Stereodivergent approach to Alzheimer's therapeutic agent (R)-(?) and (S)-(+)-arundic acid employing chiral 4-pentenol derivatives as building blocks

Article abstract of DOI:10.1016/j.tet.2017.03.002

An efficient stereodivergent total synthesis of anti-Alzheimer agent (R)-(?) and (S)-(+)-arundic acid has been achieved from both chiral and nonchiral materials. This strategy features an efficient approach to separable diastereomeric C-2 chiral 4-pentenol intermediates employing proline catalysed asymmetric α-aminooxylation and [3,3] sigmatropic Claisen rearrangement are the highlights of present synthesis.

Full text of DOI:10.1016/j.tet.2017.03.002

Accepted Manuscript
Stereodivergent approach to Alzheimer's therapeutic agent (R)-(−) and (S)-(+)-
arundic acid employing chiral 4-pentenol derivatives as building blocks
Viraj A. Bhosale, Suresh B. Waghmode
PII:
S0040-4020(17)30214-4
10.1016/j.tet.2017.03.002
TET 28508
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 10 December 2016
Revised Date: 27 February 2017
Accepted Date: 1 March 2017
Please cite this article as: Bhosale VA, Waghmode SB, Stereodivergent approach to Alzheimer's
therapeutic agent (R)-(−) and (S)-(+)-arundic acid employing chiral 4-pentenol derivatives as building
blocks, Tetrahedron (2017), doi: 10.1016/j.tet.2017.03.002.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT
Graphical Abstract
Stereodivergent approach to Alzheimer’s therapeutic agent Leave this area blank for abstract info.
R)-(-) and (S)-(+)-arundic acid employing chiral 4-pentenol
(
derivatives as building blocks
Viraj A. Bhosale* and Suresh B. Waghmode*
Department of Chemistry, Savitribai Phule Pune University (Formerly University of Pune), Ganeshkhind, Pune
411007, India

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
Stereodivergent approach to Alzheimer’s therapeutic agent (R)-(-) and (S)-(+)-arundic
acid employing chiral 4-pentenol derivatives as building blocks
Viraj A. Bhosale* and Suresh B. Waghmode*
Department of Chemistry, Savitribai Phule Pune University (Formerly University of Pune), Ganeshkhind, Pune 411007, India
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
An efficient stereodivergent total synthesis of anti-Alzheimer agent (R)-(-) and (S)-(+)-arundic
acid has been achieved from both chiral and nonchiral materials. This strategy features an
efficient approach to separable diastereomeric C-2 chiral 4-pentenol intermediates employing
proline catalysed asymmetric α-aminooxylation and [3,3] sigmatropic Claisen rearrangement are
the highlights of present synthesis.
Available online
Keywords:
Arundic acid
2
009 Elsevier Ltd. All rights reserved.
Claisen rearrangement
D-glyceraldehyde
Swearn oxidation
Wittig olefination
1
. Introduction
other neurodegenerative diseases including Alzheimer's disease,
amyotrophic lateral sclerosis (Lou Gehrig's disease), and
Alzheimer's disease (AD) is chronic neurodegenerative
4b,4c
Parkinson's disease are recently completed.
Arundic acid
process, which causes a progressive dysfunction of central
nervous system. It affects parts of brain characterized by control
of thought, memory and language. It reduces appetite or the
ability to recognize and also associated with disorientation, mood
swings, loss of motivation and behavioral issues, which becomes
clinically identified as useful drug which attenuates retinal
ganglion cell death by increasing glutamate/aspartate transporter
4d
expression.
The interesting biological activities of (R)-(-)-arundic acid
prompted many synthetic efforts, which resulted in several
1
major concern for human health. Although, a great efforts has
been devoted to study of its origin, fight and prevention, only
palliative treatments have been developed so far. Few
medications are currently used to treat the cognitive problems of
AD, which includes use of acetylcholinsterase inhibitors (tacrine,
rivastigmine, galanthamine donepezil) and NMDA receptor
racemic and asymmetric total syntheses. The strategies used for
5
syntheses 6 relied on recemates resolution,
asymmetric
7
alkylation,
use of chiral 8 auxiliaries,
photochemical
9
diastereoselective deconjugation, crotylation using metal, [3,3]
sigmatropic Johnson–Claisen rearrangement and recently used
10
11
2
Pd/Cu catalyzed cross-coupling reaction. Although, a range of
different approaches has been developed, a concise synthesis of
arundic acid from commercially available material with better
overall yield remains a worthy objective.
antagonist (memantine) but unfortunately in most of the cases
3
benefit from their use is very small. Research into fighting this
ever-growing disease is towards development of new therapeutic
drugs and synthesis of analogues of this class.
Figure. 1 Arundic acids
Figure. 2 General scheme for Wittig olefination-Claisen
rearrangement protocol
(
R)-(-)-arundic acid (Fig. 1) was discovered as a novel emerging
compound as neuroprotective agent as well as it is necessary for
the treatment of spinal cord injury (SCI) in combination with
other drugs. The phase II clinical trials of arundic acid for the
treatment of acute ischemic stroke and clinical development in
As part of our on-going research programs on the total
4a
12-14
synthesis of bioactive natural products and heterocycles,
we
were encouraged to pursue the total synthesis of both

2
enantiomers of arundic acid. Herein, we descr
A
ibe
C
a
C
c
E
on
P
ci
T
se
E
a
D
nd MAcy
N
clo
U
he
S
x
C
ed
R
en
I
e
PTprotection of
D-mannitol and C–C bond
scalable stereodivergent synthesis of both enantiomers of arundic
acid by employing proline catalysed asymmetric α-
aminooxylation and Wittig olefination-Claisen rearrangement
protocol as key steps (Fig. 2).
scissoring using silica supported NaIO (see experimental
4
section).
Our retrosynthetic strategy towards the synthesis of (R)-(-)-
arundic acid and (S)-(+)-arundic acid is outlined in Scheme 1.
The carboxylic acids 1 and ent-1 could be accessible via
hydrogenation of alkenes following oxidative cleavage of diol.
While alkenes 11 and 9 would be the product of a Wittig
olefination reaction on aldehyde, which in turns conceived to
derive by performing Wittig olefination-Claisen rearrangement
protocol on aldehyde 5. Intermediate (R)-2,3-O-cyclohexylidene
D-glyceraldehyde 5 could be obtained either by performing
proline catalysed asymmetric α-aminooxylation of nonchiral
aldehyde 2 or from D-mannitol.
