Ruthenium-Catalyzed Intramolecular Double Hydroalkoxylation of Internal Alkynes

Article abstract of DOI:10.1021/acs.orglett.8b03368

Intramolecular double hydroalkoxylation of internal alkynes could be achieved using a Grubbs-type ruthenium carbene complex or its modified species to deliver a series of bridged- and spiroacetal derivatives in moderate to good yields. This study represen

Full text of DOI:10.1021/acs.orglett.8b03368

Letter
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
pubs.acs.org/OrgLett
Ruthenium-Catalyzed Intramolecular Double Hydroalkoxylation of
Internal Alkynes
†
‡
‡
,†
Kei Iio, Shusuke Sachimori, Tomomi Watanabe, and Haruhiko Fuwa*
†Department of Applied Chemistry, Faculty of Science and Engineering, Chuo University, 1-13-27 Kasuga, Bunkyo-ku, Tokyo
1
‡
12-8551, Japan
Graduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, Japan
S Supporting Information
*
ABSTRACT: Intramolecular double hydroalkoxylation of internal
alkynes could be achieved using a Grubbs-type ruthenium carbene
complex or its modified species to deliver a series of bridged- and
spiroacetal derivatives in moderate to good yields. This study represents
a new example of nonmetathetic reactions catalyzed by Grubbs-type
ruthenium carbene complexes.
he emergence of Grubbs-type ruthenium carbene
complexes 1−4 (Figure 1) as olefin metathesis catalysts
intramolecular double hydroalkoxylation of internal alkynes
T
using ruthenium carbene complexes or their modified species,
providing a series of bridged- and spiroacetals in moderate to
good yields.
Initially, we investigated intramolecular double hydroalkox-
22
ylation of alkyne diol 5a as a model substrate under the
influence of a variety of ruthenium complexes, as shown in Table
1
. Ruthenium carbene complexes 1−3 were mostly ineffective
for the present reaction, giving bridged acetal 6a in only low
yield (Table 1, entries 1−3). In contrast, when the reaction was
carried out using complex 4, acetal 6a was isolated in 50% yield
Figure 1. Structures of Grubbs-type ruthenium carbene complexes.
(
Table 1, entry 4). Running the reaction in xylenes at 125 °C, 6a
was obtained in 66% yield (Table 1, entry 5). In this case, diene
a was isolated in 8% yield alongside, which should originate
1
has revolutionized organic synthesis. The versatility of these
7
complexes has already been showcased in numerous metathetic
reactions implicated in complex molecule synthesis. Mean-
2
from 6-exo addition of the primary hydroxy group to the internal
while, ruthenium carbene complexes are also known to promote
alkyne, followed by dehydration of the secondary hydroxy
3
a number of nonmetathetic reactions including olefin isomer-
group. [RuCl (p-cymene)] was also effective and gave 6a in
2 2
4
5
6
ization, cycloaddition, cycloisomerization, cyclopropana-
40% yield (Table 1, entry 6). Other ruthenium complexes such
as RuCl (PPh ) , RuClH(CO)(PPh ) or RuH (PPh ) did not
7
8
9
10
tion, hydrogenation, hydrosilylation, Kharasch addition,
and hetero-Michael addition.
2
3 3
3 3
2
3 4
11−13
The integration of metathetic
catalyze the present reaction (Table 1, entries 7−9). Screening
and nonmetathetic reactions using a ruthenium carbene
complex enables the rapid generation of molecular complexity
of additives led us to find that pretreatment of complex 4 with
23
DMF at 120 °C for 12 min, generating “modified 4,” and
performing the reaction in toluene at reflux resulted in a
significant improvement of the product yield (Table 1, entry
3
,14
from simple starting materials.
Thus, identification of
ruthenium carbene-catalyzed nonmetathetic reactions would
expand the versatility of ruthenium carbene complexes in
organic synthesis.
