Synthesis of substituted 3-iodocoumarins and 3-iodobutenolides via electrophilic iodocyclization of ethoxyalkyne diols

Article abstract of DOI:10.1021/jo400499r

A convenient and general synthesis of various 4-substituted 3-iodocoumarins and 4,5-disubstituted 3-iodobutenolides is described via an exclusive 6-endo-dig iodocyclization of 3-ethoxy-1-(2-alkoxyphenyl)-2-yn-1-ols and 5-endo-dig iodocyclization of 1-alkoxy-4-ethoxy-3-yn-1,2-diols, respectively. The reaction is carried out under very mild conditions using I₂ in CH₂Cl₂ or toluene at room temperature. Oxygens in OMe and OMOM groups were used as efficient nucleophiles for this intramolecular cyclization to obtain the products in good to excellent yields.

Full text of DOI:10.1021/jo400499r

Subscriber access provided by Univ. of Tennessee Libraries
Article
Synthesis of Substituted 3-Iodocoumarins and 3-Iodobutenolides
via Electrophilic Iodocyclization of Ethoxyalkyne Diols.
Maddi Sridhar Reddy, Nuligonda Thirupathi, Madala Hari Babu, and Surendra Puri
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/jo400499r • Publication Date (Web): 24 May 2013
Downloaded from http://pubs.acs.org on June 3, 2013
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
The Journal of Organic Chemistry is published by the American Chemical Society.
1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 36
The Journal of Organic Chemistry
1
2
3
4
5
6
Synthesis of Substituted 3ꢀIodocoumarins and 3ꢀIodobutenolides via
Electrophilic Iodocyclization of Ethoxyalkyne Diols.
7
8
9
Maddi Sridhar Reddy,* Nuligonda Thirupathi, Madala Hari Babu, Surendra Puri
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Medicinal & Process Chemistry Division, CSIRꢀCentral Drug Research Institute, Chattar Manzil Palace,
Lucknowꢀ226 001, U.P., India. Phone: 91ꢀ5222612411ꢀ8, Extn: 2358. Fax: 91ꢀ5222623405.
Email Address: msreddy@cdri.res.in, sridharreddymaddi@yahoo.com
Abstract: A convenient and general synthesis of various 4ꢀsubstitutedꢀ3ꢀiodocoumarins and 4,5ꢀ
disubstitutedꢀ3ꢀiodobutenolides is described via an exclusive 6ꢀendoꢀdigꢀiodocyclization of 3ꢀethoxyꢀ1ꢀ
(2ꢀalkoxyphenyl)ꢀ2ꢀynꢀ1ꢀols and 5ꢀendoꢀdigꢀiodocyclization of 1ꢀalkoxyꢀ4ꢀethoxyꢀ3ꢀynꢀ1,2ꢀdiols
respectively. The reaction is carried out in very mild conditions using I2 in CH2Cl2 or toluene at room
temperature. Oxygen in OMe and OMOM groups were used as efficient nucleophiles for this
intramolecular cyclization to obtain the products in good to excellent yields.
Introduction
Electrophilic cyclization of alkynols and alkynamines is intensely explored in current chemistry for the
construction of various novel heterocyclic moieties and, the synthesis of known structures with a
substantially increased ease with novel substitution patterns.1,2,3,4 The fair reason being the easy access to
alkyne intermediates and the identification of variety of alkynophilic catalysts including various metal
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 36
1
2
3
4
5
6
7
8
9
catalysts based on Au, Ag, Pd, Pt, Fe, etc.,1ꢀ4 apart from the standardization/control of selectivity (5ꢀ or 6ꢀ
or exo or endo etc.) in the cyclization.2 These cyclizations together with tandem eliminations,
isomerizations and coupling reactions proved to be powerful synthetic tools. Apart from the metal
catalysts, various electrophilic halogen sources showed enormous applications in this kind of cyclization
to give halo substituted heterocycles facilitating a lever for further substitution reactions.3 This has further
gained the focus due to the proved biological importance of halo substitutions.5
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
On the other hand, organic chemists often encounter with protected hydroxyl groups which need to be
deprotected before further operations. The protected hydroxy group generally acts as a weaker
nucleophile, but there are precedents in which protected oxygen acted as nucleophile in intramolecular
reactions which thereafter facilitated the insitu cleavage of protecting group, affording a step economical
process.6 Recently, Larock et al reported a synthesis of 3ꢀiodobenzofurans from 1ꢀ(2ꢀmethoxyaryl)ꢀ1ꢀynes
(Scheme 1, eq 1)6a and, 3ꢀiodochromones from 2ꢀmethoxyarylꢀalkynones (Scheme 1, eq 2)6b employing
methoxy group as the reactive intramolecular nucleophile. Based on this and on our earlier work on the
synthesis of 3ꢀunsubstituted coumarins (Scheme 1, eq 3)4b, we devised a new approach for the synthesis
of 3ꢀiodocoumarins via an electrophilic iodocyclization (Scheme 1, eq 4).
SCHEME 1. Development of Our Idea at the Outset.
ACS Paragon Plus Environment

Page 3 of 36
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Utilization of a coumarin substructure as a scaffold in the search for novel biologically functional
molecules has been highly investigated.7 3ꢀhalocoumarins are often used for the introduction of various
functionalities.8 Surprisingly there are no general methods for their synthesis till now. Recently, Alami et
al reported the synthesis of 3ꢀbromocoumarins from 2ꢀhydroxybenzaldehyde but the method was
restricted to 4ꢀunsubstitutedcoumarins.9 Moreover, iodo group is considered as easily replaceable
compared to bromide. 3ꢀhalocoumarins were earlier achieved from corresponding presynthesized 3ꢀ
unsubstituted coumarins.10 The method often leads to additional halogenation in the presence of electron
donating groups.11 As part of our ongoing program on electrophilic cyclization of alkynols and
alkynamines for the synthesis of various heterocycles,4 we devised a new synthesis of 4ꢀsubstitutedꢀ3ꢀ
iodocoumarins via 6ꢀendoꢀdigꢀiodocyclization of 3ꢀethoxyꢀ1ꢀ(2ꢀalkoxyphenyl)ꢀ2ꢀynꢀ1ꢀols (Scheme 1, eqn
4). In the event, we not only succeeded in defining appropriate conditions for this transformation but also
found substrates with different protecting groups suitable, and the synthesis of iodobutenolides possible
via similar 5ꢀendoꢀdigꢀcyclization of 1ꢀalkoxyꢀ4ꢀethoxyꢀ3ꢀynꢀ1,2ꢀdiols.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Results and Discussion
Initially we chose 5a, prepared from methoxybenzaldehyde 1a and ethoxyacetylide, for our initial trials.
When 5a was treated with I2 in CH2Cl2 no reaction occurred. Even when heated to reflux, no reaction but
a partly decomposition occurred (entry 1). Change of reagent to NIS and ICl also proved to be unfruitful
leading only to decomposition but no trace of product (entry 4). Screening of various solvents with I2
finally revealed that the reaction was somewhat smoother in DCE at reflux temperature affording the
product 9a but in moderate yield of 50%. Other reagents like ICl and NIS in the same solvent led only to
the decomposition (entry 5) or low productivity (20%, entry 4). In parallel, we tuned the reaction by
changing the protecting group to MOM, Bn and PMB. To our delight, 6a with MOM protection cleanly
formed the product (9a, 73%) at room temperature using I2 as the reagent in CH2Cl2 (entry 6), whereas 7a
and 8a were proved to be unsuitable substrates (poor or no yield of the product) after screening various
conditions (entries 8ꢀ11).
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 36
1
2
3
4
TABLE 1. Optimization Studies.
5
6
7
8
9
O
OH
EtO
nBuLi
THF, -78 oC-rt
I
Table
H
OEt
OP
1a, 2a,3a,4a
O
O
OP
5a,6a,7a,8a
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
9a
entry substrate P reagenta solvent
temp
reflux
reflux
reflux
reflux
reflux
rt
time
12 h
4 h
yield (9a)b
nr
1
5a
5a
5a
5a
5a
6a
6a
7a
7a
8a
8a
Me
CH2Cl2
DCE
I2
2
Me
I2
50%
--c
3
Me
CH2Cl2
DCE
4 h
NIS
NIS
ICl
I2
4
Me
12 h
4 h
20%
--c
5
Me
DCE
6
MOM
MOM
Bn
CH2Cl2
DCE
4 h
73%
63%
--c
7
rt
4 h
I2
8
reflux
reflux
reflux
reflux
DCE
12 h
12 h
12 h
12 h
I2
--c
9
Bn
DCE
NIS
I2
10
11
PMB
PMB
DCE
30%
--c
DCE
ICl
a all reactions were carried out using 2 mmols of substrates with
2.6 mmols of reagent in 0.25 M concentration. b isolated yields.
c decomposition of the SM
With the optimized conditions in hand, we set out to investigate the scope of the reaction with respect to
substitution on phenyl ring and at C1 position of the substrates. The results are summarized in Table 2. As
is evident from the table, various electron rich, neutral and poor substrates with cyclizing groups as OMe
and OMOM smoothly underwent the reaction to give corresponding products in good to moderate yields.
Initially, we performed the reaction on methoxyphenyl derivatives (5aꢀ5f) since various
methoxyphenylcarbonyl compounds are commercially available. Thus, various 4ꢀsubstituted/4ꢀ
unsubstituted coumarins 9aꢀf were prepared from 5aꢀf in 50ꢀ72% yield. Surprisingly and to our delight,
unlike in case of model substrate 5a (in Table 1), no heating was required for any of the substrates 5bꢀf
and the reactions were complete in less than an hour affording the products in better yields (58ꢀ72%
compared to 50% of 9a).
ACS Paragon Plus Environment

Page 5 of 36
The Journal of Organic Chemistry
1
2
3
4
5
6
TABLE 2. Synthesis of Substituted 3ꢀIodocoumarins 9 via Electrophilic Cyclization of Alkyne Diols
5 or 6.
7
8
9
O
R
OH
R
EtO
nBuLi, THF
I2, solventa
rtb
I
R
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
OEt
OP
1a-f, 2a-p
O
O
X
-78 oC-rt
OP
5a-f, 6a-p
X
X
9a-pc
OH
OH
OH
OH
Me
OH
Ph
Cl
OEt
OEt
OEt
OEt
OEt
MeO
OMe
OMe
5c
product: 9c, 20 min, 60%
OMe
OMe
OMe
5a
5b
5e
5d
product: 9a, 4 h, 50%
product: 9b, 20 min, 65%
product: 9e, 20 min, 70%
product: 9d, 1h, 58%
OH
Ph
OH
Me
OH
OH
OH
Cl
OEt
OEt
OEt
MeO
OMe
OEt
OEt
OMOM
OMOM
6d
OMOM
6c
product: 9c, 30 min,78%
5f
MeO
OMOM
6a
6b
product: 9d, 2 h, 82%
product: 9f, 20 min, 68%
product: 9a, 4 h, 72%
product: 9b, 20 min, 85%
OH
Ph
OH
Ph
OH
OH
OH
OEt
OEt
OEt
OEt
OEt
MeO
OMOM
OMOM
OMOM
6g
product: 9g, 4 h, 71%
OMOM
OMOM
6f
6e
Me
product: 9f, 20 min, 80%
6h
6i
Et
product: 9e, 10 min, 78%
iPr
product: 9h, 4h, 74%
product: 9i, 4h, 70%
OH
OH
OEt
OH
O2N
HO
OH
Cl
Ph
OEt
OEt
OMOM
OEt
OMOM
OMOM
6l
product: 9l, 12 h, 52%
OMOM
6k
OEt
6j
tBu
product: 9j, 4 h, 58%
OMOM
Br
6m
6n
product: 9k, 20 min, 70%
product: 9m, 4 h, 85%
product: 9n, 4 h, 65%
OH
OH
Me
Me
OEt
OEt
Me
OMOM
MeO
OMOM
6o
product: 9o, 2h, 80%
6p
product: 9p, 30 min, 84%
a DCE for 5a-f and CH2Cl2 for 6a-p. all reactions were carried out using 2 mmols of substrates with 2.6 mmols of I2 in
0.25 M concentration. breflux temperature needed for only 5a. c isolated yields.
We then tested the reaction on various substrates with OMOM as cyclizing group. These substrates (6aꢀp)
were more productive (52ꢀ85%) compared to their methoxy counterparts. Various electron rich & poor, 4ꢀ
substituted & non substituted 3ꢀiodocoumarins were obtained with a variety of substitution patterns. A
notable impact of the electron density was observed on both rate and yield of the reaction. Thus, electron
rich substrate 6b and 6f underwent the reaction cleanly in 20 minutes to give 9b and 9f in 85% and 80%
yields respectively whereas electron poor substrate 6l gave the product in 52% yield in 12h. 3ꢀ
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 36
1
2
3
4
5
6
7
8
9
alkylsubstituted substrates (6gꢀj) also reacted with lower rate (4h) may be due to steric factors. Halogen
substituted 3ꢀiodocoumarins 9c (from 6c) and 9k (from 6k) were obtained in 78 and 70% yields
respectively. The reaction was equally good for installing alkyl and aryl groups at C4 coumarin thus
giving 9dꢀf, 9o & 9p in 78ꢀ84% yields.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Before proposing a plausible reaction pathway, we wanted to know the influence of aromatic system on
the nucleophilicity of the alkoxy group and on the elimination of propargyl hydroxyl group, which is also
a benzylic hydroxyl system that in general is easily cleaved. For that, we prepared substrate 11 from 1012
and treated with I2 in toluene (better solvent compared to CH2Cl2). To our pleasure, the corresponding
product 12 was obtained at ambient temperature and in excellent yield of 85% suggesting that there is no
role of aromatic system in the promotion of the reaction.
SCHEME 2. Synthesis of α,βꢀUnsaturated 3ꢀIodoꢀ2ꢀpyrone 12 from 11.
Based on above observation, a plausible reaction pathway is described in Scheme 3. I2 induced 6ꢀendo dig
cyclization of alkoxy group on to alkyne group led to oxonium ion intermediate A which on expulsion of
protecting group with the help of iodide ion gave B. Allylic hydroxy group on B, with its high tendency
to cleave off, was eliminated in presence of I2 to give another oxonium intermediate C. The expelled
hydroxy group attacked on ethoxy group to relieve oxygen from its positive charge to yield the required
product 9.
ACS Paragon Plus Environment

