Stereoselective access to highly substituted vinyl ethers via trans-difunctionalization of alkynes with alcohols and iodine(iii) electrophile

Article abstract of DOI:10.1021/jacs.0c04140

A method for the regio- and stereoselective synthesis of highly substituted vinyl ethers via trans-1,2-difunctionalization of alkynes with a cyclic λ³-iodane electrophile (benziodoxole triflate) and alcohols is reported. The reaction tolerates a variety of internal and terminal alkynes as well as various alcohols, affording β-λ³-iodanyl vinyl ethers in good yields with high regio- and stereoselectivities. The benziodoxole moiety of the products can be used as a versatile linchpin for the synthesis of structurally diverse vinyl ethers that are difficult to access by other means.

Full text of DOI:10.1021/jacs.0c04140

Subscriber access provided by UNIV OF NEW ENGLAND ARMIDALE
Communication
Stereoselective Access to Highly Substituted Vinyl Ethers via trans-
Difunctionalization of Alkynes with Alcohols and Iodine(III) Electrophile
Wei Ding, Jinkui Chai, Chen Wang, Junliang Wu, and Naohiko Yoshikai
J. Am. Chem. Soc., Just Accepted Manuscript • Publication Date (Web): 03 May 2020
Downloaded from pubs.acs.org on May 3, 2020
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 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 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.
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 7
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
Stereoselective Access to Highly Substituted Vinyl Ethers via trans-
Difunctionalization of Alkynes with Alcohols and Iodine(III) Electrophile
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
Wei Ding,†,§ Jinkui Chai,†,‡,§ Chen Wang,†,# Junliang Wu,*,‡ and Naohiko Yoshikai*,†
†Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological
University, Singapore 637371, Singapore
‡College of Chemistry, Henan Institute of Advanced Technology, Zhengzhou University, Zhengzhou 450001, P.R. China
#Zhejiang Key Laboratory of Alternative Technologies for Fine Chemical Process, Shaoxing University, Shaoxing 312000,
P.R. China
Supporting Information Placeholder
1b),13-15 while this vinyl ether synthesis requires
ABSTRACT: A method for the regio- and stereoselective
individual preparation of each iodane reagent and does
not allow access to tetrasubstituted derivatives.
synthesis of highly substituted vinyl ethers via trans-1,2-
difunctionalization of alkynes with a cyclic λ3-iodane
In contrast to the above known approaches,
electrophile (benziodoxole triflate) and alcohols is
stereoselective addition of an alcohol to an electrophile
reported. The reaction tolerates a variety of internal and
(E+)-activated alkyne appears to offer an attractive
terminal alkynes as well as various alcohols, affording
approach to a highly substituted vinyl ethers using a
single reagent, provided that the group “E” can be used
β-λ3-iodanyl vinyl ethers in good yields with high regio-
and stereoselectivities. The benziodoxole moiety of the
as a versatile handle for subsequent transformations.
products can be used as a versatile linchpin for the
However, no such transformation has been reported for
synthesis of structurally diverse vinyl ethers that are
unactivated terminal and internal alkynes using common
difficult to access by other means.
halogen electrophiles such as Br2, I2, and N-
halosuccinimide.16 In this respect, our attention was
drawn to trivalent iodine species as potentially viable
Vinyl ethers are useful electron-rich olefins in organic
synthesis as well as in polymer chemistry.1 They have
been utilized for valuable C–C bond forming reactions
such as cycloaddition and Claisen rearrangement,2 and
continue to serve as workhorses for new synthetic
methodology development.3 A variety of methods for
the synthesis of vinyl ethers have been developed,4
including hydroalkoxylation of alkynes,5 C–O coupling
between alkenyl halides or -boronates and alcohols,6
acid- or metal-catalyzed vinyl ether exchange,7
isomerization of allyl ethers,8 and Horner–Wittig
olefination, among others (Scheme 1a).9 Nevertheless,
the stereoselective synthesis of multisubstituted vinyl
electrophiles. Thus, iodonium reagents containing
triflate or fluoride have been shown to promote trans-
difunctionalization of alkynes with I(III) and the internal
nucleophile (Scheme 1c),17-20 while conversion of the
resulting vinyl triflate into the corresponding ethers is
nontrivial. Meanwhile, our group reported Zhdankin’s
benziodoxole triflate (BXT; 1)21 as an I(III) electrophile
to promote “iodo(III)cyclization” of alkynes bearing
nucleophilic moieties, affording heteroarenes and
polycyclic arenes bearing a synthetically versatile
benziodoxole group.22,23 Herein, we report a method to
stereoselectively synthesize highly substituted vinyl
ethers via trans-1,2-difunctionalization of alkynes using
BXT and alcohols (Scheme 1d). The method is
applicable to a variety of internal and terminal alkynes
as well as various alcohols, affording the corresponding
β-λ3-iodanyl vinyl ethers in good yields under mild and
metal-free conditions. The λ3-iodanyl group of the
products can be readily utilized for the access to
structurally diverse vinyl ethers that are difficult to
synthesize by existing methods.
ethers remains
a
formidable challenge,10 which
constitutes a major barrier for their applications with
stereocontrol of tertiary and quaternary centers. The
hydroalkoxylation is known for long time11 and remains
a subject of active research in homogeneous catalysis,12
but is mostly limited to terminal alkynes.
