extracted with Et2O (2 mL x 3), dried over Na2SO4, and concentrated in vacuo. The residue was purified
by
flash
column
chromatography
(EtOAc-hexanes,
1:49)
to
give
31
(S)-(+)-2-(methoxydiphenylmethyl)tetrahydrothiophene as a colorless oil (132 mg, 92 % yield). [α]D
=
+93.2 (c 1.0, CHCl3); IR (neat) 3056, 2934, 1491, 1444, 1073, 755, 701, 645 cm−1; 1H NMR (400 MHz,
CDCl3) δ 7.50 (2H, dd, J = 7.9, 1.7 Hz), 7.37 (2H, dd, J = 8.1, 1.6 Hz), 7.31-7.23 (6H, m), 4.59 (1H, t, J
= 7.04 Hz), 3.06 (3H, s), 2.65 (1H, dt, J = 11.4, 5.8 Hz), 2.34 (2H, ddd, J = 10.1, 7.5, 6.2 Hz), 2.01 (1H,
td, J = 12.7, 5.9 Hz), 1.81-1.63 (2H, m), 1.31 (1H, qd, J = 10.2, 4.3 Hz); 13C NMR (100 MHz, CDCl3) δ
142.7, 141.3, 129.5, 129.2, 127.4, 127.3, 127.1, 127.0, 85.9, 53.6, 51.6, 32.6, 31.6, 30.3; HRMS (ESI+,
TOF) calcd. for C18H21OS [(M+H)+] 285.1313, found 285.1307.
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(S)-(+)-(Diphenyl(tetrahydrothiophen-2-yl)methoxy)trimethylsilane (2b): To a stirred solution of
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3
o
((S)-(-)-thiolan-2-yl)diphenylmethanol (2) (135 mg, 0.5 mmol) in CH2Cl2 (0.5 mL) at 0 C was slowly
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5
6
7
8
added imidazole (102 mg, 1.5 mmol) followed by TMSCl (90 uL, 1.0 mmol). The reaction mixture was
warmed to room temprature and stirred overnight. The reaction mixture was quenched with sat. NH4Cl
9
o
(2 mL) at 0 C, extracted with CH2Cl2 (3 mL x 3), dried over Na2SO4, and concentrated in vacuo. The
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residue was purified by flash column chromatography (EtOAc-hexanes, 1:49) to give
(S)-(+)-(diphenyl(tetrahydrothiophen-2-yl)methoxy)trimethylsilane as a colorless oil (165 mg, 96 %
yield). m.p. 47-50 oC; [α]D29 = +15.1 (c 1.0, CHCl3); IR (neat) 2953, 2929, 2859, 1446, 1245, 1123, 834,
700 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.45 (2H, dd, J = 6.6, 1.3 Hz), 7.31-7.15 (8H, m), 4.39 (1H, t,
J = 6.8 Hz), 2.77 (1H, dt, J = 9.3, 4.5 Hz), 2.56 (1H, m), 1.71-1.59 (4H, m), -0.10(9H, s); 13C NMR (100
MHz, CDCl3) δ147.4, 145.5, 128.5, 127.6, 127.3, 127.2, 127.0, 126.8, 83.8, 57.5, 33.5, 32.3, 30.2, 2.1;
HRMS (FAB+, magnetic sector) calcd. for C20H25OSiS [(M-H)+] 341.1395, found 341.1389.
(S)-(+)-2-((Benzyloxy)diphenylmethyl)tetrahydrothiophene (2c): To
a
stirred solution of
o
((S)-(−)-thiolan-2-yl)diphenylmethanol (2) (0.5 g, 1.9 mmol) in DMF (3.7 mL) at 0 C was added
sodium hydride (148 mg, 3.7 mmol). The reaction mixture was warmed to room temperature and stirred
for 1h. Benzyl bromide (270 uL, 2.2 mmol) was then slowly added to the reaction mixture. After 16 h
o
stirring at room temperature, the reaction mixture was quenched with sat. NH4Cl (1 mL) at 0 C,
extracted with Et2O (5 mL x 3), dried over Na2SO4, and concentrated in vacuo. The residue was purified
by
flash
column
chromatography
(EtOAc-hexanes,
1:49)
to
give
(S)-(+)-2-((benzyloxy)diphenylmethyl)tetrahydrothiophene as a pale yellow oil (615 mg, 92 % yield).