Scheme 2 Synthesis of Wittig precursor glyceraldehyde
5
15a
Wittig olefination of crude (R)-2,3-O-cyclohexylidene
D-
glyceraldehyde 5 with allyoxy methylene triphenyl phosphine
using t-BuOK as base provided the allyl vinyl ether 6 as an
inseparable mixture of E/Z isomers in 1:1.96 ratio. The thermal
and microwave induced [3,3] sigmatropic Claisen rearrangement
reaction of allyl vinyl ether 6 was investigated in detail to obtain
better diastereoselectivity and yield (Scheme 3).
Scheme 3 Synthesis of alcohols 8a and 8b
Table 1. Diastereoselective Claisen rearrangement of 6
a
b
Entry
Conditions
dr of
7
Yield % 8a+8b
1
2
3
4
5
6
7
8
9
neat, 180 °C, 10 min
1:1.05
1:1.40
1:2.27
1:1.65
1:3.05
1:4.16
1:3.51
89% (43+46)
91% (36+55)
94% (29+65)
92% (35+57)
94 % (22+72)
96% (19+77)
92% (20+72)
No reaction
neat, mw, 150 °C, 10 min
xylene, 140-140 °C, 8 h
xylene, mw, 120 °C, 25 min
toluene 110-115 °C, 18 h
benzene, 80-85 °C, 24 h
benzene/mw, 85 °C, 1 h
Scheme 1 Retrosynthesis of (R)-(-) and (S)-(+)-arundic acid
neat/mw, 80-85
̊
CH Cl
2 2
No reaction
2
. Result and discussion
Scheme summarizes synthetic sequence for the
c
10
2 2
CH ClCH Cl, 2 equiv., MAD, rt, 48 h
No reaction
2
a
1
enantioselective synthesis of (R)-5 from chiral and nonchiral
dr ratio of the 7 was determined by H NMR.
yields of product are referred to isolated yields of alcohol 8a and 8b obtained
after claisen followed by reduction.
MAD = methyl aluminium bis(2,6-di-tert-butyl-4-methylphenolate).
b
materials. Our synthesis commenced with aminooxylation of
15b
aldehyde 2 using nitroso benzene as oxygen source and D-
proline as a catalyst furnished crude α-aminooxy aldehyde, which
c
on subsequent reduction with NaBH provided crude aminooxy
alcohol. Treatment of the crude aminooxy alcohol with 30 mol %
4
The allyl vinyl ether 6 on heating at 180 °C provided aldehyde
as inseparable mixture of diastereomers in 1:1.05 ratio, which
on subsequent reduction provided chromatographically separable
diastereomeric alcohols 8a and 8b in 43% and 46%, respectively
7
CuSO .5H O in methanol furnished (R)-3-(benzyloxy) propane-
4
2
15b
1
,2-diol 3 in 66% yield over two steps with 95% ee. The
absolute and relative configuration of diol 3 is based on L/D-
(
Table 1, entry1). The absolute configuration of new stereogenic
proline used in the reaction and analogous to those as reported in
15b
centres of 8a and 8b were analogous with earlier studies as
our earlier studies. Later on, cyclohexedene protection of the
13
reported by our group. The same transformation could also be
diol 3 followed by deprotetion of benzyl ether over (H , Pd/C,
2
induced through microwave irradiation in a much shorter time,
with improved diastereoselectivity for 8a and 8b (Table 1;
entries 2, 4 and 7). The diastereoselectivity in Claisen
rearrangement gradually increased with lower boiling solvents
(entries 3–6). When reaction performed in benzene, aldehyde 7
MeOH) afforded (S)-(1,4-dioxaspiro [4.5] decan-2-yl) methanol
4
in 91% yield over two steps. Oxidation of alcohol 4 under
Swern oxidation condition afforded crude (R)-2,3-O-
cyclohexylidene
cyclohexylidene-
D
-glyceraldehyde
5.
(R)-2,3-O-
15a
D
-glyceraldehyde 5
also obtained via

3
obtained as diastereomeric mixture in 1:4.16
A
r
C
ati
C
o,
E
w
P
h
T
ichEDon MATh
N
e
U
sy
S
nt
C
he
R
sis
I
of (S)-(+)-arundic ent-1 is outlined in scheme 5.
P
T
reduction provided 8b as major diastereomer exclusively in 77%
and 8a in 19% yield, respectively. The neat and microwave
induced Claisen rearrangement reaction at 80-85 °C as well as in
CH Cl at 40-45 °C was failed to delivered desired product
Synthetic commenced with the preparation of alcohol 8a using
conditions in entry 1 (Table 1).
2
2
(
Table 1; entries 8 and 9). The Lewis acid catalysed
rearrangement also attempted, but to our disappointment we
could not get desired results.
The probable explanation for increase in diastereoselectivity
of Claisen rearrangement is provided in figure 3. Consider the s-
cis chair like transition states of allyl vinyl ether 6, transition
states I and II would be derived from 6-(2S,Z) and 6-(2S,E),
respectively. The transition state II is more stable and favourable
as compared to transition state I, as it encounters less steric
hindrance due to minimum number of bonding interactions. The
diastereoselective Claisen rearrangement in benzene at lower
temperature might be proceeding through kinetically favoured
transition state II, which delivers aldehyde 7b as a major
diastereomer, shown in figure 2. The increase in diastereomeric
excess in benzene is might be attributed to a partial stabilization
of dipolar transition state of Claisen rearrangement of allyl vinyl
Scheme 5 Synthesis of (S)-(+)-arundic acident-1
Swern oxidation of alcohol 8a gave aldehyde, which on
subsequent Wittig olefination with pentyl-triphenyl-
phosphonium bromide salt gave dialkene 11 as 1:1.65
mixtures of E/Z isomers in 87% yield over two steps. The
Palladium catalysed hydrogenation of dialkene 11 in
methanol and subsequent acid catalyzed deketalization
provided diol 12 in 90% yield. The treatment of diol 12
with 1-Me-AZADO (cat.), NaOCl(cat.), and NaClO caused
smooth one-pot oxidative cleavage provided one carbon
2
ꢂꢃ
unit shorter (
S)-(+)-arundic acid ent-1 in 92% yield, [ꢀ]ꢁ =
16
ether in the benzene at 80-85 °C.