Alkynylbenziodoxolones have been shown to undergo
stereoselective addition of phenols to afford vinyl ethers
bearing a versatile benziodoxolone moiety (Scheme
Scheme 1. Synthetic Approaches to Vinyl Ethers
ACS Paragon Plus Environment

Journal of the American Chemical Society
acid,21 which is rather hygroscopic, failed to promote the
Page 2 of 7
(a) Common approaches
R1
R1’
1
2
3
4
5
6
7
present iodo(III)etherification.
R1
OR2
Scheme 2. Iodo(III)etherification of 1-Phenyl-1-
butyne (2a) with 1 and Alcohola
R2OH
+
R2OH
+
OR3
X
base
Cu, Pd
acid, [M]
R1
+
R1
–
base, [M]
R3P
+
R1
R2OH
+
OR2
O
OR2
8
9
Problem:
No general approach to stereodefined tri/tetra-substituted vinyl ethers
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
(b) Addition to ethynylbenziodoxolone (ref 13)
R
O
I
R
base
+
ArOH
I
OAr
O
O
O
(c) Alkyne trans-difunctionalization by I(III) and triflate or fluoride (ref 17, 18)
Ar
X
I+
R2
X(Ar)I
“ArIX2”
R1
R2
R1
R2
X–
R1
X = OTf, F
X
aThe yields were determined by 19F NMR.
(d) This work: Alkyne trans-difunctionalization by I(III) and alcohol
R1 R2
With the optimized reaction conditions in hand, we
explored the scope of the “iodo(III)etherification” of
internal alkynes (Scheme 3). A wide variety of aryl alkyl
alkynes participated in the reaction with MeOH as
solvent to afford the corresponding β-iodanyl vinyl
ethers 4aa–4la in moderate to excellent yields with
exclusive trans-selectivity. The reaction of 1-phenyl-1-
propyne could be performed on a gram scale (3 mmol)
to afford 4ba without compromising the yield (86%).
Both electron-donating groups such as methoxy (4ea)
and methyl (4fa) and electron-withdrawing groups such
as ester (4ga), chloride (4ha), bromide (4ia), and
trifluoromethyl (4ja) could be tolerated on the aryl
group. The reaction became sluggish with 2-methyl
group presumably due to the steric hindrance (see 4ka).
A thienyl group could be well tolerated (see 4la).
Dialkyl alkynes also proved to be amenable to the
iodo(III)etherification reaction (see 4ma–4sa). Notably,
F3C
F3C
O
+
R4
R1
R2
TfO
I
O
R2
I
CF3
CF3
BXT (1)
rt
OR3
R1
OR3
60 examples
32-98% yields
+
R3OH
■ Broad scope of alkynes and alcohols
■ High regio- and stereoselectivity
■ Access to previously inaccessible vinyl ethers
Using 1-phenyl-1-butyne (2a, 0.1 mmol) as a model
alkyne, the desired difunctionalization proceeded
smoothly using 2 equiv of 1 in MeOH (3a, 0.5 mL) at
room temperature to afford the β-λ3-iodanyl vinyl ether
4aa in 98% yield with exclusive trans selectivity
(Scheme 2a). The product 4aa could be purified by
routine silica gel chromatography and proved to be
stable on exposure to open air at least for one month
without decomposition. The difunctionalization can also
be achieved using alcohol as reagent. Thus, the reaction
of 1 (2 equiv), 2a, and benzyl alcohol (3b, 5 equiv) took
place in MeCN to afford the desired product 4ab in 87%
yield. Et2O could be used in place of MeCN with
slightly decreased yield, while other solvents such as
THF, DCE, and toluene retarded the reaction. Thus, we
defined the reaction conditions using alcohol as solvent
and reagent as conditions A and B, respectively. For
both the conditions, the desired products could be
obtained in reasonable yields (68–78%) using 1–1.2
equiv of 1 (see Tables S1–S3 for details). The addition
of inorganic bases such as carbonate salts caused slight
or large negative effect, while amine bases completely
shut down the reaction. Note that 1 is non-hygroscopic,
easy to synthesize on a decagram scale and storable at
room temperature for more than a month. On the other
hand, analogous reagent derived from 2-iodobenzoic
unsymmetrical
dialkyl
alkynes
bearing
methyl/secondary alkyl groups or methyl/alkoxymethyl
groups afforded single regioisomers as a result of
methoxylation of the less hindered acetylenic carbon
(see 4na–4qa). On the other hand, those bearing
methyl/primary alkyl groups displayed modest
regioselectivity (see 4ra and 4sa). The structures of the
products 4ba and 4na were unambiguously determined
by X-ray crystallographic analysis.24 Note that diaryl
alkynes such as diphenylacetylene did not participate in
the reaction and were largely recovered.