29
1
[α]D = +63.6 (c 1.0, CHCl3); IR (neat) 3059, 2930, 1494, 1444, 1063, 758, 701, 651 cm−1; H NMR
(400 MHz, CDCl3) δ 7.57-7.55 (2H, m), 7.44 (1H, d, J = 7.2 Hz), 7.34-7.16 (11H, m), 4.66 (1H, t, J =
7.2 Hz), 4.38 (1H, d, J = 11.6 Hz), 4.21 (1H, d, J = 11.52 Hz), 2.63 (1H, m), 2.32 (1H, ddd, J = 10.1, 8.2,
6.1 Hz), 1.98 (1H, td, J = 12.7, 6.0 Hz), 1.84 (1H, m), 1.64 (1H, m), 1.34 (1H, tt, J = 11.9, 5.9 Hz); 13C
NMR (100 MHz, CDCl3) δ129.3, 128.8, 128.0, 127.4, 127.2, 127.1, 127.0, 126.9, 126.9, 85.9, 65.5,
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53.8, 32.6, 31.6, 30.2.; HRMS (FAB+, magnetic sector) calcd. for C24H25OS [(M+H)+] 361.1626, found
361.1618.
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2
3
4
5
6
7
8
General procedure for sulfur ylide-mediated epoxidations: To a stirred solution of
(S)-(+)-2-((benzyloxy)diphenylmethyl)tetrahydrothiophene (2c) (20 mg, 0.06 mmol), TBAI (52 mg,
0.14 mmol), powdered NaOH (22 mg, 0.57 mmol), LiOTf (9 mg, 0.06 mmol) and DI water (25 uL, 1.41
mmol) in t-butanol (0.9 mL) was slowly added benzyl bromide (67 uL, 0.57 mmol) and the
corresponding aldehyde (0.28 mmol) sequentially. The resulting reaction mixture was stirred at room
temperature for the corresponding reaction time (Table 3). The final mixture was diluted with DI water,
extracted with CH2Cl2, dried over Na2SO4, and concentrated to furnish the crude product for column
chromatography. The isolated yields, trans/cis ratios, and ee of trans isomers are listed in Table 3.
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(2R,3R)-2,3-diphenyloxirane (8)18: H NMR (400 MHz, CDCl3) δ 7.39-7.30 (10H, m), 3.85 (2H, s);
enantioselectivity was determined by HPLC analysis (Chiralcel-OD, 1.0 mL/min, 228 nm,
hexanes/i-PrOH 19/1); retention times: 5.8 min (enantiomer) and 8.0 min (major).
1
(2R,3R)-2-phenyl-3-(4-(trifluoromethyl)phenyl)oxirane (9)19: H NMR (400 MHz, CDCl3) δ 7.62
(2H, d, J = 8.1 Hz), 7.45 (2H, d, J = 8.1 Hz), 7.40-7.31 (5H, m), 3.91 (1H, d, J = 1.6 Hz), 3.82 (1H, d, J
= 1.7 Hz); enantioselectivity was determined by HPLC analysis (Chiralpak-AD, 1.0 mL/min, 231 nm,
hexanes/i-PrOH 19/1); retention times: 5.6 min (major) and 10.3 min (enantiomer).
(2R,3R)-2-(4-chlorophenyl)-3-phenyloxirane (10)18: 1H NMR (400 MHz, CDCl3) δ 7.39-7.25 (9H, m),
3.83 (1H, d, J = 1.8 Hz), 3.80 (1H, d, J = 1.8 Hz); enantioselectivity was determined by HPLC analysis
(Chiralcel-OD, 1.0 mL/min, 234 nm, hexanes/i-PrOH 99/1); retention times: 9.0 min (enantiomer) and
10.4 min (major).
(2R,3R)-2-(4-fluorophenyl)-3-phenyloxirane (11)18: 1H NMR (400 MHz, CDCl3) δ 7.39-7.28 (7H, m),
7.07-7.03 (2H, m), 3.83 (1H, d, J = 1.3 Hz), 3.81 (1H, d, J = 1.5 Hz); enantioselectivity was determined
by HPLC analysis (Chiralcel-OD, 1.0 mL/min, 220 nm, hexanes/i-PrOH 19/1); retention times: 6.4 min
(enantiomer) and 7.8 min (major).
