Two stereocentered HKR of anti -β,β′-diphenylpropanoxirane and anti -3-phenylethyloxiranes catalysed by Co(iii)(salen)-OAc complex: Enantioselective synthesis of (+)-sertraline and (+)-naproxen

Article abstract of DOI:10.1039/c8nj01616j

The Co^(III)(salen)OAc-catalyzed two stereocentered hydrolytic kinetic resolution (HKR) of anti-β,β′-diphenylmethyloxirane and anti-3-phenylethyloxiranes affords the corresponding anti-1,2-diols and oxiranes in high enantiomeric excess. The synthetic potential of this methodology is demonstrated by the enantioselective synthesis of (+)-sertraline, an antidepressant drug, and (+)-naproxen, an anti-inflammatory drug.

Full text of DOI:10.1039/c8nj01616j

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The role of atropisomers on the photo-reactivity and fatigue of
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Two Stereocentered HKR of anti-β,β’-diphenylpropanoxirane and
anti-3-phenylethyloxiranes Catalysed by Co(III)(salen)-OAc
Complex : An Enantioselective Synthesis of (+)-Sertraline and (+)-
Naproxen
avansReceived 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
Rohit B. Kamble,a,c Dattatraya Devalankar b and Gurunath Suryavanshi a*
www.rsc.org/
The Co(III)(salen)OAc catalyzed two stereocentered hydrolytic The exclusive examples contains, sertraline (1) acts as
kinetic resolution (HKR) of anti-β,β’-diphenylmethyloxirane and antidepressant,6a 2-naphthol derived (2)6b substituent used to
anti-3-phenylethyloxiranes affords corresponding anti-1,2-diols treat breast cancer, natural product podophyllotoxin (3),6c and
and oxiranes in high enantiomeric excess. The synthetic potential MK-8718 (4) an HIV protease inhibitor.6d Also these moieties
of this methodology has been shown by the enantioselec-tive were often used as basic unit in supramolecular structures
synthesis of (+)-sertraline an antidepressant drug and (+)- such as macrocycles, catenanes, and rotaxanes.6e Whereas,
naproxen an anti-inflammatory drug.
optically active 3-phenyl alkyls moieties was used from long
time as non-steroidal anti inflammatory drugs such as
naproxen (5)6f and ibuprofen an analgesic drug. These motifs
were present in number of natural products like turmerone (6)
Introduction
The substituted diarylmethanes are present in variety of which shows an promising inductors of neural stem cell
biological active pharmaceutical as well as natural products as proliferation.6g Hence, keeping the importance of such
a core unit which shows anti-inflammatory activity,1 SERMs,2 moieties in mind, we applied our methodlogy to two
dopamine transport ligands,3 NMDA receptor antagonist,4 and stereocentered
HKR
to
synthesize
eantiopure
anticancer activities5 (Fig. 1).
diphenylmethane and 3-phenyl alkyl moieties.
Previously, enantiomerically pure 3,3’-diarylsubstituted
functionality were synthesized under asymmetric hydrogenation
using transition metals such as Rh8a, Cu8b,c and organometallic 1,4-
addition on α,
β
-unsaturated compounds8d,e
.
Even though
asymmetric hydrogenation has been used as powerful approach to
synthesis of enantiopure 3,3’-diarylsubstituted compounds but to
achieve the high enantioselectivity these compounds required
assistance of a coordinating group attached to C-C bond.
Fig 2: Jacobsen Catalyst for HKR
Fig 1: Bioactive and Natural Products containing substituted diarylmethanes and
3-phenylalkyl moieties
Jacobsen’s hydrolytic and phenolic kinetic resolution (HKR &
PKR) of terminal epoxides with one stereocenter catalyzed by
Co(III)-salen complex 7 employ water and phenol as a nucleophile
9,10
respectively
(Fig. 2). Even though having impressive scope for
the HKR, it was extensively used for the resolution of terminal
epoxide with one chiral centre.11 The kinetic resolution has been
studied comprehensively to understand its mechanistic and
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synthetic aspects, that include some recent studies relating to aryl epoxides and aryl diols depending upon the chiral ligand
kinetic resolution of racemic terminal epoxides bearing adjacent C- chosen. Accordingly the racemic anti-aryl and alkyl epoxides the
O and C-N binding substituents to furnish enantiopure syn- or anti- substrates for the HKR were efficiently prepared in a highly
alkoxy and azido epoxides and the corresponding 1,2-diols.7a,12 In diastereoselective manner from the corresponding allylic alcohols
2013, Sudalai et. al. applied two stereocentered HKR to synthesis via a simple sequential steps which mainly includes (i) Heck
enantiopure substituted γ-butyrolactones and epoxy esters from coupling of phenyl methyl cinnamate 8 with arenediazonium
racemic epoxy esters bearing adjacent C-C binding substituents tetrafluoroborate 9 to obtain the (E)-β,β’- diphenylcinnamate 10. 15
(Scheme 1).13 Despite these impressive achievements HKR has only (ii) The obtained (E)-β,β’-diphenylcinnamate 10 reduced to allylic
been applied to epoxyesters to offer optically active butyrolactone.
alcohol 11 using DIBAL-H. (iii) The boranedimethylsulphide and
H2O2 mediated hydroboration of 11 offered diphenylpropan-1,2-
diol 12. (iv) Catalytic selective monotosylation and subsequent base
mediated epoxidation of 12 gives desired racemic epoxide (±)-13
(Scheme 2).
Initially, hydroboration under reflux conditions using BH3.DMS
(1.5eq.) and 30% H2O2 (2eq.) resulted in the formation of 1:1
diastereomeric mixture of (±)-12 and 14. We have noticed that
during hydroboration of allylic alcohol, epimerization at benzylic
position takes place due to less sterric difference between two aryl
substituents.
To overcome this difficulty we decided to control the reaction
parameters of hydroboration such as concentration of BH3.DMS,
temperature and time of reaction. Firstly, we changed the
temperature of reaction from reflux to ambient temperature but no
change in the diastereomeric ratio were observed instead yield of
the reaction decreased from 78 to 72% (Table1,entry b). Further we
decreased the temperature of reaction from room temperature to 0
oC, to our delight the diastereomeric ration increases to 9:1 but
reaction yield further decreases to 67% (Table1, entry c).
