A concise diastereoselective synthesis of 5′-epi synargentolide-B

Article abstract of DOI:10.1016/j.tet.2015.06.080

A concise linear synthesis of 5′-epi synargentolide-B has been accomplished with i) catalytic asymmetric transfer hydrogenation for the genesis of chirality, ii) regioselective Sharpless asymmetric dihydroxylation iii) a vinylogous Mukaiyama aldol reactio

Full text of DOI:10.1016/j.tet.2015.06.080

Tetrahedron 71 (2015) 5472e5477
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
A concise diastereoselective synthesis of 50-epi synargentolide-B
,
b
,
a
a
Gullapalli Kumaraswamya , Nimmakayala Raghu , Neerasa Jayaprakash ,
*
Kukkadapu Ankamma a
a Organic & Biomolecular Chemistry Division, Indian Institute of Chemical Technology, Hyderabad 500 607, India
b Academy of Scientific and Innovative Research, India
a r t i c l e i n f o
a b s t r a c t
A concise linear synthesis of 50-epi synargentolide-B has been accomplished with i) catalytic asymmetric
transfer hydrogenation for the genesis of chirality, ii) regioselective Sharpless asymmetric dihydrox-
ylation iii) a vinylogous Mukaiyama aldol reaction to ensure 5,6-dihydro-2H-pyran-2-one reactions as
pivotal steps.
Article history:
Received 6 May 2015
Received in revised form 18 June 2015
Accepted 20 June 2015
Available online 26 June 2015
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
50-epi Synargentolide-B
Asymmetric transfer hydrogenation
Mukaiyama aldol
5,6-Dihydro-a-pyrones
Sharpless’ AD reaction
1. Introduction
pyran-2-one.5 Subsequently, a couple of synthetic routes for 5,6-
dihydro-
prevalent approach used for the introduction of 5,6-dihydro-a-
a
-pyrone 1b have been reported6 (Fig. 1). Thus far, the
A significant number of natural products with the underlying
structural pattern of the 5,6-dihydro-
a
-pyrones were isolated from
pyrone is the ring-closing metathesis protocol, and an alternative
dihydroxy stereogenic motif was installed from either the chiral
auxiliaries or resident chirality, thereby restricting the potential to
introduce stereochemical diversity.
various plants.1 Owing to their privileged 6-substituted
a
-pyrone
scaffold, these natural product molecules exhibit potent inhibitory
activities.2 Among them, the intriguing natural product of three
bioactive 5,6-dihydro-a-pyrones, which were isolated initially as
minor constituents from Hyptis oblongifolia were shown in diverse
structural prototypes. Furthermore, their structures were eluci-
dated with the relative stereochemistry of their stereogenic centers
as 60R-[50R, 60S-(diacetoxy)-10R-(hydroxy)-20R-(methoxy)-30E-hep-
tenyl]-5,6 dihydro-2H-pyran-2-one 1a, 60R-[50R, 60S-(diacetoxy)-
10S,
20R-(dihydroxy)-30E-heptenyl]-5,6-dihydro-2H-pyran-2-one
1b, and the respective derivative 60R-[10R,20R,50R,60S-(tetraacety-
loxy)-30E-heptenyl]-5,6-dihydro-2H-pyran-2-one 1c by means of
spectral, chiro-optical and chemical evidence.3
Later, this generic structural motif was also found in a family of
natural product synargentolides AeE, as isolated from Syncoloste-
mon argenteus by Rivett’s group.4 Subsequently, total synthesis of
synargentolides B (1b) ensued and the structure was not only val-
idated as its tetraacetate by X-ray crystallography, but was
also assigned absolute stereochemistry unequivocally as 6R-[5R,
6S-(diacetoxy)-1S, 2R-(dihydroxy)-3E-heptenyl]-5,6-dihydro-2H-
Fig. 1. Diastereomers of synargentolide-B.
2. Results and discussion
The intriguing stereochemical diversity coupled with the
promising biological activities of the family of synargentolides led
* Corresponding author. Tel.: þ91 40 27193154; fax: þ91 40 27193275; e-mail
address: gkswamy_iict@yahoo.co.in (G. Kumaraswamy).
http://dx.doi.org/10.1016/j.tet.2015.06.080
0040-4020/Ó 2015 Elsevier Ltd. All rights reserved.

G. Kumaraswamy et al. / Tetrahedron 71 (2015) 5472e5477
5473
us to initiate a general synthetic protocol for the family of syn-
argentolides in general and in particular the development of a ste-
reo-divergent route for the synthesis of a diastereoisomer of
synargentolide B (1d). In our continuous design of shorter and
simpler synthetic routes for bioactive molecules,7 herein we report
a potential stereo-divergent route for the synthesis of a di-
astereoisomer of synargentolide B (1d) based on the following
three catalytic steps: (a) a catalytic asymmetric transfer hydroge-
nation (CATHy) reaction, (b) catalytic asymmetric dihydroxylation,
and (c) catalytic vinylogous Mukaiyama aldol condensation.
At the outset, we envisioned that the pyrone motif of 1d could
be installed by a catalytic vinylogous Mukaiyama aldol reaction
employing precursor aldehyde derived from 2 and silyl dienolate.
We choose the enantioenriched hydroxy furyl moiety 4 to generate
a five-carbon unit embedded with hydroxy-prochiral keto func-
tionality 3 that in turn will become a logical tool to achieve the
intended regioselective catalytic asymmetric dihydroxylation. The
stereogenic center in 4 could be derived through catalytic asym-
metric transfer hydrogenation, presenting the option of generating
both enantiomers with a low level of catalyst loading.8 The prob-
able corresponding retrosynthesis is exemplified in Scheme 1.
Scheme 2. Synthesis of bis-TBS ether dienoate 9.
rather than the a,b
-unsaturated double-bond ester.11 The diene 9
was initially exposed to 1.0 mol % of (DHQD)2PHAL, 1.1 mol % of
K2OsO4$2H2O, 3 equiv of K3Fe(CN)6e, and K2CO3 each, and 1.0 equiv
MeSO2NH2 in 1:1 tBuOH:H2O, stirring for 48 h at 0 ꢀC yielded, only
a trace amount of the product (Table 1, entry 1).
Table 1
Asymmetric dihydroxylation of ethyl dienoate 9
Entry
Ligand
Yield, % (10)a,c
drd
Scheme 1. Retro-synthetic analysis of 1d.