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(2R,3R)-2-(4-methoxyphenyl)-3-phenyloxirane (12)18: H NMR (400 MHz, CDCl3) δ 7.38-7.29 (5H,
m), 7.27 (1H, m), 7.25 (1H, m), 6.91 (1H, m), 6.89 (1H, m), 3.84 (1H, d, J = 1.9 Hz), 3.80 (3H, s), 3.80
(1H, d, J = 1.9 Hz); enantioselectivity was determined by HPLC analysis (Chiralpak-AD, 1.0 mL/min,
234 nm, hexanes/i-PrOH 17/3); retention times: 6.8 min (major) and 13.8 min (enantiomer).
1
1
2
3
4
5
6
7
8
9
1
(2R,3R)-2-(3-methoxyphenyl)-3-phenyloxirane (13)20: H NMR (400 MHz, CDCl3) δ 7.41-7.25 (6H,
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m), 6.93 (1H, d, J = 7.6, 1.1 Hz), 6.89-6.83 (2H, m), 3.83 (2H, s), 3.81 (3H, s); enantioselectivity was
determined by HPLC analysis (Chiralpak-AD, 1.0 mL/min, 220 nm, hexanes/i-PrOH 9/1); retention
times: 6.9 min (major) and 14.4 min (enantiomer).
1
(2R,3R)-2-(2-methoxyphenyl)-3-phenyloxirane (14)21: H NMR (400 MHz, CDCl3) δ 7.41-7.24 (7H,
m), 6.97 (1H, t, J = 7.6 Hz), 6.87 (1H, d, J = 7.9 Hz), 4.23 (1H, d, J = 1.7 Hz), 3.80 (3H, s), 3.77 (1H, d,
J = 1.9 Hz); enantioselectivity was determined by HPLC analysis (Chiralpak-AD, 1.0 mL/min, 234 nm,
hexanes/i-PrOH 19/1); retention times: 6.8 min (major) and 11.0 min (enantiomer).
1
(2R,3R)-2-(3,4-dimethoxyphenyl)-3-phenyloxirane (15)22: H NMR (400 MHz, CDCl3) δ 7.40-7.28
(5H, m), 6.92 (1H, dd, J = 8.2, 1.9 Hz), 6.86 (1H, d, J = 8.2 Hz), 6.83 (1H, d, J = 1.9 Hz), 3.89 (3H, s),
3.88 (3H, s), 3.83 (1H, d, J = 1.9 Hz), 3.81 (1H, d, J = 1.9 Hz); enantioselectivity was determined by
HPLC analysis (Chiralpak-AD, 1.0 mL/min, 231 nm, hexanes/i-PrOH 9/1); retention times: 9.9 min
(major) and 20.0 min (enantiomer).
1
(2R,3R)-2-phenyl-3-(p-tolyl)oxirane (16)18: H NMR (400 MHz, CDCl3) δ 7.39-7.16 (9H, m), 3.84
(1H, d, J = 1.9 Hz), 3.81 (1H, d, J = 1.9 Hz), 2.35 (3H, s); enantioselectivity was determined by HPLC
analysis (Chiralcel-OD, 1.0 mL/min, 231 nm, hexanes/i-PrOH 19/1); retention times: 5.4 min
(enantiomer) and 6.4 min (major).
1
(2R,3R)-2-phenyl-3-(m-tolyl)oxirane (17)20: H NMR (400 MHz, CDCl3) δ 7.42-7.24 (6H, m), 7.14
(2H, s), 7.12 (1H, s), 3.84 (1H, d, J = 1.9 Hz), 3.82 (1H, d, J = 1.9 Hz), 2.35 (3H, s); enantioselectivity
was determined by HPLC analysis (Chiralpak-AD, 1.0 mL/min, 231 nm, hexanes/i-PrOH 19/1);
retention times: 5.4 min (major) and 12.3 min (enantiomer).