Next, the iodo(III)etherification reactions of 2a with
various alcohols were examined. The reaction of 2a with
CD3OD as reagent produced the product 4aa-d3 in 90%
yield. A variety of primary and secondary alcohols took
part in the present reaction to afford the corresponding
vinyl ethers 4ab–4ao in moderate to good yields. The
ACS Paragon Plus Environment

Page 3 of 7
Journal of the American Chemical Society
Conditions A
R3OH (3; solvent)
rt, 24 h
reaction tolerated functional groups such as hydroxy
(4ag), methoxy (4ah), cyano (4ai), bromo (4aj and 4ak),
silyl (4al), allyl (4am), and carbonyl (4ao) groups on the
alcohol substrate, while conditions A using alcohol as
solvent gave higher yields for some functionalized
alcohols (see 4ag–4ak). Naturally occurring alcohols
such as (-)-menthol and androsterone were also
amenable to the present iodo(III)etherification (see the
F3C
F3C
O
TfO
I
O
1
2
3
4
5
6
7
8
CF3
CF3
R2
R1
R2
+
I
Conditions B
R3OH (3; 5 equiv)
MeCN, rt, 24 h
2
R1
OR3
1
4
R
BX
R
Ph
OMe
BX
Bu
products
4an
and
4ao).
Less
nucleophilic
4aa (R = Et), 98% (A)
4ba (R = Me), 89% (86%)b (A)
4ca (R = Cy), 91% (A)
4da (R = (CH2)5CONMe2), 87% (A)
OMe
9
trifluoroethanol afforded the desired product 4ap in
good yield using toluene as the solvent, while tertiary
alcohols such as t-BuOH failed to participate in the
reaction. When the yield of the iodo(III)etherification
product was low, the alkyne was typically recovered but
1 was largely decomposed to the 2-iodobenzyl alcohol
derivative.
4ea (R = OMe), 78% (A)
4fa (R = Me), 91% (A)
4ga (R = CO2Et), 62% (A)
4ha (R = Cl), 92% (A)
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
4ba (X-ray)
S
R
BX
Bu
BX
nC6H13 OMe
4ka, 32% (A)
BX
Me
OMe
Bu
OMe
4ia (R = Br), 66% (A)
4ja (R = CF3), 82% (A)
4la, 93% (A)
Attempts on using nucleophiles other than aliphatic
alcohols, such as phenols, carboxamides, sulfonamides,
and thiols, were largely futile (Figure S1), and in such
BX
Pr
Pr
BX
R
Me
OMe
OMe
cases the decomposition of
1
was observed.
4ma, 92% (A)
4na (R = iPr), 85% (A)
4oa (R = Cy), 82% (A)
4na (X-ray)
Me
OMe
Nonetheless, 2-hydroxypyridine, acetic acid, and
pyrazole took part in the present difunctionalization to
afford the desired products 4aq–4as in good yields.
BX
Me
BX
Me
BX
RO
OMe
OMe
Scheme 3. Iodo(III)etherification of Internal
Alkynesa
4pa (R = Ph), 74% (A)
4qa (R = Bn), 82% (A)
4ra, 82% (A)
4sa, 92% (A)
r.r. = 3.8:1c
r.r. = 1.8:1c
BX
Et
Ph
4aa-d3 (R = CD3), 90% (B)
BX
Et
Ph
4ab (R = Bn), 85% (B)
4ac (R = Et), 94% (A)
4ad (R = iPr), 91% (A)
4ae (R = Bu), 69% (A)
4af (R = Cy), 81% (B)
O
R
OR
4ag (R = OH), 89% (A); 65% (B)
4ah (R = OMe), 86% (A); 70% (B)
4ai (R = CN), 91% (A); 46% (B)
4aj (R = Br), 85% (A); 42% (B)
BX
Et
Ph
O
BX
Ph
O
BX
Et
Ph
O
Et
Br
4ak, 77% (A); 55% (B)
SiMe3
4al, 90% (B)
4am, 45% (B)d
BX
Et
Ph
H
BX
Et
Ph
O
H
H
BX
Et
Ph
O
H
Me
OCH2CF3
Me
O
4ap, 83% (B)e
4an, 91% (B)
from (-)-menthol
4ao, 57% (B)
from androsterone
BX
Et
Ph
N
BX
Et
Ph
O
BX
Et
Ph
N
OAc
N
4aq, 89% (B)
4ar, 81% (A)
4as, 80% (B)f
aThe reaction was performed on a 0.1 mmol scale. The
symbol BX in the product formula refers to the
benziodoxole moiety. bThe yield for a 3 mmol-scale
reaction is given in the parentheses. cr.r = regioisomer ratio.