10
ꢂꢃ
+
6.3 ( =0.50, EtOH); lit [ꢀ]ꢁ = +6.6 (c =0.54, EtOH).
c
After confirming possibility of chromatography separation of
diastereomeric diols 10 and 12, we developed a more facile
enantioselective route to anti-Alzheimer agent 1 in which
reduction/oxidation sequence is avoided (Scheme 6). For the
synthesis of 1, the Claisen rearrangement of allyl vinyl ether 6
was carried out in benzene to give aldehyde 7, after evaporation
of solvent 7 was subsequently subjected to Wittig olefination
with pentyl-triphenyl-phosphonium bromide salt gave dialkene 9
as an inseparable mixture of diastereomers in 92% yield over two
steps.
O
H
O
O
O
O
O
O
6
-(2S,Z)
syn-7a CHO
reduction
syn-8a
minor diastereomer
sterically hindered TS I
more bonding interactions
benzene
OH
OH
(E/Z)-6
80-85
C
+
°
O
O
O
O
anti-8b
major diastereomer
O
O
O
CHO
anti-7b
H
6
-(2S,E)
kinetically favoured
kinetically favoured
sterically favoured TS II
less bonding interactions
Figure 3 Probable mechanistic explanation for observed
diastereoselectivity in Claisen rearrangement
With stereo chemically assigned alcohols 8a and 8b in hand,
we proceeded for completion of the synthesis of the anti
Alzheimer therapeutic agent (
R
)-(-)-arundic acid
1 and ent-
1
. The synthesis of ( )-(-)-arundic acid 1
R
is shown in
Scheme 4. Accordingly, the synthetic sequence commenced
with the synthesis of alcohol 8b using conditions in Table 1;
entry 6. Further, oxidation of alcohol 8b under swern
oxidation condition gave aldehyde, which without any
further chromatographic purification subjected for next
reaction. Wittig olefination of crude aldehyde with pentyl-
Scheme 6 Synthesis of (R)-(-)-arundic acid 1
triphenyl-phosphonium bromide salt at -15 °C using
as base gave dialkene as an inseparable mixture of E/Z
isomers in 86% yield over two steps. From H NMR spectra
of , ratio of the E/Z isomers found to be 1:1.10.
n-BuLi
Further, palladium catalysed hydrogenation followed by acid
catalyzed deketalization afforded separable diastereomeric diols
9
1
1
0 and 12 in 73% and 18% yields, respectively. The
9
17
organocatalytic one-pot oxidative cleavage of terminal 1,2-diols
in 10 afforded (R)-(-)-1 in 92% yield.
The synthesis of (S)-(+)-arundic ent-1 commenced from aldehyde
7
obtained by employing condition in entry-1(Table 1). The
olefination of crude aldehyde with pentyl-triphenyl-
7
phosphonium bromide salt at -15 °C using n-BuLi as base gave
dialkene (±)-9 as an inseparable mixture of E/Z isomers in 88%
yield. Later on, palladium catalysed hydrogenation followed by
acid catalyzed deketalization provided separable diastereomeric
diols 10 and 12 in 46% and 44% yields, respectively. Oxidative
Scheme 4 Synthesis of (R)-(-)-arundic acid 1
The palladium catalysed hydrogenation of 9 followed by acid
catalyzed deketalization of the spiroketal provided diol 10 in 90%
yield. The organocatalytic one-pot oxidative cleavage of
1
7
17
cleavage of terminal 1,2-diol of 12 under previously employed
condition afforded (S)-(+)-ent-1 in 92% yield.
terminal 1,2-diol 10 by combination of 1-Me-AZADO (cat.),
NaOCl (cat.), and NaClO under mild conditions gave one-
2
ꢂꢃ
carbon-unit-shorter (R)-(-)-arundic acid 1 in 92% yield. [ꢀ] = -
ꢁ
7c
ꢂꢄ
3. Conclusion
5
.8 (c =2.00, EtOH); lit [ꢀ] = -6.1 (c =2.00, EtOH).
ꢁ

4
In conclusion, short and efficient syn
Alzheimer agent ( )-(-)-arundic as well as (
acid ent has been developed using proline catalysed
A
th
C
es
S
C
is
E
o
P
f
TEan
D
ti- MAsti
N
rre
U
d
S
fo
C
r
R
10IP
h. The reaction mixture was quenched with
T
R
1
)-(-)-arundic
saturated aqueous NH Cl and extracted with ethyl acetate (3 x 50
mL), washed with brine, dried over anhydrous Na SO and
4
-
1
2
4
asymmetric α-aminooxylation and Wittig olefination-
Claisen rearrangement protocol. Following are some
highlighted features of the synthesis strategy, (i) shorter
concentrated under reduced pressure. The residue was purified by
silica gel chromatography using ethyl acetate/hexane (1:5) to
give diol 3 (0.727 g, 66%) as a viscous liquid.
route for the synthesis of the (
and ( )-(+)-arundic ent (4 steps, 28%) from chiral
glyceraldehyde starting material (ii) synthesis of the (
-arundic in 32% and ( )-(+)-arundic ent in 17% overall
yield from nonchiral starting aldehyde in 9 steps. (iii) The
key intermediate 4-pentenal obtained through performing
3,3] Claisen rearrangement can be useful for the synthesis
R
)-(-)-arundic
1
(4 steps, 51%)
[Spectral data of 3]: R = 0.3 (EtOAc/ hexane, 1:5);
f
ꢂꢃ
S
-
1
D
-
[α] = +5.56 (c 1.0, CHCl );
ꢅ
3
-1
5
R
)-(-
IR: 3417, 2920, 2880, 1085 cm
1
)
1
S
-1
H NMR (400 MHz, CDCl ) δ 7.47 – 7.23 (5H, m), 4.55 (2H, s),
3
2
3.93 – 3.86 (1H, m), 3.68 (1H, dd, J = 3.6, 11.2 Hz,), 3.63 – 3.49
(3H, m), 3.25 (2H, s);
13
[
C NMR (101 MHz, CDCl ) δ 137.7, 128.5, 127.9, 127.8, 73.5,
3
of other related analogues by changing the Wittig reagent.
Further study towards the improvement of the
diastereoselectivity in the [3,3] sigmatropic Claisen
71.6, 70.8, 64.0;
+
+
HRMS (ESI )[M+Na] : found 205.0837. C H NaO requires
10
14
3
205.0841.
rearrangement of allyl vinyl ether
strategy for the synthesis of bioactive molecules is under
progress
6 and application of this
4.2 (S)-(1,4 Dioxaspiro [4.5]decan-2-yl)methanol (4)
.