10). Running the reaction in xylenes at 125 °C was equally
effective to that in toluene at reflux (Table 1, entry 11). It was
also found that the reaction of 5a proceeded smoothly by the
action of “modified 3”, prepared in situ from complex 3 by
Transition metal-catalyzed intramolecular double hydro-
alkoxylation of alkynes is an atom-economical transformation
15
for the synthesis of acetal derivatives. Previous work has shown
that molybdenum, tungsten, palladium, gold, platinum,
rhodium, and iridium complexes or salts can be used for
23
heating in DMF at 120 °C for 12 min, giving 6a in 76% yield
(
Table 1, entry 12). These data imply that ruthenium complexes
16
3 and 4 were transformed into more reactive ruthenium species
hydroalkoxylation of alkynes. It is also known that ruthenium-
23
under these conditions. A series of other solvents, including
CH Cl , ClCH CH Cl, Et O, THF, and CH CN, were also
(
II) complexes are able to catalyze intramolecular hydro-
1
7−19
2
2
2
2
2
3
alkoxylation of bis-homopropargylic alcohols,
which
involves a ruthenium vinylidene species as the key intermediate
20,21
in the catalytic cycle.
However, the substrate scope has been
Received: October 22, 2018
limited to those having a terminal alkyne. Herein, we report
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b03368
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
Table 1. Screening of Reaction Conditions
69% and 74% yields, respectively (Table 2, entries 6, 7). These
results imply that, in the present reaction, the reactivity of
electron-rich alkynes would be higher than that of electron-
deficient ones.
To further explore the scope of the ruthenium-catalyzed
intramolecular double hydroalkoxylation of internal alkynes, the
synthesis of a series of aliphatic spiroacetals was investigated
(Table 3). Treatment of alkyne 8a with 4 (5 mol %) in toluene at
80 °C provided the corresponding 5,5-spiroacetal 9a in 81%
entry
Ru complex
6a (yield)
7a (yield)
1
2
3
4
5
6
7
8
9
1
2
3
4
4
no reaction
(7%)
(13%)
(50%)
(66%)
(40%)
(5%)
no reaction
(trace)
(75%)
b
24
(N/D)
(N/D)
(N/D)
yield with 2:1 diastereoselectivity. Under the same reaction
b
conditions, 8b also underwent intramolecular double hydro-
alkoxylation, but gave 5,6-spiroacetal 9b in only 51% yield as 2:1
b
c
24
(8%)
(N/D)
(N/D)
mixture of diastereomers. The yield of 9b could be improved
b
[RuCl (p-cymene)]
up to 87%, by using 4 (5 mol %) pretreated with DMF, further
underscoring the effectiveness of modified 4 in this reaction.
Intramolecular double hydroalkoxylation of 8c provided an
approximately 1:1 mixture of 5,6- and 6,5-spiroacetals 9b and 9c
2
2
b
RuCl (PPh )
3 3
2
RuHCl(CO)(PPh3)3
RuH (PPh )
b
(N/D)
2
3 4
d
24
10
11
12
4 + DMF
4 + DMF
3 + DMF
(7%)
(trace)
(trace)
in 85% yield. Likewise, the reaction of 8d delivered a 1:2
e
24
(75%)
(76%)
mixture of 5,7- and 6,6-spiroacetals 9da and 9db in 60% yield.
e
These results indicate that ruthenium-catalyzed intramolecular
double hydroalkoxylation of internal alkynes could be an
effective means to synthesize aliphatic spiroacetals, although in
some cases, the reaction occurred in an essentially non-
a
All reactions were performed using ruthenium complex (5 mol %) in
toluene at 80 °C for 12 h unless otherwise noted. N/D = not
detected. Reaction performed in xylenes at 125 °C. Ru complex 4
was pretreated with DMF at 120 °C for 12 min and reaction was
performed in toluene at reflux. Ru complex 3 or 4 was pretreated
with DMF at 120 °C for 12 min and reaction was performed in
xylenes at 125 °C.
b
c
d
25
regioselective fashion.
e
Next, the synthesis of benzannulated spiroacetals was
examined. Exposure of alkyne 8e to modified 4 (5 mol %) in
xylenes at 125 °C afforded 5,5-spiroacetal 9e in 67% yield. The
reaction of alkyne 8f under the same reaction conditions
provided a 2:1 mixture of 6,5- and 5,6-spiroacetals 9fa and 9fb in
examined for the present reaction, but none of these solvents
performed better than toluene and xylenes.
