Reversible chemoselective transetherification of vinylogous esters using Fe-catalyst under additive free conditions

Article abstract of DOI:10.1039/c9ob00307j

An additive/Br?nsted acid/base free, highly efficient and chemoselective transetherification of electron deficient vinylogous esters and water mediated de-alkylation using an earth-abundant Fe-catalyst under very mild reaction conditions is described. This reaction is highly selective to primary alcohols over secondary alcohols, has good functional group tolerance, is scalable to gram scale and a purification free sequential transetherification in a continuous flow mode is demonstrated.

Full text of DOI:10.1039/c9ob00307j

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DOI: 10.1039/C9OB00307J
ARTICLE
Reversible Chemoselective Transetherification of Vinylogous Ester
Using Fe-Catalyst under Additive Free Condition
Nenavath Parvathalu,‡ Sandip G. Agalave,‡ Nirmala Mohanta and Boopathy Gnanaprakasam*
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
An additive/Bronsted acid/base free, highly efficient and chemoselective transetherification of electron deficient
vinylogous esters and water mediated de-alkylation using earth-abundant Fe-catalyst under very mild reaction condition is
described. This reaction is highly selective to primary alcohols over the secondary alcohols, well functional group tolerant,
scalable to the gram and demonstrated a purification free sequential transetherification in continuous flow mode.
Introduction
Ethers are prevalent motifs in a various range of natural
products, pharmaceuticals, agrochemicals, polymers,
Rate of transetherification using alcohols
R1
R1 R2
O
R1
R1
R2
R1 R2
fragrances, and materials.1 Traditionally, Williamson
etherification employs stochiometric sodium alkoxide and alkyl
halides to generate symmetrical and unsymmetrical ethers2
involves few drawbacks; a requirement of stochiometric strong
bases, generation of stoichiometric amount of inorganic waste,
toxic and expensive genotoxic organohalides derived from
alcohols, making the ether synthesis an eventual multistep
process.3 During the past decades, several approaches utilizing
homogeneous catalysts such as Brønsted acid or Lewis acid
were developed for the synthesis of ethers from diverse
functional groups to avoid these shortcomings.4 Nevertheless
these methods have advantages, but suffers from poor atom
economy, need of stochiometric additives, limited substrate
scope, absence of chemoselectivity and a special stochiometric
reagent for the hydrolysis/ethereal C-O bond cleavage.
Alternatively, it has been synthesized via transetherification
reactions by using a metal catalyst with additives and also
promoted by a stoichiometric amount of bases and acids5
which encompasses only electronically rich substrates having
benzyl and allyl groups. In general, syntheses of ethers via
transetherification reactions are reversible in nature; hence
the excess amount of alcohol is used to shift the equilibrium in
the forward direction in the presence of the catalyst. The
relative strength of the C-O bond in various ethers and their
reactivities towards various alcohols is shown in Scheme 1.
Ethers having allyl, benzyl and alkyl group facilitated the C-
O bond dissociation via the resonance stabilization and thus
R
O
R2
O
B
R3
R
O
R2
R
O
R3
R
O
A
R3
D
E
C
Strength of C-O bond
Scheme 1. Relative strength and ease of substitution on ethers
Previous reports
R1
Disadvantages:
1) metal catalyst,
stoichiometric
additive
Electron rich ether substrates and
activated ethers; Assisted by
additives
R3
and stoichiometric hazardous acids;
Non-Chemoselectivity over primary vs
secondary alcohols; Require special
reaction for hydrolysis; difficult in
continuous transetherification
+
R2
R3
OH
R
O
R
O
2) Stoichiometric
acids and bases
R = alkyl, Bn, CH=CH2
This work
O
O
O
OH
FeCl3
+
R5
+
+
R4
OH
R5
R6
Batch and
continuous
flow
R1
R1
R1
O
R6
O
R4
OR3
R2
R2
R2
Exclusive selectivity on primary alcohols
Vinylogous esters
Batch and continuous flow synthesis
Electron deficient unsymmetrical ether substrates
Chemoselective and catalytic reaction
Functional group tolerance and solvent free
Continuous multi-transetherification
Wide substrate scope and gram scale synthesis
Assisted by chelation of Fe with C=O group
Novel Fe-catalyzed de-alkylation using water
Scheme 2. State of art for the transetherification reaction
assisted easy substitution of the alkoxy group by the alcohols.
On the other hand, this transformation was more difficult with
electron deficient ethers such as vinylogous esters due to the
conjugated C=O group which makes stronger alkenyl C-O bond.
Hence, the activation of alkenyl C−O bond and concomitant
substitution reaction by various nucleophile is one of the
challenges in synthetic organic chemistry, where it is often
used to form C-C and C-N bond in cross-coupling reactions.6
Moreover, vinylogous esters are electron deficient ethers and
become an attractive feedstock in several chemical
transformations such as coupling reaction,7 ene reactions,8
photocycloaddition reaction,9 and many other organic
transformations.10
a. Department of Chemistry, Indian Institute of Science Education and Research,
Pune-411008, India. E-mail: gnanaprakasam@iiserpune.ac.in
b. † Nenavath Parvathalu,‡ and Sandip G. Agalave,‡ contributed equally.
Development of metal catalyzed chemoselective
transetherification is one of the challenges in synthetic
c. Electronic Supplementary Information (ESI) available: [copies of 1H NMR and 13
NMR]. See DOI: 10.1039/x0xx00000x
C
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Organic & Biomolecular Chemistry
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ARTICLE
Journal Name
Table 1. Optimization for transetherification reaction in batcha
methodology.11 While transetherification of ethers having
alkyl, allyl, and benzyl substituent were reported Scheme 2,
the metal-catalyzed transetherification of electron deficient
vinylogous ester and chemoselective transetherification were
not studied in the literature.
View Article Online
DOI: 10.1039/C9OB00307J
O
O
5 mol% catalyst
MeOH, rt
O
O
1a
2a
Besides, continuous flow organic reactions are immensely
attracted by synthetic chemist since it has several advantages
over the conventional batch reactions that include improved
safety, great efficiency, reproducibility, precise control of
reaction conditions, and easy scale-up.12 Furthermore,
vinylogous esters are highly reversible in nature in the
presence of the acid/catalyst, which requires shorter reaction
time to avoid the exposure of the reaction mixture under
prolonged acidic or catalytic reaction condition. Hence,
continuous flow approach can overcome the existing problems
associated with the transetherification reaction.