Page 7 of 36
The Journal of Organic Chemistry
1
2
3
4
SCHEME 3. Proposed Mechanistic Pathway.
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Encouraged by the above results, we next set out to examine the reaction manifold for 5ꢀendoꢀdigꢀ
cyclization, by curtailing a carbon between the nucleophile (OMOM) and the alkyne moeity, to achieve
the synthesis of hitherto formidable 3ꢀiodobunenolides. Butenolides are an important class of heterocycles
with a broad range of potential biological activities.13 Recently, much attention has been focused on the
efficient and diverse synthesis of these compounds.14 Insertion of halide on such interesting small
molecules facilitates the installation of various additional pharmacophores that may lead to a variety of
SAR (Structure Activation Relationship) studies. Ma et al reported the synthesis of 4ꢀiodobutenolides15
while no general report is available for the synthesis of 3ꢀiodobutenolides.16,17 Conversion of 3,4ꢀ
dibromobutenolides to 4ꢀsubstitutedꢀ3ꢀbromobutenolides is reported by Zhang and Bellina but the
substitution was restricted to C4 and aryl groups.18 Moreover, in light of the increased feasibility of metal
mediated substitution of iodo group compared to its counterparts (Br, Cl, OTs and OTf), installation of
iodide in the intermediates is always of a higher priority.
To screen the conditions for our aimed 5ꢀendoꢀdigꢀcyclization, we chose 14a with OMOM as the
intramolecular nucleophile as it facilitated a smooth cyclization in the above 3ꢀiodocoumarin synthesis.
After some experimentation, we found that the alkoxy alkynol 14a smoothly reacted with I2 in toluene at
room temperature, to afford the expected product 15a in 85% yield.19 Similarly, various substrates 14bꢀf
with aliphatic substitution at C4 and C5 were also converted to the corresponding products 15bꢀf in good
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 36
1
2
3
4
yields (80ꢀ89%). 4ꢀaryl substituted butenolides were also obtained (15gꢀl from 4gꢀl) but with a slightly
5
6
diminished reactivity and reduced yields. The probable pathway of the reaction is described in Table 3.
7
8
9
TABLE 3. Synthesis of 3ꢀIodobutenolides 15 via Electrophilic Iodocyclization of Alkyne Diols 14.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Conclusion
In conclusion, a simple and a versatile new approach to a wide variety of 3ꢀiodocoumarins and 3ꢀ
iodobutenolides has been achieved from the electrophilic iodocyclization of various semi protected 1ꢀ
ethoxyꢀ1ꢀalkyne diols. The reactions proceed under mild conditions and tolerate considerable
functionality. A systematic study was done to optimize the conditions as well as cyclizing groups for each
of the cyclization.
ACS Paragon Plus Environment

Page 9 of 36
The Journal of Organic Chemistry
1
2
3
4
Experimental Section
5
6
General Information: All reagents and solvents were purchased from commercial sources and used
7
8
1
without purification. NMR spectra were recorded with a 200 or 300 MHz spectrometer for H NMR, 50,
9
75 or 100 MHz for 13C NMR spectroscopy. Chemical shifts are reported relative to the residual signals of
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
13
tetramethylsilane in CDCl3 or deuterated solvent CDCl3/[D6]DMSO for H and C NMR spectroscopy.
Multiplicities are reported as follows: singlet (s), doublet (d), doublet of doublets (dd), doublet of triplets
(dt), triplet (t), quartet (q), multiplet (m). HRMS were recorded by using QTof and MALDIꢀToF/ToF
mass spectrometers. Column chromatography was performed with silica gel (100–200 mesh) as the
stationary phase. All reactions were monitored by using TLC. The purity and characterization of
compounds were further established by using HRMS.
General Procedure A for the synthesis of ethoxyalkynols (5aꢀf, 6aꢀp, 7a, 8a, 11, 14aꢀl) taking 5a as
the model substrate: nBuLi (1.6 M in THF, 9.1 mL, 2 eq) was added slowly to ethoxyacetylene (40
o
Wt/vol % in hexane, 2.57 mL, 2eq) in THF (10 mL) at ꢀ78 C and the mixture was stirred at the same
o
o
temperature for 2h and at 0 C for another 2h. Then the reaction mixture was reꢀcooled to ꢀ78 C before
o
adding 1a (1g in 10mL THF, 7.35 mmol, 1eq) to it. The mixture was then stirred at ꢀ78 C for 1h and at
room temperature for 2h before diluting with water at 0 oC. The mixture was extracted with EtOAc (2x25
mL) and the combined extracts were washed with brine (15 mL) and dried over Na2SO4. After removal of
the solvent in vacuo the crude product was purified on silica (using 10% EtOAc/hexane) to get 5a ( 1.36
g, 90%) as an yellow oil.
3ꢀethoxyꢀ1ꢀ(2ꢀmethoxyphenyl)propꢀ2ꢀynꢀ1ꢀol (5a): 5a (1.36 g) was obtained from 1a20 (1 g, 7.35 mmol)
1
following general procedure A. Yield 90 %; yellow oil; Rf = 0.40 (SiO2, 20% EtOAc/hexanes); H NMR
(400 MHz, CDCl3): δ = 7.57 (1H, d, J = 7.3 Hz), 7.28 (1H, t, J = 7.3 Hz), 6.97 (1H, t, J = 7.3 Hz), 6.89
(1H, d, J = 8.2 Hz), 5.76 (1H, d, J = 5.3 Hz), 4.15 (2H, q, J = 7.0 Hz), 2.87 (1H, d, J = 5.3 Hz), 1.39 (3H,
13
t, J = 7.0 Hz) ppm; C NMR (75 MHz, CDCl3) δ = 156.6, 130.0, 129.3, 127.8, 120.7, 110.7, 95.1, 74.6,
60.9, 55.5, 37.9, 14.4 ppm. IR (neat): ν = 3436, 3019, 2974, 2933, 2266, 1486, 1217, 1029, 670, 628 cmꢀ1;
HRMS (ESIꢀTOF): calcd. for C12H15O3 [M + H]+ 207.1021; found 207.1015.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 36
1
2
3
4
1ꢀ(2,4ꢀdimethoxyphenyl)ꢀ3ꢀethoxypropꢀ2ꢀynꢀ1ꢀol (5b): 5b (1.27 g) was obtained from 1b20 (1 g, 6.02
5
6
1
mmol) following general procedure A. Yield 90 %; brown oil; Rf = 0.45 (SiO2, 30% EtOAc/hexanes); H
7
8
9
NMR (300 MHz, CDCl3): δ = 7.17 (1H, d, J = 1.4 Hz), 6.80 (2H, d, J = 9.0 Hz), 5.72 (1H, d, J = 5.5 Hz),
4.14 (2H, q, J = 7.0 Hz), 3.83 (3H, s), 3.78 (3H, s), 2.98 (1H, d, J = 5.5 Hz), 1.38 (3H, t, J = 7.0 Hz) ppm.
13C NMR (100 MHz, CDCl3) δ = 152.6, 149.7, 130.1, 112.8, 112.5, 110.8, 93.9, 73.6, 59.7, 55.0, 54.6,
36.9, 13.3 ppm. IR (neat): ν = 3432, 3019, 2969, 2266, 1464, 1217, 1042, 761, 670, cmꢀ1; ESIꢀMS m/z =
259 [M + Na]+. HRMS (ESIꢀTOF) m/z: [M + Na]+ calcd. for C13H16NaO4 259.0946; found 259.0941.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1ꢀ(5ꢀchloroꢀ2ꢀmethoxyphenyl)ꢀ3ꢀethoxypropꢀ2ꢀynꢀ1ꢀol (5c): 5c (993 mg) was obtained from 1c20 (800
mg, 4.70 mmol) following general procedure A. Yield 88 %; brown oil; Rf = 0.32 (SiO2, 20%
1
EtOAc/hexanes); H NMR (300 MHz, CDCl3): δ = 7.55 (1H, d, J = 2.4 Hz), 7.21 (1H, dd, J = 8.7, 2.4,
Hz), 6.79 (1H, d, J = 8.7 Hz), 5.70 (1H, d, J = 5.2 Hz), 4.14 (2H, q, J = 7.08 Hz), 3.85 (3H, s), 2.84 (1H,
d, J = 5.2 Hz), 1.38 (3H, t, J = 7.08 Hz) ppm. 13C NMR (75 MHz, CDCl3) δ = 155.2, 131.7, 128.8, 127.9,
125.8, 111.9, 95.4, 74.8, 60.3, 55.9, 37.4, 14.4 ppm. IR (neat): ν = 3408, 3017, 2934, 2265, 1485, 1217,
1125, 758, 669 cmꢀ1; ESIꢀMS m/z = 263 [M + Na]+. HRMS (ESIꢀTOF) m/z: [M + Na]+ calcd. for
C12H13NaClO3 263.0451; found 263.0443.
4ꢀethoxyꢀ2ꢀ(2ꢀmethoxyphenyl)butꢀ3ꢀynꢀ2ꢀol (5d): 5d (1.31 mg) was obtained from 1d20 (1 g, 6.66
mmol) following general procedure A. Yield 90 %; brown oil; Rf = 0.40 (SiO2, 20% EtOAc/hexanes); 1H
NMR (300 MHz, CDCl3): δ = 7.59 (1H, d, J = 8.9 Hz), 7.27 (1H, dd, J = 15.6, 1.4 Hz), 6.98ꢀ6.92 (2H,
13
m), 4.46 (1H, s), 4.12 (2H, q, J = 7.1 Hz), 3.93 (3H, s), 1.85 (3H, s), 1.38 (3H, t, J = 7.1 Hz) ppm. C
NMR (100 MHz, CDCl3) δ = 156.7, 133.6, 128.7, 126.7, 120.9, 11.5, 93.3, 74.4, 69.8, 55.5, 42.1, 31.1,
14.4 ppm. IR (neat): ν = 3412, 2928, 2263, 1599, 1455, 1384, 1238, 912, 860 cmꢀ1; ESIꢀMS m/z = 243 [M
+ Na]+. HRMS (ESIꢀTOF) m/z: [M + Na]+ calcd. for C13H16NaO3 243.0997; found 243.0989.
3ꢀethoxyꢀ1ꢀ(2ꢀmethoxyphenyl)ꢀ1ꢀphenylpropꢀ2ꢀynꢀ1ꢀol (5e): 5e (1.19 g) was obtained from 1e20 (1 g,
4.71 mmol) following general procedure A. Yield 90 %; brown oil; Rf = 0.50 (SiO2, 30%
ACS Paragon Plus Environment