Scheme1
diphenylpropanoxirane
:
Two stereocentered HKR of epoxiester and anti-β,β’-
In the present work it is of interest to extend its scope to include
the terminal epoxides bearing C-C binding substituents with
different aryl groups instead of ester functionality. The aim of such
an investigation was to obtain enantioenriched aryl epoxides and
aryl diols bearing C-C binding substitution by an unswerving method
from the respective racemic materials, thus complementing other
tedious routes.14
Table No.1: Co-catalysed HKR of racemic anti-β,β’-
diphenylpropanoxirane
In this communication we wish to report a flexible, novel
single step method that employs Co-catalyzed HKR of racemic
3-substituted epoxy aryls with two stereocenters to produce
epoxy aryls bearing adjacent C-C binding substituents and
corresponding diols in high optical purities (Scheme 1).
Cl
Cl
Cl
Cl
Cl
Cl
i) A, THF,
OH
OH
Time, Temp
ii) Oxidationb
Ph HO
Ph
OH
Ph HO
11
12
14
Result and Discussion
Entry
BH3.DMS
(A)(equi.)
H2O2
(equi.)
Temp. Time Yield
dra
(12:14)
We anticipated that the extension of HKR to the two
stereocentered racemic aryl epoxides bearing C-C binding
substituents would enable us to procure both enantiomers of
(oC)
(hr)
(%)
a
b
c
1
2
2
70
25
0
8
8
8
4
78
72
67
62
1:1
1:1
1
1.5
1.5
2
9:1
d
2.5
0
>20:1
From above observation it was confirmed that temperature and
time are the key factors for determination diastereoselectivity.
Hence, we added BH3.DMS (1.5eq.) in allylic alcohol at 0 oC and
increased slowly to room temperature & kept for 4 hr followed by
addition of 30% H2O2 and NaOH (3N). To our delight this reaction
condition gave diastereoselective diol 12 with >20:1
diastereoselectivity (Table1, entry d). Hence, having optimized
reaction conditions for hydroboration reaction we synthesized
various substituted racemic diols.
However, the Heck coupling of the aryl diazonium
tetrafluoroborate bearing electron donating substituent like
methoxy and methyl with methyl cinnamate 8 resulted in the
Scheme 2 : Synthesis of racemic anti-β,β’-diphenylpropanoxirane
2 | J. Name., 2012, 00, 1-3
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inseperable mixture of diastereomers. In this scheme 2, the relative The carbon at benzylic position next to epoxide bearing high bulky
stereochemistry between the C-C binding substituent and the group such as isobutyl 17b gives the corresponding optically pure
epoxide group is established prior to the HKR itself in the epoxide 18b and diol 19b (Table 3). The change in aromatic ring i.e.
hydroboration reaction and in this way a simple asymmetric phenyl to naphthyl, there was no change in the either in optical
reaction can be used to obtain vital enantiomerically pure aryl purity or in yield (Entry c, Table 3).
epoxides and aryl diols respectively.
Thus, when HKR of
Among the various applications of this two stereocentered HKR,
the
racemic
anti-β,
β’- an enantioselective synthesis of (+)-Sertraline (1) and naproxen (5)
diphenylpropanoxirane was performed with (S,S)-Co(III)(salen)- OAc attracted our attention due to their pharmaceutical importance.
complex (5 mol%) and water (0.5 equiv), the corresponding anti-β, (+)-Sertraline (1) is a selective serotonin reuptake inhibitor (SSRI),
β’-diphenylpropanoxirane 15 yield and ee (15a-e, Table 2) and anti- discovered by Pfizer chemist Reinhard Sarges in 1970.16 For the
β, β’-diphenylpropan-1,2-diol 16 yield and ee (16a-e, Table 2) were synthesis of Sertraline chiral diol 16a was chosen as the starting
obtained.
material (Scheme 3). NaIO4 mediated oxidative cleavage of 16a to
aldehyde 20 followed by the two carbon Wittig extension afforded
α, β- unsaturated ester 21. The Pd/C catalyzed reductive
hydrogenation of unsaturated ester to 22 was achieved in 90%
yield. Followed by known protocol affords the (+)-Sertraline.
Table No.2: Co-catalysed HKR of racemic anti-β,β’- diphenylpropan
-oxirane
OH
O
O
R
OH
R
R
(S,S)-7
(0.5 mol%),
H2O (0.5 equiv)
12 h
(±)-13
(2RS, 3RS)
15
(2S,3S)
16
(2R,3R)
Entry
R (13)
Epoxide (15)
Diol (16)
Yielda
(%)
eeb
(%)
Yielda eeb
(%)
(%)
a
b
c
3,4-diChlorophenyl
4-Bromophenyl
4-Chlorophenyl
4-Flurophenyl
50
50
47
50
49
94
48
48
50
49
48
98
96
94
98
90
94
98
91
92
d
e
2-Flurophenyl
aisolated yields, bEantiomeric Excess determined by HPLC
Scheme 3. Synthesis of (+)-Sertraline
A variety of substrates were screened for the HKR process that led
to the isolated yields of product as shown in Table 2 with complete
stereocontrol.
The synthesis of (+)-Naproxen (5) commences from the
corresponding enantiopure diol 19c as shown in scheme 4. The diol
was subjected for the oxidative cleavage using sodium periodate to
give aldehyde in quantitative yield. The aldehyde was in situ
oxidized to give (+)-naproxen (5) in 90% yield (Scheme 4).
CH3
Table No.3: Co-catalysed HKR of racemic anti-3-phenylethyloxiranes
-ne
CH3 OH
(a) NaIO4, CH2Cl2,
25 oC, 1h,
COOH
95%;
OH
(b) NaClO2, NaH2PO4,
2-methylbut-2-ene,
tBuOH, H2O, 1h,
90%
O
O
19c
(+)-Naproxen (5)
Entry
Ar
R
Epoxide (18)
Diol (19)
Yielda eeb
(%) (%)
49
Scheme 4: Synthesis of (+)-Naproxen
Yielda
(%)
eeb
(%)
Conclusions
a
b
c
Phenyl
Phenyl
Methyl
Isobutyl
methyl
48
49
48
96
93
95
92
95
97
50
48
In conclusion, the (salen)Co(III)-catalyzed HKR of racemic anti-
β,β’- diphenylpropanoxirane provides a highly practical route
to the synthesis of enantiopure key intermediate anti-β,β’-
diphenylpropanoxirane and anti-β,β’-diphenylpropandiol in
single step. The key steps involved diastereoselective
hydroboration of allylic alcohol and two stereocentered HKR.
This method has been successfully applied to the
enantioselective synthesis of (+)-sertraline and (+)-naproxen.