dThe reaction was performed using 2a (0.1 mmol), 1 (0.3
mmol), and allyl alcohol (3m; 0.3 mmol) in MeCN (0.5
mL). eThe reaction was performed in toluene. fPyrazole was
used as the nucleophile.
The scope of the iodo(III)etherification reaction could
be extended to terminal alkynes (Scheme 4). A variety
ACS Paragon Plus Environment

Journal of the American Chemical Society
aThe reaction was performed on a 0.1 mmol scale. The
Page 4 of 7
of aryl acetylenes reacted regio- and stereoselectively
with BXT and MeOH to afford the corresponding β-
iodanyl vinyl ethers 6aa–6ga in moderate to high yields.
The structure of 6aa was confirmed by X-ray
crystallographic analysis.24 The reactions of 1-hexyne
and cyclohexylacetylene also proceeded smoothly to
afford the corresponding products 6ha and 6ia in good
yield. Enynes such as 2-methylbut-1-en-3-yne and 1-
1
2
3
4
5
6
7
8
symbol BX in the product formula refers to the
benziodoxole moiety. bThe reaction was performed with 5a
(0.1 mmol), BXT (0.3 mmol), and allyl alcohol (0.3 mmol),
and MeCN (0.5 mL).
The present iodo(III)etherification is considered to
involve electrophilic activation of the alkyne by a BX
cation upon dissociation of triflate from BXT.15 This
would trigger nucleophilic addition of the alcohol to the
C≡C bond in a trans-fashion with Markovnikov-type
regioselectivity, eventually affording the β-iodanyl vinyl
ether along with HOTf. DFT calculations supported this
mechanistic picture, and also reproduced the
regioselectivity trend observed for 4-methylpent-2-yne
and hex-2-yne (see 4na/4sa and Figures S8–S10).
ethynylcyclohexene
underwent
chemoselective
9
functionalization of the acetylenic moiety to furnish the
1-iodanyl-2-alkoxy-1,3-dienes 6ja and 6ka in 92% and
49% yields, respectively. In contrast to these cases,
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
trimethylsilylacetylene
underwent
the
iodo(III)etherification with opposite regioselectivity to
afford the β-silyl vinyl ether 6la in 81% yield,
presumably due to the ability of the silyl group to
stabilize positive charge at the β-position.17a,24 Like the
reactions of internal alkynes, a variety of primary and
secondary alcohols took part in the reaction with
phenylacetylene to afford the products 6ab–6at in
moderate to high yields.
Kinetic
studies
on
the
reaction
of
4-
F
trifluoromethylphenylacetylene (5b) in MeOH, using 19
NMR, revealed first-order dependence on both 1 and 5b
(Figures S6 and S7), in support of rate-limiting trans-
iodo(III)etherification. It is notable that the vinyl ether
product remains intact in the presence of strongly acidic
HOTf, presumably due to steric and electronic
protection by the bulky and electron-withdrawing
iodanyl group.
Scheme 4. Iodo(III)etherification of Terminal
Alkynesa
Conditions A
R3OH (3; solvent)
F3C
F3C
The β-iodanylvinyl ethers obtained by the present
method serve as versatile starting materials for the
stereoselective synthesis of highly substituted vinyl
ethers. As illustrated in Scheme 5a, the product 4ba
smoothly underwent Pd-catalyzed Stille, Sonogashira,
and Suzuki–Miyaura coupling to afford conjugated vinyl
ethers 7, 8, and 9, respectively, in good yields with
retention of the stereochemistry.14c-e In addition,
Rosenmund–von Braun cyanation25 and reduction of the
benziodoxole moiety in 4ba could be selectively
achieved at different temperatures. Thus, β-cyano and -
iodo vinyl ethers 10 and 11 were obtained in good yields
at 90 °C and 50 °C, respectively. The Pd-catalyzed
hydrodehalogenation of the BX moiety in 4ba also
proceed smoothly, and the product then took part in
ytterbium triflate-catalyzed Mannich reaction,26 inverse
electron-demand hetero-Diels–Alder reaction with in
O
TfO
I
O
rt, 24 h
CF3
CF3
R1
R1
+
I
H
Conditions B
R3OH (3; 5 equiv)
MeCN, rt, 24 h
5
OR3
H
1
6
R
R
BX
BX
H
H
OMe
OMe
6ea (R = OMe), 87% (A)
6fa (R = CF3), 82% (A)
6aa (R = H), 91% (A)
6ba (R = CF3), 82% (A)
6aa (X-ray)
6ca (R = CO2Me), 48% (A)
6da (R = CN), 42% (A)
BX
H
Me
OMe
BX
H
Bu
BX
H
BX
H
Me
OMe
OMe
OMe
6ja, 92% (A)
6ha, 86% (A)
6ia, 77% (A)
6ga, 67% (A)
situ
generated
1,2-diaza-1,3-diene,27
and
BX
BX
H
cyclopropanation with dichlorocarbene, affording -
amino ketone 12, tetrahydropyridazine 13, and
cyclopropane 14, respectively, in moderate yields over
two steps (Scheme 5b). Furthermore, β-iodanylvinyl
allyl ethers 4am and 6am underwent Cu-promoted
reduction and Claisen rearrangement to afford α-iodo
homoallyl ketones 16a and 16b, respectively, in good
yields (Scheme 5c).