1
2
3
4
5
6
7
8
(DHQD)2PHAL (1 mol %)
(DHQD)2PHAL (1 mol %)
(DHQD)2PHAL (3 mol %)
(DHQD)2PHAL (5 mol %)
(DHQD)-9 phen (5 mol %)
(DHQD)2PYR (5 mol %)
(DHQD)2AQN (5 mol %)
(DHD)2PHAL (5 mol %)
Traceb
20
40
87
35
75
40
5
NDe
90:10
90:10
90:10
60:40
96:4
Our synthesis commenced with a commercially available furyl
ketone 5, which was reduced asymmetrically with the (S,S)-Noyori
catalyst (0.1 mol %) to afford the enantioenriched secondary alcohol
4 at a yield of 95% with >98% ee.8 Then, protection of secondary
alcohol as TBS-ether 6 (TBDMSCl, imidazole, DCM) followed by the
74:26
NRf
a
All reactions were carried out on a scale of 0.5 mmol using 5.0 mol % of ligand,
4.0 mol % of K2OsO4$2H2O, 3 equiv of K3Fe(CN)6, and K2CO3 each, and 1.0 equiv
t
MeSO2NH2 at 1:1 BuOH:H2O, while stirring for 48 h at an ambient temperature.
NBS-promoted furan oxidation of
6 under basic conditions,
The reaction was carried out at 0 ꢀ C.
b
resulting in the desired -keto -unsaturated aldehyde 7, at an
g
a,b
c
Isolated yields but not optimized.
excellent yield (88%, after two steps).9 The aldehyde 7 was sub-
jected to Wittig olefination to give the keto conjugated unsaturated
ester 3 at a yield of 90% with a 20:1(E:Z) ratio. The reduction of 3
under Luche conditions10 delivered the expected syn diol 8 with
a 97:3 diastereomeric ratio (as judged by the 1H NMR spectra) at
a yield of 88%. The relative stereochemistry was assigned by ana-
logy.7a Then, subsequent protection of the alcohol of 8 with TBSOTf
under basic conditions resulted in bis-TBS dienoate ether 9 at an
86% isolated yield (Scheme 2).
d
Determined by 1H NMR.
e
ND¼not determined.
f
NR¼No reaction.
On the other hand, the same reaction at an ambient temperature
under otherwise identical conditions resulted in 10 at a 20% iso-
lated yield as an inseparable diastereomeric mixture (Table 1, entry
2). To our surprise, the product was unambiguously characterized
With the requisite di-TBS ether 9 in hand, we considered the
application of a typical Sharpless’ AD reaction. Initially, we ex-
pected that the oxidation of a double bond can occur proximal to
the TBS-ether stereogenic center (electron withdrawing-effect)
as
a
,
b
-dihydroxylated product 10, and no trace of the anticipated
g,d-dihydroxylated product was observed. The relative stereo-
chemistry was assigned by analogy with the Sharpless model. After
considerable experimentation (Table 1, entry 3), it was found that

5474
G. Kumaraswamy et al. / Tetrahedron 71 (2015) 5472e5477
5.0 mol % of (DHQD)2PHAL, 4.0 mol % of K2OsO4$2H2O, 3 equiv of
K3Fe(CN)6, and K2CO3 each, and 1.0 equiv MeSO2NH2 at 1:1
tBuOH:H2O under stirring for 48 h at an ambient temperature
provided only regio- and diastereomer 10 at an 87% yield (Table 1,
entry 4). Remarkably, no regioisomer was detected, and only
unreacted starting material 9 was isolated at a 20% yield. In order to
enhance the diastereoselectivity of 10, we also screened common
AD ligands for the dihydroxylation of 9 (Table 1, entries 5, 6 and 7).
As expected, only the (DHQD)2PYR ligand under the above typical
conditions resulted in 10 with improved diastereoselectivity but
compromising the chemical yield (Table 1, entry 6). The significant
regioselectivity of 10 can be rationalized on the basis of the steric
effect caused by the resident stereogenic TBS-protecting group,
wherein the more electron rich olefinic phase is effectively
3. Conclusion
In conclusion, we achieved a concise diversity-oriented dia-
stereoselective synthesis of 50-epi synargentolide-B in 14 steps (the
longest linear sequence) at an overall yield of 12.9%, starting from
commercially available 2-acetylfuran 5. The salient feature of this
strategy is all stereogenic centers in the target molecule induced by
means of a sub-stoichiometric amount of chiral ligand. This flexible
protocol has the potential to generate probable diastereo members
of the synargentolide family by switching over to a corresponding
complementary ligand. Further optimization and application of this
strategy for the synthesis of synargentolide family members
and related natural molecules are at present under investigation in
our lab.
shielding and thereby facilitating the dihydroxylation of the
unsaturated double-bond ester.
a,b-
4. Experimental section
4.1. General procedure
Further, we planned to synthesize epimer 10 by employing
a pseudo-enantiomeric ligand (DHQ)2PHAL and 9 under otherwise
identical conditions as described in the case of 9. To our dismay, no
trace of epi-10 was formed, and only starting material 9 was re-
covered12 (Table 1, entry 8).
Subsequent protection of the resulting diol 10 with 2,2-
dimethoxypropane under acidic conditions furnished 11 at a 92%
yield. The reduction of the ester using DIBAL-H then gave the pri-
mary alcohol 2 at a yield of 90%. Following the Swern oxidation of
alcohol 2 produced crude aldehyde that was subjected to a catalytic
vinylogous Mukaiyama aldol reaction to ensure 5,6-dihydro-2H-
pyran-2-one.13
Spectra were recorded at 300, 400 & 500 MHz, and 13C NMR 75
& 125 MHz in CDCl3. The J values were recorded in hertz and ab-
breviations used were as follows: sdsinglet, dddoublet, tdtriplet,
qdquartet, mdmultiplet, brdbroad, ddddoublet of doublet,
dddddoublet of doublet of doublet, ddtddoublet of doublet of
triplet. Chemical shifts (
d) are reported relative toTMS (
d¼0.0) as an
internal standard. The IR (FTIR) spectra were measured using KBr
pellet or as film. Mass spectral data were compiled using MS (ESI),
HRMS mass spectrometers. Column chromatography was carried
out using Silica gel 100e200 mesh (commercial suppliers).