The reaction is convenient to carry out under mild conditions,
displaying a wide range of substrate scope. We think that this
6-MeO-
Naphtahyl
aisolated yields, bEantiomeric Excess determined by HPLC
When the HKR of racemic 2-(1-phenylethyl)oxiranes carried out
under standard reaction conditions, the corresponding enantiopure
epoxides and diols was achieved in high optical purity and yield
respectively (18a-c and 19a-c, Table 3).
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HKR strategy will find enormous scope as well as applications (2S, 3S)-3-[(4-bromophenyl)-3-(phenyl)]methyloxirane: (15b)
in the synthesis of bioactive molecules owing to the flexible Yield: 50%, [α]25 -22.18 (c 0.5, CHCl3); Optical purity: 96% ee
nature of the synthesis of starting material and the ready determined from HPLC analysis [Chiral OD-H column, n-hexane/ 2-
D
availability of Co-catalysts in both enantiomeric forms.
propanol (97.5:2.5), 0.5 mL/min, 254 nm]; Retention time: tminor =
13.92 and tmajor = 15.83 min. HRMS (ESI) calculated [M+H]+ for
C15H14BrO: 289.0223, found: 289.0213
Conflicts of interest
(±)- (4-bromophenyl)-3-phenylpropane-1,2-diol (12b):
Yield: 62% (409 mg) , colorless gummy, IR(CHCl3, cm-1)- 3351
(broad), 1488, 1453, 1009, 698;1H NMR: (200 MHz, CDCl3) δ 3.21-
3.46 (m, 4H), 3.83-3.87 (d, 1H, J=8Hz), 4.22-4.28 (t, 1H, J = 6Hz),
7.13-7.29 (m, 7H), 7.35-7.40 (d, 2H, J = 10Hz); 13C NMR (50 MHz,
CDCl3) δ 54, 64.7, 73.6, 120.6, 126.9, 128.0, 128.8, 130.4, 131.6,
140.5, 141.C15H15BrO2 requires: C, 58.65; H, 4.92; found C, 58.63; H,
4.89%.
“There are no conflicts to declare”.
Experimental Section
General Procedure for Hydrolytic kinetic resolution:
To a solution of (S,S)/(R,R)-Co-salen (0.5 mol%) in toluene (2 mL),
AcOH (0.036 mmol) was added. It was allowed to stir at 25 °C in
open air for 30 min. During this time the colour changed from
orange-red to a dark brown, it was then dried under vacuum. To
(2R, 3R)-3-[(4-bromophenyl)-3-(phenyl)]propane-1,2-diol (16b)
Yield: 48%, colorless oil; [α] D25 =+30.46 (c 1, CHCl3); Optical purity:
94% ee determined from HPLC analysis [Chiral OD-H column, n-
hexane/ 2-propanol (95:05), 0.5 mL/min, 254 nm]; Retention time:
tmajor = 40.837 and tmajor = 66.29 min. IR(CHCl3, cm-1)- 3351 (broad),
1488, 1453, 1009, 698;
this racemic anti-β,β ’-diphenylmethyloxirane (1 mmol) and H2O
(0.5 mmol) was added at 0 °C. Then the reaction was allowed to stir
for 12 h at 25 °C. After completion of reaction (monitored by TLC),
the crude product was purified by column chromatography over
(±)- (4-chlorophenyl)(phenyl)methyl)oxirane (13c)
Yield: 93% (326 mg) ; colorless oil; 1H NMR (200 MHz, CDCl3) δ 2.48-
2.52 (q, 1H, J = 4Hz), 2.82-2.86 (q, 1H, J = 8Hz), 3.42-3.48 (m, 1H),
3.77-3.80 (d,1H, J = 6Hz), 7.14-7.22 (m, 5H), 7.25-7.35 (m, 4H); 13C
NMR (50 MHz, CDCl3) δ 46.4, 52.8, 54.7, 127.1, 128.4, 128.6, 128.7,
130.0, 132.8, 139.5, 140.6; C15H13ClO requires : C, 73.62; H, 5.35; Cl,
14.49; O, 6.54 found C, 73.58; H, 5.29%;
silica gel to give chiral anti-β,β ’-diphenylmethyloxirane (15a-e) and
anti- ’-diphenylpropane-1,2-diol (16a-e).
β,β
(±)-(3,4-dichlorophenyl)(phenyl)methyl) oxirane (13a)
Yield: 85%, colorless oil; IR (CHCl3, cm-1): υmax 690, 810, 904, 1081,
1209, 1371, 1443, 3062, 3390, 756; 1H NMR (200 MHz, CDCl3): δ
2.50-2.53 (m, 1H), 2.83-2.87, (m, 1H), 3.42-3.46 (m, 1H), 3.74-3.77
(m, 1H), 7.10-7.39 (m, 8H) ; 13C NMR (50 MHz, CDCl3): δ 46.3, 52.6,
54.4, 127.4, 128.0, 128.3, 128.8, 130.3, 130.5, 131.0, 132.6, 139.9,
141.3;
(2S, 3S)-3-(3,4-Dichlorophenyl)-3-(phenyl)methyl)oxirane (15a)
Yield: 50%, colourless oil; [α]D25 = -23.6 (c 1, CHCl3); Optical purity:
94% ee determined from HPLC analysis [OD-H column, n-hexane/ 2-