H
OMe
Me3Si
OMe
6ka, 49% (A)
6la, 81% (A)
6la (X-ray)
BX
H
Ph
BX
H
Ph
O
BX
H
Ph
O
OR
R
6ab (R = Bn), 88% (A)
6ac (R = Et), 92% (A)
6ad (R = iPr), 88% (A)
6af (R = Cy), 80% (A)
Br
6ah (R = OMe), 56% (A)
6ai (R = CN), 87% (A)
6aj (R = Br), 65% (A)
6ak, 48% (A)
BX
H
Ph
O
Scheme 5. Product Transformations
BX
H
Ph
O
Me
O
6am, 76% (B)b
6at, 52% (B)
ACS Paragon Plus Environment

Page 5 of 7
Journal of the American Chemical Society
Crystallographic data for 4ba (CIF)
1
2
3
4
5
Crystallographic data for 4na (CIF)
Crystallographic data for 6aa (CIF)
Crystallographic data for 6la (CIF)
6
7
8
9
AUTHOR INFORMATION
Corresponding Author
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
*wujl@zzu.edu.cn
*nyoshikai@ntu.edu.sg
Author Contributions
§These authors contributed equally.
Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENT
This work was supported by the Ministry of Education
(Singapore) and Nanyang Technological University
(MOE2016-T2-2-043 and RG114/18). We thank Dr.
Yongxin Li (Nanyang Technological University) for his
assistance with the X-ray crystallographic analysis.
REFERENCES
(1) Fischer, P. In The Chemistry of Functional Groups; Patai, P.,
Ed.; John Wiley & Sons: Chichester, 1980; Vol. Suppl. E., Chapter
17.
(2) Lempenauer, L.; Lemière, G.; Duñach, E. Cyclisation Reactions
Involving Alkyl Enol Ethers. Adv. Synth. Catal. 2019, 361, 5284-
5304.
In summary, we have developed a regio- and
stereoselective trans-1,2-difunctionalization reaction of
alkynes with a cyclic λ3-iodane electrophile and alcohols
as a versatile approach to highly substituted vinyl ethers.
The present iodo(III)etherification proceeds under
simple and mild conditions and tolerates various internal
and terminal alkynes as well as a broad range of
alcohols, affording air- and moisture-stable trans--
iodanylvinyl ethers. The benziodoxole moiety of the
products can be utilized as a synthetic linchpin in
various transformations, allowing for stereocontrolled
preparation of multisubstituted vinyl ethers. We
anticipate that previously unimaginable stereodefined
vinyl ethers, which are made accessible by the present
method, will not only enhance the scope and the utility
of existing vinyl ether transformations but also inspire
the development of their new synthetic transformations.
Further studies on the use of benziodoxole triflate and
related compounds as electrophilic λ3-iodanation agents
are also ongoing in our laboratory.
(3) For selected recent examples, see: (a) Saito, K.; Sogou, H.;
Suga, T.; Kusama, H.; Iwasawa, N. Platinum(II)-Catalyzed
Generation and [3+2] Cycloaddition Reaction of Alpha,Beta-
Unsaturated Carbene Complex Intermediates for the Preparation of
Polycyclic Compounds. J. Am. Chem. Soc. 2011, 133, 689-691. (b)
Briones, J. F.; Davies, H. M. L. Enantioselective Gold(I)-Catalyzed
Vinylogous [3 + 2] Cycloaddition between Vinyldiazoacetates and
Enol Ethers. J. Am. Chem. Soc. 2013, 135, 13314-13317. (c) Iwasaki,
T.; Miyata, Y.; Akimoto, R.; Fujii, Y.; Kuniyasu, H.; Kambe, N.