Herein, we report additive free, highly efficient and
chemoselective transetherification of vinylogous ester using
Fe-catalyst in the absence of stochiometric strong acids or
bases. Advantages of this novel approach include easily and
rapidly integrable into continuous flow mode, purification free
continuous flow sequential transetherification and scalable in
grams in short duration. In addition, a novel approach for the
reversible reaction of this vinylogous ester and water-
mediated de-alkylation under a very mild reaction condition is
also demonstrated.
entry
catalyst
MeOH
solvent
time
(h)
21
21
11
3
6
40
3
yield
(%)
-
40
90
95
93
-
1
2
3
4
5
6
7
8
9
-
10
10
-
Ru(bpy)3Cl2.6H2O
Ru(bpy)3Cl2.6H2O
RuCl3. 6H2O
[Ru(p-cymene)Cl2]2
Ru-MACHO
FeCl3.6H2O
Fe-zeolite
(CH3COO)3Mn·
2H2O
ACN
excess
excess
excess
excess
excess
excess
excess
-
-
-
-
-
-
-
98
95
-
3
3
10
11
12
13
MnCl2· 2H2O
NiBr2. 2H2O
CuCl2· 2H2O
CoCl3· 2H2O
excess
excess
excess
excess
-
-
-
-
3
3
3
3
-
30
25
40
aReaction condition: 1a (1 mmol), catalyst (5 mol%), and methanol (2 mL)
were stirred at room temperature.
O
O
O
O
O
O
C8H17
O
C6H13
O
O
Ph
O
O
O
OC3H7
2a (98%, 3h)
2c (98%, 9h)
2e (97%, 11h)
2d (98%, 11h)
2b (92%, 9h)
2f (98%, 7h)
Results and discussion
O
O
O
O
O
O
Br
To examine the optimal condition for transetherification of
vinylogous ester, 3-ethoxycyclohex-2-en-1-one (1a) was used
as a model substrate in the presence of catalytic amounts of
various metals. The results are listed in table 1. In a controlled
experiment, in the absence of a catalyst, no transetherification
product 2a was observed (Table 1, entry 1). A subsequent
survey of the reaction by addition of 5 mol% of RuCl3.6H2O and
[Ru(p-cymene)Cl2]2 catalysts significantly proceeded to yield 2a
in 95% and 93% yield respectively (Table 1, entries 2 and 3).
However, this reaction was less efficient with Ru-complexes
such as Ru(bpy)3Cl2.6H2O in acetonitrile (ACN) and Ru-MACHO
(Table 1, entries 4-6). To identify an earth-abundant catalyst,
this reaction was investigated with Mn, Fe, Co, Ni, and Cu-
precursor. No reaction was notified while using Mn-salts such
as MnCl2·2H2O, (CH3COO)3Mn·2H2O as a catalyst (Table 1,
entries 9-10). Other transition metal salts viz Co, Ni, and Cu
give a poor yield of 2a (Table 1, entries 11-13). Interestingly, a
best-optimized condition was obtained by 5 mol% FeCl3.6H2O
catalyst in methanol as a solvent to afford 2a in 98% yield
(Table 1, entry 12).
O
O
Ph
O
OC3H7
O
O
2g (98%, 20h)
2i (98%, 10h)
2hb (52%, 24h)
2j (98%, 5h)
2k (40 %, 16h)
2l (68%, 25h)
O
O
O
O
O
O
O
O
O
Ph
O
2n (98%, 6h)
2m (78 %, 9h)
2o (72%, 25h)
2p (52 %, 20h)
2q (98 %, 6h)
O
O
O
O
H
H
O
H
H
H
H
2t (0 %, 11h)
O
O
2rb ( 90%, 20h)
2sb (92%, 20h)
aReaction conditions: Vinylogous ester (1 mmol), FeCl3.6H2O (5 mol %), alcohols
(2 mL), were stirred at room temperature. bvinylogous ester (1 mmol), alcohols
(3 mmol), FeCl3.6H2O (5 mol %), 1,2-dichloroethane (2 mL) were stirred at 80 C
for 20 h.
Scheme 3. Substrates scope under batch conditiona
transetherification product 2b-d in excellent yield (Scheme 3).
Other substituted primary alcohols; 2-methoxy ethanol, 3-
phenylpropan-1-ol, benzyl alcohol, and 2-bromo benzylalcohol
were also reacted well with 1a to afford the corresponding
products 2e-h in very good yield (Scheme 3). Interestingly, this
reaction is well tolerant to olefin and alkyne functional groups;
for example, allyl alcohol, 3-methylbut-2-en-1-ol, and but-3-
yn-1-ol reacted smoothly to afford the transetherified
products 2i and 2j in 98% except for 2k (40%) (Scheme 3).
With the optimized conditions in hand, the substrate scope
of this reaction was explored further by using a variety of
vinylogous ester with various aliphatic or aromatic alcohols.
Thus, the reaction of vinylogous ester 1a with various aliphatic
alcohols such as n-propanol, n-hexanol, and n-octanol in the
presence of 5 mol% of FeCl3 afforded the respective
2 | J. Name., 2012, 00, 1-3
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Organic & Biomolecular Chemistry
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Journal Name
ARTICLE
Substituted vinylogous ester, 3-ethoxy-5,5-dimethylcyclohex- Increasing both the catalyst loading (5 mol %) andVtieewmAprtieclreaOtnulirnee
DOI: 10.1039/C9OB00307J
2-en-1-one was also reacted well with the n-propanol to afford (80 C) with residence time 50 minutes resulted in the best
the product 2l in 68% yield. Fascinatingly, this reaction was yield of 2a around 98% (Table 2, entry 6). There was no
effective for sterically hindered secondary alcohols (iso-propyl improvement in the yield of the reaction while increasing the
alcohol,
cyclopentanol,
1-phenylethanol,
2-hexanol, temperature to 100 °C (Table 2, entry 7).
With optimized conditions in hand, we set out to
cholesterol, and esterol) to afford the corresponding products
2m-s in good to excellent yield (Scheme 3). Unfortunately, investigate a range of substrates in a continuous flow and the
sterically hindered tertiary butanol was incompatible in this results are shown in Scheme 4. The yields were generall
reaction and did not generate the desired product 2t (Scheme comparable to the batch reaction, but reactions are completed
3).
in a shorter duration of time (Scheme 4). A slight decrease in
To examine our hypothesis in continuous-flow, a flow set yield of 2o and 2p was observed when the reaction was carried
up was assembled (Figure S1, ESI) by using the pump, coil out with cyclopentanol and 1-phenylethanol. To demonstrate
reactor and BPR. Initial reactions of 0.1 M, 3-ethoxycyclohex-2- gram scale synthetic utility of this strategy, we also conducted
en-1-one (1a) with methanol in continuous flow at 60 C in 10 mmol scales transetherification reaction with hexanol,
without any catalyst were unsuccessful (Table 2, entry 1). which provided 2c in 1.9 g (97 %).