Next, the intramolecular double hydroalkoxylation of internal
alkynes 5b−5h was examined under the optimized reaction
conditions (Table 2). It was found that phenyl, p-(n-butyl)-
61% yield. Meanwhile, the reaction of alkyne 8g proceeded very
sluggishly and gave a 2:1 mixture of 5,7- and 6,6-spiroacetals 9ga
and 9gb in only 13% yield. Increasing the loading of modified 4
to 10 mol % resulted in a marginal improvement, giving 9ga/9gb
in 28% yield. Thus, benzannulated spiroacetals could also be
synthesized by means of ruthenium-catalyzed intramolecular
double hydroalkoxylation of internal alkynes in moderate to
good yields.
a
Table 2. Synthesis of Bridged Acetals
To gain an insight into the reaction mechanism, we performed
experiments using appropriately protected derivatives of 8e, as
shown in Scheme 1. Upon treatment with 5 mol % of modified 4
in xylenes at 125 °C, the reaction of 10 afforded 5-endo-dig
cyclization product, cyclic enol ether 11 in 57% yield (with
recovery of 10 in 16% yield), while that of alkynol 12 under the
same reaction conditions only gave traces of 6-endo-dig
entry
5, R
6 (yield)
7 (yield)
b
c
1
5b, C H5
6b (70%)
6c (76%)
6d (70%)
6e (51%)
6f (12%)
6g (69%)
6h (74%)
7b (N/D)
7c (13%)
7d (9%)
6
2
3
4
5c, p-(n-C H )C H
4
4
9
6
5d, 2-naphthyl
b
c
1
5e, p-MeO CC H
7e (N/D)
cyclization product 13 as judged by H NMR analysis of the
2
6
4
c
5
6
7
5f, p-NO C H
7f (N/D)
crude reaction mixture. No trace amount of the corresponding
5-exo-dig cyclization product was detected. The starting alkynol
12 was recovered in 55% yield. It appears that the ruthenium-
catalyzed intramolecular hydroalkoxylation of internal alkynes
2
6
4
c
5g, n-hexyl
5h, cyclohexyl
7g (N/D)
7h (N/D)
c
a
All reactions were performed using modified 4 (5 mol %) in toluene
at reflux for 12 h, unless otherwise noted. Reaction performed in
xylenes at 125 °C. N/D = not detected.
26
b
favors endo-dig cyclization, as was the case with 5a−5h. From
these observations, we considered that, in the double hydro-
alkoxylation of 8e, a 5-endo-dig addition of the alkyl−OH
occurred predominantly over a 6-endo-dig addition of the
benzyl−OH, thereby generating a five-membered cyclic enol
ether, to which the benzyl−OH added intramolecularly to
deliver spiroacetal 9e. Meanwhile, no reaction occurred when
alkyne 14 was subjected to the same reaction conditions (91%
recovery of 14), which suggested that the mechanism by which
cyclic enol ether 11 was produced did not involve alkyne
hydration.
c
phenyl, and 2-naphthyl derivatives 5b−5d underwent the
hydroalkoxylation smoothly to deliver the corresponding
bridged acetals 6b−6d in 70−76% yields, which is comparable
to that of 6a (Table 2, entries 1−3). Dienes 7c and 7d were also
isolated as side products in entries 2 and 3, respectively. The
reaction of p-methoxycarbonylphenyl derivative 5e gave bridged
acetal 6e in slightly lower yield (Table 2, entry 4). p-Nitrophenyl
derivative 5f did not perform effectively, and bridged acetal 6f
was isolated in only 12% yield (Table 2, entry 5). Aliphatic
substituents such as n-hexyl and cyclohexyl (i.e., 5g and 5h)
were well tolerated and provided bridged acetals 6g and 6h in
On the basis of the above considerations, we propose the
mode-of-cyclization of 8a−8d, 8f, and 8g as follows: the reaction
of 8a and 8b took place via a 5-endo-dig addition of the
B
DOI: 10.1021/acs.orglett.8b03368
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Table 3. Synthesis of Spiroacetals
Scheme 1. Intramolecular Hydroalkoxylation of Protected
Alkynes
secondary hydroxy group to the alkyne, and that of 8c and 8f
involved a 6-endo-dig attack of either hydroxy group to the
alkyne. Interestingly, a reversal of the preference was observed
for 8d and 8g: the mode-of-cyclization of 8d favored 6-endo-dig
over 7-endo-dig, whereas that of 8g showed a slight preference
for 7-endo-dig over 6-endo-dig. We assume that, in the case of 8g,
the preference for the 7-endo-dig cyclization might be ascribable
to the conjugation of the alkyne with the aromatic ring.