(2S, 3S)-3-[(4-chlorophenyl)-3-(phenyl)]methyloxirane (15c)
Yield: 48%, [α]25D=–16.14 (c 0.5, CHCl3); Optical purity: 90% ee
determined from HPLC analysis (Chiral OD-H column, n-hexane/ 2-
propanol (97.5:2.5), 0.5 mL/min, 254 nm); Retention time: tmajor
=
18.190 and tminor= 20.97 min.; HRMS (ESI) calculated [M+H]+ for
C15H14ClO: 245.0728, found: 245.0778
(±)- (4-chlorophenyl)-3-phenylpropane-1, 2-diol (12c)
Yield: 63% (351 mg); Colorless gummy; 1H NMR: (200 MHz, CDCl3) δ
3.21-3.48 (m, 4H), 3.80-3.84 (d, 1H, J = 8Hz), 4.20 (bs, 1H), 7.18 (s,
9H); 13C NMR (50 MHz, CDCl3) δ 54.0, 64.7, 73.1, 127.0, 128.1,
128.7, 128.9, 130.1. 132.5, 140.0, 141.2; C15H15ClO2 requires; C,
68.57; H, 5.75; Cl, 13.49; O, 12.18 found C, 68.51; H, 5.70%.;
(2R, 3R)-3-(4-chlorophenyl)-3-phenylpropane-1, 2-diol (16c)
Yield: 47%, [α]25D=+ 19.23 (c 1, CHCl3); Optical purity: 94% ee
determined from HPLC analysis (Chiral OD-H column, n-hexane/ 2-
propanol (97.5:2.5), 0.5 mL/min, 254 nm]; Retention time: tmajor
=
24.01 and tminor = 29.13 min. Anal. Calcd for C15H12OCl2 requires C,
64.54; H, 4.33; found C, 64.55; H, 4.35%; HRMS (ESI) calculated
[M+H]+ for C15H12Cl2O: 279.0331, found: 279.0338
(±)-3-(3,4-Dichlorophenyl)-3-phenylpropane-1,2-diol (12a)
Yield: 67%, colorless oil; IR (CHCl3, cm-1): υmax 749, 850, 1011,
1236, 1462, 1620, 2844, 3456; 1H NMR (200 MHz, CDCl3): δ 1.62 (br
s, 1H), 2.28 (br s, 1H), 3.43 (dd, J = 6.3 Hz, 11.1 Hz, 1H), 3.61 (dd, J =
3.0, 11.1 Hz, 1H), 4.00 (d, J = 9.2 Hz, 1H), 4.40 (m, 1H), 7.19-7.47 (m,
8H); 13C NMR (50 MHz, CDCl3): δ 54.1, 64.3, 73.3, 127.2, 128.0,
129.0, 130.4, 130.6, 130.7, 132.5, 140.5, 141.8;
propanol (95.5:5), 0.5 mL/min, 254 nm); Retention time: tminor
=
27.2 and tmajor = 30.607 min. HRMS (ESI) calculated [M+H]+ for
C15H15ClO2Na: 285.0653, found: 285.0645
(2R, 3R)-3-(3,4-dichlorophenyl)-3-phenylpropane-1,2-diol (16a)
Yield: 48%, colourless oil; [α]D = -28.5 (c 1, CHCl3); Optical purity:
98% ee determined from HPLC analysis [Chiral OD-H column, n-
(±)- (4-fluorophenyl)(phenyl)methyl)oxirane (13d)
25
Yield: 86% (245 mg) ; Colorless oil; 1H NMR: (200 MHz, CDCl3) δ
2.47-2.51 (q, 1H, J = 4Hz), 2.82-2.86 (q, 1H, J = 4Hz), 3.42-3.48
(m,1H), 3.78-3.82 (d,1H, J = 8Hz), 6.94-7.03 (t, 2H, J = 10Hz), 7.16-
7.23 (m, 5H), 7.25-7.31 (m, 2H); 13C NMR (50 MHz, CDCl3) δ
45.2,52.6, 63.0, 115.2-115.8 (d, J = 21 Hz), 126.6, 128.2, 129.4,
130.1-130.4 (d, J = 8Hz), 137.0, 141.2, 164.5; C15H13FO requires C,
78.93; H, 5.74; F, 8.32; O, 7.01 found C, 78.87; H, 5.69;
hexane/ 2-propanol (90:10), 0.5 mL/min, 254 nm]; Retention time:
t
minor = 45.637 and tmajor = 50.037 min.; IR (CHCl3, cm-1): υmax 749,
850, 1011, 1236, 1462, 1620, 2844, 3456; Anal. Calcd for
C
15H14O2Cl2 requires C, 60.63; H, 4.75; found C, 60.75; H, 4.70%.
HRMS (ESI) calculated [M+H]+ for C15H14Cl2ONa: 319.0264, found:
319.0263
(2S , 3S)-3-(4-fluorophenyl)(phenyl)methyl)oxirane (15d)
Yield: 50 %, colorless oil; [α]25D =+2.82 (c 0.5, CHCl3);Optical purity:
98% ee determined from HPLC analysis [Chiral OD-H column, n-
hexane/ 2-propanol (97.5:2.5), 0.5 mL/min, 254 nm]; Retention
time: tmajor = 10.157 and tminor = 11.353 min. HRMS (ESI) calculated
[M+H]+ for C15H13FONa: 251.0843, found: 251.0841
(±)- (4-bromophenyl)(phenyl)methyl)oxirane (13b)
Yield: 92% (352 mg) , colorless gummy; 1H NMR: (200 MHz, CDCl3) δ
2.46-2.50 (q, 1H, J=4Hz), 3.40 (3.47 (m, 1H), 3.74-3.78 (d, 1H, J =
8Hz), 7.11-7.26 (m,6H), 7.30-7.35 (m, 1H), 7.38-7.45 (dt, J = 8Hz,
2H); 13C NMR (50 MHz, CDCl3) δ 46.4, 52.9, 54.6, 120.9, 127.1,
128.4, 128.7, 131.4, 131.6, 140.1, 140.5; Anal. Calcd for C15H13BrO
requires C, 62.30; H, 4.53; Br, 27.63; O, 5.53; found C, 62.28; H,
4.52%.