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(2R,3R)-2-phenyl-3-(o-tolyl)oxirane (18)20: H NMR (400 MHz, CDCl3) δ 7.45-7.26 (5H, m),
7.24-7.08 (4H, m), 3.98 (1H, d, J = 1.8 Hz), 3.75 (1H, d, J = 1.9 Hz), 2.33 (3H, s); enantioselectivity
was determined by HPLC analysis (Chiralpak-AD, 1.0 mL/min, 228 nm, hexanes/i-PrOH 99/1);
retention times: 6.9 min (major) and 8.9 min (enantiomer).
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3
4
5
6
7
8
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(2R,3R)-2-mesityl-3-phenyloxirane (19)23: 1H NMR (400 MHz, CDCl3) δ 7.41-7.31 (5H, m), 6.84 (2H,
s), 3.88 (1H, s), 3.79 (1H, d, J = 2.2 Hz), 2.38 (6H, s), 2.27 (3H, s); enantioselectivity was determined
by HPLC analysis (Chiralpak-AD, 1.0 mL/min, 228 nm, hexanes/i-PrOH 49/1); retention times: 5.2 min
(major) and 5.9 min (enantiomer).
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(2R,3R)-2-(naphthalen-2-yl)-3-phenyloxirane (20)22: H NMR (400 MHz, CDCl3) δ 7.86-7.81 (4H,
m), 7.55-7.44 (2H, m), 7.44-7.24 (6H, m), 4.02 (1H, d, J = 1.8 Hz), 3.95 (1H, d, J = 1.8 Hz);
enantioselectivity was determined by HPLC analysis (Chiralpak-AD, 1.0 mL/min, 231 nm,
hexanes/i-PrOH 9/1); retention times: 7.2 min (major) and 12.9 min (enantiomer).
(2R,3R)-2-phenyl-3-((E)-styryl)oxirane (21)18: 1H NMR (400 MHz, CDCl3) δ 7.47-7.22 (9H, m), 6.80
(1H, d, J = 16.0 Hz), 6.06 (1H, dd, J = 16.0, 7.7 Hz), 3.87 (1H, s), 3.51 (1H, d, J = 7.6 Hz);
enantioselectivity was determined by HPLC analysis (Chiralcel-OD, 1.0 mL/min, 220 nm,
hexanes/i-PrOH 99/1); retention times: 12.5 min (enantiomer) and 13.7 min (major).
Acknowledgment. This research was generously supported by Academia Sinica and the National
Science Council, Taiwan. We are grateful to the Mass Lab and the X-ray Lab of the Institute of
Chemistry, Academia Sinica for compound characterization. We also thank Professor Kevin Brown of
Indiana University for the helpful discussion on the synthesis of 2.
Supporting Information Available: Experimental details, characterization data, and crystallographic
data (CIF) of (S)-(−)-2. This material is available free of charge via the Internet at http://pubs.acs.org.
References and Notes:
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(1) (a) Palomo, C.; Mielgo, A. Angew. Chem. Int. Ed. 2006, 45, 7876-7880; (b) Mielgo, A.; Palomo, C.
Chemistry-an Asian Journal 2008, 3, 922-948.
1
2
3
4
5
6
7
8
(2) Kapfhammer, J.; Matthes, A. In Hoppe-Seyler´s Zeitschrift für physiologische Chemie 1934, 223,
43.
9
(3) (a) Corey, E. J.; Bakshi, R. K.; Shibata, S. J . Am. Chem. Soc. 1987, 109, 5551-5553; For review,
see: (b) Corey, E. J.; Helal, C. J. Angew. Chem. Int. Ed. 1998, 37, 1986-2012.
(4) (a) Hu, Q.-Y.; Zhou, G.; Corey, E. J. J. Am. Chem. Soc. 2004, 126, 13708-13713; For reviews, see:
(b) Corey, E. J. Angew. Chem. Int. Ed. 2002, 41, 1650-1667; (c) Corey, E. J. Angew. Chem. Int. Ed.
2009, 48, 2100-2117.
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(5) Marigo, M.; Wabnitz, T. C.; Fielenbach, D.; Jørgensen, K. A. Angew. Chem. Int. Ed. 2005, 44,
794-797.
(6) Hayashi, Y.; Gotoh, H.; Hayashi, T.; Shoji, M. Angew. Chem. Int. Ed. 2005, 44, 4212-4215.