We propose that the ruthenium-catalyzed intramolecular
double hydroalkoxylation of internal alkynes would proceed via
the mechanism shown in Scheme 2. Previous studies have
described that ruthenium complexes catalyze trans-addition of
17,27
carboxylic acids and alcohols to terminal alkynes.
Thus, it is
plausible that the catalytic cycle initiates with coordination of
starting alkyne I (represented by 8e) to the electrophilic
ruthenium(II) species, followed by intramolecular trans-
Scheme 2. Proposed Catalytic Cycle
a
Reaction performed using 4 (5 mol %) in toluene at 80 °C for 12 h
b
unless otherwise noted. Reaction performed using modified 4 (5 mol
%
%
c
) in toluene at reflux. Reaction performed using modified 4 (5 mol
d
) in xylenes at 125 °C. Reaction performed using modified 4 (10
mol %) in xylenes at 125 °C.
C
DOI: 10.1021/acs.orglett.8b03368
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
addition of a hydroxy group to the triple bond of ruthenium η2-
alkyne II, to generate vinyl ruthenium species III. After 1,3-
proton shift to oxocarbenium ion IV, intramolecular addition of
the second hydroxy group to the oxocarbenium ion moiety
occurs to deliver ruthenated acetal V. Finally, protoderuthena-
tion produced spiroacetal VI with regeneration of the catalyti-
cally active ruthenium(II) species.
REFERENCES
■
(
2
1) For selected reviews, see: (a) Grubbs, R. H. Angew. Chem., Int. Ed.
006, 45, 3760. (b) Vougioukalakis, G. C.; Grubbs, R. H. Chem. Rev.
010, 110, 1746.
(2) For selected reviews, see: (a) Deiters, A.; Martin, S. F. Chem. Rev.
2004, 104, 2199. (b) Nicolaou, K. C.; Bulger, P. G.; Sarlah, D. Angew.
Chem., Int. Ed. 2005, 44, 4490. (c) Gradillas, A.; Per
Angew. Chem., Int. Ed. 2006, 45, 6086. (d) Furstner, A. Chem. Commun.
011, 47, 6505. (e) Jacques, R.; Pal, R.; Parker, N. A.; Sear, C. E.; Smith,
P. W.; Ribaucourt, A.; Hodgson, D. M. Org. Biomol. Chem. 2016, 14,
875.
3) For reviews, see: (a) Alcaide, B.; Almendros, P.; Luna, A. Chem.
Rev. 2009, 109, 3817. (b) Kotha, S.; Misra, S.; Sreevani, G.; Babu, B. V.
Curr. Org. Chem. 2013, 17, 2776.
4) (a) Kinderman, S. S.; van Maarseveen, J. H.; Schoemaker, H. E.;
Hiemstra, H.; Rutjes, F. P. J. T. Org. Lett. 2001, 3, 2045. (b) Sutton, A.
E.; Seigal, B. A.; Finnegan, D. F.; Snapper, M. L. J. Am. Chem. Soc. 2002,
124, 13390. (c) Donohoe, T. J.; Chiu, J. Y. K.; Thomas, R. E. Org. Lett.
007, 9, 421. (d) Hekking, K. F. W.; Waalboer, D. C. J.; Moelands, M.
A. H.; van Delft, F. L.; Rutjes, F. P. J. T. Adv. Synth. Catal. 2008, 350, 95.
(e) Ascic, E.; Jensen, J. F.; Nielsen, T. E. Angew. Chem., Int. Ed. 2011, 50,
2
́
ez-Castells, J.
̈
It is known that some of nonmetathetic reactions catalyzed by
Grubbs-type ruthenium alkylidene complexes are actually
catalyzed by ruthenium hydrides, derived in situ from ruthenium
methylidenes through decomposition under high temperature
2
5
(
3
,28
conditions.