(±)- (4-fluorophenyl)-3-phenylpropane-1, 2-diol (12d)
Yield: 68% (308 mg); Colorless gummy; 1H NMR: (200 MHz, CDCl3) δ
3.01(bs, 2H), 3.26-3.52 (m,2H), 3.89-.394 (d,1H, J = 10Hz), 4.26-4.32
4 | J. Name., 2012, 00, 1-3
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(t, 1H, J = 6Hz), 6.91-6.99 (m. 4H), 7.16-7.29 (m, 5H); 13C NMR (50 Yield: 46%, [α]25 = –4.33 (c 1, CHCl3), Optical purity 92% ee
D
MHz, CDCl3) δ 53.9, 64.7, 74.0, 115.3-115.8 (d, J = 21Hz), 126.9, determined from HPLC analysis (Chiral AD-H column, n-hexane/ 2-
128.1, 128.8, 130.1-130.2 (d,
J = 8Hz), 136.9, 141.4, 164.1; propanol (90:10); Retention time: tminor = 25.4 and tmajor = 28.067
C15H15FO2 requires C, 73.15; H, 6.14; F, 7.71; O, 12.99 found C, min HRMS (ESI) calculated [M+]+ for C10H14O2Na: 189.0886 found:
73.09; H, 6.11;
189.0887
(2R, 3R)-3-(4-fluorophenyl)-3-phenylpropane-1, 2-diol (16d)
(±)-3-methyl-1-phenylbutyloxirane (17b)
Yield: 49%, [α]25D= –122.4 (c 1, CHCl3);Optical purity: 91% ee Yield: 89% (290 mg); Colorless Oil; 1H NMR (200 MHz, CDCl3) δ 0.85-
determined from HPLC analysis [Chiral OD-H column, n-hexane/ 2- 0.89 (dd, 6H, J = 2.53 and 4 Hz), 1.40-1.60 (m,1H), 1.70-1.82 (m,
propanol (90:10), 0.5 mL/min, 220 nm]; Retention time: tminor
=
2H),2.2-2.4 (q, 1H, J = 7.58 Hz),2.46-2.50 (q, 1H, J = 2.78 Hz), 2.63-
26.78 and tmajor = 29.63 min.; HRMS (ESI) calculated [M+H]+ for 2.67(q, 1H, J = 4Hz), 2.94-3.01 (m, 1H),7.5-7.35 (m, 5H); 13C NMR
C15H15FO2Na: 269.0948, found: 269.0940
(100 MHz, CDCl3) 21.8, 23..5, 25.2, 42.3, 46.5, 47.0, 56.8, 126.8,
127.9, 128.6 ; C13H18O requires C, 82.06; H, 9.54; O, 8.41 found C,
(±)- (2-fluorophenyl)(phenyl)methyl)oxirane (13e)
Yield: 89% (290 mg); Colorless Oil; 1H NMR (200 MHz, CDCl3) δ 2.52- 82.10; H, 9.52
2.56 (q, 1H, J= 2.66 Hz), 2.88-2.92 (q, 1H, J = 3.91 Hz), 3.56-3.63 (m, (R)-2-((R)-3-methyl-1-phenylbutyl)oxirane (18b)
1H), 4.25-4.28 (d, 1H, J = 6.4 Hz), 7.03-7.10 (m, 1H), 7.13-7.18 (m, Yield: 47%, [α]25 =+ 6.84 (c 1, CHCl3), Optical purity 92% ee
D
1H), 7.31-7.43 (m, 7H); 13C NMR (50 MHz, CDCl3) δ 46.2, 46.6, 53.8, determined from HPLC analysis (Chiral AD-H column, n-hexane/ 2-
115.4 (d, J = 23 Hz), 124.1 (d, J = 2.87 HZ), 127.0, 128.3, 128.5, propanol (90:10); Retention time: t major = 9.673 and t minor = 11.977
128.6, 129.9, (d, J = 3.83 Hz), 140.1; C15H13FO requires C, 78.93; H, min;
5.74; F, 8.32; O, 7.01 found C, 78.88; H, 5.72;
(±)-5-methyl-3-phenylhexane-1,2-diol (12g)
Yield: 84% (363 mg); White solid; H NMR (200 MHz, CDCl3) δ 0.81-
1
(2R, 3R)-3-(2-fluorophenyl)(phenyl)methyl)oxirane (15e)
Yield: 49%, colorless oil; [α]25 = –26.85 (c 0.5, CHCl3), Optical purity 0.85 (dd, 6H,J = 1.64 and 6.57 Hz), 1.17 -1.36 (m, 1H), 1.66-1.79(m,
D
90% ee determined from HPLC analysis [Chiral OD-H column, n- 2H), 1.98 (bs, 2H), 2.66-2.77 m, 1H), 3.21-3.41 (m, 2H), 3.60-3.75
hexane/ 2-propanol (97.5:2.5) Retention time: tminor = 16.253 and (m,1H), 7.13-7.16( dd, 2H, J = 6Hz);13C NMR (100 MHz, CDCl3) δ
tmajor = 17.317 min. HRMS (ESI) calculated [M+H]+ for C15H13FONa: 21.1, 24.2, 25.1, 65.2, 76.3, 126.9, 128.2, 128.6, 141.6; C13H20O2
251.0843, found: 251.0840
requires C, 74.96; H, 9.68; O, 15.36 found C, 74.99; H, 9.67;
(±)-(2-fluorophenyl)-3-phenylpropane-1, 2-diol (12e)
(2S, 3S)-5-methyl-3-phenylhexane-1,2-diol (19b)
Yield: 65% (352 mg) ; Colorless gummy; 1H NMR (200 MHz, CDCl3) δ Yield: 50%, [α]25D= – 17.94 (c 1, CHCl3); Optical purity 92% ee
2.88 (bs, 1H), 2.97 (bs, 1H), 3.28-3.33 (q, 1H, J = 6Hz), 3.46-3.49 (d, determined from HPLC analysis (Chiral AD-H column, n-hexane/ 2-
1H, J = 11.4 Hz), 4.29-4.31 (d, 1H, J = 9 Hz), 4.35-4.39 (t, 1H, J = 7Hz), propanol (90:10); Retention time: tminor = 25.4 and tmajor = 28.067
6.93-6.96 (dt, 1H, J = 10 Hz), 7.02-7.08 (m, 1H), 7.11-7.23 (m, 5H), min.; HRMS (ESI) calculated [M+H]+ for C13H20O2Na: 231.1356
7.27-7.33 (m, 1H), 7.41-7.45 (dt, 1H, J = 1.83, 7 Hz); 13C NMR (50 found: 231.1355
MHz, CDCl3) δ 47.0, 64.8, 73.2, 115.6 (d, J = 23 Hz), 124.1 (d, J = 3.84 (±)-1-(6-methoxynaphthalen-2-yl) ethyl) oxirane (17c)
1
Hz), 126.9, 128.2, 128.3, 128.1, 128.9, 129.3 (d, J = 3.84), 140.6, Yield: 86% (231 mg); Colorless Oil; H NMR (200 MHz, CDCl3) δ 1.37-
159.9, 162.4; C15H15FO2 requires C, 73.15; H, 6.14; F, 7.71; O, 12.99 1.41 (d, 3H, J = 8Hz), 2.55-2.59 (q, 1H, J = 2Hz), 2.82 (q, 1H, J = 4Hz),
found C, 73.12; H, 6.09;