Page 11 of 36
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
EtOAc/hexanes); 1H NMR (400 MHz, CDCl3): δ = 7.49 (3H, t, J = 5.4 Hz), 7.30ꢀ7.21 (4H, m), 6.95 (1H,
t, J = 7.4 Hz), 6.89 (1H, d, J = 8.2 Hz), 4.82 (1H, s), 4.13 (2H, q, J = 7.0 Hz), 3.70 (3H, s), 1.36 (3H, t, J
= 7.0 Hz) ppm. 13C NMR (100 MHz, CDCl3) δ = 156.7, 146.2, 133.6, 129.2, 128.6, 127.8, 127.0, 126.0,
120.8, 112.1, 74.8, 74.7, 55.7, 41.3, 14.5 ppm. IR (neat): ν = 3497, 3018, 2929, 2266, 1597, 1382, 1217,
759,670 cmꢀ1; ESIꢀMS m/z = 283 [M + H]+. HRMS (ESIꢀTOF) m/z: [M + H]+ calcd. for C18H19O3
283.1334; found 283.1328.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1ꢀ(2,4ꢀdimethoxyphenyl)ꢀ3ꢀethoxyꢀ1ꢀphenylpropꢀ2ꢀynꢀ1ꢀol (5f): 5f (1 g) was obtained from 1f20 (900
mg, 3.71 mmol) following general procedure A. Yield 87 %; yellow oil; Rf = 0.46 (SiO2, 30%
EtOAc/hexanes); 1H NMR (300 MHz, CDCl3): δ = 7.48 (2H, d, J = 7.7 Hz), 7.38 (1H, d, J = 8.2 Hz), 7.28
(2H, t, J = 7.7 Hz), 7.22 (1H, t, J = 7.1 Hz), 6.45 (2H, d, J = 7.4 Hz), 4.68 (1H, s), 4.12 (2H, q, J = 6.7
Hz), 3.79 (3H, s), 3.68 (3H, s), 1.35 (3H, t, J = 6.7 Hz) ppm. 13C NMR (75 MHz, CDCl3) δ = 160.6,
157.6, 146.4, 129.2, 127.7, 126.9, 126.3, 125.9, 103.9, 100.0, 96.2, 74.6, 74.3, 55.6, 55.3, 41.5, 14.4 ppm.
IR (neat): ν = 3504, 3009, 2265, 1609, 1499, 1211, 1159, 1122, 700, 668 cmꢀ1; ESIꢀMS m/z = 335 [M +
Na]+. HRMS (ESIꢀTOF) m/z: [M + Na]+ calcd. for C19H20NaO4 335.1259; found 335.1254.
3ꢀethoxyꢀ1ꢀ(2ꢀ(methoxymethoxy)phenyl)propꢀ2ꢀynꢀ1ꢀol (6a): 6a (1.17 g) was obtained from 2a21 (1 g,
6.02 mmol) following general procedure A. Yield 83 %; brown oil; Rf = 0.38 (SiO2, 20%
EtOAc/hexanes); 1H NMR (300 MHz, CDCl3): δ = 7.58 (1H, dd, J = 1.3, 7.5 Hz), 7.26 (1H, t, J = 7.5 Hz),
7.10 (1H, d, J = 8.0 Hz), 7.02 (1H, t, J = 7.5 Hz), 5.77 (1H, d, J = 5.7 Hz), 5.25 (2H, dd, J = 10.1, 6.6 Hz),
13
4.13 (2H, q, J = 7.1 Hz), 3.50 (3H, s), 2.85 (1H, d, J = 5.7 Hz), 1.38 (3H, t, J = 7.1 Hz) ppm. C NMR
(100 MHz, CDCl3) δ = 153.3, 129.9, 128.3, 126.8, 121.0, 113.4, 93.9, 93.6, 73.6, 59.7, 55.2, 37.0, 13.4
ppm. IR (neat): ν = 3401, 3018, 2927, 2265, 1632, 1263, 1217, 1154, 770, 669 cmꢀ1; ESIꢀMS m/z = 259
[M + Na]+. HRMS (ESIꢀTOF) m/z: [M + Na]+ calcd. for C13H16NaO4 259.0946; found 259.0949.
3ꢀethoxyꢀ1ꢀ(4ꢀmethoxyꢀ2ꢀ(methoxymethoxy)phenyl)propꢀ2ꢀynꢀ1ꢀol (6b): 6b (1.12 g) was obtained
from 2b22 (1 g, 5.10 mmol) following general procedure A. Yield 83 %; yellow oil; Rf = 0.45 (SiO2, 30%
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 36
1
2
3
4
5
6
7
8
9
EtOAc/hexanes); 1H NMR (300 MHz, CDCl3): δ = 7.50 (1H, d, J = 8.3 Hz), 6.69 (1H, s), 6.55 (1H, d, J =
8.3 Hz), 5.72 (1H, d, J = 5.4 Hz), 5.23 (2H, dd, J = 9.8, 6.5 Hz), 4.14 (2H, q, J = 7.0 Hz), 3.79 (3H, s),
3.50 (3H, s), 2.66 (1H, d, J = 5.4 Hz), 1.38 (3H, t, J = 7.0 Hz) ppm. 13C NMR (100 MHz, CDCl3) δ =
159.6, 154.3, 127.6, 122.6, 105.3, 100.6, 93.8, 93.7, 73.6, 59.2, 55.2, 54.4, 37.2, 13.4 ppm. IR (neat): ν
=3433, 3019, 2969, 2265, 1608, 1259, 1216, 1158, 1111, 760 cmꢀ1; ESIꢀMS m/z = 289 [M + Na]+. HRMS
(ESIꢀTOF) m/z: [M + Na]+ calcd. for C14H18NaO5 289.1052; found 289.1044.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1ꢀ(5ꢀchloroꢀ2ꢀ(methoxymethoxy)phenyl)ꢀ3ꢀethoxypropꢀ2ꢀynꢀ1ꢀol (6c): 6c (756 mg) was obtained from
2c23 (700 mg, 3.5 mmol) following general procedure A. Yield 80 %; yellow oil; Rf = 0.40 (SiO2, 20%
1
EtOAc/hexanes); H NMR (300 MHz, CDCl3): δ = 7.57 (1H, d, J = 2.3 Hz), 7.21 (1H, dd, J = 8.7, 2.3
Hz), 7.04 (1H, d, J = 8.7 Hz), 5.73 (1H, d, J = 5.6 Hz), 5.22 (2H, dd, J = 10.7, 6.8 Hz), 4.15 (2H, q, J =
7.1 Hz), 3.49 (3H, s), 2.67 (1H, d, J = 5.6 Hz), 1.39 (3H, t, J = 7.1 Hz) ppm. 13C NMR (75 MHz, CDCl3)
δ = 152.7, 132.7, 128.9, 127.8, 127.0, 115.8, 95.1, 94.8, 74.8, 60.0, 56.3, 37.6, 14.4 ppm. IR (neat): ν
=3431, 3020, 2977, 2266, 1535, 1262, 1216, 1122, 761, 670 cmꢀ1; ESIꢀMS m/z = 293 [M + Na]+. HRMS
(ESIꢀTOF) m/z: [M + Na]+ calcd. for C13H15NaClO4 293.0557; found 293.0553.
4ꢀethoxyꢀ2ꢀ(2ꢀ(methoxymethoxy)phenyl)butꢀ3ꢀynꢀ2ꢀol (6d): 6d (1.19 g) was obtained from 2d24 (1 g,
5.55 mmol) following general procedure A. Yield 86 %; yellow oil; Rf = 0.47 (SiO2, 20%
EtOAc/hexanes); 1H NMR (400 MHz, CDCl3): δ = 7.58 (1H, d, J = 7.5 Hz), 7.22 (1H, t, J = 7.5 Hz), 7.14
(1H, d, J = 8.0 Hz), 6.99 (1H, d, J = 6.9 Hz), 5.30 (2H, dd, J = 7.8, 6.8 Hz), 4.28 (1H, s), 4.10 (2H, q, J =
7.1 Hz), 3.53 (3H, s), 1.87 (3H, s), 1.36 (3H, t, J = 7.1 Hz) ppm. 13C NMR (100 MHz, CDCl3) δ = 154.5,
134.0, 128.7, 126.5, 121.8, 114.7, 94.6, 93.1, 74.4, 69.4, 56.3, 42.2, 30.9, 14.4 ppm. IR (neat): ν = 3428,
3017, 2928, 2264, 1600, 1385, 1216, 1158, 669 cmꢀ1; ESIꢀMS m/z = 273 [M + Na]+. HRMS (ESIꢀTOF)
m/z: [M + Na]+ calcd. for C14H18NaO4 273.1103; found 273.1107.
3ꢀethoxyꢀ1ꢀ(2ꢀ(methoxymethoxy)phenyl)ꢀ1ꢀphenylpropꢀ2ꢀynꢀ1ꢀol (6e): 6e (1.10 g) was obtained from
2e25 (1 g, 4.13 mmol) following general procedure A. Yield 86 %; yellow oil; Rf = 0.40 (SiO2, 20%
ACS Paragon Plus Environment