[Spectral data of 4]: R = 0.5 (EtOAc/ hexane, 1:4);
f
ꢂꢃ
[
α] = -4.2 (c 1.0, CHCl );
ꢅ
3
4
. Experimental section
-1
IR (neat): 3520, 1450, 1090, 937 cm ;
1
H NMR (400 MHz, CDCl ) δ 4.29 – 4.15 (1H, m), 4.15 – 3.90
3
General Experimental Details
(2H, m), 3.83 – 3.64 (2H, m), 3.67 – 3.51 (1H, m, OH), 1.65 –
1
.37 (10H, m);
1
3
C NMR (101 MHz, CDCl ) δ 109.9, 75.7, 65.3, 63.1, 34.7,
All reagents were obtained from commercial suppliers unless
otherwise stated and solvents were used as received with the
following exceptions. Tetrahydrofuran (THF) was distilled from
benzophenone and sodium immediately prior to use. All moisture
sensitive reactions were carried out under a nitrogen atmosphere
with dry solvents under anhydrous conditions, unless otherwise
noted. Reactions were magnetically stirred and monitored by
analytical thin-layer chromatography (TLC) E. Merck 0.25 mm
silica gel 60 F254. TLC plates were visualized by exposure to
ultraviolet light (UV, 254 nm) and/or exposure to an aqueous
3
3
4.7, 25.1, 24.0, 23.7;
HRMS (ESI )[M+ Na] : found 199.0995. C H NaO requires
+
+
10 16
3
1
99.0997.
4
.3(S)-2-(2-(Allyloxy)-vinyl)-1,4-dioxospiro[4.5]-decane(6)
Oxalyl chloride (2.24 mL, 0.0261 mol, 1.5 equiv.) was gradually
added to a solution of DMSO (3.71 mL, 0.052 mol, 3 equiv.) in
CH Cl (50 mL) at -78 °C over a period of 5 min. After stirring
2
2
for 10 min, a solution of alcohol 4 (3 g, 0.0174 mol) in CH Cl (5
2
2
mL) was added, and the mixture was stirred for 1 h. Then NEt3
solution of potassium permanganate (KMnO ), an acidic solution
4
(
10.9 mL, 0.078 mol, 4.5 equiv.) was added, and the mixture was
stirred for 30 min. The mixture was gradually warmed to room
temperature, and then it was diluted with CH Cl (20 mL). Water
of anisaldehyde or a solution of PMA followed by heating with a
heat gun. Chromatography was performed using silica gel (100-
2
00 mesh) with solvents distilled prior to use. Yields refer to
2
2
1
13
(
20 mL) was added, and then the phases were separated, and the
chromatographically and spectroscopically ( H and C NMR)
pure material. All spectra were recorded at 25 °C. H NMR
1
aqueous phase was extracted with CH Cl (3 x 25 mL). The
2
2
combined organic extracts were washed with water and brine,
dried (Na SO ), and concentrated to give the crude ketone (0.187
spectra were recorded on 500 MHz and 400 MHz spectrometers
13
and C NMR spectra were obtained at 500 NMR (126 MHz) and
00 (101 MHz) spectrometer using CDCl3 as solvent.
2
4
g), which was used directly in the next reaction. To a suspension
of crude 2,3-O-Cyclohexylidene- -glyceraldehyde 5 and allyloxy
methylene triphenyl-phosphonium chloride (9.61 g, 0.0261 mol,
4
1
D
Tetramethylsilane (0.00 ppm) served as an internal standard in H
NMR and CDCl (77.0 ppm) in C NMR. Chemical shifts were
13
3
1
0
1
.5 equiv) in dry THF (150 mL), potassium t-butoxide (2.92 g,
.0261 mol, 1.5 equiv) was added portion wise over the period of
0 min. The reaction was stirred for 1 h at the same temperature.
recorded in ppm, and coupling constants (J) were in Hz.
HRESIMS were taken on Bruker Impact HD quadrupole plus ion
trap at CIF Savitribai Phule Pune University. Infrared spectra
were recorded on a Nicolet Nexus 470 FT-IR spectrometer. The
following abbreviations are used for the multiplicities: s: singlet,
d: doublet, t: triplet, m: multiplet, bs: broad singlet dd: doublet of
doublet for proton spectra. Optical rotations were measured on a
digital polarimeter
After completion of reaction (TLC check), THF was removed
under reduced pressure. Residue was suspended in water and
extracted with ethyl acetate (3 x 50 mL). The combined organic
layers were washed with water, dried over anhydrous Na SO and
2
4
concentrated under reduced pressure. The crude product was
purified by silica gel column chromatography using petroleum
ether as eluent, gave pure allyl vinyl ether 6as colourless thick
liquid. The product in hand was the inseparable mixture of E- and
Z- isomers (1:1.96) 3.32 g (85%) over two steps.
Experimental section:
4
.1 (R)-3-(Benzyloxy) propane-1,2-diol (3)
To a stirred solution of aldehyde 2 (2 g, 12.2 mmol) and
From protected
of cyclohexedene protected diol (3 g, 0.0087 mmol) in CH Cl
2
D-mannitol- To a magnetically stirred solution
nitrosobenzene (1 g, 9.34 mmol) in CH CN (25 mL) was added
3
D-proline (0.270 g, 2.43 mmol) at -20 °C. The reaction mixture
2
(20 mL) silica supported NaIO (4:1) was added and stirring was
was stirred for 24 h at the same temperature, then diluted with
4
continued for 2 h at rt. The mixture was then filtered through a
cotton plug, and the residue was washed with CH Cl (3 x 25
mL). The filtrate was concentrated to give the crude aldehyde 5
which without any purification subjected to Wittig olefination
with allyoxy methylene triphenyl phosphine using same
procedure above to give allyl-vinyl ether 6 (1.63 g, 83%) yield.
MeOH (15 mL) and to this solution was added NaBH (1.06 g,
4
2
8 mmol). After 30 min, the reaction mixture was carefully
2
2
quenched with saturated aqueous NaHCO , extracted with ethyl
3
acetate (3 x 50 mL), dried over Na SO and concentrated under
2
4
reduced pressure. The CuSO .5H O (0.7 g, 2.8 mmol) was added
4
2
at 0 °C to the solution of crude product in MeOH (20 mL) and

5
#
Preparation of silica gel supported NaIO4
A
(
C
4:1
C
):
E
1
P
g
T
,
E
4.