Diarylrhodates as Promising Active Catalysts for the Arylation of
Vinyl Ethers with Grignard Reagents. J. Am. Chem. Soc. 2014, 136,
9260-9263. (d) Chen, W.; Li, Y.; Chen, Y.; Ho, C. Y. (NHC)NiH-
Catalyzed Regiodivergent Cross-Hydroalkenylation of Vinyl Ethers
with Alpha-Olefins: Syntheses of 1,2- and 1,3-Disubstituted Allyl
Ethers. Angew. Chem. Int. Ed. 2018, 57, 2677-2681.
(4) Winternheimer, D. J.; Shade, R. E.; Merlic, C. A. Methods for
Vinyl Ether Synthesis. Synthesis 2010, 2497-2511.
(5) (a) Alonso, F.; Beletskaya, I. P.; Yus, M. Transition-Metal-
Catalyzed Addition of Heteroatom-Hydrogen Bonds to Alkynes.
Chem. Rev. 2004, 104, 3079-3159. (b) Goodwin, J. A.; Aponick, A.
Regioselectivity
in
the
Au-Catalyzed
Hydration
and
Hydroalkoxylation of Alkynes. Chem. Commun. 2015, 51, 8730-
8741.
(6) (a) Nordmann, G.; Buchwald, S. L. A Domino Copper-
Catalyzed C-O Coupling-Claisen Rearrangement Process. J. Am.
Chem. Soc. 2003, 125, 4978-4979. (b) Shade, R. E.; Hyde, A. M.;
Olsen, J. C.; Merlic, C. A. Copper-Promoted Coupling of Vinyl
Boronates and Alcohols: A Mild Synthesis of Allyl Vinyl Ethers. J.
Am. Chem. Soc. 2010, 132, 1202-1203.
ASSOCIATED CONTENT
Experimental procedures and characterization data for all
the new products (PDF).
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 6 of 7
(7) (a) Okimoto, Y.; Sakaguchi, S.; Ishii, Y. Development of a
Ethers via Coiodination of Acetylenic Ketones. Tetrahedron Lett.
Highly Efficient Catalytic Method for Synthesis of Vinyl Ethers. J.
Am. Chem. Soc. 2002, 124, 1590-1591. (b) Bosch, M.; Schlaf, M.
Synthesis of Allyl and Alkyl Vinyl Ethers Using an in Situ Prepared
Air-Stable Palladium Catalyst. Efficient Transfer Vinylation of
Primary, Secondary, and Tertiary Alcohols. J. Org. Chem. 2003, 68,
5225-5227.
(8) (a) Su, C.; Williard, P. G. Isomerization of Allyl Ethers
Initiated by Lithium Diisopropylamide. Org. Lett. 2010, 12, 5378-
5381. (b) Martinez-Erro, S.; Sanz-Marco, A.; Bermejo Gomez, A.;
Vazquez-Romero, A.; Ahlquist, M. S. G.; Martin-Matute, B. Base-
Catalyzed Stereospecific Isomerization of Electron-Deficient Allylic
Alcohols and Ethers through Ion-Pairing. J. Am. Chem. Soc. 2016,
138, 13408-13414.
(9) (a) Earnshaw, C.; Wallis, C. J.; Warren, S. Synthesis of E- and
Z-Vinyl Ethers by the Horner-Wittig Reaction. J. Chem. Soc., Perkin
Trans. 1 1979, 3099-3106. (b) Balti, M.; Efrit, M. L.; Leadbeater, N.
E. Preparation of Vinyl Ethers Using a Wittig Approach, and Their
Subsequent Hydrogenation Employing Continuous-Flow Processing.
Tetrahedron Lett. 2016, 57, 1804-1806.
(10) Barluenga, J.; Rodriguez, A.; Campos, P. J. Synthesis of 2-
Functionalized 1,1-Diiodo-1 Alkenes. Generation and Reactions of 1-
Iodo-1-Lithio-1 Alkenes and 1,1-Dilithio-1-Alkenes. J. Am. Chem.
Soc. 1988, 110, 5567-5568.
2014, 55, 1065-1067.
1
2
3
4
5
6
7
8
(17) (a) Kitamura, T.; Furuki, R.; Taniguchi, H.; Stang, P. J.
Stereoselective anti-Addition of PhIO•TfOH to Terminal Alkynes.
Preparation of (E)-(β-Trifluoromethanesulfonyloxyvinyl)-Iodonium
Triflates. Tetrahedron Lett. 1990, 31, 703-704. (b) Kitamura, T.;
Furuki, R.; Taniguchi, H.; Stang, P. J. Electrophilic Additions of
Iodosylbenzene Activated by Trifluoromethanesulfonic Acid, [PhIO-
TfOH], to Alkynes. Tetrahedron 1992, 48, 7149-7156. (c) Tóth, B.