Page 13 of 36
The Journal of Organic Chemistry
1
2
3
4
1
EtOAc/hexanes); H NMR (300 MHz, CDCl3): δ = 7.63 (1H, dd, J = 1.2, 7.5 Hz), 7.48 (2H, d, J = 7.5
5
6
Hz), 7.30ꢀ7.18 (4H, m), 7.06 (1H, d, J = 8.2 Hz), 7.01 (1H, t, J = 7.5 Hz), 4.99 (2H, dd, J = 26.5, 6.6 Hz),
7
8
13
4.54 (1H, s), 4.14 (2H, q, J = 7.1 Hz), 3.13 (3H, s), 1.36 (3H, t, J = 7.1 Hz) ppm. C NMR (100 MHz,
9
CDCl3) δ = 153.0, 145.4, 132.8, 128.1, 127.4, 126.7, 125.9, 124.7, 120.5, 113.7, 95.5, 93.0, 73.6, 73.4,
66.9, 54.9, 40.0, 13.4 ppm. IR (neat): ν = 3515, 3062, 2960, 2266, 1595, 1230, 1157, 1080 cmꢀ1; HRMS
(ESIꢀTOF) m/z: [M + Na]+ calcd. for C19H20NaO4 335.1259; found 335.1248.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
3ꢀethoxyꢀ1ꢀ(4ꢀmethoxyꢀ2ꢀ(methoxymethoxy)phenyl)ꢀ1ꢀphenylpropꢀ2ꢀynꢀ1ꢀol (6f): 6f (1.09 g) was
obtained from 2f25 (1 g, 3.67 mmol) following general procedure A. Yield 87 %; brown oil; Rf =
0.36(SiO2, 30% EtOAc/hexanes); 1H NMR (300 MHz, CDCl3): δ = 7.52 (1H, d, J = 8.6 Hz), 7.48 (2H, d,
J = 7.8 Hz), 7.28 (3H, t, J = 6.4 Hz), 6.66 (1H, s), 6.53 (1H, d, J = 8.6 Hz), 4.97 (2H, dd, J = 24.1, 6.7
13
Hz), 4.42 (1H, s), 4.13 (2H, q, J = 6.9 Hz), 3.79 (3H, s), 3.13 (3H, s), 1.35 (3H, t, J = 6.9 Hz) ppm. C
NMR (100 MHz, CDCl3) δ = 160.4, 155.0, 146.7, 129.1, 127.7, 126.8, 126.6, 125.8, 105.3, 102.2, 96.4,
94.2, 74.6, 74.1, 55.9, 55.3, 41.3, 14.4 ppm. IR (neat): ν = 3522, 3016, 2929, 2265, 1608, 1449, 1298,
1217, 1159, 1116, 669, 630, 589 cmꢀ1; ESIꢀMS m/z = 365 [M + Na]+. HRMS (ESIꢀTOF) m/z: [M + Na]+
calcd. for C20H22NaO5 365.1365; found 365.1357.
3ꢀethoxyꢀ1ꢀ(2ꢀ(methoxymethoxy)ꢀ3ꢀmethylphenyl)propꢀ2ꢀynꢀ1ꢀol (6g): 6g (716 mg) was obtained from
2g26 (600 mg, 3.33 mmol) following general procedure A. Yield 86 %; yellow oil; Rf = 0.40 (SiO2, 20%
1
EtOAc/hexanes); H NMR (400 MHz, CDCl3): δ = 7.54 (1H, d, J = 7.4 Hz), 7.15 (1H, d, J = 7.3 Hz),
7.07 (1H, t, J = 7.4 Hz), 5.82 (1H, d, J = 4.5 Hz), 5.08 (1H, d, J = 5.9 Hz), 4.97 (1H, d, J = 5.9 Hz), 4.15
(2H, q, J = 7.1 Hz), 3.63 (3H, s), 3.44 (1H, d, J = 4.5 Hz), 2.28 (3H, s), 1.38 (3H, t, J = 7.1 Hz) ppm. 13C
NMR (100 MHz, CDCl3) δ = 153.8, 135.7, 131.3, 130.9, 126.1, 124.8, 99.6, 94.9, 74.6, 59.8, 57.5, 38.2,
16.8, 14.4 ppm. IR (neat): ν = 3430, 3016, 2932, 2267, 1593, 1389, 1218, 1159, 991, 858, 760, 669 cmꢀ1;
HRMS (ESIꢀTOF) m/z: [M + Na]+ calcd. for C14H18NaO4 273.1103; found 273.1094.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 36
1
2
3
4
5
6
3ꢀethoxyꢀ1ꢀ(3ꢀethylꢀ2ꢀ(methoxymethoxy)phenyl)propꢀ2ꢀynꢀ1ꢀol (6h): 6h (819 mg) was obtained from
2h27 (700 mg, 3.60 mmol) following general procedure A. Yield 86 %; yellow oil; Rf = 0.40 (SiO2, 20%
7
8
1
EtOAc/hexanes); H NMR (400 MHz, CDCl3): δ = 7.56 (1H, dd, J = 7.5, 1.6 Hz), 7.19 (1H, dd, J = 7.5,
9
1.6 Hz), 7.12 (1H, t, J = 7.5 Hz), 5.83 (1H, d, J = 4.8 Hz), 5.08 (1H, d, J = 5.9 Hz), 4.96 (1H, d, J = 5.9
Hz), 4.15 (2H, q, J = 7.1 Hz), 3.64 (3H, s), 3.46 (1H, d, J = 4.8 Hz), 2.64 (2H, q, J = 7.6 Hz), 1.38 (3H, t,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
13
J = 7.1 Hz), 1.22 (3H, t, J = 7.6 Hz) ppm. C NMR (100 MHz, CDCl3) δ = 153.4, 136.9, 135.8, 129.5,
126.1, 125.0, 100.1, 94.9, 74.6, 60.6, 59.7, 57.4, 38.3, 23.1, 14.6 ppm. IR (neat): ν = 3406, 2927, 2265,
1650, 1456, 1219, 1157, 1065, 759, 668 cmꢀ1. HRMS (ESIꢀTOF) m/z: calcd. for C15H20NaO4 [M + Na]+
287.1259; found 287.1253.
3ꢀethoxyꢀ1ꢀ(3ꢀisopropylꢀ2ꢀ(methoxymethoxy)phenyl)propꢀ2ꢀynꢀ1ꢀol (6i): 6i (534 mg) was obtained
from 2i28 (500 mg, 2.40 mmol) following general procedure A. Yield 84 %; brown oil; Rf = 0.47 (SiO2,
20% EtOAc/hexanes); 1H NMR (400 MHz, CDCl3): δ = 7.56 (1H, dd, J = 1.5, 7.5 Hz), 7.25 (1H, dd, J =
1.5, 7.5 Hz), 7.15 (1H, t, J = 7.5 Hz), 5.84 (1H, d, J = 4.0 Hz), 5.09 (1H, d, J = 5.9 Hz), 4.95 (1H, d, J =
5.9 Hz), 4.15 (2H, q, J = 7.0 Hz), 3.65 (3H, s), 3.44 (1H, d, J = 4.0 Hz), 3.23 (1H, sp, J = 6.7 Hz), 1.39
13
(3H, t, J = 7.0 Hz), 1.25 (6H, d, J = 6.7 Hz) ppm. C NMR (75 MHz, CDCl3) δ = 152.6, 141.8, 135.8,
126.9, 126.0, 125.3, 100.6, 95.0, 74.6, 59.9, 57.6, 41.9, 38.3, 23.5, 14.4 ppm. IR (neat): ν = 3401, 2926,
2265, 1652, 1384, 1217, 1155, 1021, 769, 668 cmꢀ1. HRMS (ESIꢀTOF) m/z: calcd. for C16H22NaO4 [M +
Na]+ 301.1416; found 301.1409.
1ꢀ(3ꢀtertꢀbutylꢀ2ꢀ(methoxymethoxy)phenyl)ꢀ3ꢀethoxypropꢀ2ꢀynꢀ1ꢀol (6j): 6j (526 mg) was obtained
from 2j29 (500 mg, 2.25 mmol) following general procedure A. Yield 80 %; brown oil; Rf = 0.40 (SiO2,
20% EtOAc/hexanes); 1H NMR (400 MHz, CDCl3): δ = 7.67 (1H, dd, J = 7.5, 1.5 Hz), 7.32 (1H, dd, J =
7.8, 1.5 Hz), 7.11 (1H, t, J = 7.8 Hz), 5.84 (1H, d, J = 5.0 Hz), 5.09 (1H, d, J = 5.9 Hz), 4.95 (1H, d, J =
5.9 Hz), 4.14 (2H, q, J = 7.0 Hz), 3.69 (3H, s), 3.44 (1H, d, J = 5.0 Hz), 1.39 (12 H, s) ppm. 13C NMR
(100 MHz, CDCl3) δ = 154.6, 143.0, 136.8, 127.6, 127.5, 124.6, 100.9, 94.8, 74.7, 59.6, 57.4, 39.1, 35.1,
ACS Paragon Plus Environment

Page 15 of 36
The Journal of Organic Chemistry
1
2
3
4
5
31.3, 14.5 ppm. IR (neat): ν = 3430, 3018, 2960, 2265, 1637, 1392, 1216, 1156, 854, 757, 669 cmꢀ1.
HRMS (ESIꢀTOF) m/z: calcd. for C17H24NaO4 [M + Na]+ 315.1572; found 315.1580.
6
7
8
9
1ꢀ(3ꢀbromoꢀ5ꢀchloroꢀ2ꢀ(methoxymethoxy)phenyl)ꢀ3ꢀethoxypropꢀ2ꢀynꢀ1ꢀol (6k): 6k (969 mg) was
obtained from 2k30 (900 mg, 3.24 mmol) following general procedure A. Yield 86 %; brown oil; Rf = 0.42
(SiO2, 20% EtOAc/hexanes); 1H NMR (400 MHz, CDCl3): δ = 7.67 (1H, d, J = 2.4 Hz), 7.52 (1H, d, J =
2.4 Hz), 5.80 (1H, d, J = 4.2 Hz), 5.13 (2H, dd, J = 48.0, 6.0 Hz), 4.18 (2H, q, J = 7.1 Hz), 3.66 (1H, s),
3.54 (1H, d, J = 4.2 Hz), 1.40 (3H, t, J = 7.1 Hz) ppm. 13C NMR (100 MHz, CDCl3) δ = 151.5, 139.1,
132.7, 130.7, 128.0, 117.6, 100.4, 95.5, 74.9, 59.5, 58.0, 37.1, 14.4 ppm. IR (neat): ν = 3456, 3036, 2928,
2266, 1314, 1232, 1125, 872, 732, 580 cmꢀ1; ESIꢀMS m/z = 370 [M + Na]+. HRMS (ESIꢀTOF) m/z: [M +
Na]+ calcd. for C13H14NaBrClO4370.9662; found 370.9657.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
3ꢀethoxyꢀ1ꢀ(2ꢀ(methoxymethoxy)ꢀ5ꢀnitrophenyl)propꢀ2ꢀynꢀ1ꢀol (6l): 6l (1.14 g) was obtained from 2l31
(1 g, 4.73 mmol) following general procedure A. Yield 85 %; yellow oil; Rf = 0.40 (SiO2, 50%
EtOAc/hexanes); 1H NMR (300 MHz, CDCl3): δ = 8.54 (1H, s), 8.17 (1H, d, J = 9.1 Hz), 7.20 (1H, d, J =
9.1 Hz), 5.79 (1H, s), 5.35 (2H, s), 4.17 (2H, q, J = 7.1 Hz), 3.51 (3H, s), 2.54 (1H, s), 1.40 (3H, t, J = 7.1
Hz) ppm. 13C NMR (75 MHz, CDCl3) δ = 125.2, 124.7, 123.7, 122.8, 113.8, 95.5, 94.5, 75.0, 59.7, 56.7,
37.4, 14.4 ppm. IR (neat): ν = 3432, 2938, 2254, 1632, 1542, 1442, 1368, 1311, 1232, 1178, cmꢀ1. ESIꢀ
MS m/z = 304 [M + Na]+. HRMS (ESIꢀTOF) m/z: [M + Na]+ calcd. for C13H15NaNO6 304.0797; found
304.0791.
3ꢀethoxyꢀ1ꢀ(4ꢀ(methoxymethoxy)biphenylꢀ3ꢀyl)propꢀ2ꢀynꢀ1ꢀol (6m): 6m (665 mg) was obtained from
2m32 (600 mg, 2.47 mmol) following general procedure A. Yield 86 %; yellow oil; Rf = 0.48 (SiO2, 20%
EtOAc/hexanes); 1H NMR (400 MHz, CDCl3): δ = 7.82 (1H, s), 7.56 (2H, d, J = 7.8 Hz), 7.48 (1H, dd, J
= 8.4, 1.4 Hz), 7.42 (2H, t, J = 7.5 Hz), 7.31 (1H, t, J = 7.5 Hz), 7.18 (1H, d, J = 8.4 Hz), 5.83 (1H, d, J =
5.1 Hz), 5.29 (2H, dd, J = 11.5, 6.7 Hz), 4.14 (2H, q, J = 7.1 Hz), 3.53 (3H, s), 2.81 (1H, d, J = 5.1 Hz),
1.38 (3H, t, J = 7.1 Hz) ppm. 13C NMR (100 MHz, CDCl3) δ = 153.7, 140.6, 135.0, 131.3, 128.7, 127.7,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 36
1
2
3
4
5
6
7
8
126.8, 126.6, 114.8, 95.0, 94.7, 74.6, 60.7, 56.3, 38.2, 14.4 ppm. IR (neat): ν = 3406, 2926, 2264, 1611,
1482, 1227, 1153, 1006, 763 cmꢀ1; ESIꢀMS m/z = 335 [M + Na]+. HRMS (ESIꢀTOF) m/z: [M + Na]+
calcd. for C19H20NaO4 335.1259; found 335.1255.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
3ꢀethoxyꢀ1ꢀ(2ꢀ(methoxymethoxy)naphthalenꢀ1ꢀyl)propꢀ2ꢀynꢀ1ꢀol (6n): 6n (575 mg) was obtained from
2n33 (500 mg, 2.31 mmol) following general procedure A. Yield 87 %; yellow oil; Rf = 0.42 (SiO2, 20%
EtOAc/hexanes); 1H NMR (300 MHz, CDCl3): δ = 8.50 (1H, d, J = 8.5 Hz), 7.77 (2H, t, J = 7.3 Hz), 7.51
(1H, t, J = 7.3 Hz), 7.38 (2H, t, J = 4.6 Hz), 6.49 (1H, d, J = 6.4 Hz), 5.31 (2H, dd, J = 8.7, 6.7 Hz), 4.04
(2H, q, J = 7.05 Hz), 3.56 (3H, s), 3.11 (1H, d, J = 6.4 Hz), 1.30 (3H, t, J = 7.05 Hz) ppm. 13C NMR (100
MHz, CDCl3) δ = 150.5, 130.1, 129.3, 128.9, 127.4, 125.3, 123.4, 123.2, 123.1, 115.5, 94.7, 93.5, 73.4,
56.4, 55.4, 38.6, 13.3 ppm. IR (neat): ν = 3421, 3016, 2933, 2261, 1626, 1467, 1217, 1154, 1012, 923,
759, 669 cmꢀ1; ESIꢀMS m/z = 309 [M + Na]+. HRMS (ESIꢀTOF) m/z: [M + Na]+ calcd. for C17H18NaO4
309.1103; found; 309.1098.
4ꢀethoxyꢀ2ꢀ(2ꢀ(methoxymethoxy)ꢀ4ꢀmethylphenyl)butꢀ3ꢀynꢀ2ꢀol (6o): 6o (1.14 g) was obtained from
2o34 (1 g, 5.15 mmol) following general procedure A. Yield 84 %; yellow oil; Rf = 0.55 (SiO2, 30%
EtOAc/hexanes); 1H NMR (300 MHz, CDCl3): δ = 7.44 (1H, d, J = 7.8 Hz), 6.96 (1H, s), 6.80 (1H, d, J =
7.8 Hz), 5.28 (2H, s), 6.80 (1H, d, J = 7.8 Hz), 5.28 (2H, s), 4.27 (1H, s), 4.09 (2H, q, J = 7.2 Hz), 3.53
13
(3H, s), 2.32 (3H, s), 1.85 (3H, s), 1.36 (3H, t, J = 7.2 Hz) ppm. C NMR (75 MHz, CDCl3) δ = 154.3,
138.9, 131.2, 126.3, 122.4, 115.4, 94.5, 92.6, 74.4, 69.2, 56.4, 42.3, 30.9, 21.2, 14.4 ppm. IR (neat): ν =
3411, 3018, 2927, 2264, 1612, 1245, 1216, 1156, 927, 853, 753 cmꢀ1. HRMS (ESIꢀTOF) m/z: [M + Na]+
calcd. for C15H20NaO4 287.1259; found 287.1252.
4ꢀethoxyꢀ2ꢀ(4ꢀmethoxyꢀ2ꢀ(methoxymethoxy)phenyl)butꢀ3ꢀynꢀ2ꢀol (6p): 6p (655 mg) was obtained
from 2p24 (600 mg, 2.85 mmol) following general procedure A. Yield 82 %; brown oil; Rf = 0.38 (SiO2,
1
20% EtOAc/hexanes); H NMR (300 MHz, CDCl3): δ = 7.48 (1H, d, J = 8.5 Hz), 6.74 (1H, d, J = 2.3
Hz), 6.51 (1H, dd, J = 2.3, 8.5 Hz), 5.28 (2H, s), 4.16 (1H, s), 4.10 (2H, q, J = 7.0 Hz), 3.79 (3H, s), 3.52
ACS Paragon Plus Environment