D
69 MA3.
N
65
U
(2
S
H
C
, m
R
),
I
2.05 – 1.99 (2H, m), 1.82 – 1.76 (1H, m), 1.62 –
P
T
mmol) of sodium periodate are suspended in 2 mL of water.
Under magnetic stirring the mixture is heated to 70°C in a 50 mL
flask. To this slightly cloudy solution is added silica (4 g 230–
1.56 (8H, m), 1.40 (2H, bs);
13
C NMR (126 MHz, CDCl ) δ 135.5, 117.0, 109.7, 79.0, 68.4,
3
64.6, 43.82, 36.2, 35.0, 32.9, 25.0, 24.0, 23.8;
+
+
4
00 mesh) in one go (at 70 °C). The flask is removed from the
HRMS (ESI )[M+ Na] : found 249.1467. C H NaO requires
13 22 3
heating bath fitted with a stopper and swirled until a fine
homogenous powder has developed.
249.1462.
[
Spectral data of 6]: R = 0.6 (EtOAc/ hexane, 1:4);
[Spectral data of 8b]: R = 0.3 (EtOAc/ hexane, 1:4);
f
f
-
1
ꢂꢃ
IR (neat): 2940, 1690, 1105, 930 cm ;
[ꢀ] = +0.7 (c =3.00, CHCl3);
ꢁ
1
-1
H NMR (500 MHz, CDCl ) δ 6.19 (1H, d, J = 12.9 Hz, E-
IR (neat): 3467, 2943, 1637, 1447, 1109, 925 cm ;
3
1
isomer), 5.97 (1H, d, J = 7.0 Hz, Z-isomer), 5.95 – 5.85 (1H, m),
H NMR (500 MHz, CDCl ) δ 5.82 (1H, ddt, J = 17.3, 10.0, 7.1
3
5
.31 (1H, m), 5.27 – 5.19 (2H, m), 4.45 – 4.39 (1H, m), 4.29 (1H,
Hz), 5.11 – 5.02 (2H, m), 4.23 (1H, dd, J = 8.4, 6.2 Hz), 4.02
(1H, dd, J = 8.1, 6.4 Hz), 3.75 (1H, t, J = 8.0 Hz), 3.72 – 3.62
(2H, m), 2.18 – 2.10 (2H, m), 1.99 – 1.93 (1H, m), 1.65 – 1.57
(8H, m), 1.40 (2H, bs);
d, J = 5.4 Hz), 4.23 – 4.17 (2H, m), 4.05 (1H, dd, J = 8.0, 6.6
Hz), 3.96 (1H, dd, J = 8.1, 6.5 Hz), 3.70 (1H, t, J = 8.0 Hz, E-
isomer), 3.63 (1H, t, J = 8.0 Hz, Z-isomer), 1.70 – 1.62 (8H, m),
13
1
.41 – 1.32 (2H, m);
C NMR (126 MHz, CDCl ) δ 136.3, 116.7, 109.2, 79.9, 66.2,
3
13
C NMR (126 MHz, CDCl ) δ 144.1, 143.2, 133.8, 133.7, 117.5,
63.0, 42.4, 36.1, 34.7, 31.8, 25.1, 24.0, 23.8;
+ +
3
1
3
17.5, 110.9, 109.2, 101.8, 101.5, 72.8, 72.7, 71.4, 67.0, 66.5,
5.9, 35.1, 30.3, 25.3, 23.9;
HRMS (ESI )[M+ Na] : found 249.1467. C H NaO requires
13 22 3
249.1462.
+
+
HRMS (ESI )[M+ Na] : found 247.1312. C H NaO requires
13
20
3
2
47.1310.
4.6(S)-2-((R)-Deca-1,5-dien-4-yl)-1,4-dioxaspiro[4.5]decane (9)
Oxalyl chloride (0.28 mL, 3.33 mmol, 1.5 equiv.) was gradually
added to a solution of DMSO (0.47 mL, 6.66 mmol, 3 equiv.) in
4
.4 (S)/(R)-2-(1,4-Dioxaspiro[4.5]-decan-2-yl)-pent-4-enal (7)
The isomeric mixture of allyl vinyl ether 6 (0.5g, 2.46 mmol) was
dissolved in benzene (5 mL) (Entry 6) and the solution was
refluxed for 24 h. After completion of the reaction (TLC check),
the benzene was removed under reduced pressure to afford pure
CH
for 10 min, a solution of 8b (0.500 g, 2.22 mmol) in CH
mL) was added, and the mixture was stirred for 1.5 h. Et N (1.42
2
Cl
2
(25 mL) at –78 °C over a period of 5 min. After stirring
Cl (5
2
2
3
mL, 9.99 mmol, 4.5 equiv.) was added, and the mixture was
stirred for 30 min. The mixture was gradually warmed to room
4
-pentenal as colourless oil. The product in hand was the mixture
of two inseparable diastereoisomers in a ratio of 1:4.10.
Spectral data of 6]: R = 0.7 (EtOAc/ hexane, 1:4);
temperature, and then it was diluted with CH
(20 mL) was added, and then the phases were separated, and the
aqueous phase was extracted with CH Cl (3 x 25 mL). The
combined organic extracts were washed with water and brine,
dried (Na SO ), and concentrated to give the crude aldehyde
Cl (20 mL). Water
2
2
[
f
-
1
IR (neat): 2930, 1725, 1650, 1101, 915 cm ;
2
2
1
H NMR (400 MHz, CDCl ) δ 9.79 (1H, d, J = 2.7 Hz, minor
3
isomer), 9.77 (1H, d, J = 1.3 Hz, major isomer), 5.89 – 5.71 (m,
2
4
1
(
H), 5.13 (2H, tdt, J = 17.5, 6.3, 1.4 Hz), 4.35 – 4.29 (1H, m),
1H, m), 4.17 – 4.11 (1H, m), 3.75 (1H, dd, J = 7.9, 6.2 Hz,
minor isomer), 3.67 (1H, dd, J = 8.5, 6.6 Hz, major isomer), 2.72
2.64 (1H, m), 2.63 – 2.44 (2H, m), 1.70 – 1.52 (8H, m), 1.42
(0.488 g), which was used directly in the next reaction. n-BuLi
(1.6 m in hexane; 1.63 mL, 2.61 mmol, 1.2 equiv.) was added to
a suspension of pentyltriphenylphosphonium bromide (1.08 g,
2.61 mmol, 1.2 equiv.) in dry THF (15 mL) at -15 °C. After
stirring at -15 °C for 30 min, a solution of the crude aldehyde in
dry THF (5 mL) was added, and the resulting mixture was stirred
at 0°C for 3 h. The reaction was then quenched with a few drops
of water, and the organic phase was filtered through a cotton
–
(
2H, bs);
1
3
C NMR: (75 MHz, CDCl ): δ 203.0, 202.9, 134.4, 134.2, 117.6,
3
1
3
09.9, 109.4, 74.7, 73.6, 67.2, 67.1, 54.4, 36.1, 36.0, 34.7, 34.5,
0.5, 30.0, 25.0, 23.9, 23.8 and 23.6;
+
+
HRMS (ESI )[M+ Na] : found 247.1312. C H NaO requires
2
plug. The residue was washed with Et
concentrated and extracted with Et O (3 x 15 mL). Organic layer
was washed with water and brine, dried (Na SO ), and
2
O (5 mL). The filtrate was
13
20
3
47.1310.