2.84-2.97 (q, 1H, J = 6Hz), 3.10-3.17 (m, 1H), 7.09-7.14 (m, 2H),
7.34-7.39 (dd, 1H, J = 6Hz), 7.60-7.70 (t, 3H, J = 8Hz, 12Hz) 13C NMR
(2S, 3S)-3-(2-fluorophenyl)-3-phenylpropane-1, 2-diol (16e)
Yield: 48%, [α]25 = +6.25 (c 1, CHCl3), Optical purity 92% ee (50 MHz, CDCl3) δ 17.0, 41.3, 45.8, 55.2, 56.4, 105.5, 118.9, 125.7,
D
determined from HPLC analysis (Chiral AD-H column, n-hexane/ 2- 126.6, 126.9, 129.0, 129.2, 133.6, 137.8, 157.5; C15H16O2 requires C,
propanol (90:10); Retention time: tmajor = 25.810 and tminor = 30.13
78.92; H, 7.06; O, 14.02 found C, 78.89; H, 7.04 ;
min. HRMS (ESI) calculated [M+H]+ for C15H15FO2Na: 269.0948 (2R, 3R)-3-(6-methoxynaphthalen-2-yl) ethyl) oxirane (18c)
found: 269.0940
Yield: 50%, [α]25
=
+8.42 (c 1, CHCl3), Optical purity 93% ee
D
(±)-1-phenylethyl oxirane (17a)
determined from HPLC analysis (Chiral AD-H column, n-hexane/ 2-
Yield: 89% (261 mg); Colorless Oil; 1H NMR (200 MHz, CDCl3) δ 1.30- propanol (90:10) Retention time: tmajor = 14.36 and tmajor = 19.88
1.33 (d, 3H, J = 6 Hz), 2.52-2.56 (q, 1H, J = 2, 4Hz), 2.70-2.84 (m, 2H), min. HRMS (ESI) calculated [M+H]+ for C15H17O2: 229.1223 found:
3.04-3.10 (m, 1H, J = 2 and 6Hz), 7.18-7.26 (m, 2Hz), 7.29-7.36 (m, 229.1223
3H); 13C NMR (50 MHz, CDCl3) δ 17.0, 41.3, 45.7, 56.3, 126.7, 127.5, (±)-3-(6-methoxynaphthalen-2-yl) butane-1, 2-diol (12h)
128.5, 142.7; C10H12O requires C, 81.04; H, 8.16; O, 10.80 found C, Yield: 82 % (291 mg); Colorless Oil; 1H NMR (200 MHz, CDCl3) δ
81.05; H, 8.18;
1.31-1.34 (d, 3H, J = 6Hz), 2.06 (bs, 2H), 2.89-3.03 ( m, 1H), 3.49-
3.58 (q, 1H, J = 6Hz, 4Hz), 3.74-3.83 (dt, 2H, J = 10Hz, 4Hz), 3.91 (s,
(2R, 3R)-3-phenylethyl-2,3-oxirane (18a)
Yield: 49%, [α]25 = +10.07 (c 1, CHCl3), Optical purity 96% ee 3H), 7.09-7.154 (m, 2H), 7.29-7.34 (dd, 1H, J = 8Hz), 7.57 (s, 1H),
D
determined from HPLC analysis (Chiral AD-H column, n-hexane/ 2- 7.64-7.70 ( dd, 2H, J = 4Hz, 8Hz); C15H18O3 requires C, 73.15; H, 7.37;
propanol (97.5:2.5)]; Retention time: tminor = 10.23 and tmajor = 11.79 O, 19.49 found C, 73.12; H, 7.38;
min.; HRMS (ESI) calculated [M+H]+ for C10H13O: 149.0961 found: (2S, 3S)-3-(6-methoxynaphthalen-2-yl) butane-1, 2-diol (19c)
149.0961
(±)-3-phenylbutane-1, 2-diol (12f)
Yield: 48%, [α]25D= –76.5 (c 1, CHCl3), Optical purity 97% ee
determined from HPLC analysis (Chiral AD-H column, n-hexane/ 2-
1
Yield: 82% (339 mg); Colorless Oil; H NMR (200 MHz, CDCl3) δ 1.27- propanol (90:10); Retention time: tminor = 19.10 and tmajor = 20.407
1.30 (d, 3H, J = 6Hz), 1.99 (bs, 2H), 2.79-2.94 (qui, 1H, J = 7Hz), 3.49- min. HRMS (ESI) calculated [M+H]+ for C15H18O3Na: 269.1148 found:
3.82 (m, 3H), 7.16-7.26 (m, 3H), 7.28-7.38 (m, 2H); 13C NMR (50 269.1148
MHz, CDCl3) δ 17.9, 42.9, 64.5, 76.3, 127.0, 128.0, 128.8, 143.1; Synthesis of Sertraline:
C10H14O2 requires C, 72.26; H, 8.49; O, 19.25 Found C, 72.24; H, (R)-2-(3,4-Dichlorophenyl)-2-phenylacetaldehyde (20)
8.44;
To stirred solution of diol (-)-15b ( 1 g, 3.3 mmol) in ethanol/H2O (15
mL, 2:1) at 20 oC, NaIO4 (0.863 g, 4.0 mmol) was added and the
(2S, 3S)-3-phenylbutane-1, 2-diol (19a)
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reaction mixture was stirred for 4 h. After completion of reaction Yield: 90%; White amorpous solid; [α]D = +61.1 (c = 0.50, CH2Cl2)
25
(monitored by TLC), it was quenched with water (10 mL) and {lit.18 [α]D = 60.09 (c = 0.56, CH2Cl2)}, 1H NMR (500 MHz, CDCl3 ): δ
product was extracted with EtOAc (3 x 20 mL). The combined 1.62 (d, 3H, J = 7.2 Hz), 3.86 - 3.91 (m, 1H), 3.93 (s, 3H), 7.09 - 7.21
organic phases were dried over anhydrous Na2SO4 and (m, 2H), 7.44 (dd, 1H, J = 8.6, 1.7 Hz), 7.65 - 7.81 (m, 3H); 13C NMR
concentrated to give the crude product 12 which was taken up for (126 MHz, CDCl3): δ 18.1 , 45.3, 55.3 , 105.6, 119.0, 126.1, 126.2,
further reaction without purification.
127.2, 128.9, 129.3, 133.8, 134.8, 157.7, 181.0. These spectroscopic
25
Yield: 82%, colorless oil; [α]D = +4.2 (c 1, CHCl3); IR (CHCl3, cm-1): data correspond to reported data.12
υmax 698, 1030, 1136, 1178, 1380, 1448, 1466, 1720, 2853, 2929 ; 1H
NMR (200 MHz, CDCl3): δ 4.85 (d, J = 1.3 Hz, 1H), 7.24 -7.52 (m, 8H),
9.92 (d, J = 1.2 Hz, 1H); 13C NMR (50 MHz, CDCl3) δ 45.4, 126.7,
127.2, 128.9, 129.1, 129.4, 130.7, 132.9, 133.3, 138.8, 139.5, 197.2;
Anal. Calcd for C14H10OCl2 requires C, 63.42; H, 3.80; found C, 63.45;
H, 3.81%.