Page 17 of 36
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
(3H, s), 1.84 (3H, s), 1.36 (3H, t, J = 7.0 Hz) ppm. 13C NMR (75 MHz, CDCl3) δ = 160.0, 155.4, 127.1,
126.8, 105.6, 102.2, 94.7, 92.9, 74.4, 69.0, 56.4, 55.4, 42.4, 31.1, 14.4 ppm. IR (neat): ν = 3422, 2933,
2263, 1610, 1254, 1217, 1158, 1129, 923, 851, 760 cmꢀ1; ESIꢀMS m/z = 303 [M + Na]+. HRMS (ESIꢀ
TOF) m/z: [M + Na]+ calcd. for C15H20NaO5 303.1208; found 303.1202.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1ꢀ(2ꢀ(benzyloxy)phenyl)ꢀ3ꢀethoxypropꢀ2ꢀynꢀ1ꢀol (7a): 7a (1.11 g) was obtained from 3a35 (1 g, 4.71
mmol) following general procedure A. Yield 84 %; yellow oil; Rf = 0.55 (SiO2, 30% EtOAc/hexanes); 1H
NMR (400 MHz, CDCl3): δ = 7.50 (1H, d, J = 6.6 Hz), 7.38ꢀ7.16 (6H, m), 6.88 (2H, t, J = 8.7 Hz), 5.72
(1H, d, J = 5.8 Hz), 5.07ꢀ5.04 (2H, m), 4.04 (2H, q, J = 7.0 Hz), 2.83 (1H, d, J = 5.8 Hz), 1.29 (3H, t, J =
7.0 Hz) ppm. 13C NMR (125 MHz, CDCl3) δ = 155.7, 136.6, 130.4, 129.1, 128.5, 127.9, 127.8, 127.1,
121.0, 112.0, 94.9, 74.5, 40.1, 60.9, 38.1, 14.3 ppm. IR (neat): ν = 3486, 2988, 2254, 1568, 1378, 1323,
1254, 812 cmꢀ1. HRMS (ESIꢀTOF) m/z: [M + Na]+ calcd. for C18H18NaO3 301.1154; found 301.1145.
3ꢀethoxyꢀ1ꢀ(2ꢀ(4ꢀmethoxybenzyloxy)phenyl)propꢀ2ꢀynꢀ1ꢀol (8a): 8a (825 mg) was obtained from 4a36
(800 mg, 3.30 mmol) following general procedure A. Yield 80 %; brown oil; Rf = 0.50 (SiO2, 30%
1
EtOAc/hexanes); H NMR (400 MHz, CDCl3): δ = 7.56 (1H, d, J = 7.2 Hz), 7.37 (2H, d, J = 8.3 Hz),
7.28ꢀ7.24 (1H, m), 6.99ꢀ6.95 (2H, m), 6.91 (2H, d, J = 8.3 Hz), 5.76 (1H, d, J = 5.7 Hz), 5.06 (2H, d, J =
36. Hz), 4.12 (2H, q, J = 7.01 Hz), 3.81 (3H, s), 2.92 (1H, d, J = 5.7 Hz), 1.37 (3H, t, J = 7.08 Hz) ppm.
13C NMR (100 MHz, CDCl3) δ = 159.4, 155.8, 130.5, 129.2, 129.0, 128.7, 127.8, 120.9, 114.0, 112.1,
94.9, 74.6, 70.1, 61.1, 55.2, 38.0, 14.3 ppm. IR (neat): ν = 3410, 2929, 2263, 1609, 1455, 1241, 1175,
827, 756 cmꢀ1. HRMS (ESIꢀTOF) m/z: [M + Na]+ calcd. for C19H20NaO4 335.1259; found 335.1254.
1ꢀ(ethoxyethynyl)ꢀ2ꢀ(methoxymethoxy)cyclopentanol (14a): 14a (624 mg) was obtained from 13a37
(500 mg, 3074 mmol) following general procedure A. Yield 84 %; yellow oil; Rf = 0.40 (SiO2, 20%
1
EtOAc/hexanes); H NMR (300 MHz, CDCl3): δ = 4.77 (2H, dd, J = 27.6, 6.3 Hz), 4.06 (2H, q, J = 7.0
Hz), 3.96 (1H, t, J = 7.1 Hz), 3.40 (3H, s), 2.84 (1H, s), 2.00ꢀ1.57 (6H, m), 1.34 (3H, t, J = 7.0 Hz) ppm.
13C NMR (100 MHz, CDCl3) δ = 94.9, 91.3, 83.4, 73.4, 72.4, 54.4, 39.7, 37.7, 27.5, 18.3, 13.3 ppm. IR
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 36
1
2
3
4
5
(neat): ν = 3445, 2968, 2274, 1352, 1251, 1202, 1135 cmꢀ1; ESIꢀMS m/z = 237 [M + Na]+. HRMS (ESIꢀ
TOF) m/z: [M + Na]+ calcd. for C11H18NaO4 237.1103; found 237.1094.
6
7
8
9
1ꢀ(ethoxyethynyl)ꢀ2ꢀ(methoxymethoxy)cyclohexanol (14b): 14b (496 mg) was obtained from 13b38
(400 mg, 2.5 mmol) following general procedure A. Yield 86 %; yellow oil; Rf = 0.52 (SiO2, 30%
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
EtOAc/hexanes); H NMR (400 MHz, CDCl3): δ = 4.78 (2H, dd, J = 27.7, 6.6 Hz), 4.07 (2H, q, J = 7.1
Hz), 3.59 (1H, dd, J = 7.6, 3.6 Hz), 3.40 (3H, s), 2.73 (1H, s), 1.94 – 1.39 (8H, m), 1.34 (3H,t, J = 7.1 Hz)
ppm. 13C NMR (75 MHz, CDCl3) δ = 97.1, 96.0, 92.9, 87.0, 80.5, 74.3, 71.8, 69.3, 55.5, 50.5, 40.9, 38.6,
37.5, 27.7, 24.2, 23.5, 22.9, 21.8, 21.6, 14.2 ppm. IR (neat): ν = 3488, 2978, 2263, 1388, 1336, 1264,
1163, 1032, cmꢀ1. HRMS (ESIꢀTOF) m/z: [M + H]+ calcd. for C12H20NaO4 251.1259; found 251.1250.
1ꢀ(ethoxyethynyl)ꢀ2ꢀ(methoxymethoxy)cycloheptanol (14c): A mixture of 2ꢀhydroxyheptanone39 (450
mg, 3.51 mmol) and DIPEA (680 mg, 5.27 mmol) in CH2Cl2 (6 mL) was added MOMCl (365 mg, 4.56
o
mmol) at 0 C and stirred the contents at room temperature over the night. After diluting with water, the
mixture was extracted with CH2Cl2 (2x10 mL) and the combined organic layers were washed with brine
(6 mL) and dried over Na2SO4. After removing the solvent in vacuo, the crude product was filtered
through a silica bed using 20% EtOAc/hexane. The product 13c was as such used (considering as 100%
yield) in the next step without further purification and analysis.
14c (590 mg) was obtained from 13c (600mg, 3.48 mmol) following general procedure A. Combined
yield 70 %; yellow oil; Rf = 0.55 (SiO2, 20% EtOAc/hexanes); 1H NMR (300 MHz, CDCl3): δ = 4.75
(2H, dd, J = 14.9, 6.6 Hz), 4.07 (2H, q, J = 7.0 Hz), 3.69 (1H, d, J = 7.8 Hz), 3.421 (3H, s), 3.09 (1H, s),
1.89ꢀ1.66 (10H, m), 1.35 (3H, t, J = 7.0 Hz) ppm. 13C NMR (100 MHz, CDCl3) δ = 95.3, 91.4, 83.6, 73.3,
71.5, 54.8, 40.9, 37.6, 27.0, 26.5, 21.9, 20.1, 13.3 ppm. IR (neat): ν = 3434, 3016, 2933, 2261, 1387,
1216, 1150, 1098 cmꢀ1; ESIꢀMS m/z = 265 [M + Na]+. HRMS (ESIꢀTOF) m/z: [M + Na]+ calcd. for
C13H22NaO4 265.1416; found 265.1408.
ACS Paragon Plus Environment