2
2
4
concentrated. The residue was purified by silica gel column
chromatography to afford title compound 9 (0.535 g) in 87%
yield over two steps.
4
.5(S)-2-((S)-1,4-Dioxaspiro[4.5]decan-2-yl)pent-4-en-1-ol
(
(
8a)/(R)-2-((S)-1,4-dioxaspiro[4.5]decan-2-yl)pent-4-en-1-ol
8b)
[
Spectral data of 9]: R = 0.6 (EtOAc/ hexane, 1:5);
f
To the solution of crude mixture of aldehyde 7 in 5% aqueous
methanol (5 mL), sodium borohydride (1.5 equiv.) was added
portion wise over a period of 10 min at 0 °C. The reaction
mixture was stirred at same temperature for 30-35 min. After
completion of reaction (TLC check), the methanol was removed
under reduced pressure, residue was diluted with water and
extracted with ethyl acetate (3 x 5 mL). The combined organic
ꢂꢄ
[
ꢀ] = +12.10 (c =0.42, MeOH);
ꢁ
-1
IR (neat): 1680, 1665, 1109, 925cm ;
1
H NMR (500 MHz, CDCl ) δ 5.81 – 5.71 (1H, m), 5.50 (1H,
3
dtd, J = 11.1, 7.3, 0.6 Hz,), 5.08 – 5.01 (2H, ddt, J = 5.6, 2.7, 1.7
Hz,), 5.01 – 4.95 (1H, m), 3.95 – 3.88 (2H, m), 3.57 (1H, t, J =
6
.6 Hz,), 2.62 – 2.55 (1H, m), 2.54 – 2.46 (1H, m), 2.09 – 2.00
(3H, m), 1.69 – 1.56 (10H, m), 1.43 – 1.32 (6H, m), 0.91 (3H, t, J
phases were washed with water, dried over anhydrous Na SO4
2
=
7.1 Hz);
and concentrated under reduced pressure. The crude product was
purified by silica gel column chromatography using petroleum
ether: ethyl acetate (97: 3) to give the alcohol 8a (0.095 g, 19%)
and 8b (0.388 g, 77%) as colourless liquids.
13
C NMR (126 MHz, CDCl ) δ 136.5, 132.7, 128.2, 115.9, 109.5,
3
7
2
8.2, 67.8, 41.9, 36.7, 36.6, 35.2, 31.8, 27.7, 25.2, 24.0, 23.9,
2.4, 14.0;
+
+
HRMS (ESI )[M+Na] : found 301.2141. C H NaO requires
18
30
2
[
Spectral data of 8a]: R = 0.3 (EtOAc/ hexane, 1:4);
f
3
01.2143.
ꢂꢃ
[
ꢀ] = -0.5 (c =2.00, CHCl );
ꢁ
3
-
1
IR (neat): 3463, 2930, 1623, 1454, 1098, 937 cm ;
4.7(2S,3R)-3-Propylnonane-1,2-diol (10):
1
H NMR (500 MHz, CDCl ) δ 5.75 (1H, ddt, J = 17.2, 10.0, 7.2
To a solution of 9 (0.500 g, 10 mmol) in MeOH (20 mL), 10%
palladium on charcoal (0.190 g, 10 mol %) was added and the
mixture was kept under hydrogen (1 atm). The reaction mixture
3
Hz), 5.10 – 5.02 (2H, m), 4.11 (1H, dd, J = 7.9, 6.2 Hz), 4.05
(1H, dd, J = 8.2.1, 6.5 Hz), 3.76 (1H, dd, J =8.3, 6.4 Hz), 3.72 –

6
was stirred at room temperature for 1 h and th
A
en
C
th
C
e
E
su
P
sp
TED
on MANUSCRIPT
en
si
was filtered through a pad of Celite, washed with ethyl acetate (2
x 50 mL) and the solvent was evaporated to yield the crude
product, which without any chromatographic purification directly
subjected in the next reaction. Solution of the above crude 1,4-
dioxaspiro compound in methanol add 0.5 mL of conc. HCl was
stirred at rt for 6 h. After completion of reaction, the reaction
mixture was diluted with ethyl acetate (50 mL) and washed
4.10 (2S,3S)-3-Propylnonane-1,2-diol) (12):
The title compound was prepared from 11 (0.200 g, 0.718 mmol)
according to a procedure similar to that described for the
conversion 9 to 10 to give 12(0.131 g 90%) as colourless thick
oil.
[Spectral data of 12]: R = 0.2 (EtOAc/ hexane, 4:6);
f
ꢂꢄ
[ꢀ] = +5.14 (c= 0.21, MeOH);
ꢁ
-
1
repeatedly with saturated aqueous NH OH solution (3 x 15 mL)
IR (neat): 3570, 3554 cm ;
4
1
till it was alkaline. The organic layer was dried and concentrated.
Column chromatography of the residual mass [ethyl
acetate/petroleum ether (1:1)] afforded the corresponding diol 10
H NMR (500 MHz, CDCl ) δ 3.72 – 3.66 (2H, m), 3.55 (1H, dd,
J = 10.8, 8.6 Hz,), 2.42 (2H, bs, exchangeable with D O), 1.46 –
1.16 (15H, m), 0.91 (3H, t, J = 7.1 Hz,), 0.87 (3H, t, J = 7.4 Hz,);
C NMR (126 MHz, CDCl ) δ 74.2, 65.0, 40.7, 32.1, 31.8, 29.7,
3
2
13
(0.328 g) in 90% yield over two steps.