L.; Béke, F.; Egyed, O.; Bényei, A.; Stirling, A.; Novák, Z. Synthesis
of Multifunctional Aryl(trifloxyalkenyl)iodonium Triflate Salts. ACS
Omega 2019, 4, 9188-9197.
9
(18) (a) Hara, S.; Yoshida, M.; Fukuhara, T.; Yoneda, N. Stereo-
and Regio-Selective Addition of Iodotoluene Difluoride to Alk-1-
ynes. Selective Synthesis of 2-Fluoro-1-iodoalk-1-enes. Chem.
Commun. 1998, 965-966. (b) Yoshida, M.; Kawakami, K.; Hara, S.
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
An
Efficient
Stereoselective
Synthesis
of
(E)-β-
Fluoroalkenyliodonium Salts. Synthesis 2004, 2821-2824. (c)
Kitamura, T.; Mizuno, S.; Muta, K.; Oyamada, J. Synthesis of β-
Fluorovinyliodonium Salts by the Reaction of Alkynes with
Hypervalent Iodine/HF Reagents. J. Org. Chem. 2018, 83, 2773-2778.
(19) (a) Ochiai, M.; Kunishima, M.; Fuji, K.; Shiro, M.; Nagao, Y.
Synthesis and Structural Analysis of a Vinyliodonium Salt with an Α-
Silyl Substituent, and Generation of an Iodonium Ylide from It. J.
Chem. Soc., Chem. Commun. 1988, 1076-1077. (b) Ochiai, M.;
Hirobe, M.; Yoshimura, A.; Nishi, Y.; Miyamoto, K.; Shiro, M.
Internal Delivery of Soft Chlorine and Bromine Atoms:
Stereoselective Synthesis of (E)-β-Halogenovinyl(aryl)-λ3-iodanes
through Domino λ3-Iodanation–1,4-Halogen Shift–Fluorination of
Alkynes. Org. Lett. 2007, 9, 3335-3338.
(20) For the stereoselective synthesis of alkenyl triflates via
organo-triflation of alkynes with organoiodonium triflates, see: (a)
Suero, M. G.; Bayle, E. D.; Collins, B. S. L.; Gaunt, M. J. Copper-
Catalyzed Electrophilic Carbofunctionalization of Alkynes to Highly
Functionalized Tetrasubstituted Alkenes. J. Am. Chem. Soc. 2013,
135, 5332-5335. (b) Wang, X.; Studer, A. Regio- and Stereoselective
Cyanotriflation of Alkynes Using Aryl(cyano)iodonium Triflates. J.
Am. Chem. Soc. 2016, 138, 2977-2980. (c) Wang, X.; Studer, A.
Regio- and Stereoselective Radical Perfluoroalkyltriflation of
Alkynes Using Phenyl(perfluoroalkyl)iodonium Triflates. Org. Lett.
2017, 19, 2977-2980.
(21) Zhdankin, V. V.; Kuehl, C. J.; Krasutsky, A. P.; Bolz, J. T.;
Simonsen, A. J. 1-(Organosulfonyloxy)-3(1H)-1,2-Benziodoxoles:
Preparation and Reactions with Alkynyltrimethylsilanes. J. Org.
Chem. 1996, 61, 6547-6551.
(22) Wu, B.; Wu, J.; Yoshikai, N. Benziodoxole Triflate as a
Versatile Reagent for Iodo(III)Cyclization of Alkynes. Chem. Asian J.
2017, 12, 3123-3127.
(23) Godoi, B.; Schumacher, R. F.; Zeni, G. Synthesis of
Heterocycles via Electrophilic Cyclization of Alkynes Containing
Heteroatom. Chem. Rev. 2011, 111, 2937-2980.
(24) CCDC 1919101-1919104 contain the supplementary
crystallographic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre.
(25) Wang, D.; Kuang, L.; Li, Z.; Ding, K. L-Proline-Promoted
Rosenmund-Von Braun Reaction. Synlett 2008, 69-72.
(11) Reppe, W. Vinylation. 1. Vinyl Ethers and Vinyl Esters.
Liebigs Ann. Chem. 1956, 601, 84-111.
(12) Kondo, M.; Kochi, T.; Kakiuchi, F. Rhodium-Catalyzed Anti-
Markovnikov Intermolecular Hydroalkoxylation of Terminal
Acetylenes. J. Am. Chem. Soc. 2011, 133, 32-34.
(13) (a) Caramenti, P.; Declas, N.; Tessier, R.; Wodrich, M. D.;
Waser, J. Stereoselective Synthesis of Alkyl-, Aryl-, Vinyl- and
Alkynyl-Substituted Z-Enamides and Enol Ethers. Chem. Sci. 2019,
10, 3223-3230. (b) Liu, B.; Lim, C. H.; Miyake, G. M. Light-Driven
Intermolecular
Charge
Transfer
Induced
Reactivity
of
Ethynylbenziodoxol(on)e and Phenols. J. Am. Chem. Soc. 2018, 140,
12829-12835.