Page 19 of 36
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
1ꢀ(ethoxyethynyl)ꢀ2ꢀ(methoxymethoxy)cyclooctanol (14d): A mixture of 2ꢀhydroxyoctanone40 (305 mg,
2.14 mmol) and DIPEA (414 mg, 3.21 mmol) in CH2Cl2 (5 mL)was added MOMCl (222 mg, 2.78 mmol)
at 0 oC and stirred the contents at room temperature over the night. After diluting with water, the mixture
was extracted with CH2Cl2 (2x8 mL) and the combined organic layers were washed with brine (5 mL)
and dried over Na2SO4. After removing the solvent in vacuo, the crude product was filtered through a
silica bed using 20% EtOAc/hexane. The product 13d was as such used (considering as 100% yield) in
the next step without further purification and analysis.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
14d (374 mg) was obtained from 13d (400 mg, 2.15 mmol) following general procedure A. Combined
1
yield 68 %; yellow oil; Rf = 0.48 (SiO2, 20% EtOAc/hexanes); H NMR (300 MHz, CDCl3): δ = 4.81ꢀ
4.62 (3H, m), 4.18ꢀ4.03 (2H, m), 3.79 (1H, d, J = 8.5 Hz), 3.43 (2H, s), 3.34 (1H, s), 3.07 (1H, s), 2.48ꢀ
13
2.44 (1H, m), 2.15ꢀ1.39 (16H, m), 1.34 (4H, t, J = 7.1 Hz) ppm. C NMR (100 MHz, CDCl3) δ = 94.9,
94.9, 91.2, 81.5, 79.5, 73.3, 71.8, 54.8, 54.7, 40.5, 38.8, 33.6, 30.5, 28.3, 27.0, 25.9, 24.9, 24.6, 24.0, 23.8,
21.8, 20.9, 13.3 ppm. IR (neat): ν = 3452, 3017, 2932, 2259, 1620, 1334, 1215, 1150, 1033 cmꢀ1; ESIꢀMS
m/z = 279 [M + Na]+. HRMS (ESIꢀTOF) m/z: [M + Na]+ calcd. for C14H24NaO4 279.1572; found
279.1565.
1ꢀethoxyꢀ3ꢀ((methoxymethoxy)methyl)decꢀ1ꢀynꢀ3ꢀol (14e): A mixture of 1ꢀhydroxyꢀ2ꢀnonanone41 (547
mg, 3.46 mmol) and DIPEA (670 mg, 5.19 mmol) in CH2Cl2 (8 mL)was added MOMCl (360 mg, 4.49
o
mmol) at 0 C and stirred the contents at room temperature over the night. After diluting with water, the
mixture was extracted with CH2Cl2 (2x10 mL) and the combined organic layers were washed with brine
(8 mL) and dried over Na2SO4. After removing the solvent in vacuo, the crude product was filtered
through a silica bed using 20% EtOAc/hexane. The product 13e was as such used (considering as 100%
yield) in the next step without further purification and analysis.
14e (660 mg) was obtained from 13e (700 mg, 3.46 mmol) following general procedure A. Combined
yield 70 %; brown oil; Rf = 0.40 (SiO2, 20% EtOAc/hexanes); 1H NMR (300 MHz, CDCl3): δ = 4.70 (2H,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 20 of 36
1
2
3
4
5
6
7
8
9
13
s), 4.08 (2H, q, J = 6.8 Hz), 3.61ꢀ3.46 (2H, m), 3.40 (3H, s), 2.82 (1H, s), 1.38ꢀ1.25 (18H, m) ppm. C
NMR (100 MHz, CDCl3) δ = 96.1, 92.4, 74.9, 73.5, 69.4, 54.4, 38.1, 38.1, 30.8, 28.6, 28.2, 23.3, 21.6,
21.6, 13.3, 13.0 ppm. IR (neat): ν = 3424, 3020, 2928, 2858, 2262, 1642, 1462, 1216, 1152 cmꢀ1; ESIꢀMS
m/z = 295 [M + Na]+. HRMS (ESIꢀTOF) m/z: [M + Na]+ calcd. for C15H28NaO4 295.1885; found;
295.1877.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1ꢀethoxyꢀ3ꢀ((methoxymethoxy)methyl)undecꢀ1ꢀynꢀ3ꢀol (14f): A mixture of 1ꢀhydroxyꢀ2ꢀdecanone41
(398 mg, 2.31 mmol) and DIPEA (447 mg, 3.47 mmol) in CH2Cl2 (6 mL)was added MOMCl (240 mg,
3.00 mmol) at 0 oC and stirred the contents at room temperature over the night. After diluting with water,
the mixture was extracted with CH2Cl2 (2x8 mL) and the combined organic layers were washed with
brine (6 mL) and dried over Na2SO4. After removing the solvent in vacuo, the crude product was filtered
through a silica bed using 20% EtOAc/hexane. The product 13f was as such used (considering as 100%
yield) in the next step without further purification and analysis.
14f (430 mg) was obtained from 13f (500 mg, 2.31 mmol) following general procedure A. Yield 65 %;
1
yellow oil; Rf = 0.48 (SiO2, 20% EtOAc/hexanes); H NMR (400 MHz, CDCl3): δ = 4.70 (2H, dd, J =
10.9, 6.5 Hz), 4.08 (2H, q, J = 6.9 Hz), 3.54 (2H, dd, J = 35.9, 10.1 Hz), 3.40 (3H, s), 2.80 (3H, s), 1.64ꢀ
13
1.29 (18H, m) ppm. C NMR (100 MHz, CDCl3) δ = 96.0, 92.4, 74.9, 73.5, 69.4, 54.4, 38.1, 38.1, 30.8,
28.8, 28.5, 28.2, 23.3, 21.6, 13.3, 13.0 ppm. IR (neat): ν = 3429, 3019, 2929, 2263, 1638, 1466, 1215,
1151, 1112, cmꢀ1. ESIꢀMS m/z = 309 [M + Na]+. HRMS (ESIꢀTOF) m/z: [M + Na]+ calcd. for
C16H30NaO4 309.2042; found 309.2035.
4ꢀethoxyꢀ1ꢀ(methoxymethoxy)ꢀ2ꢀphenylbutꢀ3ꢀynꢀ2ꢀol (14g): 14g (1.16 g) was obtained from 13g42 (1g,
5.55 mmol) following general procedure A. Yield 84 %; yellow oil; Rf = 0.37 (SiO2, 20%
EtOAc/hexanes); 1H NMR (400 MHz, CDCl3): δ = 7.64 (2H, d, J = 7.3 Hz), 7.35 (2H, t, J = 7.3 Hz), 7.29
(1H, d, J = 7.3 Hz), 4.69 (2H, dd, J = 17.1, 6.5 Hz), 4.14 (2H, q, J = 7.0 Hz), 3.70 (2H, dd, J = 40.5, 10.3
Hz), 3.44 (1H, s), 3.35 (3H, s), 1.38 (3H, t, J = 7.0 Hz) ppm. 13C NMR (125 MHz, CDCl3) δ = 142.4,
ACS Paragon Plus Environment

Page 21 of 36
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
128.1, 127.7, 126.0, 97.1, 94.5, 78.1, 74.7, 72.2, 55.5, 39.8, 14.4 ppm. IR (neat): ν = 3431, 3017, 2928,
2264, 1625, 1216, 1153, 1110, 704, 669 cmꢀ1; ESIꢀMS m/z = 273 [M + Na]+. HRMS (ESIꢀTOF) m/z: [M
+ Na]+ calcd. for C14H18NaO4 273.1103; found 273.1094.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2ꢀ(4ꢀchlorophenyl)ꢀ4ꢀethoxyꢀ1ꢀ(methoxymethoxy)butꢀ3ꢀynꢀ2ꢀol (14h): 14h (708 mg) was obtained
from 13h43 (600 mg, 2.80 mmol) following general procedure A. Yield 89 %; brown oil; Rf = 0.50 (SiO2,
1
30% EtOAc/hexanes); H NMR (300 MHz, CDCl3): δ = 7.57 (2H, d, J = 8.4 Hz), 7.31 (2H, d, J = 7.4
Hz), 4.67 (2H, dd, J = 12.7, 6.6 Hz), 4.13 (2H, q, J = 6.9 Hz), 3.74 – 3.59 (3H, m), 3.34 (3H, s), 1.38
(3H,t, J = 6.9 Hz) ppm. 13C NMR (75 MHz, CDCl3) δ = 141.0, 133.4, 128.0, 127.4, 97.0, 94.5, 77.8, 74.7,
71.7, 55.4, 39.4, 14.3 ppm. IR (neat): ν = 3472, 2966, 2234, 1464, 1312, 1252, 1178, 712 cmꢀ1; ESIꢀMS
m/z = 307[M + Na]+. HRMS (ESIꢀTOF) m/z: [M + Na]+ calcd. for C14H17NaClO4 307.0713; found
;307.0708.
4ꢀethoxyꢀ2ꢀ(4ꢀfluorophenyl)ꢀ1ꢀ(methoxymethoxy)butꢀ3ꢀynꢀ2ꢀol (14i): 14i (595 mg) was obtained from
13i43 (500 mg, 2.52 mmol) following general procedure A. Yield 88 %; yellow oil; Rf = 0.52 (SiO2, 30%
EtOAc/hexanes); 1H NMR (300 MHz, CDCl3): δ = 7.63 (1H, d, J = 5.4 Hz), 7.61 (1H, d, J = 5.4 Hz), 7.02
(2H, t, J = 8.6 Hz), 4.69 (2H, dd, J = 16.1, 6.6 Hz), 4.14 (2H, q, J = 7.0 Hz), 3.67 (2H, dd, J = 42.7, 10.3
Hz), 3.56 (1H, s), 3.53 (3H, s), 1.39 (3H, t, J = 7.0 Hz) ppm. 13C NMR (75 MHz, CDCl3) δ = 163.6,
161.2, 138.3, 127.9, 127.8, 114.9, 114.7, 97.1, 94.6, 78.1, 74.8, 71.9, 55.6, 39.6, 14.8 ppm. IR (neat): ν =
3466, 2968, 2242, 1502, 1379, 1312, 1245, 1136,1012 cmꢀ1; ESIꢀMS m/z = xxx [M + H]+. HRMS (ESIꢀ
TOF) m/z: [M + H]+ calcd. for C14H18FO4 269.1189; found 269.1180
4ꢀethoxyꢀ1ꢀ(methoxymethoxy)ꢀ2ꢀpꢀtolylbutꢀ3ꢀynꢀ2ꢀol (14j): 14j (591 mg) was obtained from 13j43 (500
mg, 2.57 mmol) following general procedure A. Yield 87 %; brown oil; Rf = 0.47 (SiO2, 20%
1
EtOAc/hexanes); H NMR (400 MHz, CDCl3): δ = 7.52 (2H, d, J = 7.9 Hz), 7.15 (2H, d, J = 7.9 Hz),
4.68 (2H, dd, J = 16.4, 6.5 Hz), 4.13 (2H, q, J = 7.0 Hz), 3.68 (2H, dd, J = 38.5, 10.3 Hz), 3.41 (1H, s),
13
3.36 (3H, s), 2.34 (3H, s), 1.38 (3H, t, J = 7.0 Hz) ppm. C NMR (100 MHz, CDCl3) δ = 139.5, 137.3,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 22 of 36
1
2
3
4
5
6
7
8
128.7, 125.8, 97.0, 94.3, 78.0, 74.6, 72.0, 55.4, 39.9, 21.0, 14.4 ppm. IR (neat): ν = 3426, 2930, 2263,
1613, 1450, 1383, 1216, 1153, 818, 757, 667 cmꢀ1. HRMS (ESIꢀTOF) m/z: [M + Na]+ calcd. C15H21NaO4
287.1259; found 287.1250.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2ꢀ(2,4ꢀdimethylphenyl)ꢀ4ꢀethoxyꢀ1ꢀ(methoxymethoxy)butꢀ3ꢀynꢀ2ꢀol (14k): A mixture of hydroxy 2,4ꢀ
dimethylꢀ2'ꢀhydroxyacetophenone25 (473 mg, 2.88 mmol) and DIPEA (558 mg, 4.32 mmol) in CH2Cl2 (6
o
mL) was added MOMCl (300 mg, 3.74 mmol) at 0 C and stirred the contents at room temperature over
the night. After diluting with water, the mixture was extracted with CH2Cl2 (2x8 mL) and the combined
organic layers were washed with brine (6 mL) and dried over Na2SO4. After removing the solvent in
vacuo, the crude product was filtered through a silica bed using 20% EtOAc/hexane. The product 13k was
as such used (considering as 100% yield) in the next step without further purification and analysis.
14k (600 mg) was obtained from 13k (600 mg, 2.88 mmol) following general procedure A. Combined
1
yield 75 %; brown oil; Rf = 0.45 (SiO2, 20% EtOAc/hexanes); H NMR (400 MHz, CDCl3): δ = 7.56
(1H, d, J = 8.5 Hz), 6.98 (2H, d, J = 6.8 Hz), 4.72 (2H, dd, J = 17.3, 6.5 Hz), 4.10 (2H, q, J = 6.9 Hz),
3.85 (2H, dd, J = 24.1, 10.3 Hz), 3.38 (3H, s), 2.58 (3H, s), 2.29 (3H, s), 1.35 (3H, t, J = 6.9 Hz) ppm. 13C
NMR (100 MHz, CDCl3) δ = 137.2, 136.5, 135.8, 133.0, 126.3, 126.2, 97.1, 94.5, 75.3, 74.5, 71.6, 55.5,
39.8, 21.3, 20.8, 14.4 ppm. IR (neat): ν = 3412, 3017, 2929, 2264, 1614, 1442, 1384, 1216, 1151,926,756
cmꢀ1; ESIꢀMS m/z = 301 [M + Na]+. HRMS (ESIꢀTOF) m/z: [M + Na]+ calcd. for C16H22NaO4 301.1416;
found 301.1409.
4ꢀethoxyꢀ2ꢀ(furanꢀ2ꢀyl)ꢀ1ꢀ(methoxymethoxy)butꢀ3ꢀynꢀ2ꢀol (14l): A mixture of 1ꢀ(furanꢀ2ꢀyl)ꢀ2ꢀ
hydroxyethanone44 (370 mg, 2.94 mmol) and DIPEA (569 mg, 4.41 mmol) in CH2Cl2 (5 mL) was added
o
MOMCl (305 mg, 3.82 mmol) at 0 C and stirred the contents at room temperature over the night. After
diluting with water, the mixture was extracted with CH2Cl2 (2x6 mL) and the combined organic layers
were washed with brine (5 mL) and dried over Na2SO4. After removing the solvent in vacuo, the crude
ACS Paragon Plus Environment