3
[
Spectral data of 10]: R = 0.2 (EtOAc/ hexane, 4:6);
29.3, 27.1, 22.6, 20.3, 14.4, 14.1;
+ +
f
ꢂꢄ
[
ꢀ] = +7.54 (c =0.21, MeOH);
HRMS (ESI )[M+ Na] : found 255.1832. C H NaO requires
12 26 2
ꢁ
-
1
IR (neat): 3567, 3540, 925 cm ;
255.1830.
1
H NMR (500 MHz, CDCl ) δ 3.74 – 3.65 (4H, m), 3.56 (2H, dd,
3
J = 10.8, 8.6 Hz), 2.40 (3H, s), 1.47 – 1.18 (15H, m), 0.91 (3H, t,
J = 7.3 Hz), 0.87 (3H, t, J = 7.0 Hz,);
4.11 (S)-(-)-Arundic acid (1)
The title compound was prepared from 12 (0.040 g, 0.198 mmol)
according to a procedure similar to that described for the
conversion of 10 to 1 to give ent-1 (0.034 g, 84%) as colourless
13
C NMR (126 MHz, CDCl ) δ, 74.3, 65.0, 40.7, 31.8, 31.6, 29.8,
3
2
9.7, 27.1, 22.6, 20.2, 14.5, 14.1;
+
+
HRMS (ESI )[M+ Na] : found 255.1832. C H NaO requires
oil.
12
26
2
ꢂꢃ
2
55.1830.
[Spectral data of (S)-(-)-arundic acid ent-1]: [ꢀ] = +6.3 (c =0.50,
ꢁ
1
0
ꢂꢃ
EtOH); lit [ꢀ]ꢁ = +6.6 (c =0.54, EtOH);
-
1
4
.8(R)-(-)-Arundic acid (1):
IR (neat): 1700 cm ;
H NMR (400 MHz, CDCl ) 11.27 (1H, s), 2.29–2.20 (1H, m),
1
To A mixture of 4-phenyl-1,2-butanediol 28 (80 mg, 0.395
mmol) and 1-Me-AZADO (5.90 mg, 0.0395 mmol) in MeCN
3
1.56–1.19 (14H, m), 0.92 (3H, t, J = 7.4 Hz), 0.90 (3H, t, J = 7.6
(1.5 mL) and Phosphate buffer (0.7 mL, pH = 6.8) was stirred at
Hz);
1
3
room temperature. Then NaClO (96.3 mg, 80%, 1.186 mmol in
C NMR (101 MHz, CDCl
29.3, 27.0, 22.5, 20.3, 14.3, 14.1;
3
) δ 184.8, 45.7, 34.5, 32.4, 31.6,
2
0
.3 mL H O) and dilute bleach (0.247 mL, 0.0395 mmol) were
2
+
+
added simultaneously over 30 seconds. The mixture was stirred
at room temperature for 3 h. It was quenched with phosphate
buffer (3 mL, pH = 2.3), added NaCl and extracted with CH Cl .
HRMS (ESI )[M+ H] : found 187.1696. C11
187.1698.
H23NaO requires
2
2
2
The organic layer was dried over MgSO and concentrated under
Acknowledgments
4
reduced pressure. The crude materials was purified by flash
column chromatography to give (R)-(-)-Arundic acid 27 (67.7
mg, 92%).
Financial support from the UGC, New Delhi is acknowledged.
[
Spectral data of (R)-(-)-arundic acid 1]-[ꢀ] ꢂꢁ ꢃ= -5.8 (c =2.00,
References and notes
7c
ꢂꢄ
EtOH); lit [ꢀ] = -6.1 (c =2.00, EtOH);
ꢁ
-
1
IR: 1700 cm ;
1. (a) Burns, A.; Iliffe, S., BMJ. 2009, 338, b158. (b) Liuzzi, F. J.;
Lasek, R. J. Science 1987, 237, 642–645; (c) Uchida, Y.;
Tomonaga, M., Brain Res. 1989, 481, 190–193; (d) Moundijian,
A.; Antel, J. P.; Yong, V. W.Brain Res. 1991, 547, 223–228.
1
H NMR (500 MHz, CDCl ) δ 11.46 (1H, s), 2.29–2.21 (1H, m),
3
1
.57–1.33 (14H, m), 1.01 (3H, t, J = 7.2 Hz), 0.99 (3H, t, J = 7.5
Hz);
2
.
Pohanka M. Biomed Pap. Med. Fac. Univ Palacky Olomouc
Czech Repub. 2011, 155, 219-229.
13
C NMR (126 MHz, CDCl ) δ 184.4, 45.7, 34.8, 32.4, 31.53,
3
2
9.7, 27.8, 23.0, 20.4, 14.1, 14.0;
3. Birks, J.; Harvey R. J. The Cochrane Database of Systematic
Reviews. January 2006; 1, CD001190.
+
+
HRMS (ESI )[M+ H] : found 187.1696. C H NaO requires
1
1
1
23
2
4
.
(a) Tateishi, N.; Mori, T., Kagamiishi, Y.; Satoh, S.; Katsube, N.;
Morikawa, E.; Morimoto, T.; Matsui, T.; Asano, T. J., Cereb.
Blood Flow Metab. 2002, 22, 723-734; (b) Mitsuru H.; Ryuichi
S., Michihito M.; Tatsuya Y.; Koji T.; Yuki S.; Shiro I.; Naoki I.
and Yukihiro M. Journal of the Neurological Sciences, 2014, 337,
186-192; (c) Fernandes, R. A.; Ingle, A. B. Curr. Med. Chem.,
87.1698.
4
.9(R)-2-((R)-Deca-1,5-dien-4-yl)-1,4dioxaspiro[4.5]decane(11):
The title compound was prepared from 8a (0.250 g, 1.11 mmol)
according to a procedure similar to that described for the
conversion 8b to 9 to give 11(0.268 g 87%) as colourless oil.
2
013, 20, 2315-2329; (4d) Yanagisawa, M.; Aida, T.; Takeda,
T.; Namekata, K.; Harada, T.; Shinagawa, R. and Tanaka, K. Cell
Death and Disease, 2015, 6, e1693.