However, flowing the reactants and 3 mol % FeCl3.6H2O
Subsequently,
a
sequential transetherification of
catalyst with 0.2 mL/min flow rate at room temperature vinylogous ester was investigated under continuous flow
providing 3-methoxycyclohex-2-en-1-one (2a) in 65% isolated condition (Scheme 5). Hence, the vinylogous ester 1a and FeCl3
yield (Table 2, entry 2). We continued to evaluate the effect of in methanol were flown (0.2 mL/min) into the coil reactor at
o
catalyst loading, temperature, and residence time (Table 2).
80 C afforded the product 2a in 98% yield. The product 2a in
hexanol was further flown into the SS coil reactor to afford the
2c in 98% yield. Further, the product 2c was continuously
transformed into 2n and subsequently, the product 2n was
transformed into 1a in excellent yield under continuous
transetherification condition. In addition, the catalyst
recyclability for this transformation was demonstrated by
flowing the vinylogous ester 1a in methanol to the column
packed with Fe-supported on zeolite13 using syringe addition
Table 2. Optimization in a continuous flow
entry
FeCl3.6H2O
(mol%)
temp.
(°C)
60
Flow rate
(mL/min.)
0.2
tR
(min.)
50
50
50
50
50
50
50
yield
(%)
-
65
82
85
92
98
98
o
pump and heated at 60 C to afford the product 2a in 99%
yield with residence time tR = 7 min. (Scheme 6).
1
2
3
4
5
6
7
-
3
3
3
5
5
5
rt
60
80
60
80
100
0.2
0.2
0.2
0.2
0.2
0.2
O
O
O
O
O
C3H7
C6H13
C8H17
O
O
O
O
O
O
2b
2a
2c
2d
2e
10 mmol,
97%
98%
98%
98%
98%
after 1 run
tR = 50 min
after 1 run
tR = 50 min
after 1 run
tR = 50 min
after 1 run
tR = 50 min
after 1 run
tR = 50 min
O
O
O
O
O
O
Ph
C3H7
O
Ph
O
2i
O
2j
O
2f
2g
2l
98%
after 1 run
tR = 50 min
98%
after 1 run
tR = 50 min
O
98%
after 1 run
tR = 50 min
98%
after 1 run
tR = 50 min
92%
after 1 run
tR = 50 min
Scheme 5. Sequential transetherification under continuous flow
O
O
O
O
O
O
O
Ph
2m
2o
2p
2n
72%
after 1 run
tR = 50 min
52 %
after 1 run
tR = 50 min
98%
after 1 run
tR = 50 min
98%
after 1 run
tR = 50 min
Reaction conditions: aAll reactions were run on a 0.1 M scale in 10 mL of alcohol
using 5 mol% of FeCl3.6H2O catalyst at 80 C and maintained at a pressure of 1.2
bar using a BPR.
Scheme 4. Substrates scope under continuous flow a
Scheme 6. Recyclable Fe-Zeolite catalyzed transetherification under continuous flow
mode
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J. Name., 2013, 00, 1-3 | 3
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To study the chemoselectivity of alcohols, we have Interestingly, the reaction of vinylogous ester 2a and 1-
View Article Online
investigated intermolecular transetherification of vinylogous phenylethane-1,2-diol afforded the spiDroOI:p1r0o.1d0u39c/tC92O-pB0h0e3n0y7lJ-
ester using primary and secondary alcohols (Table 3). Thus, an 1,4-dioxaspiro[4.5]decan-7-one 4 in 58% yield via tandem
equivalent amount of methanol and IPA was reacted with transetherification and 1,4-addition with a conjugated ketone.
vinylogous ester 1a in the presence of 5 mol% of FeCl3 Furthermore, the vinylogous ester 2h was easily converted
afforded the products 2b and 2e in the ratio 75:25% (Table 3, into 2,3,4,6-tetrahydro-1H-benzo[c]chromen-1-one 5 via Pd-
entry 1). Interestingly, selectivity was increased to 95:5% in catalysed intramolecular Heck reaction (95%).7c
case of MeOH/1-phenylethanol mixture (Table 3, entry 2).
The mechanism for the Fe-catalysed transetherification of
Excellent selectivity (100%) and exclusive reactivity of the a vinylogous ester is proposed in Scheme 9. Vinyl ether is
primary alcohols was observed while using diphenylmethanol, known to cleave a C-O bond in the presence of the metal
bis(4-methoxyphenyl)methanol
and
phenyl(3- catalyst or acid. In contrast to this, vinylogous ester C-O bond
(trifluoromethyl)phenyl)methanol (Table 3, entries 3-5).
Similarly, higher selectivity (90:10) with the aliphatic and less
substituted methanol was observed (Table 3, entry 6).
To probe the ether cleavage, Fe-catalysed water-mediated
hydrolysis of vinylogous ester was investigated (Scheme 7). A
solution of vinylogous ester 1a and FeCl3 in water was allowed
to stir at room temperature for 5-12 hrs results in complete
deprotection of vinylogous ester to cyclohexane-1,3-dione
(Scheme 7). Under similar reaction condition other vinylogous
esters 2c, 2i, 2o, 2p, and 2q were easily hydrolyzed to
respective 1,3-diketone in >99% conversion using 5 mol %
FeCl3 under a very mild and environmentally benign condition
in 5-12 hrs.
O
3
O
2
5 mol% FeCl3
R
H2O, rt
>99% conversion
O
O
O
O
O
hexyl
O
O
O
2c
(12 h)
1a
(12 h)
2i
(5 h)
O
O
O
O
Ph
O
O
2q
(12 h)
2p
(12 h)
2o
(5 h)
Next, we have explored the synthetic application of the
vinylogous ester (Scheme 8). Thus, the vinylogous ester 2a was
reacted I2 in methanol at 60 C to afford the corresponding
Scheme 7. Fe-catalysed hydrolysis of the vinylogous ester
o
OH
1,3-dimethoxy benzene 3 in 85% yield.