Accordingly, the reaction of the crude aldehyde with silyl
dienolate 12 in the presence of 10 mol % (R)-Tol-BINAP-CuF2 at
ꢁ78 ꢀC led to the
a
,b
-unsaturated
d-lactone 13 as a single di-
4.1.1. (S)-1-(Furan-2-yl)ethanol (4). To a solution of 1-(furan-2-yl)
ethanone (5) (5.0 g, 45.5 mmol) in dry EtOAc (50 mL) under argon
was added a formic acidetriethylamine azeotropic mixture (5:2,
10 mL) followed by the addition of Ru-catalyst S,S (24.0 mg, 0.1 mol
%), which was pre-dissolved in DCM (5 mL). The resulting reaction
mixture was slowly warmed to 50 ꢀC and allowed to stir until
completion (18 h), as indicated by TLC analysis. The reaction mix-
ture was diluted with water (50 mL) and extracted with EtOAc
(3ꢂ40 mL). The combined organic layers were washed with an
aqueous saturated solution of NaHCO3, dried over anhydrous
Na2SO4, filtered and concentrated under reduced pressure. The
crude residue was purified by silica gel flash column chromatog-
raphy eluting with 10% EtOAc:hexanes to furnish the desired al-
astereomer at a yield of 70%. The configuration of a new stereogenic
center was not determined at this point, however, we assumed that
(R)-Tol-BINAP would induce R chirality.13c Eventually, 13 was ex-
posed to HF/pyridine followed by the protection of the resulting
diol with Ac2O under basic conditions, after which a treatment with
PPTS furnished the target compound 1d at a 52% isolated yield
(over three steps). The spectral and chirooptical data of 1d were in
full agreement with those reported in the literature5 ([
a]
23 þ45.6 (c
D
23
1.2, CHCl3) {lit.5
[
a
]
D
þ47.3 (c 0.7, CHCl3)}) (Scheme 3), which in
turn also corroborated the assigned stereochemistry at the 6, 10, 20,
and 50 stereogenic centers.
cohol 4 (4.8 g, 95% yield) as colorless oil; Rf230.20 (hexanes/EtOAc,
24
9:1); [
a
]
ꢁ24.2 (c 0.48 in ethanol); [lit. [
a
]
ꢁ24.3 (c 6.0 in eth-
D
D
anol)]; 1H NMR (300 MHz, CDCl3):
d
7.37 (1H, d, J¼0.9 Hz, ArH), 6.32
(1H, dd, J¼3.2, 1.8 Hz, ArH), 6.22 (1H, d, J¼3.2 Hz, ArH), 4.87 (1H, q,
J¼6.6 Hz, C2HOH), 2.15 (1H, s, OH), 1.54 (3H, d, J¼6.6 Hz, CC1H3); 13
C
NMR (125 MHz, CDCl3):
d 157.5, 141.8, 110.0, 105.0, 63.5, 21.2; IR
(neat, cmꢁ1): 3462, 2985, 2935, 1668, 1149, 877, 731.
4.1.2. (S)-tert-Butyl(1-(furan-2-yl)ethoxy)dimethylsilane) (6). A so-
lution of alcohol (4) (4.5 g, 40.2 mmol) in anhydrous dichloro-
methane (50 mL) was cooled to 0 ꢀC. To this cold solution was
added imidazole (3.0 g, 44.2 mmol) followed by tert-butyldime-
thylsilyl chloride (7.3 g, 48.24 mmol). Progress of the reaction was
monitored by thin-layer chromatography. After completion (0.5 h)
the reaction mixture was quenched by addition of a saturated so-
lution of NH4Cl (30 mL). The reaction mixture was transferred to
a separating funnel and the aqueous layer was extracted with
dichloromethane (3ꢂ20 mL). The combined organic layers were
washed with brine (20 mL) and dried over anhydrous Na2SO4, fil-
tered and evaporated under reduced pressure. The resulting crude
oil was purified by flash column chromatography with 2% EtOA-
c:hexanes to afford pure TBS ether 6 as colorless liquid; (8.7 g, 96%
Scheme 3. Synthesis of 5-epi synargentolide-B.
yield); Rf 0.50 (hexanes/EtOAc, 19:1); [
a
]
D
24 ꢁ34.6 (c 0.8, CHCl3); 1H

G. Kumaraswamy et al. / Tetrahedron 71 (2015) 5472e5477
5475
NMR (500 MHz, CDCl3):
d
7.33 (1H, dd, J¼1.8, 0.8 Hz, ArH), 6.29 (1H,
filtered with EtOAc (3ꢂ80 mL). The combined organic contents
were washed with brine solution (30 mL), dried over anhydrous
Na2SO4, filtered and concentrated under reduced pressure. The
crude residue was purified by silicagel flash column chromatogra-
dd, J¼3.2, 1.8 Hz, ArH), 6.16 (1H, d, J¼3.2 Hz, ArH), 4.86 (1H, q,
J¼6.4 Hz, C2HOH), 1.47 (3H, d, J¼6.4 Hz, CC1H3), 0.89 (9H, s, t-BuSi),
0.08 (3H, s, SieCH3), 0.02 (3H, s, SieCH3); 13C NMR (125 MHz,
CDCl3):
d
158.3, 141.2, 109.9, 104.7, 64.5, 25.8, 22.9, 18.2, ꢁ4.9, ꢁ4.0;
phy eluting with 18% EtOAc:hexanes to afford desired alcohol 8 as
24
IR (neat, cmꢁ1): 3398, 2978, 2922, 1759, 1011, 915, 739; MS (ESI) m/
z: 225 (MꢁH)þ; HRMS:calcd for C12H23O3Si 244.1732; found
244.1735.