However, the present reaction does not involve
olefin metathesis, and therefore, ruthenium methylidene species
is not generated under the reaction conditions. Moreover,
ruthenium hydride complexes such as RuHCl(CO)(PPh ) and
(
3
3
RuH (PPh ) were found ineffective for the present reaction
2
3 4
(Table 1, entries 8 and 9). Also, the present reaction was not
2
inhibited by the addition of 1,4-benzoquinone, a known
2
9,30
scavenger of ruthenium hydride species.
Given that 4 is
2
8
thermally stable, it is likely that 4 itself is able to catalyze the
present reaction (e.g., Table 1, entries 4 and 5).
5
1
(
1
188. (f) Clark, J. R.; Griffiths, J. R.; Diver, S. T. J. Am. Chem. Soc. 2013,
35, 3327. (g) Petersen, M. T.; Nielsen, T. E. Org. Lett. 2013, 15, 1986.
Meanwhile, we consider that modified 3 and 4 might be
ruthenium carbonyl species. Kalck et al. have shown that DMF is
an effective source of carbonyl ligand of ruthenium complexes
h) Liniger, M.; Liu, Y.; Stoltz, B. M. J. Am. Chem. Soc. 2017, 139,
3944.
5) (a) Desroy, N.; Robert-Peillard, F.; Toueg, J.; Hen
R.; Rager, M.-N.; Savignac, M.; Genet, J.-P. Synthesis 2004, 2004, 2665.
(b) Lopez, F.; Delgado, A.; Rodríguez, J. R.; Castedo, L.; Mascarenas, J.
(
́
aut, C.; Duboc,
3
1
via decarbonylation under high temperature conditions.
Indeed, Perez-Castells and co-workers reported that modified
showed an IR absorption at 1947 cm , suggesting the
̂
́
́
̃
−1
3
L. J. Am. Chem. Soc. 2004, 126, 10262. (c) Young, D. D.; Senaiar, R. S.;
Deiters, A. Chem. - Eur. J. 2006, 12, 5563. (d) Medina, S.; Domínguez,
23
presence of a CO ligand coordinated to the ruthenium.
G.; Per
P.; Kim, M.; Lee, D. J. Am. Chem. Soc. 2012, 134, 10783. (f) Alvarez, S.;
Medina, S.; Domínguez, G.; Perez-Castells, J. J. Org. Chem. 2015, 80,
436. (g) Nada, T.; Yoneshige, Y.; Ii, Y.; Matsumoto, T.; Fujioka, H.;
Shuto, S.; Arisawa, M.; et al. ACS Catal. 2016, 6, 3168.
6) (a) Arisawa, M.; Terada, Y.; Nakagawa, M.; Nishida, A. Angew.
́
ez-Castells, J. Org. Lett. 2012, 14, 4982. (e) Yun, S. Y.; Wang, K.-
In conclusion, we have identified that intramolecular double
hydroalkoxylation of internal alkynes could be catalyzed by
ruthenium carbene complexes or their modified species to afford
bridged- and spiroacetals. The present study represents a new
example of nonmetathetic reactions catalyzed by Grubbs-type
ruthenium carbene complexes and also expands the scope of
ruthenium-catalyzed addition of O-nucleophiles to alkynes.
́
2
(
Chem., Int. Ed. 2002, 41, 4732. (b) Terada, Y.; Arisawa, M.; Nishida, A.
Angew. Chem., Int. Ed. 2004, 43, 4063. (c) Medina, S.; Domínguez, G.;
́
́
ez-Castells, J. Org. Lett. 2012, 14, 4982. (d) Mallagaray, A.;
Per
Mohammadiannejad-Abbasabadi, K.; Medina, S.; Domínguez, G.;
Perez-Castells, J. Org. Biomol. Chem. 2012, 10, 6665. (e) Alvarez, S.;
Medina, S.; Domínguez, G.; Perez-Castells, J. J. Org. Chem. 2013, 78,
995. (f) Alvarez, S.; Medina, S.; Domínguez, G.; Perez-Castells, J. J.