OH
O
O
Table 3. Chemoselective transetherification
O
I2/MeOH, 60 o
85%
C
O
5 mol% FeCl3,
8h, 58 %
R
O
O
O
2
O
O
O
Pd(OAc)2, KOAc,
TBAB, tolune, 80 oC, 95%
5 mol% FeCl3
4
OH
R3
R2
3
+
+
+
CH2OH
R1
R2
O
R3
R
3h
O
R1
O
O
entry vinylog
-ous
primary
alcohol
secondary
alcohols
Selectivity
based
O
ester
on GC-MS
and
5
Scheme 8. Synthetic utility of vinylogous esters
1H-NMR
75:25
1
2
1a
1a
methanol
methanol
IPA
1-
95:5
phenylethanol
methanol diphenylmetha
nol
Hard centre
Fe3+
Fe3+
O
C
O
O
3
4
1a
1a
100:0
100:0
FeCl3
Hard metal
R1
n-
bis(4-methoxy
phenyl)methan
ol
phenyl(3-
(trifluor
omethyl)phenyl
)methanol
-
O
R2
R
O
O
O
Vinyl ether cleavage
A
propanol
B
Soft centre
O
R1
5
6
1a
1a
n-
hexanol
100:0
90:10
Fe3+
Fe3+
O
R2
R
O
O
O
E
-Et-OH
-Fe3+
Vinylogous ester cleavage
D
O
E
O
O
O
methanol
:benzyl
alcohol
F
OH
excess
Scheme 9. Plausible mechanism for transetherification
4 | J. Name., 2012, 00, 1-3
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ARTICLE
General procedure for the transetherification of enolether in
cleavage proceeds as shown in Scheme 9 due to the activation
of the hard C=O center which is in conjugation with the vinyl
ethers. Initially hard Fe3+ coordinate to the hard C=O centre of
the cyclic vinylogous ester A to form the intermediate B. The
intermediate B is resonance stabilized to generate the
intermediates C and D. Further, an addition of alcohol to the
oxonium intermediate D to afford the ketal intermediate E.
Finally, the keto-enol tautomerism assisted elimination of
ethanol from the intermediate E to form the transetherified
product F.
View Article Online
DOI: 10.1039/C9OB00307J
a continuous flow:
Transetherification reactions were performed in a Vapourtec
R-series continuous flow system equipped with high-
temperature SS coil reactor (10 mL, stainless steel, 1.00 mm
i.d.). 0.1 M solution of vinylogous ester in different alcohols is
passed through tube reactors at 0.2 mL/min. flow rate, 1.8 bar
pressure and at 80 °C. After completion of the reaction,
alcohol was removed using vacuum pressure and the crude
reaction mixture was purified by column chromatography to
afford the pure transetherification product.
Experimental
General procedure for Iodine catalyzed aromatization of
vinylogous ester (3)
To a solution of compound 1a (1 mmol, 0.140 g) in methanol,
Iodine 0.508g (2 equiv.) was added and the resulting mixture
was stirred at 60 °C temperature for 2 hrs. Once TLC confirms
complete consumption of the starting material, the reaction
mixture was quenched with cold sodium thiosulfate and
extracted with ethyl acetate. The organic layer was evaporated
and purified through column chromatography (10-90% EtOAc
in hexane) to obtain the desired compounds 3.
General information and data collection:
Materials and methods: All the chemicals are purchased Sigma
Aldrich or Alfa-Aesar. Deuterated solvents were used as
received. All the solvents used were dry grade and stored over
4 Å molecular sieves. Column chromatographic separations
performed over 100−200 Silica-gel. Visualization was
accomplished with UV light and PMA, CAM stain followed by
heating. The iron (III) chloride (product number: 44939) was
purchased from Sigma Aldrich. All the experiments were
carried out without maintaining the inert condition. The flow
chemistry experiments were carried on Vaportec R-series. 1H
and 13C NMR spectra were recorded on 400 and 100 MHz,
respectively, using a Bruker 400 MHz or JEOL 400 MHz
spectrometers. Abbreviations used in the NMR follow-up
experiments: b,broad; s,singlet; d,doublet; t,triplet; q, quartet;
m, multiplet. High-resolution mass spectra were recorded with
Waters-synapt G2 using electrospray ionization (ESI-TOF).
Fourier-transform infrared (FT-IR) spectra were obtained with
a Bruker Alpha-E Fourier transform infrared spectrometer.
Representative procedure for coupling reactions: synthesis of
2,3,4,6-tetrahydro-1H-benzo[c]chromen-1-one (5):
3-((2-bromobenzyl)oxy)cyclohex-2-en-1-one (280 mg, 1ꢀ
equiv.), TBAB (1ꢀequiv.), KOAc (2.5ꢀequiv.), Pd(OAc)2 (0.02ꢀ
equiv.) and toluene (7ꢀmL) were added in sequence to a
Schlenk tube and stirred under N2 at 130ꢁ°C. After 3.5ꢀh, water
(10ꢀmL) and EtOAc (10ꢀmL) were added. The mixture was
extracted with EtOAc (2ꢁ×10ꢀmL) and the combined organic
layers were washed with water (10ꢀmL), brine (10ꢀmL), dried
and the solvents evaporated. The crude material obtained was
purified by column chromatography (silica, 1:1 hexane/EtOAc)
to afford the product 5 in 95% yield.
General procedure for the transetherification of enol ether in
Batch reaction (2a-2p):
Fe catalyzed the hydrolysis of vinylogous esters:
To a solution of vinylogous ester in water, FeCl3.6H20 (5 mol %)
was added and the reaction mixture was stirred at room
temperature for respective time (Scheme 7, main manuscript).
After completion, the reaction mixture was diluted with ethyl
acetate and extracted 3 times with ethyl acetate. Organic
layers were dried on sodium sulfate and concentrated in
vacuum affording quantitative yields of 1, 3-diketone.
Vinylogous ester (1mmol), FeCl3.6H20 (5 mol%) and 2 mL of
alcohol was added to a 10 mL round bottom flask with a
0
magnetic bar and stirred at room temperature (25 C) in open
air for respective time (Scheme 2, main manuscript). After
completion of the reaction, alcohol was removed using a
vacuum and the crude reaction mixture was purified by
column chromatography affording the pure transetherification
product.
Analytical data for the product:
3-methoxycyclohex-2-en-1-one (2a): Yellowish oil (Batch-
0.123 g, 98%; Continuous flow-0.123 g, 98%). H NMR (400
General procedure for the transetherification of compounds
2h, 2r and 2s in batch reaction:
1
MHz, CDCl3) δ 5.36 (s, 1H), 3.68 (s, 3H), 2.40 (t, J = 6.4 Hz, 2H),
2.34 (t, J = 6.4 Hz, 2H), 2.01 – 1.93 (m, 2H). 13C NMR (101 MHz,
CDCl3) δ 199.9, 178.9, 102.4, 55.7, 36.8, 28.9, 21.4. FTIR (neat):
2952.28, 2311.97, 1727.07, 1601.11, 1453.93, 1380, 1232.65,
1183.99, 1001.03, 758.03, 597.32 cm-1. HRMS (ESI) m/z
calculated for C7H11O2 (M+H)+: 127.0759, found: 127.0762
3-propoxycyclohex-2-en-1-one (2b): Yellowish oil (Batch-
Vinylogous ester (1 mmol), FeCl3.6H20 (5 mol%) was added to a
solution of alcohols (1mmol) in Dichloroethane (10 mL). The
solution was heated at 80 °C for 20 h. The reaction was
allowed to cool to room temperature. The solvent was
removed using a vacuum and the crude reaction mixture was
purified by column chromatography on silica gel with eluent
afforded respective products.