viscous liquid; (7.0 g, 88% yield); Rf 0.20 (hexanes/EtOAc, 7:3); [a]
D
ꢁ6.0 (c 0.8, CHCl3); 1H NMR (300 MHz, CDCl3)
7.28 (1H, dd, J¼15.3,
d
11.1 Hz, C3H), 6.45 (1H, dd, J¼15.3, 11.1 Hz, C4H), 6.08 (1H, dd,
J¼15.3, 5.5 Hz, C5H), 5.89 (1H, d, J¼15.3 Hz, C2H), 4.2 (2H, q,
J¼7.8 Hz, CH2 of OEt), 3.97 (1H, t, J¼5.3 Hz, C6H), 3.77e3.69 (1H, m,
CHCH3), 1.30 (3H, t, J¼7.8, Hz, CH3 of OEt), 1.18 (3H, d, J¼6.2 Hz,
CH3), 0.89 (9H, s, t-BuSi), 0.09 (3H, s, SieCH3), 0.07 (3H, s, SieCH3);
4.1.3. (S,E)-5-(tert-Butyldimethylsilyloxy)-4-oxohex-2-enal (7). To
a solution of TBS ether 6 (8.0 g, 35.4 mmol) in acetoneewater
(50 mL, 10:1 v/v) was added NaHCO3 and cooled to ꢁ15 ꢀC. A
mixture of N-bromosuccinimide (6.9 g, 38.9 mmol) in acetonee-
water (50 mL, 10:1 v/v) was added drop wise over a period of 1 h
to the cooled reaction mixture. The resulting reaction mixture was
stirred at the same temperature for 1 h, and then furan (2 mL,
32.7 mmol) was added to the mixture to quench excess N-bro-
mosuccinimide. After 10 min, pyridine (5.7 mL, 70 mmol) was
added to the mixture. The resulting reaction mixture was stirred
at ambient temperature for 2 h. Then, acetone was removed under
reduced pressure at ambient temperature. The residue was diluted
with EtOAc and washed with cold 1 N HCl solution (2ꢂ30 mL) to
remove excess pyridine. The organic layers were washed with an
aqueous saturated solution of NaHCO3 and dried over anhydrous
Na2SO4, filtered and concentrated under reduced pressure at room
temperature. The crude residue was purified by silicagel flash
column chromatography eluting with 15% EtOAc:hexanes to afford
13C NMR (125 MHz, CDCl3)
d 167.0, 143.7, 141.6, 129.0, 121.5, 76.0,
71.5, 60.3, 25.7, 20.0, 18.0, 14.2, ꢁ4.3, ꢁ4.8; IR (neat, cmꢁ1): 3489,
2930, 1711, 1253, 1130, 1093, 1001, 833, 754; MS (ESI) m/z: 332
(MþNH4)þ; HRMS:calcd for C16H34O4NSi 332.2251; found
332.2249.
4.1.6. (2E,4E,6S,7S)-Ethyl 6,7-bis(tert-butyldimethylsilyloxy)octa-2,4-
dienoate (9). To a stirred solution of alcohol 8 (6.0 g, 19.1 mmol) in
DCM (70 mL) at 0 ꢀC was added 2,6-lutidine (4.5 mL) and TBSOTf
(5.7 mL, 24.83 mmol), respectively. After completion of the re-
action (0.5 h) ice cold water was added. Then, the aqueous layer
was extracted with dichloromethane (3ꢂ80 mL) and the com-
bined organic layers were washed with 1 N HCl (30 mL) to remove
the excess 2,6-lutidine. The organic phase was washed with brine
solution and dried over anhydrous Na2SO4, filtered and concen-
trated under reduced pressure. The crude residue was purified by
silicagel flash column chromatography eluting with 5% EtOA-
c:hexanes to afford di-TBS ether 9 as a clear liquid; (7.0 g, 86%
aldehyde 7 as a pale yellow liquid; (7.8 g, 92% yield); Rf 0.40
(hexanes/EtOAc, 7:3);
(300 MHz, CDCl3):
J¼16.0 Hz, C3H), 6.93 (1H, dd, J¼16.0, 7.6 Hz, C2H), 4.37 (1H, q,
J¼6.8 Hz, C5HOH), 1.37 (3H, d, J¼6.8 Hz, CH3), 0.92 (9H, s, t-BuSi),
0.11 (3H, s, SieCH3), 0.09 (3H, s, SieCH3); 13C NMR (125 MHz,
24
[
a
]
ꢁ11.7 (c 0.8, CHCl3); 1H NMR
D
d
9.78 (1H, d, J¼7.6, C1HO), 7.43 (1H, d,
yield); Rf 0.40 (hexanes/EtOAc, 9:1); [
NMR (500 MHz, CDCl3)
a
]
24 ꢁ29.1 (c 0.8, CHCl3); 1H
D
d
7.37e7.28 (1H, m, C3H), 6.39 (1H, dd,
J¼15.3, 11.1 Hz, C4H), 6.25 (1H, dd, J¼15.3, 3.9 Hz, C5H), 5.84 (1H, d,
J¼15.5 Hz, C2H), 4.21 (2H, q, J¼7.2 Hz, CH2 of OEt), 3.83e3.75 (1H,
m, CHeCH3), 1.3 (3H, t, J¼7.2 Hz, CH3 of OEt), 0.98 (3H, d, J¼6.23
CH3), 0.91 (9H, s, t-BuSi), 0.89 (9H, s, t-BuSi), 0.06 (6H, s, 2-
SieCH3), 0.05 (3H, s, SieCH3), 0.04 (3H, s, SieCH3); 13C NMR
CDCl3):
d
201.1, 192.9, 140.1, 138.5, 74.3, 25.6, 20.6, 18.0, ꢁ4.8, ꢁ5.1;
IR (neat, cmꢁ1): 2931, 2857, 1769, 1739, 1255, 1112, 833, 779; MS
(ESI) m/z: 242 (M)þ; HRMS:calcd for C12H23O3Si 243.1411; found
243.1410.
(125 MHz, CDCl3)
d 167.2, 144.3, 142.4, 128.0, 120.3, 75.2, 71.3, 6.2,
4.1.4. (S,2E,4E)-Ethyl 7-(tert-butyldimethylsilyloxy)-6-oxoocta-2,4-
dienoate (3). The above aldehyde (7) (7.0 g, 29 mmol) was dis-
solved in dichloromethane (60 mL) and cooled to 0 ꢀC. To this, ethyl
(triphenylphosphoranylidene)acetate (12.0 g, 34.8 mmol) was
added. The resulting reaction mixture warmed to room tempera-
ture and stirred for 4 h. Then, dichloromethane was removed under
reduced pressure, and the resulting crude residue was purified by
silicagel column chromatography using 15% EtOAc:hexanes to give
25.8, 18.1, 18.0, 17.3, 14.3, ꢁ4.6, ꢁ4.8, ꢁ4.9, ꢁ4.9; IR (neat, cmꢁ1):
2930, 2857, 1714, 1255, 1215, 1104, 1003, 833, 749; MS (ESI) m/z:
451 (MþNa)þ; HRMS:calcd for C22H48O4NSi2. 446.3116; found
446.3120.