ASSOCIATED CONTENT
■
́
*
S
Supporting Information
́
9
́
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.8b03368.
Org. Chem. 2015, 80, 2436. (g) Ohno, S.; Takamoto, K.; Fujioka, H.;
Arisawa, M. Org. Lett. 2017, 19, 2422. (h) Takamoto, K.; Ohno, S.;
Hyogo, N.; Fujioka, H.; Arisawa, M. J. Org. Chem. 2017, 82, 8733.
(7) (a) Kim, B. G.; Snapper, M. L. J. Am. Chem. Soc. 2006, 128, 52.
b) Mallagaray, A.; Domínguez, G.; Gradillas, A.; Per
Lett. 2008, 10, 597.
8) (a) Menozzi, C.; Dalko, P. I.; Cossy, J. Synlett 2005, 2449.
(b) Børsting, P.; Nielsen, P. Chem. Commun. 2002, 2140. (c) Finnegan,
D. F.; Snapper, M. L. J. Org. Chem. 2011, 76, 3644. Connolly, T.; Wang,
Z.; Walker, M. A.; McDonald, I. M.; Peese, K. M. Org. Lett. 2014, 16,
444. (e) Renom-Carrasco, M.; Gajewski, P.; Pignataro, L.; de Vries, J.
G.; Piarulli, U.; Gennari, C.; Lefort, L. Adv. Synth. Catal. 2015, 357,
223. (f) Zielinski, G. K.; Majtczak, J.; Gutowski, M.; Grela, K. J. Org.
Experimental procedures, spectroscopic data, copies of
1
13
H and C NMR spectra (PDF)
(
́
ez-Castells, J. Org.
(
AUTHOR INFORMATION
■
*
Corresponding Author
E-mail: hfuwa.50m@g.chuo-u.ac.jp.
4
ORCID
2
Haruhiko Fuwa: 0000-0001-5343-9023
Notes
Chem. 2018, 83, 2542.
(9) (a) Maifeld, S. V.; Miller, R. L.; Lee, D. Tetrahedron Lett. 2002, 43,
363. (b) Denmark, S. E.; Pan, W. Org. Lett. 2002, 4, 4163. (c) Arico, C.
6
The authors declare no competing financial interest.
S.; Cox, L. R. Org. Biomol. Chem. 2004, 2, 2558. (d) Maifeld, S. V.; Tran,
M. N.; Lee, D. Tetrahedron Lett. 2005, 46, 105. (e) Bokka, A.; Jeon, J.
Org. Lett. 2016, 18, 5324.
10) (a) Tallarico, J. A.; Malnick, L. M.; Snapper, M. L. J. Org. Chem.
999, 64, 344. (b) Lee, B. T.; Schrader, T. O.; Martín-Matute, B.;
Kauffman, C. R.; Zhang, P.; Snapper, M. L. Tetrahedron 2004, 60, 7391.
c) Seigal, B. A.; Fajardo, C.; Snapper, M. L. J. Am. Chem. Soc. 2005,
27, 16329. (d) McGonagle, F. I.; Brown, L.; Cooke, A.; Sutherland, A.
ACKNOWLEDGMENTS
■
(
1
We thank Professor Makoto Sasaki (Tohoku University) for
generous support for the early stage of this work. This work was
financially supported in part by a Grant-in-Aid for Scientific
Research (C) (Grant No. JP17K01941) from JSPS and a Grant
from the Tokyo Ohka Foundation for The Promotion of Science
and Technology.
(
1
Org. Biomol. Chem. 2010, 8, 3418. (e) Diaba, F.; Martínez-Laporta, A.;
Bonjoch, J. J. Org. Chem. 2014, 79, 9365.
D
DOI: 10.1021/acs.orglett.8b03368
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(
11) (a) Fustero, S.; Jimen
́
ez, D.; San
́
chez-Rosello,
́
M.; del Pozo, C. J.
Schuster, A. M.; Rominger, F. Angew. Chem., Int. Ed. 2009, 48, 8247.
(c) Laroche, C.; Kerwin, S. M. J. Org. Chem. 2009, 74, 9229.