1
0.141 g, 92%; Continuous flow-0.150 g, 98%). H NMR (400
MHz, CDCl3) δ 5.34 (s, 1H), 3.78 (t, J = 6.5 Hz, 2H), 2.40 (t, J =
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6.4 Hz, 2H), 2.34 (t, J = 6.0 Hz, 2H), 2.03 – 1.92 (m, 2H), 1.80- HRMS (ESI) m/z calculated for C13H15O2 (M+H)+: 203.1072,
View Article Online
1.68 (m, 2H), 0.98 (t, J = 7.6 Hz, 3H). 13C NMR (101 MHz, CDCl3) found: 203.1079.
DOI: 10.1039/C9OB00307J
δ 200.1 (s), 178.3, 102.8, 77.5, 76.8, 70.1, 36.9, 29.2, 22.0, 3-((2-bromobenzyl)oxy)cyclohex-2-en-1-one (2h): Yellowish
21.4, 10.5. FTIR: 2953.87, 2315.29, 1724.89, 1590.46, 1458.78, oil (Batch- 0.146 g, 52%) 1H NMR (400 MHz, CDCl3) δ 7.59 (dd, J
1369.83, 1226.41, 1179.69 1060.78, 753.04, 601.90 cm-1. = 8.0, 1.1 Hz, 1H), 7.43 (dd, J = 7.7, 1.5 Hz, 1H), 7.37 – 7.32 (m,
HRMS (ESI) m/z calculated for C9H15O2 (M+H)+: 155.1072, 1H), 7.22 (td, J = 7.9, 1.8 Hz, 1H), 5.50 (s, 1H), 4.97 (s, 2H), 2.51
found: 155.1078.
(t, J = 6.3 Hz, 2H), 2.43 – 2.35 (m, 2H), 2.08 – 2.00 (m, 2H). 13
C
3-(hexyloxy)cyclohex-2-en-1-one (2c): Yellowish oil (Batch- NMR (101 MHz, CDCl3) δ 199.8, 177.3, 134.5, 133.1, 130.1,
1
0.192 g, 98%; Continuous flow-0.950 g, 97%). H NMR (400 129.4, 127.8, 103.8, 69.9, 36.9, 29.0, 21.4. FTIR: 3056.27,
MHz, CDCl3) δ 5.34 (s, 1H), 3.81 (t, J = 6.8 Hz, 2H), 2.39 (t, J = 3016.68, 2984.66, 2298.97, 1731.92, 1643.92, 1594.96,
6.4 Hz, 2H), 2.34 (t, J = 6.4 Hz, 2H), 2.01 – 1.93 (m, 2H), 1.71 (p, 1401.18, 1270.41, 1216.91, 1179.39 cm-1. HRMS (ESI) m/z
J = 6.7 Hz, 3H), 1.43-1.36 (m, 2H), 1.13-1.28 (m, 2), 0.89 (t, J = calculated for C13H14BrO2 (M+H)+: 281.0177, found: 281.0177.
6.9 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 200.1, 178.3, 102.8, 3-(allyloxy)cyclohex-2-en-1-one (2i): Yellowish oil (Batch-
68.7, 36.9, 31.6, 29.2, 28.6, 25.7, 22.7, 21.4, 14.1. FTIR: 0.149 g, 98%; Continuous flow-0.149 g, 98%). 1H NMR (400
2944.26, 2834.76, 2310.19, 1718.52, 1589.98, 1465.80, MHz, CDCl3) δ 6.02 – 5.90 (m, 1H), 5.36 (qt, J = 1.5, 1.4 Hz, 1H),
1298.50, 1110.66, 1034.34, 786.44, 610.97 cm-1. HRMS (ESI) 5.36 (s, 2H), 5.30 (ddd, J = 10.5, 2.4, 1.3 Hz, 2H), 4.37 (dt, J =
m/z calculated for C12H21O2 (M+H)+: 197.1463, found: 5.6, 1.3 Hz, 2H), 2.43 (t, J = 6.3 Hz, 2H), 2.34 (dd, J = 7.3, 6.0 Hz,
197.1469.
2H), 1.98 (m, 2H). 13C NMR (101 MHz, CDCl3) δ 199.9, 177.6,
3-(octyloxy)cyclohex-2-en-1-one (2d): Yellowish oil (Batch- 131.5, 119.1, 103.3, 69.2, 36.9, 29.1, 21.3. FTIR: 3016.17,
0.219 g, 98%; Continuous flow-0.219 g, 97%). 1H NMR (400 2981.44, 2316.54, 1716.45, 1640.31, 1555.80, 1463.91,
MHz, CDCl3) δ 5.34 (s, 1H), 3.81 (t, J = 6.6 Hz, 2H), 2.40 (t, J = 1366.11, 1218.94, 1140.12 cm-1. HRMS (ESI) m/z calculated for
6.4 Hz, 2H), 2.34 (t, J = 6.0 Hz, 2H), 2.01 – 1.93 (m, 2H), 1.77 – C9H13O2 (M+H)+: 153.0915, found:153.0916.
1.65 (m, 3H), 1.33 – 1.26 (m, 9H), 0.89 (t, J = 6.8 Hz, 3H).13C 3-((3-methylbut-2-en-1-yl)oxy)cyclohex-2-en-1-one
(2j):
NMR (101 MHz, CDCl3) δ 200.0, 178.3, 102.8, 68.8, 36.9, 31.9, Yellowish oil (Batch- 0.176 g, 98%; Continuous flow-0.176 g,
29.4, 29.3, 29.1, 28.7, 26.1, 22.8, 21.4, 14.2. FTIR (neat): 98%). 1H NMR (400 MHz, CDCl3) δ 5.41-5.38 (m, 1H)5.38 (s,
2929.90, 2862.30, 2314.45, 1727.50, 1592.35, 1461.24, 1H), 4.37 (d, J = 6.9 Hz, 2H), 2.41 (t, J = 6.4 Hz, 2H), 2.35 (t, J =
1233.15, 1184.78, 1090.23, 756.55, 607.87 cm-1. HRMS (ESI) 6.4 Hz, 2H), 1.98 (dd, J = 13.0, 6.5 Hz, 2H), 1.78 (s, 3H), 1.70 (s,
m/z calculated for C14H25O2 (M+H)+: 225.1854, found: 3H). 13C NMR (101 MHz, CDCl3) δ 200.1, 178.1, 139.7, 118.0,
225.1861.