4.1.7. (2S,3R,6S,7S,E)-Ethyl 6,7-Bis(tert-butyldimethylsilyloxy)-2,3-
dihydroxyoct-4-enoate (10). In an argon fitted round bottom flask
t-BuOH (10 mL) and water (20 mL) was added. To this K2CO3 (2.9 g,
21.1 mmol), K3Fe(CN)6 (6.9 g, 21.1 mmol), MeSO2NH2 (665 mg,
the desired product 3 in 20:1 ratio as light yellow oil; (8.1 g, 90%
24
yield); Rf 0.30 (hexanes/EtOAc, 7:3); [
NMR (500 MHz, CDCl3)
a
]
D
ꢁ23.4 (c 0.6, CHCl3); 1H
7 mmol), (DHQD)2PYR (248 mg, 0.28 mmol), K2OsO4$2H2O
d
7.38e7.30 (2H, m, C3H]C5H), 6.99e6.92
(77.2 mg, 0.21 mmol) were added at room temperature in the same
order and allowed to stirred for 15 min. To this pale yellow reaction
mixture was added pre-dissolved solution of diene 9 (3.0 g,
7 mmol) in t-BuOH (10 mL) and allowed to stir at same tempera-
ture in a dark place for 48 h. The reaction was quenched by ad-
dition of solid Na2SO3 and stirred for 0.5 h at 0 ꢀC. Reaction
mixture was diluted and extracted EtOAc (3ꢂ20 mL). The com-
bined organics contents were washed with brine solution and
dried over anhydrous Na2SO4, filtered and concentrated under
reduced pressure. The crude residue was purified over silicagel
flash column chromatography eluting with 20% EtOAc:hexanes to
afforded diol 10 as colorless oil in 96:4 dr (inseparable). The dr
ratio determined based on NMR spectra. The yield of 10 was 2.4 g
(1H, m, C4H), 6.29e6.21 (1H, m, C2H), 4.30e4.22 (2H, m, OeCH2),
1.34e1.30 (6H, m, CH3CH, CH3 of OEt), 0.91 (9H, s, t-BuSi), 0.08 (3H,
s, SieCH3), 0.07 (3H, s, SieCH3); 13C NMR (125 MHz, CDCl3)
d 201.8,
166.0, 141.4, 139.7, 130, 129.3, 74.5, 60.9, 25.7, 21.0, 18.1, 14.2, ꢁ4.8,
ꢁ5.0; IR (neat, cmꢁ1): 2930, 2857, 1718, 1694, 1594, 1240, 1134, 834,
779; MS (ESI) m/z: 313 (MþH)þ. HRMS:calcd for C16H29O4Si
313.1827; found 313.1826.
4.1.5. (2E,4E,6S,7S)-Ethyl 7-(tert-butyldimethylsilyloxy)-6-
hydroxyocta-2,4-dienoate (8). CeCl3$7H2O (11.5 g, 30.7 mmol) and
keto-TBS ether 3 (8.0 g, 25.6 mmol) were dissolved in methanol at
room temperature and stirred for 10 min. Then, NaBH4 (1.1 g,
30.7 mmol) was added at ꢁ78 ꢀC to the mixture in four portions
over a period of 20 min and was stirred for 2 h at same temperature.
After completion of the reaction, the reaction mixture was
quenched by addition of a saturated solution of NH4Cl (5 mL). After
removal of MeOH under reduced pressure, the crude residue was
(75% yield), based on starting material recovery. Starting material
24
was recovered 0.2 g (20%); Rf 0.20 (hexanes/EtOAc, 8:2); [a]
D
ꢁ29.1 (c 1.2, CHCl3); 1H NMR (300 MHz, CDCl3)
d 5.93 (1H, dd,
J¼15.9, 4.5 Hz, C5H), 5.83 (1H, dd J¼15.6, 6.0 Hz, C4H), 4.49e4.47
(1H, m, C2H), 4.30 (2H, q, J¼6.8 Hz, CH2 of OEt), 4.16 (2H, m, C3H,

5476
G. Kumaraswamy et al. / Tetrahedron 71 (2015) 5472e5477
C6H), 3.80e3.75 (1H, m, C7H), 1.33 (3H, t, J¼6.8 Hz, CH3 of OEt), 1.00
(3H, d, J¼6.0 Hz, CH3), 0.90 (9H, s, t-BuSi), 0.89 (9H, s, t-BuSi), 0.06
(6H, s, 2-SieCH3), 0.05 (3H, s, SieCH3), 0.04 (3H, s, SieCH3); 13C
0.22 mmol) in anhydrous THF (3 mL) was stirred for 30 min at room
temperature to form a pale yellow solution. To this, anhydrous THF
(2 mL) solution of TBAT (dried under vacuum for 15 min) (154 mg,
0.4 mmol) was then added via cannula. The resulting bright yellow
solution was stirred for an additional 15 min. Then, pre-dissolved
solution of silyl dienolate 12 in THF (684 mg, 3 mmol) was added
drop wise with cannula and subsequent the crude aldehyde
(458 mg, 1 mmol) that was dissolved in 3 mL of THF. The resulting
reaction mixture was stirred 8 h at ambient temperature. Then the
reaction mixture was quenched by addition of a saturated solution
of NH4Cl (5 mL). The aqueous layers was extracted with EtOAc
(3ꢂ10 mL). The combined organic layers were washed with brine
solution (10 mL) and dried over anhydrous Na2SO4, transferred and
concentrated under reduced pressure. The residue was purified
over silicagel flash column chromatography eluting with 25%
NMR (125 MHz, CDCl3)
d 172.8, 132.1, 129.0, 75.0, 73.7, 73.0, 71.2,
62.0, 25.8, 18.1, 18.1, 17.2, 14.2, ꢁ4.7, ꢁ4.7, ꢁ4.7, ꢁ4.9; IR (neat,
cmꢁ1): 3451, 2927, 2855, 1737, 1465, 1252, 1100, 833, 774; MS (ESI)
m/z: 485 (MþNa)þ; HRMS:calcd for C22H50O6NSi2 480.3160; found
480.3164.