(14) For other examples of vinylbenziodoxol(on)e synthesis, see:
(a) Kitamura, T.; Fukuoka, T.; Fujiwara, Y. Synthesis of Novel
Vinylbenziodoxolones from Alkynyl(o-carboxphenyl)iodonium Salts.
Synlett 1996, 659-660. (b) Stridfeldt, E.; Seemann, A.; Bouma, Dey,
C.; Ertan, A.; Olofsson, B. Synthesis, Characterization and Unusual
Reactivity of Vinylbenziodoxolones—Novel Hypervalent Iodine
Reagents. Chem. Eur. J. 2016, 22, 16066-16070. (c) Wu, J.; Deng, X.;
Hirao, H.; Yoshikai, N. Pd-Catalyzed Conversion of Alkynyl-λ3-
Iodanes to Alkenyl-λ3-Iodanes via Stereoselective 1,2-Iodine(III)
Shift/1,1-Hydrocarboxylation. J. Am. Chem. Soc. 2016, 138, 9105-
9108. (d) Wu, J.; Xu, K.; Hirao, H.; Yoshikai, N. Pd-Catalyzed,
Ligand-Enabled
Stereoselective
1,2-Iodine(III)
Shift/1,1-
Carboxyalkynylation of Alkynylbenziodoxoles. Chem. Eur. J. 2017,
23, 1521-1525. (e) Wu, J.; Deng, X.; Yoshikai, N. Stereocontrolled
Synthesis of Halovinylbenziodoxoles by Hydro- and Iodochlorination
of Ethynylbenziodoxoles. Chem. Eur. J. 2019, 25, 7839-7842.
(15) For reviews on (cyclic) hypervalent iodine reagents, see: (a)
Brand, J. P.; Gonzalez, D. F.; Nicolai, S.; Waser, J. Benziodoxole-
Based Hypervalent Iodine Reagents for Atom-Transfer Reactions.
Chem. Commun. 2011, 47, 102-115. (b) Li, Y.; Hari, D. P.; Vita, M.
V.; Waser, J. Cyclic Hypervalent Iodine Reagents for Atom-Transfer
Reactions: Beyond Trifluoromethylation. Angew. Chem. Int. Ed.
2016, 55, 4436-4454. (c) Waser, J. Benziodoxol(on)e Reagents as
Tools in Organic Synthesis: The Background Behind the Discovery at
the Laboratory of Catalysis and Organic Synthesis. Synlett 2016, 27,
2761-2773. (d) Yoshimura, A.; Zhdankin, V. V. Advances in
Synthetic Applications of Hypervalent Iodine Compounds. Chem.
Rev. 2016, 116, 3328-3435. (e) Hari, D. P.; Caramenti, P.; Waser, J.
Cyclic Hypervalent Iodine Reagents: Enabling Tools for Bond
Disconnection via Reactivity Umpolung. Acc. Chem. Res. 2018, 51,
3212-3225.
(26) (a) Kobayashi, S.; Ishitani, H. A Novel Mannich-Type
Reaction in Aqueous Media. Lanthanide Triflate-Catalysed
Condensation of Aldehydes, Amines and Vinyl Ethers for the
Synthesis of β-Amino Ketones. J. Chem. Soc., Chem. Commun. 1995,
1379-1379. (b) Keck, G. E.; Truong, A. P. Directed Reduction of β-
Amino Ketones to syn or anti 1,3-Amino Alcohol Derivatives. Org.
Lett. 2002, 4, 3131-3134.
(27) Gao, S.; Chen, J.-R.; Hu, X.-Q.; Cheng, H.-G.; Lu, L.-Q.;
Xiao, W.-J. Copper-Catalyzed Enantioselective Inverse Electron-
Demand Hetero-Diels–Alder Reactions of Diazadienes with Enol
Ethers: Efficient Synthesis of Chiral Pyridazines. Adv. Synth. Catal.
2013, 355, 3539-3544.
(16) Xie, M.; Zhang, J.; Ning, P.; Zhang, Z. G.; Liu, X.; Wang, L.
Regio- and Stereoselective Synthesis of Highly Functionalized Vinyl
ACS Paragon Plus Environment

Page 7 of 7
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
R1
TfO
R2
F3C
O
+
+
F3C
R4
R1
R2
I
O
R2
I
CF3
CF3
rt
OR3
R1
OR3
60 examples
32-98% yields
R3OH
■ Broad scope of alkynes and alcohols
■ High regio- and stereoselectivity
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
■ Access to previously inaccessible vinyl ethers
7
ACS Paragon Plus Environment