Notes and references
1
2
S. Cardinal, P-A. Paquet-Côté , J. Azelmat , C. Bouchard , D.
Grenier , N. Voyer, Bioorganic & Medicinal Chemistry, 2017,
25, 2043.
a) I. Shiina, Y. Sano, K. Nakata, M.Suzuki, T. Yokoyama, A.
Sasaki, T. Orikasa, T. Miyamoto, M. Ikekita, Y. Nagahara, Y.
Hasome, Bioorg. Med. Chem., 2007, 15, 7599, b) T. Kojima ,
T. Ogawa, S. Kitao , M. Sato , A. Oda , K. Ohta , Y. Endo,
Bioorganic & Medicinal Chemistry , 2015, 23, 6900.
a) P.S. Kharkar, A. M. Batman, J. Zhen, P. M. Beardsley, M. E.
Methyl (R, E)-4-(3,4-dichlorophenyl)-4-phenylbut-2-enoate (21)
To a solution of aldehyde 19 (0.9 g, 3.55 mmol) in dry benzene (25
mL), was added Ph3P=CHCO2Me (1.42 g, 4.26 mmol) at 25 oC. The
reaction mixture was refluxed for 10 h, and then quenched with
water (5 mL). The product was extracted with EtOAc (3 x 20 mL) and
washed with water (3 x 15 mL). The combined organic phases were
dried over anhydrous Na2SO4 and concentrated to give the crude
products which upon column chromatographic purification with
silica gel using petroleum ether: ethyl acetate (8:2) as eluent gave
pure 20 as colourless oil.
3
A. Reith, A. K. Dutta, ChemMedChem, 2009, 4, 1075, b) L-W.
Hsin, C. M. Dersch, M. H. Baumann, D. Stafford, J.R. Glowa,
R. B. Rothman, A. E. Jacobson, K. C. Rice, J. Med. Chem.
2002, 45, 1321, (c) S.P. Runyon, F. I.Carroll, Current Topics in
25
Yield: 92%, colourless oil; [α]D = +1.2 (c 1, CHCl3) {lit.9[α]D20 +1.0 (c
Medicinal Chemistry, 2006, 6, 1825-1843 (d) J. Cao, R. D.
1.12, CHCl3)}; IR (CHCl3, cm-1): υmax 636, 700, 818, 918, 983, 1030,
1130, 1170, 1377, 1652, 1713, 2946; 1H NMR (200 MHz, CDCl3): δ
3.75 (s, 3H), 4.84 (d, J = 7.3 Hz, 1H), 5.75 (d, J = 15.6 Hz, 1H), 7.09
(m, 1H), 7.26-7.42 (m, 8H); 13C NMR (50 MHz, CDCl3): δ 51.6, 52.3,
123.1, 127.2, 127.8, 128.4, 128.9, 130.3, 130.9, 133.3, 140.2, 141.6,
148.6, 165.2; Anal. Calcd for C17H14O2Cl2 requires C, 63.57; H, 4.39;
found C, 63.60; H, 4.40%.
Slack, O. M. Bakare, C. Burzynski,R. Rais, B. S. Slusher, T.
Kopajtic, A. Bonifazi, M. P. Ellenberger, H. Yano, Y. He, G-H.
Bi,Z.-X. Xi, C. J. Loland, A. H. Newman, J. Med. Chem. 2016,
59, 10676, e) J. Lee, S. U. Kang, J. O. Lim, H. K. Choi, M. K. Jin,
A. Toth, L. V. Pearce, R. Tran, Y. Wang, T. Szabo, P. M.
Blumberg, Bioorg. Med. Chem., 2004, 12, 371, f) J. G.
Cumming, A. E.Cooper, K. Grime, C. J. Logan, S. McLaughlin,
J. Oldfield, J. S. Shaw, H. Tucker, J. Winter, D. Whittaker,
Bioorg. Med. Chem. Lett., 2005, 15, 5012;
(a) S. T. Moe, D. L. Smith, E. G. DelMar, S. M. Shimizu, B. C.
Van Wagenen, M. F. Balandrin, Y. Chien, J. L. Razkiewicz, L. D.
Artman, H. S. White, A. L. Mueller, Bioorg. Med. Chem. Lett.,
2000, 10, 2411;
a) V. Srivastava, A. S. Negi, J. K. Kumar, M. M. Gupta and S. P.
S. Khanuja, Bioorg. Med. Chem., 2005, 13, 5892, b) D. E.
Schteingart, J. E. Sinsheimer, R. S. Benitez, D. F. Homan, T. D.
Johnson and R. E. Counsell, Anticancer Res., 2012, 32,
2711,c) Q. Hu, L. Yin, C. Jagusch, U. E. Hille, R. W. Hartmann,
J. Med. Chem. 2010, 53, 5049.
a) Welch, W. M. Adv. Med. Chem. 1995, 3, 113; b) B. Das, C.
R. Reddy, J.Kashanna, S. K.Mamidyala, C. G.Kumar, Med
Chem Res, 2012, 21, 3321, (c) A. L. Eyberger, R. Dondapati, J.
R.Porter, J. Nat. Prod., 2006, 69, 1121; d) C. J. Bungard, P.D.
Williams, J. E. Ballard, et al., ACS Med.Chem.Lett., 2016, 7,
702; For more specific biological activities of diphenylmethyl
moiety please see ref. D. Ameen, T. J. Snape, Med. Chem.
Comm., 2013, 4, 893; e) J. C. Ma, D. A. Dougherty, Chem.
Rev. 1997, 97, 1303, f) Brogden, R. N.; Heel, R. C.; Speight, T.
M.; Avery, G. S. Naproxen Up to Date: a Review of Its
Pharmacological Properties and Therapeutic Efficacy and Use
in Rheumatic Diseases and Pain States. Drugs, 1979, 18, 241.
g) J. Hucklenbroich, R. Klein, B.Neumaier, R. Graf, G. R.Fink,
M. Schroeter, M. A. Rueger, Stem Cell Research & Therapy
(R)-Methyl-4-(3,4-dichlorophenyl)-4-phenylbutanoate (22)
To a solution of ester 20 (0.85 g, 2.66 mmol) in methanol (20 mL),
was added 10% Pd/C (60 mg) and stirred under hydrogen
atmosphere (1 atm) at 25 oC. The reaction mixture was further
stirred at 25 oC for 6 h, and the progress monitored by TLC. After
completion of reaction, it was filtered through a Celite pad and
washed with EtOAc (3 x 20 mL). The combined organic phase was
concentrated under vacuum. The crude product thus obtained was
purified by column chromatography on silica gel using using
petroleum ether: ethyl acetate (8:2) as eluent to give pure 21 as
colorless oil.