4.1.8. (4S,5R)-Ethyl 5-((3S,4S,E)-3,4-bis(tert-butyldimethylsilyloxy)
pent-1-enyl)-2,2-dimethyl-1,3-dioxolane-4-carboxylate (11). A solu-
tion of diol 10 (2.0 g, 3.98 mmol) in acetone (25 mL) was cooled to
0
ꢀC. To this cooled mixture was added 2,2-dimethoxypropane
(0.5 mL, 4.4 mmol) and p-TsOH$H2O (760 mg, 0.4 mmol) and the
reaction mixture was stirred at room temperature for 2 h. The re-
action mixture was quenched by addition of NaHCO3 (840 mg) at
EtOAc:hexanes to afford desired the lactone 13 as white viscous
24
0
ꢀC and stirred for additional 10 min and then filtered through
liquid; (350 mg, 70% yield); Rf 0.40 (hexanes/EtOAc, 1:1); [a]
D
a pad of Celite. Acetone was removed and the crude residue was
purified over silicagel flash column chromatography eluting with
8% EtOAc:hexanes to afford desired acetonide protected diol 11 as
þ10.5 (c 1.0, CHCl3); 1H NMR (500 MHz, CDCl3)
6.91 (1H, dd, J¼9.6,
d
6.0 Hz, C4H), 6.05e6.02 (1H, m, C3H), 5.97 (1H, dd, J¼15.5, 4.0 Hz,
0
C4H), 5.77 (1H, dd, J¼15.5, 6.8C3H), 4.50e4.44 (2H, m, CH6,2 ),
24
0
0
colorless oil; (1.8 g, 92% yield); Rf 0.40 (hexanes/EtOAc, 8:2); [
a
]
4.15e4.12 (1H, m, C1 H), 3.98 (1H, dd, J¼7.6, 5.0 Hz, C5 H), 3.79e3.74
D
ꢁ17.0 (c 1.0, CHCl3); 1H NMR (500 MHz, CDCl3)
d
5.98 (1H, dd,
(1H, m, C6 H), 2.62 (1H, ddt, J¼21.0, 11.8, 2.5 Hz, C5Ha), 2.47e2.41
0
J¼15.5, 3.7 Hz, C5H), 5.78 (1H, dd, J¼15.4, 8.9 Hz, C4H), 4.59 (H, t,
J¼7.4 Hz, C6H), 4.26 (2H, qdd, J¼10.2, 7.2, 3.1 Hz, C3,6H), 4.19e4.15
(2H, m, CH2 of OEt), 3.80e3.75 (1H, m, C2H), 1.49 (3H, s, CH3 of
acetonide), 1.48 (3H, s, CH3 of acetonide), 1.28 (3H, t, J¼7.2, CH3 of
OEt), 0.99 (3H, d, J¼6.2 Hz, CH3), 0.91 (9H, s, t-BuSi), 0.88 (9H, s, t-
BuSi), 0.06 (6H, s, 2-SieCH3), 0.05 (6H, s, 2-SieCH3); 13C NMR
(1H, m, C5Hb), 1.44 (3H, s, CH3 of acetonide), 1.43 (3H, s, CH3 of
acetonide), 0.98 (3H, d, J¼6.2 Hz, CH3), 0.90 (9H, s, t-BuSi), 0.88 (9H,
s, t-BuSi), 0.05 (12H, s, 4-SieCH3); 13C NMR (125 MHz, CDCl3)
d
163.1, 144.7, 133.5, 128.0, 121.4, 110.0, 81.3, 78.8, 77.2, 74.8, 71.1,
27.1, 27.0, 25.8, 25.3, 18.1, 18.0, 17.2, ꢁ4.6, ꢁ4.7, ꢁ4.7, ꢁ4.9; IR (neat,
cmꢁ1): 2930, 2856, 1739, 1377, 1248, 1105, 1068, 832, 774; MS (ESI)
m/z: 549 (MþNa)þ; HRMS:calcd for C27H51O6Si2 527.3234; found
527.3234.
(125 MHz, CDCl3)
d 170.4, 133.9, 126.9, 111.1, 80.0, 79.4, 74.7, 71.1,
61.3, 27.0, 25.8, 25.8, 18.2, 18.0, 17.0, 14.2, ꢁ4.6, ꢁ4.7, ꢁ4.7, ꢁ4.9; IR
(neat, cmꢁ1): 2931, 2857, 1756, 1723, 1375, 1253, 1214, 1101, 832,
750; MS (ESI) m/z: 525 (MþNa)þ; HRMS:calcd for C26H56O6Si2
520.3493; found 520.3493.
4.1.11. (2S,3S,E)-5-((4R,5R)-2,2-Dimethyl-5-((R)-6-oxo-3,6-dihydro-
2H-pyran-2-yl)-1,3-dioxolan-4-yl)pent-4-ene-2,3-diyl
diacetate
(14). TBS ether 13 (200 mg, 0.38 mmol) was dissolved in acetoni-
trile containing plastic vial with a magnetic stir bar and cooled 0 ꢀC.
Hydrogen fluorideepyridine (0.4 mL) was added in one portion and
the reaction mixture warmed to ambient temperature and stirred
for 6 h. Then, the reaction mixture was quenched by careful addi-
tion of an aqueous saturated solution of NaHCO3 drop wise at 0 ꢀC.
Reaction mixture was diluted with EtOAc and the aqueous layer
was extracted with same (3ꢂ5 mL). The combined organics con-
tents were washed with brine solution and dried over Na2SO4 than
filtered and concentrated under reduced pressure and applied high
vacuum for 15 min. The resulting crude product was directly taken
into further step without any purification.
4.1.9. (4R,5R)-5-((3S,4S,E)-3,4-Bis(tert-butyldimethylsilyloxy)pent-1-
enyl)-2,2-dimethyl-1,3-dioxolan-4-yl)methanol (2). To a solution of
above acetonide 11 (1.5 g, 2.9 mmol) in dry DCM (30 mL) at ꢁ78 ꢀC
was added DIBAL-H (1 M solution in toluene, 6 mL). After 1 h, ex-
cess of DIBAL-H was quenched by addition of 5 drops of methanol
followed by saturated solution of sodium potassium tartrate. The
mixture was allowed to stir for 2 h at 0 ꢀC. The aqueous layers was
extracted with diethyl ether (3ꢂ10 mL). The combined organics
contents were washed with brine solution and dried over anhy-
drous Na2SO4, filtered and concentrated under reduced pressure at
20 ꢀC. The crude residue was purified over silicagel column eluting
with 20% EtOAc:hexanes to afford the desired alcohol 2 as trans-
In argon filled round bottom flask with a magnetic stir bar the
above crude diol (90 mg, 0.3 mmol), was dissolved in anhydrous
DCM. To this solution was added triethylamaine (0.1 mL, 0.9 mmol),
and DMAP (4 mg, 0.03 mmol) at 0 ꢀC. After 10 min, acetic anhydride
in DCM (75 mg, 0.75 mmol) was added drop wise to the mixture at
the same temperature. The resulting reaction mixture was allowed
to stir at ambient temperature for 2 h. Then, the solvent was
evaporated under reduced pressure. The crude residue was purified
over silicagel flash column chromatography eluting with 30%
24
parent liquid; (2.6 g in 90% yield) Rf 0.50 (hexanes/EtOAc, 1:1); [a]
D
ꢁ28.7 (c 1.0, CHCl3); 1H NMR (500 MHz, CDCl3)
d 5.93 (1H, dd,
J¼15.5, 3.9 Hz, C5H), 5.69 (1H, dd, J¼15.5, 7.8 Hz, C4H), 4.37 (1H, t,
J¼8.0 Hz, C3H), 4.15e4.12 (1H, m, C2H), 3.85e3.80 (2H, m, CH6,7),
3.78e3.73 (1H, m, CH), 3.62e3.58 (1H, m, CH), 1.44 (3H, s, CH3 of
acetonide), 1.43 (3H, s, CH3 of acetonide), 0.96 (3H, d, J¼6.2 Hz,
CH3), 0.90 (9H, s, t-BuSi), 0.88 (9H, s, t-BuSi), 0.06 (6H, s, 2-SieCH3),
0.05 (6H, s, 2-SieCH3); 13C NMR (125 MHz, CDCl3)
d 134.2, 127.5,
109.1, 81.3, 77.8, 74.8, 71.0, 61.0, 27.0, 27.0, 25.8, 18.1, 18.0, 17.2, ꢁ4.6,
ꢁ4.7, ꢁ4.8, ꢁ4.8; IR (neat, cmꢁ1): 3018, 2931, 1377, 1214, 1105, 834,
744, 667; MS (ESI) m/z: 460 (MþNa)þ; HRMS:calcd for
EtOAc:hexanes to afford the desired diacetate as a viscous liquid;
24
(85 mg, 80% yield) Rf 0.30 (hexanes/EtOAc, 1:1); [
a
]
þ51.6 (c 1.0,
D
CHCl3); 1H NMR (300 MHz, CDCl3)
d
6.93e6.87 (1H m, C4H),
0
C
23H48O5Si2Na 483.7728; found 583.7731.