(7) Franzén, J.; Marigo, M.; Fielenbach, D.; Wabnitz, T. C.; Jørgensen, K. A. J. Am. Chem. Soc. 2005,
127, 18296-18304.
(8) G. VERMEERSCH, J. M. e. N. F.-G. Tetrahedron 1978, 34, 1453-2458.
(9) Arrayas, R. G.; Carretero, J. C. Chem. Commun. 2011, 47, 2207-2211.
(10) Shiina, I.; Konishi, K.; Kuramoto, Y. Chem. Lett. 2002, 164-165.
(11) Claeson, G.; Jonsson, H. G. 1966, 26, 247-257.
(12) Part of the related epoxidation of this work has been presented in The 5th International Conference
on Cutting-Edge Organic Chemistry in Asia (ICCEOCA-5), Hsinchu, Taiwan; For the first report of
sulfur yields, see: (a) Johnson, A. W.; LaCount, R. B. Chem. Ind. (London) 1958, 1440-1441; For
reviews, see: (b) Gololobov, Y. G.; Nesmeyanov, A. N.; lysenko, V. P.; Boldeskul, I. E. Tetrahedron
1987, 43, 2609-2651; (c) Li, A. H.; Dai, L. X.; Aggarwal, V. K. Chem. Rev. 1997, 97, 2341-2372; (d)
Aggarwal, V. K.; Richardson, J. Chem. Commun. 2003, 2644-2651; (e) Aggarwal, V. K.; Winn, C. L.
Acc. Chem. Res. 2004, 37, 611-620; (f) McGarrigle, E. M.; Myers, E. L.; Illa, O.; Shaw, M. A.; Riches,
S. L.; Aggarwal, V. K. Chem. Rev. 2007, 107, 5841-5883.
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(13) Wang, Z. X.; Tu, Y.; Frohn, M.; Zhang, J. R.; Shi, Y. J. Am. Soc. Chem. 1997, 119, 11224-11235.
(14) A 2.5 g preparation of 2 was performed successfully in this lab.
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7
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(15) (a) The role of LiOTf is still not clear. Other lithium salts such as LiBF4 and LiOH did not increase
the reaction rate; (b) The catalyst loadings of other reported chiral sulfides using the same methodology
range from 100 % to 10 % and reaction times vary from 1 day to 14 days and trans stilbene oxide 8 was
obtained in 11-97 % yield with 7-97 % ee and 67/33 to 100/0 dr. See reference 12f.
(16)(a) Ratts, K. W. Tetrahedron Lett. 1966, 7, 4707-4712; (b) Cook, A. F.; Moffatt, J. G. J. Am. Chem.
Soc. 1968, 90, 740-746; (c) Christensen, A. T.; Witmore, W. G. Acta Crystallogr. B 1969, 25, 73-78; (d)
Christensen, A. T.; Thom, E. Acta Crystallogr. B 1971, 27, 581-586; for energetic profile (DFT
calculations) of benzyl ylide reaction with benzaldehyde, see: (e) Aggarwal, V. K.; Harvey, J. N.;
Richardson, J. J. Am. Chem. Soc. 2002, 124, 5747-5756.
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(17) Masdeu-Bulto, A. M.; Dieguez, M.; Martin, E.; Gomez, M. Coord. Chem. Rev. 2003, 242, 159-201.
(18) Gui, Y.; Li, J.; Guo, C.-S.; Li, X.-L.; Lu, Z.-F. Adv. Synth. Catal. 2008, 350 (16), 2483-2487.
(19) Robiette, R.; Conza, M.; Aggarwal, V. K. Org. Biomol. Chem. 2006, 4 (4), 621-623.
(20) Oudeyer, S.; Leonel, E.; Paugam, J. P.; Nedelec, J. Y. Synthesis 2004, (3), 389-400.
(21) Solladié-Cavallo, A.; Lupattelli, P.; Bonini, C. J. Org. Chem. 2005, 70 (5), 1605-1611.
(22) Zanardi, J.; Leriverend, C.; Aubert, D.; Julienne, K.; Metzner, P. J. Org. Chem. 2001, 66 (16),
5620-5623.
(23) Aggarwal, V. K.; Ford, J. G.; Fonquerna, S.; Adams, H.; Jones, R. V. H. J. Am. Chem. Soc. 1998,
120 (33), 8328-8339.
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