4
5
6
25
20
Yield: 94%, colorless oil; [α]D = -6.0 (c 1, CHCl3) {lit.17 [α]D -6.1 (c
1.12, CHCl3)}; IR (CHCl3, cm-1): υmax 680, 2970, 1202, 1365, 1494,
1600, 1722, 2930; 1H NMR (200 MHz, CDCl3): δ 2.21-2.38 (m, 4H),
3.64 (s, 3H), 3.85-3.94 (m, 1H), 7.15-7.31 (m, 8H); 13C NMR (50 MHz,
CDCl3): δ 30.2, 32.0, 50.4, 51.4, 126.3, 127.1, 127.6, 127.8, 128.4,
128.7, 129.7, 130.4, 132.5, 142.6, 144.5, 173.0; Anal. Calcd for
C
17H16O2 Cl2 requires C, 63.17; H, 4.99; found C, 63.21; H, 4.87 %.
(S)-2-(6-methoxynaphthalen-2-yl)propanal 18
25
,2014, 5, 100
Yield: 95%, White Solid; [α]D = +62.2 (c = 0.5, CH2Cl2), {[α]D28 64.42
7
(a) R. S. Reddy, P. V. Chouthaiwale, G. Suryavanshi, V. B.
Chavan and A. Sudalai, Chem. Commun., 2010, 46, 5012; (b)
D. A. Devalankar, P. V.Chouthaiwale, A. Sudalai, Tetrahedron:
Asymmetry. 2012, 23, 240; (c) R. B. Kamble, S. H. Gadre,
G.Suryavanshi, Tetrahedron Lett. 2015, 56, 1263; (d) Rohit B.
Kamble & Gurunath Suryavanshi (2018): Synthesis of key
intermediate for (+)-tofacitinib through CoIII(salen)-catalyzed
two stereocentered hydrolytic kinetic resolution of (±)-
1
(c = 0.55, CH2Cl2)}, H NMR (400 MHz, CDCl3): δ 1.54 (d, 3H, J = 6.8
Hz), 3.77 (q, 1H, J = 7.0 Hz), 3.93 (s, 3H), 7.10 - 7.25 (m, 2H), 7.29
(dd, 1H, J = 8.3, 1.5 Hz), 7.61 (s, 1H), 7.77 (d, 1H, J = 8.3 Hz), 7.73 (d,
1H, J=8.8 Hz), 9.66 - 9.94 (m, 1H) ; 13C NMR (101 MHz, CDCl3): δ
14.6, 52.8, 55.2, 105.5, 119.2, 126.6, 126.9, 127.6, 129.0, 129.1,
132.6, 133.8, 157.8, 201.1.
(+)-Naproxen (5)
6 | J. Name., 2012, 00, 1-3
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methyl-3-(oxiran-2-yl)butanoate, Synthetic Communications,
DOI: 10.1080/00397911.2018.1434204
8
(a) Q. Yan, D. Kong, M. Li, G. Hou, G. Zi, J. Am. Chem. Soc.,
2015, 137, 10177; (b) K. Yoo, H. Kim, J. Yun, Chem. Eur. J.
2009, 15, 11134; (c) D. Lee, Y. Yang, J.Yun, Org.Lett., 2007, 9,
2749; (d) K. Takatsu, R. Shintani,T. Hayashi, Angew. Chem.
Int. Ed,. 2011, 50, 5548; (e) S. Sörgel, N. Tokunaga, K. Sasaki,
K. Okamoto, T. Hayashi, Org. Lett., 2008, 10, 589.
9
(a) S. E. Schaus, B. E. Brandes, J. F. Larrow, M. Tokunaga, K. B.
Hansen, A. E. Gould, M. E. Furrow, E. N. Jacobsen, J. Am.
Chem. Soc., 2002, 124, 1307; (b) J. M. Ready, E. N. Jacobsen,
J. Am. Chem. Soc., 1999, 121, 6086.
10 M. Tokunaga; J. F. Larrow; F. Kakiuchi, E. N. Jacobsen,
Science, 1997, 277, 936.
11 P.Kumar, P. Gupta, Synlett, 2009, 9, 1367
12 (a) D. A. Devalankar, P. V. Chouthaiwale, A. Sudalai, Synlett,
2014, 25, 102; (b) P. U Karabal, D. A. Kamble, A. Sudalai, Org.
Biomol. Chem., 2014, 12, 2349.
13 D. A. Devalankar, P. U. Karabal, A. Sudalai, Org. Biomol.
Chem., 2013, 11, 1280.
14 S. Takano, M. Yanase, K. Ogsawara, Heterocycles, 1989, 29
,
249.
15 J. C. Pastrea, C. R. D. Correia, Adv. Synth. Catal., 2009, 351
1217.
,
16 R. Sarges, J. R. Tretter, S. S. Tenen, A. Weissman, J. Med.
Chem., 1973, 16, 1003.
17 A. Alexakis, S. E. Hajjaji, D. Polet, X. Rathgeb, Org. Lett., 2007,
9, 3393.
18 L. Zhang, , Z. Zuo, X. Wan, Z. Huang , J .Am.Chem.Soc., 2014,
136, 15501.
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DOI: 10.1039/C8NJ01616J
Two Stereocentered HKR of anti-β,β’-diphenylpropanoxirane and anti-3-
phenylethyloxiranes Catalysed by Co(III)(salen)-OAc Complex : An
Enantioselective Synthesis of (+)-Sertraline and (+)-Naproxen
Rohit B. Kamble, Dattatray Devalankar and Gurunath Suryavanshi*
The Co(III)(salen)OAc catalyzed two stereocentered hydrolytic kinetic resolution (HKR) of anti-
β,β’-diphenylmethyloxirane and anti-3-phenylethyloxiranes affords corresponding anti-1,2-diols
and oxiranes in high enantiomeric excess. The synthetic potential of this methodology has been
shown by the enantioselective synthesis of (+)-sertraline an antidepressant drug and (+)-
naproxen an anti-inflammatory drug.