(d) Ramana, C. V.; Mallik, R.; Gonnade, R. G. Tetrahedron 2008, 64,
219. (e) Yamamoto, H.; Nishiyama, M.; Imagawa, H.; Nishizawa, M.
Tetrahedron Lett. 2006, 47, 8369. (f) Gulías, M.; Rodríguez, J. R.;
Am. Chem. Soc. 2007, 129, 6700. (b) Cai, Q.; Zheng, C.; You, S.-L.
Angew. Chem., Int. Ed. 2010, 49, 8666. (c) Waldeck, A. R.; Krische, M. J.
Angew. Chem., Int. Ed. 2013, 52, 4470. (d) Kammari, B. R.; Bejjanki, N.
K.; Kommu, N. Tetrahedron: Asymmetry 2015, 26, 296.
(
12) Other representative examples: (a) Gavenonis, J.; Arroyo, R. V.;
Castedo, L.; Mascarenas, J. L. Org. Lett. 2003, 5, 1975.
̃
Snapper, M. L. Chem. Commun. 2010, 46, 5692. (b) An, X.-L.; Chen, J.-
R.; Li, C.-F.; Zhang, F.-G.; Zou, Y.-Q.; Guo, Y.-C.; Xiao, W.-J. Chem. -
Asian J. 2010, 5, 2258. (c) Schmidt, B.; Krehl, S.; Jablowski, E. Org.
Biomol. Chem. 2012, 10, 5119. (d) Yun, S. Y.; Wang, K.-P.; Kim, M.;
Lee, D. J. Am. Chem. Soc. 2012, 134, 10783. (e) Arisawa, M.; Fujii, Y.;
Kato, H.; Fukuda, H.; Matsumoto, T.; Ito, M.; Abe, H.; Ito, Y.; Shuto, S.
Angew. Chem., Int. Ed. 2013, 52, 1003. (f) Schmidt, B.; Krehl, S.; Hauke,
S. J. Org. Chem. 2013, 78, 5427. (g) Dornan, P. K.; Lee, D.; Grubbs, R.
H. J. Am. Chem. Soc. 2016, 138, 6372. (h) Karmakar, R.; Wang, K.-P.;
Yun, S. Y.; Mamidipalli, P.; Lee, D. Org. Biomol. Chem. 2016, 14, 4782.
(27) (a) Mitsudo, T.; Hori, Y.; Watanabe, Y. J. Org. Chem. 1985, 50,
1566. (b) Mitsudo, T.; Hori, Y.; Yamakawa, Y.; Watanabe, Y.
Tetrahedron Lett. 1986, 27, 2125. (c) Ruppin, C.; Dixneuf, P. H.
Tetrahedron Lett. 1986, 27, 6323.
(28) Hong, S. H.; Wenzel, A. G.; Salguero, T. T.; Day, M. W.; Grubbs,
R. H. J. Am. Chem. Soc. 2007, 129, 7961.
(29) Hong, S. H.; Sanders, D. P.; Lee, C. W.; Grubbs, R. H. J. Am.
Chem. Soc. 2005, 127, 17160.
(30) Upon treatment of 5a with 4 (5 mol %) or modified 4 (5 mol %)
in the presence of 1,4-benzoquinone (10 mol %) in xylenes at 125 °C
for 12 h, 6a was isolated in 60% or 62% yield, respectively.
(
13) (a) Fuwa, H.; Noto, K.; Sasaki, M. Org. Lett. 2010, 12, 1636.
b) Fuwa, H.; Noto, K.; Sasaki, M. Heterocycles 2010, 82, 641. (c) Fuwa,
H.; Suzuki, T.; Kubo, H.; Yamori, T.; Sasaki, M. Chem. - Eur. J. 2011, 17,
678. (d) Fuwa, H.; Noguchi, T.; Noto, K.; Sasaki, M. Org. Biomol.
Chem. 2012, 10, 8108. (e) Fuwa, H.; Sasaki, M. Bull. Chem. Soc. Jpn.
016, 89, 1403. (f) Sakurai, K.; Sasaki, M.; Fuwa, H. Angew. Chem., Int.
Ed. 2018, 57, 5143.