103.1, 65.6, 36.9, 29.3, 25.9, 21.4, 18.3. FTIR (neat): 2953.38,
3-(2-methoxyethoxy)cyclohex-2-en-1-one (2e): Yellowish oil 2311.97, 1720.17, 1601.11, 1553.93, 1380.22, 1242.55,
1
(Batch- 0.164 g, 97%; Continuous flow-0.166 g, 98%). H NMR 1173.79 cm-1. HRMS (ESI) m/z calculated for C11H17O2 (M+H)+:
(400 MHz, CDCl3) δ 5.35 (s, 1H), 3.99 – 3.94 (dt, J = 8.8 Hz, 1.6 181.1228, found:181.1236.
Hz, 2H), 3.72 – 3.66 (dt, J = 9.5 Hz, 2 Hz, 2H), 3.42 (s, 3H), 2.45 3-(but-3-yn-1-yloxy)cyclohex-2-en-1-one (2k): Yellowish oil
1
(t, J = 6.4 Hz, 2H), 2.34 (t, J = 6.4 Hz, 2H), 2.02 – 1.93 (m, 2H). (Batch- 0.065 g, 40%). H NMR (400 MHz, CDCl3) δ 5.34 (s, 1H),
13C NMR (101 MHz, CDCl3) δ 199.9, 177.9, 103.1, 70.3, 67.8, 3.94 (t, J = 6.7 Hz, 2H), 2.63 (td, J = 6.7, 2.7 Hz, 2H), 2.42 (t, J =
59.3, 36.8, 29.1, 21.3. FTIR (neat): 3023.28, 2401.97, 1730.21, 6.4 Hz, 2H), 2.34 (t, J = 6.4 Hz, 2H), 1.98 (t, J = 6.4 Hz, 2H). 13
C
1602.11, 1464.39, 1217.26, 1188.16, 1001.03 cm-1.HRMS (ESI) NMR (101 MHz, CDCl3) δ 199.9, 177.5, 103.1, 79.7, 70.4, 66.3,
m/z calculated for C9H15O3 (M+H)+: 171.1021, found:171.1031. 36.8, 28.9, 21.3, 19.1. FTIR (neat): 2929.90, 2862.30, 2314.45,
3-(3-phenylpropoxy)cyclohex-2-en-1-one (2f): Yellowish oil 2140.17, 1722.50, 1600.35, 1561.24, 1237.15, 1184.78,
(Batch- 0.225 g, 98%; Continuous flow-0.225 g, 98%). 1H NMR 1090.23 cm-1. HRMS (ESI) m/z calculated for C10H13O2 (M+H)+:
(400 MHz, CDCl3) δ 7.32 – 7.27 (m, 2H), 7.23 – 7.15 (m, 3H), 165.0915, found:165.0727.
5.32 (s, 1H), 3.83 (t, J = 6.4 Hz, 2H), 2.74 (t, J = 7.2 Hz, 2H), 2.41 5,5-dimethyl-3-propoxycyclohex-2-en-1-one (2l): Yellowish oil
1
(t, J = 6.4 Hz, 2H), 2.34 (t, J = 6.0 Hz, 2H), 2.09 – 2.03 (m, 2H), (Batch- 0.123 g, 68%; Continuous flow-0.167 g, 92%). H NMR
2.02 – 1.94 (m, 2H). 13C NMR (101 MHz, CDCl3) δ 200.0, 178.1, (400 MHz, CDCl3) δ 5.34 (s, 1H), 3.79 (t, J = 6.8 Hz, 2H), 2.27 (s,
141.0, 128.6, 128.5, 126.3, 102.9, 67.7, 36.9, 32.2, 30.2, 29.1, 2H), 2.20 (s, 2H), 1.81 – 1.70 (m, 2H), 1.07 (s, 6H), 0.98 (t, J =
21.4. FTIR: 3023.67, 2847.54, 2875.98, 2365.45, 1723.13, 7.2 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 199.8, 176.5, 101.6,
1663.91, 1547.80, 1379.97, 1221.50, 1198.80cm-1. HRMS (ESI) 70.2, 50.9, 43.0, 32.6, 28.4, 22.0, 10.5. FTIR: 2959.17, 2881.44,
m/z
calculated
for
C15H19O2
(M+H)+:
231.1385, 2310.50, 1722.54, 1598.80, 1463.91, 1367.11, 1218.58,
1147.97 cm-1. HRMS (ESI) m/z calculated for C11H19O2 (M+H)+:
found:231.1387.
3-(benzyloxy)cyclohex-2-en-1-one (2g): Yellowish oil (Batch- 183.1385, found: 183.1392.
0.197 g, 98%; Continuous flow-0.197 g, 98%).1H NMR (400 3-isopropoxycyclohex-2-en-1-one (2m): Yellowish oil Yellowish
MHz, CDCl3) δ 7.42 – 7.33 (m, 5H), 5.48 (s, 1H), 4.89 (s, 2H), oil (Batch- 0.120 g, 78%; Continuous flow-0.150 g, 98%). 1H
2.47 (t, J = 6.4 Hz, 2H), 2.37 (t, J = 6.4 Hz, 2H), 2.05 – 1.96 (m, NMR (400 MHz, CDCl3) δ 5.34 (s, 1H), 4.43 (dt, J = 12.2, 5.9 Hz,
2H). 13C NMR (101 MHz, CDCl3) δ 199.9, 177.7, 135.1, 128.8, 1H), 2.40-2.31 (m, 4H), 2.01 -1.92 (m, 2H), 1.30 (s, 3H), 1.28 (s,
128.7, 128.0, 103.5, 70.5, 36.9, 29.2, 21.3. FTIR: 3029.14, 3H). 13C NMR (101 MHz, CDCl3) δ 200.1, 177.0, 103.1, 70.1,
2947.04, 2947.04, 2881.89, 2315.54, 1734.79, 1648.08, 36.8, 29.6, 21.5, 21.3. FTIR (neat): 2978.67, 2310.65, 1730.60,
1597.17, 1359.34, 1221.55, 1175.66, 863.08, 743.15 cm-1. 1641.95, 1595.51, 1461.11, 1230.90, 1187.26, 1000.27, 757.95,
6 | J. Name., 2012, 00, 1-3
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Organic & Biomolecular Chemistry
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ARTICLE
608.98 cm-1. HRMS (ESI) m/z calculated for C9H15O2 (M+H)+: 3023.79, 2954.91, 2852.40, 2387.87, 1718.3V0ie,w A1rti6cl2e9O.n4lin0e,
DOI: 10.1039/C9OB00307J
1593.84, 1524.58, 1467.16, 1429.53, 1378.29, 1328.47
155.1072, found:155.1078.