6.05e5.78 (1H, m, C3H), 5.34 (1H, t, J¼6.0 Hz, C1 H), 5.06e5.01 (1H,
0
0
0
0
Note: This alcohol was oxidized to aldehyde by using dess-
martin periodinane and used for next step without purification.
m, C5 H), 4.5e4.4 (2H, m, CH6 ,2 ), 3.85 (1H, t, J¼7.6 Hz, C3 H),
2.57e2.51 (2H, m, C5H), 2.11 (3H, s, CH3 of acetate), 2.05 (3H, s, CH3
of acetate), 1.43 (6H, s, CH3 of acetonide),1.22 (3H, d, J¼6.0 Hz, CH3);
4.1.10. (R)-6-((4R,5R)-5-((3S,4S,E)-3,4-Bis(tert-butyldimethylsily-
loxy)pent-1-enyl)-2,2-dimethyl-1,3-dioxolan-4-yl)-5,6-dihydro-2H-
pyran-2-one (13). In an argon filled double necked round bottom
flask with a magnetic stir bar a solution of Cu(OTf)2 (dried upon
P2O5 at 100 ꢀC) (72.3 mg, 0.2 mmol), (R)-tol-binap (148 mg,
13C NMR (125 MHz, CDCl3)
d 170.2, 170.0, 162.5, 144.5, 132.1, 127.4,
121.4, 110.3, 80.8, 79.2, 78.0, 74.5, 70.5, 29.7, 26.9, 26.2, 21.1, 21.0,
16.1; IR (neat, cmꢁ1): 2932, 2835, 1734, 1374, 1226, 1063, 817, 753;
MS (ESI) m/z: 405 (MþNa)þ; HRMS:calcd for C19H30O8N 400.1974;
found 405.1973.

G. Kumaraswamy et al. / Tetrahedron 71 (2015) 5472e5477
5477
4.1.12. (2S,3S,6R,7S,E)-6,7-Dihydroxy-7-((R)-6-oxo-3,6-dihydro-2H-
References and notes
pyran-2-yl)hept-4-ene-2,3-diyl diacetate (1d). In an argon fitted
round bottom flask with a magnetic stir bar acetonide protected
diol (65 mg, 0.22 mmol) was dissolved in anhydrous MeOH. To this
solution was added PPTS (160 mg, 0.66 mmol) at ambient tem-
perature and the reaction mixture was slowly warmed until the
solvent was being refluxed for 5 h. The reaction mixture was
quenched with solid NaHCO3 and stirred for 20 min at ambient
temperature, filtered and evaporated the solvent under reduced
pressure. The crude residue was diluted with EtOAc and extracted
with same (3ꢂ8 mL). The combined organic contents were washed
with brine solution and dried over Na2SO4, filtered and concen-
trated under reduced pressure. The crude residue was purified over
silicagel flash column chromatography eluting with 60% EtOA-
1. (a) Deng, Y.; Balunas, M. J.; Kim, J.-A.; Lantvit, D. D.; Chin, Y.-W.; Chai, H.; Su-
giarso, H.; Kardono, L. B. S.; Fong, H. S.; Pezzuto, J. M.; Swanson, S. M.; Carcache
de Blanco, E. J.; Douglas Kinghorn, A. J. Nat. Prod. 2009, 72, 1165e1169; (b)
Suarez-Ortiz, G. A.; Cerda-García-Rojas, C. M.; Hernandez-Rojas, A.; Pereda-
Miranda, R. J. Nat. Prod. 2013, 76, 72e78.
ꢀ
ꢀ
2. (a) Marco, J. A.; Carda, M.; Murga, J.; Falomir, E. Tetrahedron 2007, 63,
2929e2958; (b) Gupta, M. P.; Monge, A.; Karikas, G. A.; Lopez de Cerain, A.;
Solis, P. N.; de Leon, E.; Trujillo, M.; Suarez, O.; Wilson, F.; Montenegro, G.;
Noriega, Y.; Santana, A. I.; Correa, M.; Sanchez, C. Int. J. Pharmacogn. 1996, 34,
19e27; (c) Goun, E.; Cunningham, G.; Chu, D.; Nguyen, C.; Miles, D. Fitoterapia
2003, 76, 592e596; (d) Hegde, V. R.; Pu, H.; Patel, M.; Das, P. R.; Strizki, J.; Gullo,
V. P.; Chouan-C, C.; Buevich, A. V.; Chan, T. M. Bioorg. Med. Chem. Lett. 2004, 14,
5339e5342; (e) Kobayashi, S.; Tsuchiya, K.; Kurokawa, T.; Nakagawa, T.; Shi-
mada, N.; Iitaka, Y. J. Antibiot. 1994, 47, 703e707; (f) Davies-Coleman, M. T.;
Rivett, D. E. A. Fortschr. Chem. Org. Naturst. 1989, 55, 1e35; (g) Dumonter, V.;
ꢀ
ꢀ
Van Hung, N.; Adeline, M. T.; Riche, C.; Chiaroni, A.; Sevenet, T.; Gueritte, F. J.