14) (a) Shindoh, N.; Takemoto, Y.; Takasu, K. Chem. - Eur. J. 2009,
5, 12168. (b) Zielinski, G. K.; Grela, K. Chem. - Eur. J. 2016, 22, 9440.
15) For selected examples, see: (a) Liu, B.; de Brabander, J. K. Org.
Lett. 2006, 8, 4907. (b) Trost, B. M.; Weiss, A. H. Angew. Chem., Int. Ed.
(31) Serp, P.; Hernandez, M.; Richard, B.; Kalck, P. Eur. J. Inorg. Chem.
(
2001, 2327.
2
2
(
1
(
́
2
2
007, 46, 7664. (c) Zhang, Y.; Xue, J.; Xin, Z.; Xie, Z.; Li, Y. Synlett
008, 2008, 940. (d) Selvaratnam, S.; Ho, J. H. H.; Huleatt, P. B.;
Messerle, B. A.; Chai, C. L. L. Tetrahedron Lett. 2009, 50, 1125.
16) For selected reviews, see: (a) Alonso, F.; Beletskaya, I. P.; Yus, M.
Chem. Rev. 2004, 104, 3079. (b) Utimoto, K. Pure Appl. Chem. 1983, 55,
845. (c) McDonald, F. E. Chem. - Eur. J. 1999, 5, 3103. (d) Alcaide, B.;
Almendros, P.; Alonso, J. M. Org. Biomol. Chem. 2011, 9, 4405.
e) Goodwin, J. A.; Aponick, A. Chem. Commun. 2015, 51, 8730.
17) Seiller, B.; Bruneau, C.; Dixneuf, P. H. Tetrahedron 1995, 51,
3089.
18) (a) Trost, B. M.; Rhee, Y. H. J. Am. Chem. Soc. 2002, 124, 2528.
b) Varela-Fernandez, A.; Gonzalez-Rodríguez, C.; Varela, J. A.;
Castedo, L.; Saa, C. Org. Lett. 2009, 11, 5350. (c) Zacuto, M. J.; Tomita,
(
1
(
(
1
(
(
́
́
́
D.; Pirzada, Z.; Xu, F. Org. Lett. 2010, 12, 684. (d) Liu, P. N.; Su, F. H.;
Wen, T. B.; Sung, H. H.-Y.; Williams, I. D.; Jia, G. Chem. - Eur. J. 2010,
1
(
6, 7889.
19) Parrain et al. have reported some examples of intramolecular
hydroalkoxylation of terminal alkynes catalyzed by ruthenium carbene
complex 1. See: Taleb, A.; Lahrech, M.; Hacini, S.; Thibonnet, J.;
Parrain, J.-L. Synlett 2009, 2009, 1597. However, internal alkyne 5a was
found to be unreactive in the presence of 1 (Table 1, entry 1), implying
that the mechanism of Parrain’s hydroalkoxylation would be different
from that of ours.
(
20) Liu, P. N.; Wen, T. B.; Ju, K. D.; Sung, H. H.-Y.; Williams, I. D.;
Jia, G. Organometallics 2011, 30, 2571.
21) Dixneuf et al. have proposed that their reaction proceeds via a
(
2
ruthenium η -alkyne species. See ref 17.
22) See Supporting Information for the preparation of starting
materials.
23) Per
(
(
́
ez-Castells and co-workers have shown that treatment of
Grubbs-type ruthenium carbene complexes with DMF generates in situ
a new ruthenium species that catalyzes cycloisomerization of dienes and
enynes. See ref 6d.
(
24) The relative configuration of the spiroacetal product(s) could not
1
be determined unambiguously due to heavy overlap of H NMR signals.
(
25) The regioselectivity issue is also known for other transition metal-
catalyzed intramolecular double hydroalkoxylation of internal alkynes.
See ref 16.
(
26) Several reports have described transition metal-catalyzed
cyclization of internal alkynes with good to exclusive 6-endo selectivity.
See, for example: (a) Alcaide, B.; Almendros, P.; Carrascosa, R.; Lopez,
R.; Menendez, M. I. Tetrahedron 2012, 68, 10748. (b) Hashmi, A. S. K.;
́
́
E
DOI: 10.1021/acs.orglett.8b03368
Org. Lett. XXXX, XXX, XXX−XXX