3-(cyclopentyloxy)cyclohex-2-en-1-one (2n): Yellowish oil 1001.03, 758.03, 597.32 cm-1. HRMS (ESI) m/z calculated for
(Batch- 0.176 g, 98%; Continuous flow-0.176 g, 98%). 1H NMR C33H52O2 (M+H)+: 480.3967, found: 480.3967.
(400 MHz, CDCl3) δ 5.33 (s, 1H), 4.64 – 4.57 (m, 1H), 2.34 (dd, J 3-(((8R,9S,13S,14S)-3-methoxy-13-methyl-
= 12.5, 6.3 Hz, 4H), 1.95 (dt, J = 9.0, 6.5 Hz, 2H), 1.90 – 1.82 (m, 7,8,9,11,12,13,14,15,16,17-decahydro-6H-
2H), 1.82 – 1.77 (m, 2H), 1.76-1.71 (m, 2H), 1.65 – 1.56 (m, cyclopenta[α]phenanthren-17-yl)oxy)cyclohex-2-en-1-one
1
2H). 13C NMR (101 MHz, CDCl3) δ 200.1, 177.3, 103.8, 80.7, (2s): White solid (Batch- 0.349 g, 92 %). H NMR (400 MHz,
36.8, 32.8, 29.5, 24.2, 21.4. FTIR: 2995.15, 2910.56, 2344.50, CDCl3) δ 7.20 (d, J = 8.5 Hz, 1H), 6.71 (dd, J = 8.6, 2.8 Hz, 1H),
1734.64, 1599.78, 1499.91, 1304.68, 1211.78, 1122.97 cm-1. 6.63 (d, J = 2.7 Hz, 1H), 5.37 (s, 1H), 4.09 (dd, J = 8.7, 7.2 Hz,
HRMS (ESI) m/z calculated for C11H17O2 (M+H)+: 181.1228, 1H), 3.78 (s, 3H), 2.91 – 2.82 (m, 2H), 2.39 (dd, J = 6.2, 3.0 Hz,
found:181.1225.
3-(cyclopentyloxy)-5,5-dimethylcyclohex-2-en-1-one
2H), 2.34 (dd, J = 7.4, 5.8 Hz, 2H), 2.03 – 1.93 (m, 3H), 0.88 (s,
(2o): 3H).13C NMR (101 MHz, CDCl3) δ 200.1, 178.1, 157.6, 138.0,
Yellowish oil (Batch- 0.149 g, 72%; Continuous flow-0.149 g, 132.5, 126.5, 113.96, 111. 7, 103.8, 55.4, 49.8, 43.9, 43.7, 38.6,
72%).1H NMR (400 MHz, CDCl3) δ 5.32 (s, 1H), 4.60 (m, 1H), 37.5, 36.9, 29.9, 29.4, 17.9, 26.4, 23.7, 21.4, 12.3. . FTIR (neat):
2.21 (s, 2H), 2.19 (s, 2H), 1.90 – 1.56 (m, 8H), 1.05 (s, 6H). 13C 3016.59, 2966.53, 2874.26, 2437.37, 2378.87, 1724.53,
NMR (101 MHz, CDCl3) δ 199.7, 175.5, 102.6, 80.7, 50.8, 43.3, 1629.40, 1593.84, 1524.58, 1467.16, 1429.53, 1378.29,
32.8, 32.60, 28.4, 24.2. FTIR: 3012.15, 2988.66, 2388.57, 1328.74, 1101.03 cm-1. HRMS (ESI) m/z calculated for C25H33O3
1712.54, 1488.98, 1412.81, 1356.12, 1226.88, 1182.27 cm-1. (M+H)+: 381.2429, found: 381.2430.
1
HRMS (ESI) m/z calculated for C13H21O2 (M+H)+: 209.1524, 1,3-dimethoxybenzene (3): Colourless liquid (0.117 g, 85%) H
found:209.1545.
NMR (400 MHz, CDCl3) δ 7.19 (t, J = 8.2 Hz, 1H), 6.53 (d, J = 2.4
3-(1-phenylethoxy)cyclohex-2-en-1-one (2p): Yellowish oil Hz, 1H), 6.51 (d, J = 2.4 Hz, 1H), 6.48 (t, J = 2.4 Hz, 1H), 3.80 (s,
1
(Batch- 0.112 g, 52%; Continuous flow-0.112 g, 52%). H NMR 6H). 13C NMR (101 MHz, CDCl3) δ 160.9, 130.0, 106.2, 100.6,
(400 MHz, CDCl3) δ 7.36 – 7.29 (m, 2H), 7.29 – 7.23 (m, 3H), 77.5, 76.8, 55.4. FTIR: 3095.15, 2910.56, 1599.78, 1554.91,
5.26 (s, 1H), 5.19 (q, J = 6.4 Hz, 1H), 2.46-2.41 (m, 2H), 2.30- 1304.68, 1211.78, 1122.97 cm-1. HRMS (ESI) m/z calculated for
2.24 (m, 2H), 1.98-1.89 (m, 2H), 1.56 (d, J = 6.4 Hz, 2H), 0.91 – C8H11O2 (M+H)+: 139.0761, found: 139.0761.
0.81 (m, 2H). 13C NMR (101 MHz, CDCl3) δ 199.9, 176.7, 141.4, 2-phenyl-1,4-dioxaspiro[4.5]decan-7-one (4): Colourless liquid
1
128.9, 128.2, 125.5, 104.7, 76.8, 36.8, 29.5, 23.8, 21.3. FTIR: (0.134 g, 58%). H NMR (400 MHz, CDCl3) δ 7.39-7.29 (m, 5H),
3029.14, 2947.04, 2947.04, 2881.89, 2315.54, 1724.79, 5.09 (ddd, J = 10.9, 8.2, 6.1 Hz, 1H), 4.32 (ddd, J = 10.2, 8.3, 6.1
1658.08, 1587.17, 1449.34, 1266.11, 1199.44 cm-1. HRMS (ESI) Hz, 1H), 3.72 (td, J = 8.3, 2.9 Hz, 1H), 2.77 (dd, J = 23.2, 14.2 Hz,
m/z
calculated
for
C14H17O2
(M+H)+:
217.1228, 2H), 2.37 (t, J = 6.7 Hz, 2H), 2.15-2.01 (m, 2H), 2.00-1.87 (m,
2H). 13C NMR (101 MHz, CDCl3) δ 207.5 (d, J = 8.4 Hz), 138.4 (s),
found:217.1227.