Page 23 of 36
The Journal of Organic Chemistry
1
2
3
4
product was filtered through a silica bed using 20% EtOAc/hexane. The product 13l was as such used
5
6
(considering as 100% yield) in the next step without further purification and analysis.
7
8
9
14l (444 mg) was obtained from 13l (500 mg, 2.94 mmol) following general procedure A. Combined
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
yield 63 %; brown oil; Rf = 0.38 (SiO2, 20% EtOAc/hexanes); H NMR (300 MHz, CDCl3): δ = 7.28 –
7.18 (2H, m), 6.97 (1H, t, J = 4.3 Hz), 4.72 (2H, dd, J = 9.9, 6.6 Hz), 4.17 (2H, q, J = 7.0 Hz), 3.86 (1H,
s), 3.82 – 3.77 (2H, m), 3.40 (3H, s), 1.41 (3H, t, J = 7.0 Hz) ppm. 13C NMR (100 MHz, CDCl3) δ =
147.2, 126.5, 125.1, 124.6, 97.1, 94.2, 78.0, 74.8, 69.9, 55.6, 39.4, 14.4 ppm. IR (neat): ν = 3412, 3019,
2929, 2400, 1618, 1264, 1215, 1152, 928, 757, 669 cmꢀ1. HRMS (ESI): (ESIꢀTOF) m/z: [M + Na]+ calcd.
for C12H16NaO5 263.0895; found 263.0889.
General procedure for the synthesis of 3ꢀiodocoumarins 9aꢀp from 5aꢀf or 6aꢀp, and the
synthesis of 3ꢀiodobutenolides 15aꢀl from 14aꢀl. Iodine (657 mg 2.6 mmol) was added to a solution
of substrate (2 mmol of 5aꢀf or 6aꢀp or 11 or 14aꢀl) in 8 mL of DCE (5aꢀf) or CH2Cl2 (6aꢀp) or
toluene (11 or 14aꢀl). The resulting mixture was stirred at room temperature (reflux temperature for
5a) till the reaction was complete as indicated by TLC (for time see table 2). Then the reaction was
quenched by adding saturated aq. solution of Na2S2O3 and extracted with DCM (for 5aꢀf and 6aꢀp) or
EtOAc (for 11 and 14aꢀl). The combined organics were washed with brine, and dried over anhydrous
Na2SO4. After removal of solvent under reduced pressure the crude was purified by column
chromatography with silica gel using mixture of ethyl acetate and hexanes.
3ꢀiodoꢀ2Hꢀchromenꢀ2ꢀone (9a):10 Yield 72% (390 mg); white solid; mp 86ꢀ88 C; Rf = 0.50
o
(SiO2, 20% EtOAc/hexanes); 1H NMR (300 MHz, CDCl3): δ 8.36 (s, 1 H), 7.57 (t, 1 H, J = 7.7
13
Hz), 7.44 (d, 1H, J = 7.1 Hz ), 7.34ꢀ7.30 (m, 2H) ppm. C NMR (75 MHz, CDCl3): δ 157.5,
154.5, 152.2, 132.4, 126.9, 124.8, 120.2, 116.9, 86.3 ppm. IR (KBr): ν = 3021, 1606, 1127, 952,
669 cmꢀ1. ESIꢀMS m/z = 272.7 [M + H]+.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 24 of 36
1
2
3ꢀiodoꢀ7methoxyꢀ2Hꢀchromenꢀ2ꢀone (9b):11e Yield 85% (511 mg); brown solid; mp 150ꢀ153
oC; Rf = 0.45 (SiO2, 20% EtOAc/hexanes); 1H NMR (300 MHz, CDCl3): δ 8.26 (s, 1H), 7.32 (d, 1H,
J = 8.3 Hz), 6.85 (dd, 1H, J = 8.3, 2.3 Hz), 6.80 (d, 1H, J = 2.3 Hz), 3.87 (s, 3H) ppm. 13C NMR
(50 MHz, CDCl3): δ 163.3, 157.8, 155.9, 152.1, 127.9, 114.1, 113.0, 100.8, 81.2, 56.0 ppm. IR
(KBr): ν = 3020, 1617, 923, 669 cmꢀ1. ESIꢀMS m/z = 302.7 [M + H]+.
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
o
6ꢀchloroꢀ3ꢀiodoꢀ2Hꢀchromenꢀ2ꢀone (9c): Yield 78% (xx 475); yellow solid; mp 103ꢀ105 C; Rf
= 0.55 (SiO2, 20% EtOAc/hexanes); 1H NMR (300 MHz, CDCl3): δ 8.30 (s, 1H), 7.51 (dd, 1H, J =
8.8, 2.2 Hz), 7.42 (d, 1H, J = 2.2 Hz), 7.27 (d, 1H, J = 8.8 Hz) ppm. 13C NMR (75 MHz, CDCl3):
δ 156.9, 152.4, 150.9, 132.2, 130.1, 126.0, 121.0, 118.3, 88.1 ppm. IR (KBr): ν = 3021, 1605,
1083, 926, 669 cmꢀ1. ESIꢀMS m/z = 306.7 [M + H]+. HRMS (ESIꢀTOF): calcd. for C9H4ClIO2
[M + H]+: 306.9023; found: 306.9026.
o
3ꢀiodoꢀ4ꢀmethylꢀ2Hꢀchromenꢀ2ꢀone (9d): Yield 82% (467 mg); yellow solid; mp 88ꢀ90 C; Rf
= 0.55 (SiO2, 20% EtOAc/hexanes); 1H NMR (300 MHz, CDCl3): δ 7.70 (d, 1H, J = 7.7 Hz), 7.58
(t, 1H, J = 7.4 Hz), 7.36 (d, 1H, J = 7.4 Hz), 7.30 (t, 1H, J = 7.7 Hz), 2.72 (s, 3H) ppm. 13C NMR
(75 MHz, CDCl3): δ 157.7, 156.6, 152.6, 132.3, 125.2, 124.8, 119.4, 117.0, 93.2, 25.5 ppm. IR
(KBr): ν = 3019, 2400, 1598, 929, 624 cmꢀ1. ESIꢀMS m/z = 286.7 [M + H]+. HRMS (ESIꢀTOF):
calcd. for C10H8IO2 [M + H]+: 286.9569; found: 286.9565.
3ꢀiodoꢀ4ꢀphenylꢀ2Hꢀchromenꢀ2ꢀone (9e): Yield 78% (541 mg); yellow solid; mp 94ꢀ96 oC; Rf =
0.60 (SiO2, 20% EtOAc/hexanes); 1H NMR (300 MHz, CDCl3): δ 7.58ꢀ7.53 (m, 4H,) 7.39 (d, 1H, J
= 7.7 Hz), 7.24 (d, 2H, J = 6.6 Hz), 7.15 (t, 1H, J = 7.7 Hz), 7.05 (d, 1H, J = 7.7 Hz) ppm. 13C
NMR (75 MHz, CDCl3): δ 160.6, 157.7, 153.0, 138.8, 132.3, 129.2, 128.8, 127.8, 127.7, 124.5,
ACS Paragon Plus Environment

Page 25 of 36
The Journal of Organic Chemistry
1
2
119.9, 116.5, 92.2 ppm. IR (KBr) ν = 3021, 1601, 1333, 928, 669 cmꢀ1. HRMS (MALDIꢀ
3
4
5
6
TOF/TOF): calcd. for C15H10IO2 [M + H]+ : 348.9725; found: 348.9717.
7
8
9
3ꢀiodoꢀ7ꢀmethoxyꢀ4ꢀphenylꢀ2Hꢀchromenꢀ2ꢀone (9f): Yield 80% (603 mg); yellow solid; mp
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
o
110ꢀ112 C; Rf = 0.50 (SiO2, 20% EtOAc/hexanes); 1H NMR (300 MHz, CDCl3): = 7.56ꢀ7.54 (m,
3H), 7.25ꢀ7.21(m, 2H), 6.94 (d, 1H, J = 8.9 Hz), 6.88 (d, 1H, J = 2.6 Hz), 6.70 (dd, 1H, J = 8.9,
13
2.6 Hz) 3.87 (s, 3H) ppm. C NMR (75 MHz, CDCl3): δ 163.2, 160.8, 158.4, 155.0, 139.3,
129.2, 129.0, 128.9, 127.9, 114.0, 112.8, 100.5, 87.6, 55.9, 53.5 ppm. IR (KBr): ν = 3021, 2401,
1611, 954, 669 cmꢀ1. ESIꢀMS m/z = 378.4 [M + H]+. HRMS (ESIꢀTOF): calcd. for C16H12IO3 [M
+ H]+: 378.9831; found: 378.9824.
3ꢀiodoꢀ8ꢀmethylꢀ2Hꢀchromenꢀ2ꢀone (9g): Yield 71% (404 mg); colorless gum; Rf = 0.55 (SiO2,
20% EtOAc/hexanes); 1H NMR (300 MHz, CDCl3): δ 8.34 (s, 1H), 7.41 (d, 1H, J = 7.1 Hz), 7.25
13
(d, 1H, J = 6.3 Hz), 7.18 (t, 1H, J = 7.5 Hz), 2.45 (s, 3H) ppm. C NMR (75 MHz, CDCl3): δ
157.6, 152.5, 152.3, 133.6, 126.3, 124.6, 124.4, 119.9, 85.9, 15.3 ppm. IR (KBr): ν = 2963, 1599,
1131, 943, 669 cmꢀ1. ESIꢀMS m/z = 286.5 [M + H]+. HRMS (ESIꢀTOF): calcd. for C10H8IO2 [M
+ H]+: 286.9569; found:286.9565.
o
8ꢀethylꢀ3ꢀiodoꢀ2Hꢀchromenꢀ2ꢀone (9h): Yield 74% (442 mg); white solid; mp 80ꢀ82 C; Rf =
0.60 (SiO2, 20% EtOAc/hexanes); 1H NMR (300 MHz, CDCl3): δ 8.34 (s, 1H), 7.43 (dd, 1H, J =
7.5, 1.2 Hz), 7.27 (d, 1H, J = 7.5 Hz), 7.21 (t, 1H, J = 7.5 Hz), 2.88 (q, 2H, J = 7.5 Hz), 1.28 (t,
13
3H, J = 7.6 Hz) ppm. C NMR (75 MHz, CDCl3): δ 157.6, 152.6, 152.0, 132.4, 132.1, 128.8,
124.6, 120.1, 85.9, 22.4, 14.1 ppm. IR (KBr): ν = 3019, 1597, 1046, 929, 625 cmꢀ1. ESIꢀMS m/z
= 300.7 [M + H]+. HRMS (ESIꢀTOF): calcd. for C11H10IO2 [M + H]+: 300.9725; found: 300.9720.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 26 of 36
1
2
o
3
3ꢀiodoꢀ8ꢀisopropylꢀ2Hꢀchromenꢀ2ꢀone (9i): Yield 70% (438 mg); white solid; mp 131ꢀ133 C;
Rf = 0.55 (SiO2, 20% EtOAc/hexanes); 1H NMR (300 MHz, CDCl3): δ 8.35 (s, 1H), 7.49 (t, 1H, J =
4.59 Hz), 7.24 (d, 2H, J = 4.5 Hz ), 3.61 (sp, 1H, J = 6.9 Hz), 1.29 (d, 6H, J = 6.9 Hz) ppm. 13C
NMR (75 MHz, CDCl3): δ 157.6, 152.8, 151.3, 136.8, 129.5, 124.7, 124.6, 120.1, 85.7, 26.5,
22.6 ppm. IR (KBr): ν = 3020, 1595, 1131, 942, 669 cmꢀ1. HRMS (ESIꢀTOF): calcd. for
C12H12IO2 [M + H]+: 314.9882; found: 314.9884.
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
8ꢀtertꢀbutylꢀ3ꢀiodoꢀ2Hꢀchromenꢀ2ꢀone (9j): Yield 58% (380 mg); colorless gum; Rf = 0.50
(SiO2, 20% EtOAc/hexanes); 1H NMR (300 MHz, CDCl3): δ 8.34 (s, 1H), 7.56 (d, 1H, J = 7.4 Hz),
7.28 (d, 1H, J = 7.7 Hz), 7.21 (t, 1H, J = 7.4 Hz), 1.49 (s, 9H) ppm. 13C NMR (75 MHz, CDCl3):
δ 157.1, 153.1, 152.8, 138.3, 130.0, 125.4, 124.4, 120.8, 85.3, 53.5, 35.1 ppm. IR (KBr): ν =
2963, 1410, 1095, 931, 670 cmꢀ1. ESIꢀMS m/z = 329.2 [M + H]+. HRMS (ESIꢀTOF): calcd. for
C13H14IO2 [M + H]+: 329.0038; found: 329.0036.
8ꢀbromoꢀ6ꢀchloroꢀ3ꢀiodoꢀ2Hꢀchromenꢀ2ꢀone (9k): Yield 70% (536 mg); white solid; mp 174ꢀ
o
176 C; Rf = 0.60 (SiO2, 20% EtOAc/hexanes); 1H NMR (300 MHz, [D6]DMSO): δ 8.74 (s, 1H),
13
8.07 (d, 1H, J = 2.3 Hz), 7.81 (d, 1H, J = 2.3 Hz) ppm. C NMR (75 MHz, [D6]DMSO): δ
156.3, 150.7, 149.1, 133.9, 128.6, 126.0, 122.1, 109.9, 89.9 ppm. IR (KBr): ν = 3019, 1600,
1124, 853, 626 cmꢀ1. HRMS (MALDIꢀTOF/TOF): calcd. for C9H4BrClIO2 [M + H]+ : 384.8128;
found: 384.8138.
3ꢀiodoꢀ6ꢀnitroꢀ2Hꢀchromenꢀ2ꢀone (9l): Yield 52% (328 mg); colorless gum; Rf = 0.40 (SiO2,
30% EtOAc/hexanes); 1H NMR (300 MHz, DMSOꢀd6): δ 8.92 (s, 1H), 8.6 (d, 1H, J = 2.7 Hz), 8.4
(dd, 1H, J = 9.2, 2.7 Hz), 7.6 (d, 1H, J = 9.2 Hz) ppm. 13C NMR (75 MHz, [D6]DMSO): δ 157.5,
156.9, 151.7, 144.0, 127.1, 123.6, 120.8, 118.3, 90.4 ppm. IR (KBr): ν = 2928, 1613, 1346, 930,
ACS Paragon Plus Environment