Nat. Prod. 2004, 67, 858e862.
3. Pereda-Miranda, R.; Garcia, M.; Delgardo, G. Phytochemistry 1990, 29,
2971e2974.
4. Collett, L. A.; Davies-Coleman, M. T.; Rivett, D. E. A. Phytochemistry 1998, 48,
651e656.
5. Prasad, K. R.; Phaneendra, G. J. Org. Chem. 2013, 78, 3313e3322.
6. (a) Sabitha, G.; Shankaraiah, K.; Yadav, J. S. Eur. J. Org. Chem. 2013, 22,
4870e4878; (b) Konda, S.; Bhaskar, K.; Lingaiah, N.; Akkewar, D. M. Tetrahedron
Lett. 2014, 55, 3087e3089.
7. (a) Kumaraswamy, G.; Jayaprakash, N.; Rambabu, D.; Ganguly, A.; Banerjee, R.
Org. Biomol. Chem. 2014, 12, 1793e1803; (b) Kumaraswamy, G.; Padmaja, M. J.
Org. Chem. 2008, 73, 5198e5201; (c) Kumaraswamy, G.; Ramakrishna, G.;
Naresh, P.; Jagadeesh, B.; Sridhar, B. J. Org. Chem. 2009, 74, 8468e8471; (d)
Kumaraswamy, G.; Ramakrishna, G.; Sridhar, B. Tetrahedron Lett. 2011, 52,
1778e1782; (e) Kumaraswamy, G.; Ramakrishna, G.; Raju, R.; Padmaja, M.
Tetrahedron 2010, 66, 9814e9818; (f) Kumaraswamy, G.; Ramakrishna, D. S.;
Santhakumar, K. Tetrahedron: Asymmetry 2010, 21, 544e548; (g) Kumaraswamy,
G.; Jayaprakash, N. Tetrahedron Lett. 2010, 51, 6500e6502; (h) Kumaraswamy,
G.; Sadaiah, K.; Raghu, N. Tetrahedron: Asymmetry 2012, 23, 587e593.
8. (a) Fujii, A.; Hashiguchi, S.; Uematsu, N.; Ikariya, T.; Noyori, R. J. Am. Chem. Soc.
1996, 118, 2521e2522; (b) Guo, H.; O’Doherty, G. A. Angew. Chem., Int. Ed. 2007,
46, 5206e5208.
c:hexanes to afforded desired diol 1d as a clear liquid; (40 mg, 65%
24
yield); Rf 0.10 (hexanes/EtOAc, 1:1); [
NMR (500 MHz, CDCl3)
a
]
D
þ45.6 (c 1.2, CHCl3); 1H
d
6.96 (1H, ddd, J¼9.8, 5.5, 3.2 Hz, C4H), 6.04
(1H, ddd, J¼9.8, 2.3, 1.4 Hz, C3H), 5.87 (1H, ddd, J¼15.7, 5.5, 0.9 Hz,
C3H), 5.77 (1H, ddd, J¼15.7, 6.6, 1.2 Hz, C4H), 5.34 (1H, t, J¼6.0 Hz,
0
C6H), 5.11e5.05 (1H, m, C5 H), 4.51 (2H, ddd, J¼10.2, 7.0, 5.5 Hz,
0
0
0
CH2 ,6 ), 3.70 (dd, J¼6.3, 2.8 Hz, 1H, C1 H), 2.59e2.53 (2H, m, C5H2),
2.11 (3H, s, CH3 of acetate), 2.06 (3H, s, CH3 of acetate), 1.22 (3H, d,
J¼6.6 Hz, CH3); 13C NMR (75 MHz, CDCl3)
d 170.6, 170.1, 163.6, 145.6,
133.5, 127.5, 121.0, 76.8, 74.7, 74.2, 70.6, 69.4, 25.6, 21.2, 21.0, 16.2; IR
(neat, cmꢁ1): 3394, 3019, 2924, 2854, 1712, 1376, 1247, 1215, 1053,
753, 667; MS (ESI) m/z: 36O (MþNH4)þ; HRMS:calcd for C16 H22O4
Na 365.1214; found 365.1214.
Acknowledgements
9. Kobayashi, Y.; Biju Kumar, G.; Kurachi, T.; Acharya, H. P.; Yamazaki, T.; Kitazume,
T. J. Org. Chem. 2001, 66, 2011e2018.
10. Luche, J. L. J. Am. Chem. Soc. 1978, 100, 2226e2227.
We are grateful to Director, IICT, for constant encouragement.
Financial support was provided by the DST, New Delhi, India (Grant
No: SR/S1/OC-08/2011), and ORGIN (CSC-0108) programme (CSIR)
of XII Five year plan. UGC & CSIR (New Delhi) is gratefully ac-
knowledged for awarding the fellowship to N. R, N. J. and K A.
11. (a) Berker, H.; Soler, M. A.; Sharpless, K. B. Tetrahedron 1995, 51, 1345e1376; (b)
Zhang, Y.; O’Doherty, G. A. Tetrahedron 2005, 61, 6337e6351; (c) Ahmed, M.;
Mortensen, M. S.; O’Doherty, G. A. J. Org. Chem. 2006, 71, 7741e7746.
12. This result can be explained on the basis of matched/mismatched substrate
with chiral catalyst and undoubtedly, this desires further study with diverse
protecting groups along with other parameters.
€
13. (a) Kruger, J.; Carreira, E. M. J. Am. Chem. Soc. 1998, 120, 837e838; (b) Bluet, G.;
Supplementary data
ꢀ
Bazan-Tejeda, B.; Campagne, J.-M. Org. Lett. 2001, 3, 3807e3810; (c) Moreau, X.;
ꢀ
Bazan-Tejeda, B.; Campagne, J.-M. J. Am. Chem. Soc. 2005, 127, 7288e7289;
Supplementary data (copies of 1H and 13C NMR spectra) related
to this article can be found at http://dx.doi.org/10.1016/
j.tet.2015.06.080.
Harutyunyan, S. R.; Zhao, Z.; den Hartog, T.; Bouwmeester, K.; Minnaard, A. J.;
Feringa, B. L.; Govers, F. Proc. Natl. Acad. Sci. 2003, 105, 8507e8512.