3-(hexan-2-yloxy)cyclohex-2-en-1-one (2q): Colourless oil 138.1 (s), 128.7 (d, J = 4.3 Hz), 128.4 (d, J = 3.4 Hz), 126.3 (d, J =
(Batch- 0.193 g, 92 %). 1H NMR (400 MHz, CDCl3) δ 5.31 (s, 1H), 2.5 Hz), 111.1 (s), 78.32 (d, J = 29.4 Hz), 71.8 (d, J = 4.3 Hz),
4.23 (h, J = 6.2 Hz, 1H), 2.36 – 2.29 (m, 4H), 1.99 – 1.89 (m, 2H), 52.6 (s), 52.1 (s), 40.4 (s), 35.2 (s), 34.6 (s), 20.2 (d, J = 11.5 Hz).
1.69-1.61 (m, 1H), 1.55 – 1.42 (m, 1H), 1.34 – 1.24 (m, 4H), FTIR: 3023.79, 2962.12, 2873.22, 2312.25, 1711.09, 2594.96,
1.21 (s, 2H), 0.87 (t, J = 7.0 Hz, 3H). 1H NMR (400 MHz, CDCl3) δ 1465.21 cm-1. HRMS (ESI) m/z calculated for C14H17O3 (M+H)+:
5.31 (s, 1H), 4.23 (h, J = 6.2 Hz, 1H), 2.37-2.28 (m, 4H), 1.99 - 233.3070, found: 233.3075.
1.90 (m, 2H), 1.69 - 1.60 (m 1H), 1.55 - 1.43 (m, 1H), 1.34-1.24 2,3,4,6-tetrahydro-1H-benzo[c]chromen-1-one (5): Yellow
(m, 4H), 1.22 (d, J = 2.4 Hz, 2H), 0.90-0.83 (m, 3H). 13C NMR solid (0.190 g, 95%). 1H NMR (400 MHz, CDCl3) δ 8.30 (d, J =
(101 MHz, CDCl3) δ 200.1, 177.3, 102.9, 74.8, 36.8, 35.6, 29.5, 7.9 Hz, 1H), 7.32 (t, J = 7.0 Hz, 1H), 7.20 (td, J = 7.5, 1.2 Hz, 1H),
27.5, 22.6, 21.3, 19.2, 14.1. FTIR (neat): 2929.90, 2862.30, 7.02 (dd, J = 7.5, 0.7 Hz, 1H), 5.12 (s, 2H), 2.59 -2.51 (m, 4H),
2314.45, 1727.50, 1592.35, 1461.24, 1233.15, 1184.78, 2.00 (dt, J = 12.6, 6.4 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ
1090.23, 756.55, 607.87 cm-1. HRMS (ESI) m/z calculated for 196.5, 174.1, 128.7, 127. 9, 127.0, 124.9, 123.8, 113.2, 69.6,
C12H21O2 (M+H)+: 197.1541, found:197.1549.
38.4, 29.0, 20.2. FTIR: 3329.14, 2947.04, 2947.04, 2881.89,
2315.54, 1664.08 cm-1. HRMS (ESI) m/z calculated for C13H13O2
(M+H)+: 201.0915, found:201.0919.
3-(((3S,8S,9S,10R,13R,14S,17R)-10,13-dimethyl-17-((R)-6-
methylheptan-2-yl)-2,3,4,7,8,9,10,11,12,13,14,15,16,17-
tetradecahydro-1H-cyclopenta[α]phenanthren-3-yl)oxy)-5,5-
dimethylcyclohex-2-en-1-one (2r): White solid (Batch- 0.349 g,
1
Conclusions
92 %). H NMR (400 MHz, CDCl3) δ 5.35 (m, 2H), 4.07-3.46 (m,
1H), 2.40 – 2.31 (m, 3H), 1.01 (d, J = 7.2 Hz, 3H), 0.93- 0.90 (m,
3H), 0.87 (d, J = 1.2 Hz, 3H), 0.85 (d, J = 1.2 Hz, 3H), 0.67 (s,
3H). 13C NMR (101 MHz, CDCl3) δ 200.1, 176.9, 140.9, 139.3,
123.3, 121.8, 103.2, 77.8, 71.9, 56.9, 56.8, 56.3, 56.3, 50.3,
50.2, 42. 5, 39.9, 39.8, 39.7, 37.9, 37.4, 37.0, 36.8, 36.6, 36.3,
35.9, 32.0, 31.9, 31.8, 29.8, 29.7, 28.4, 28.1, 27.6, 24.4, 23.9,
22.9, 22.7, 21.3, 21.2, 21.1, 19.6, 19.5, 18.9, 12.0. FTIR (neat):
In conclusion, we have developed a novel, highly efficient and
chemoselective catalytic method for transetherification of a
variety of vinylogous ester with various primary and secondary
alcohols to afford the substituted vinylogous ester in high
yield. Furthermore, this approach was sustainable to all the
functional groups and easily integrated into continuous flow
mode to produce a variety of vinylogous ester in large scale.
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Organic & Biomolecular Chemistry
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ARTICLE
Journal Name
Aoyama, M. Tokunaga, S-I. Hiraiwa, Y. Shirogane, Y. Obora
Interestingly, a novel method for de-alkylation of vinylogous
ester was also developed by using an environmentally benign
water and Fe-catalyst. A plausible mechanism was proposed
for transetherification involves remote C=O group chelation
and followed by an alcohol attack on the double bond.
View Article Online
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Conflicts of interest
“There are no conflicts to declare”.
7
Acknowledgments
This research was supported by the DST-SERB,
(EMR/2014/000700) and Council of Scientific and Industrial
Research [02(0296/17/EMR-II)], India. N.P. thanks, IISER-Pune
for the research support. S.G.A. thanks SERB-NPDF
(PDF/2017/001286) for the research fellowship. B.G. thanks
SERB and CSIR for the research support.
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8 | J. Name., 2012, 00, 1-3
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Organic & Biomolecular Chemistry
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DOI: 10.1039/C9OB00307J
Table of Contents:
O
O
O
OH
R6
FeCl3
R5
+
+
+
R4
OH
R5
R1
R1
Batch and
continuous flow
R1
O
R4
O
R6
OR3
R2
R2
R2
Exclusive selectivity on primary alcohols
Vinylogous esters
Batch and continuous flow synthesis
Electron deficient unsymmetrical ether substrates
Chemoselective and catalytic reaction
Functional group tolerance and solvent free
Continuous multi-transetherification
Wide substrate scope and gram scale synthesis
Assisted by chelation of Fe with C=O group
Novel Fe-catalyzed de-alkylation using water
An additive/Bronsted acid/base free, highly efficient and chemoselective transetherification of
vinylogous esters and water mediated de-alkylation using Fe-catalyst is described.