Page 27 of 36
The Journal of Organic Chemistry
1
2
624 cmꢀ1. ESIꢀMS m/z = 317.3 [M + H]+. HRMS (ESIꢀTOF): calcd. for C9H4INO4 [M + H]+:
317.9263; found: 317.9255.
3
4
5
6
7
8
9
o
3ꢀiodoꢀ6ꢀphenylꢀ2Hꢀchromenꢀ2ꢀone (9m): Yield 85% (589 mg); yellow solid; mp 155ꢀ157 C;
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Rf = 0.55 (SiO2, 20% EtOAc/hexanes); 1H NMR (300 MHz, CDCl3): δ 8.42 (s,1H), 7.78 (dd, 1H, J
= 8.5, 2.0 Hz), 7.60 (d, 1H, J = 2.0 Hz), 7.56 (d, 1H, J = 8.5 Hz), 7.7 (t, 2H, J = 7.0 Hz), 7.41 (t,
13
3H, J = 8.5 Hz ) ppm. C NMR (75 MHz, CDCl3): δ 157.5, 153.4, 152.3, 139.1, 138.2, 131.3,
129.2, 128.1, 127.1, 125.0, 120.4, 117.3, 86.8 ppm. IR (KBr): ν = 3021, 2401, 1611, 954, 669
cmꢀ1. ESIꢀMS m/z = 348.5 [M + H]+. HRMS (ESIꢀTOF): calcd. for C15H10IO2 [M + H]+:
348.9725; found: 348.9733.
2ꢀiodoꢀ3Hꢀbenzo[f]chromenꢀ3ꢀone (9n): Yield 65% (417 mg); white solid; mp 148ꢀ150 oC; Rf =
0.50 (SiO2, 20% EtOAc/hexanes); 1H NMR (300 MHz, CDCl3): δ 9.09 (s, 1H), 8.20 (d, 1H, J = 8.3
Hz), 8.02 (d, 1H, J = 8.9 Hz), 7.92 (d, 1H, J = 8.3 Hz), 7.71 (t, 1H, J = 7.3 Hz), 7.59 (t, 1H, J =
7.3 Hz), 7.44 (d, 1H, J = 8.9 Hz) ppm. 13C NMR (75 MHz, CDCl3): δ 157.8, 154.0, 148.2, 133.8,
130.4, 129.1, 128.7, 127.9, 126.5, 121.3, 116.8, 114.4, 85.5 ppm. IR (KBr): ν = 3019, 1551, 928,
669, 625 cmꢀ1. ESIꢀMS m/z = 322.5 [M + H]+. HRMS (ESIꢀTOF): calcd. for C13H8IO2 [M + H]+:
322.9569; found: 322.9565.
3ꢀiodoꢀ4,7ꢀdimethylꢀ2Hꢀchromenꢀ2ꢀone (9o): Yield 80% (478 mg); yellow solid; mp 144ꢀ146
oC; Rf = 0.55 (SiO2, 20% EtOAc/hexanes); 1H NMR (300 MHz, CDCl3): δ 7.55 (d, 1H, J = 8.1 Hz),
13
7.14 (s, 1H), 7.11 (d, 1H, J = 8.1 Hz), 2.68 (s,3H), 2.43 (s, 3H) ppm. C NMR (75 MHz,
CDCl3): δ 157.8, 156.5, 152.5, 143.6, 125.9, 124.8, 116.9, 114.0, 91.4, 25.3, 21.7. ppm. IR
(KBr): ν = 3019, 2400, 1598, 929, 624 cmꢀ1. ESIꢀMS m/z = 300.7 [M + H]+. HRMS (ESIꢀTOF):
calcd. for C11H10IO2 [M + H]+: 300.9725; found: 300.9720.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 28 of 36
1
2
3ꢀiodoꢀ7ꢀmethoxyꢀ4ꢀmethylꢀ2Hꢀchromenꢀ2ꢀone (9p):11f Yield 84% (529 mg); white solid; mp
159ꢀ162 oC; Rf = 0.45 (SiO2, 20% EtOAc/hexanes); 1H NMR (300 MHz, CDCl3): δ 7.57 (d, 1H, J =
8.9 Hz), 6.85 (dd, 1H, J = 8.9, 2.5 Hz), 6.81 (d, 1H, J = 2.5 Hz), 3.88 (s, 3H), 2.65 (s, 3H) ppm.
13C NMR (75 MHz, CDCl3): δ 162.9, 157.9, 156.5, 154.1, 126.3, 113.0, 112.7, 100.4, 86.6, 55.9,
25.4 ppm. IR (KBr): ν = 3020, 1617, 923, 669 cmꢀ1. ESIꢀMS m/z = 316.6 [M + H]+. HRMS (ESIꢀ
TOF): calcd. for C11H10IO3 [M + H]+ :316.9674; found: 316.9671.
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
4ꢀiodoꢀ2ꢀoxaspiro[5.5]undecꢀ4ꢀenꢀ3ꢀone (12): Yield 85% (537 mg); colourless gum; Rf = 0.60
(SiO2, 20% EtOAc/hexanes); 1H NMR (300 MHz, CDCl3): δ 7.52 (s, 1H), 4.22 (s, 2H), 1.69ꢀ1.39
13
(m, 10H) ppm. C NMR (75 MHz, CDCl3): δ 163.3, 159.9, 87.6, 75.3, 40.1, 32.5, 25.4, 21.2
ppm. HRMS (ESIꢀTOF): calcd. for C10H13NaIO2 [M + Na]+: 314.9858; found: 314.9850.
3ꢀiodoꢀ4,5,6aꢀtetrahydroꢀ2Hꢀcyclopenta[b]furanꢀ2ꢀone (15a): Yield 85% (408 mg); colorless
gum; Rf = 0.60 (SiO2, 20% EtOAc/hexanes); 1H NMR (300 MHz, CDCl3): δ 5.07 (t, 1H, J = 7.9
13
Hz), 2.68ꢀ2.06 (m, 4H), 1.45ꢀ1.32 (m, 2H) ppm. C NMR (75 MHz, CDCl3): δ 181.6, 171.9,
86.9, 78.0, 29.57, 24.4, 22.7 ppm. IR (KBr): ν = 3021, 1605, 1272, 951, 669 cmꢀ1. ESIꢀMS m/z =
250.7 [M + H]+. HRMS (ESI): calcd. for C7H8IO2 [M + H]+ : 250.9569; found: 250.9564.
3ꢀiodoꢀ5,6,7,7aꢀtetrahydrobenzofuranꢀ2(4H)ꢀone (15b): Yield 89% (468 mg); colorless gum;
Rf = 0.60 (SiO2, 20% EtOAc/hexanes); 1H NMR (400 MHz, CDCl3): δ 4.76 (dd, 1H, J = 6.2, 5.0
Hz), 2.82 (dt, 1H, J = 14.0, 2.1 Hz), 2.48ꢀ2.43 (m, 1H), 2.27 (ddd, 1H, J = 13.6, 7.6, 6.0 Hz),
13
2.07–1.93 (m, 2H), 1.56ꢀ1.27 (m, 3H) ppm. C NMR (75 MHz, CDCl3): δ 173.9, 169.9, 83.7,
79.3, 34.3, 30.3, 26.0, 22.9 ppm. IR (KBr): ν = 3020, 1638, 1037, 669 cmꢀ1. HRMS (MALDIꢀ
TOF/TOF): calcd. for C8H10IO2 [M + H]+: 264.9725; found: 264.9731.
ACS Paragon Plus Environment

Page 29 of 36
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
3ꢀiodoꢀ4,5,6,7,8,8aꢀhexahydroꢀ2Hꢀcyclohepta[b]furanꢀ2ꢀone (15c): Yield 82% (454 mg);
colorless gum; Rf = 0.60 (SiO2, 20% EtOAc/hexanes); 1H NMR (300 MHz, CDCl3): δ 5.01 (d, 1H, J
= 6.8 Hz), 2.68ꢀ2.3 (m, 4H), 1.9–1.47 (m, 6H) ppm. 13C NMR (75 MHz, CDCl3): δ 176.4, 169.9,
86.8, 83.2, 33.5, 32.3, 29.5, 26.1, 25.1 ppm. IR (KBr): ν = 3019, 1619, 1015, 668 cmꢀ1. ESIꢀMS
m/z = 278.3 [M + H]+. HRMS (ESIꢀTOF): calcd. for C9H12IO2 [M + H]+: 278.9882; found:
278.9877.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
3ꢀiodoꢀ5,6,7,8,9,9aꢀhexahydroꢀ2Hꢀcycloocta[b]furanꢀ2ꢀone (15d): Yield 80% (467 mg);
yellow color gum; Rf = 0.60 (SiO2, 20% EtOAc/hexanes); 1H NMR (400 MHz, CDCl3): δ 5.01 (t,
1H, J = 5.2 Hz), 3.66 (s, 1H), 2.74ꢀ2.68 (m, 1H), 2.43ꢀ2.34 (m, 1H), 2.29 (t, 1H, J = 7.5 Hz),
13
2.20ꢀ2.13 (m, 1H), 2.12ꢀ2.01 (m, 1H), 1.82ꢀ1.70 (m, 3H), 1.41ꢀ1.29 (m,3H) ppm. C NMR (75
MHz, CDCl3): δ 175.3, 85.9, 84.7, 30.1, 28.6, 26.7, 26.3, 25.0, 20.7 ppm. IR (KBr): ν = 3019,
1752, 1620, 1216, 669 cmꢀ1. ESIꢀMS m/z = 293.5 [M + H]+. HRMS (ESIꢀTOF): calcd. for
C10H14IO2 [M + H]+: 293.0038; found: 293.0035.
4ꢀheptylꢀ3ꢀiodofuranꢀ2(5H)ꢀone (15e): Yield 85% (523 mg); brown oil; Rf = 0.55 (SiO2, 20%
EtOAc/hexanes); 1H NMR (300 MHz, CDCl3): δ 4.8 (s, 2H), 2.48 (t, 2H, J = 7.2 Hz), 1.4ꢀ1.24 (m,
13H) ppm. 13C NMR (100 MHz, CDCl3): δ 170.3, 169.8, 82.2, 73.2, 30.5, 30.1, 28.6, 27.8, 25.9,
21.5, 13.0 ppm. IR (KBr): ν = 3018, 2860, 1358, 1047, 668 cmꢀ1. ESIꢀMS m/z = 309.1 [M + H]+.
HRMS (ESIꢀTOF): calcd. for C11H18IO2 [M + H]+: 309.0351; found: 309.0345.
3ꢀiodoꢀ4ꢀoctylfuranꢀ2(5H)ꢀone (15f): Yield 85% (547 mg); brown oil; Rf = 0.55 (SiO2, 20%
EtOAc/hexanes); 1H NMR (400 MHz, CDCl3): δ 4.80 (s, 2H), 2.47 (t, 2H, J = 7.6 Hz), 1.57ꢀ1.51
(m, 2H), 1.40ꢀ1.20 (m, 13H) ppm. 13C NMR (75 MHz, CDCl3): δ 171.5, 170.9, 83.2, 77.5, 31.7,
31.1, 29.3, 29.1, 29.0, 26.9, 22.6, 14.1 ppm. IR (KBr): ν = 3019, 1625, 1143, 668 cmꢀ1. ESIꢀMS
ACS Paragon Plus Environment