[
Spectral data of 11]: R = 0.6 (EtOAc/ hexane, 1:5);
f
ꢂꢄ
[
ꢀ] = +17.06 (c =0.58, MeOH);
ꢁ
5. Hasegawa, T.; Kawanaka, Y.; Kasamatsu, E.; Ohta, C.; kabayashi,
K.; Okamoto, M.; Hamano, M.; Takahashi, K.; Ohuchida, S.;
Hamada, Y. Org. Process. Res. Dev. 2005, 9, 774-781.
-
1
IR (neat):1680, 1665, 1109, 925 cm ;
1
H NMR (500 MHz, CDCl ) δ 5.81 – 5.72 (1H, m), 5.56 (1H,
3
6
.
(a) Kishimoto, K.; Nakai, H. Patent 1995, 7-98328; Chem.
Abstr.1997, 126, 74487; (b) Kishimoto, K.; Nakai, H. Patent 1995,
dtd, J = 11.3, 7.5, 0.8 Hz), 5.28 – 5.18 (1H, m), 5.07 – 4.97 (2H,
m), 4.08 (1H, dd, J = 7.7, 6.3 Hz), 3.99 (1H, dd, J = 7.9, 6.3 Hz),
3
7
-102693; Chem. Abstr.1997, 126, 74488; (c) Gualandi, A.; Emer,
.64 (1H, t, J = 7.7 Hz) 2.64 – 2.58 (1H, m), 2.32 – 2.22 (1H,
E.; Capdevila, M. G. and Cozzi, P. G. Angew.Chem. Int. Ed. 2011,
50, 7842-7846; (d) Perez, M.; Fananas-Mastral, M.; Hornillos, V.;
Rudolph, A.; Bos, P. H.; Harutyunyan, S. R. and Feringa, B. L.,
Chem. Eur. J. 2012, 18, 11880-11883; (e) Afewerki, S.; Ibrahem,
S.; Rydfjord, J.; Breistein P.; and Cardova, A., Chem. Eur. J.
m), 2.10 – 2.02 (3H, m), 1.66 – 1.58 (10H, m), 1.38 – 1.31 (6H,
m), 0.94 (3H, t, J = 7.5);
1
3
C NMR (126 MHz, CDCl ) δ 136.6, 132.4, 128.6, 115.9,
3
1
2
09.1, 77.6, 66.8, 40.0, 36.1, 35.9, 35.0, 31.8, 27.5, 25.23, 23.9,
3.8, 22.4, 14.0;
2
012, 18, 2972-2977. (f) Lu, C.; Zhang, L.; Su, H.; Yang, G. and
Chen, Z., J. Chem. Res., 2012, 36, 678-679;
+
+
HRMS (ESI )[M+ Na] : found 301.2141. C H NaO requires
3
7. (a) Hasegawa, T.; Yamamoto, H. Bull. Chem. Soc. Jpn. 2000, 73,
423-428; (b) Hasegawa, T.; Yamamoto, H. Synthesis, 2003, 1181-
1
8
30
2
01.2143.

7
1
186 (c) Hasegawa, T.; Kawanaka, Y.; Kasamatsu, E.; Iguchi, Y.;
ACCEPTED MANUSCRIPT
Yonekawa, Y.; Okamoto, M.; Ohta, C.; Hashimoto, S.; Ohuchida,
S. Org. Process. Res. Dev. 2003, 7, 168-171; (d) Garcia, J. M.;
Odriozola, J. M.; Lecumberri, A.; Razkin, J.; Gonzalez, A.
Tetrahedron, 2008, 64, 10664-10669.
8
9
1
.
.
Pelotier, B.; Holmes; T.; Piva, O. Tetrahedron: Asymmetry2005,
1
6, 1513-1520.
Goswami, D. and Chattopadhyay, A. Lett. Org. Chem. 2006, 12,
22-925.
9
0. (a) Fernandes, R. A.; Dhall, A. and Ingle A. B., Tetrahedron
Lett.,2009, 50, 5903-5905; (b) Fernandes, R. A.; Ingle A. B. And
Chaudhari D. A. Eur. J. Org. Chem. 2012, 1047–1055.
1
1
1
1. Xu, S.; Lee, C. T.; Wang, G. and Negishi, E. Chem. Asian J.,
2
013, 8, 1829-1835.
2. Bhosale,V. A.; Ukale, D. U. and Waghmode, S. B. New Journal of
Chemistry, 2016, 9432-9440 and references cited therein.
3. (a) Bhosale, V. A. and Waghmode, S. B. Chemistry Select, 2017,
Supplementary Material
2
, 1262-1266 and references cited therein. (b) Kulkarni, M. G.;
Borhade, A. S.; Shaikh, Y. B.; Dhondge, A. P.; Birhade, D. R.
and Dhatrak, N. R. Tetrahedron Letters, 2011, 52, 5559-5562.
4. (a) Sawant, R. T. and Waghmode, S. B. Tetrahedron 2009, 65,
1
1
599-1602; (b) Sawant, R. T.; Jadhav, S. G. and Waghmode, S. B.
Eur. J. Org. Chem. 2010, 4442-4249; (c) Sawant, R. T. and
Waghmode, S. B. Synth. Commun., 2010, 40, 2269-2277; (d)
Sawant, R. T. and Waghmode, S. B. Synth. Commun., 2011, 41,
2
385-2391; (e) Patil, V. P.; Ghosh, A.; Sonavane, U.; Joshi, R.;
Sawant, R.; Jadhav, S. and Waghmode, S. B.
Tetrahedron:Asymmetry., 2014, 25, 489-496.
1
1
5. (a) Sugiyama, T.; Sugawara, H.; Watanabe, M.; Yamashita, K.
Agric. Biol. Chem. 1984, 48, 1841–1844; (b) Sawant, R. T. and
Waghmode, S. B. Tetrahedron, 2010, 66, 2010-2014.
6. (a) Coates, R. M.; Rogers, B. D.; Hobbs, S. J.; Peck, D. R. and
Curran, D. P., J. Am. Chem. SOC. 1987, 109, 1160-1170 and
references cited therein; (b) Gajewski, J. J. Acc. Chem. Res. 1997,
3
0, 219-225.
1
7. Shibuya, M.; Doi, R.; Shibuta, T.; Uesugi, S. and Iwabuchi, Y.,
Org. Lett., 2012, 14, 5006-5009.
Click here to remove instruction text...