10.1002/anie.201807418
Angewandte Chemie International Edition
COMMUNICATION
To gain deeper insight into the mechanism, we decided to
prepare reagent 3f*, in which the β-carbon of the acetylene is
13C-labelled and simultaneously bears a TIPS substituent. The
selection of the TIPS group is crucial because in vinyl
carbenoide intermediates 1,2-migration of silicon rests is
reported to be significantly faster than that of alkyl or sulfur-
based substituents.[21] Hence, the detection after alkyne transfer
of the TIPS group attached to the non-labelled carbon can be
consider proof of a β-attack. All our attempts to prepare 3f*
exclusively labelled at the β-position failed due to the low
regioselectivity of the electrophilic attack of 6 to acetylene 38.
Note that in 38 both carbon atoms are Si-substituted and
electronically very similar.[27] In any case, 3f* was reproducibly
obtained as a mixture of isotopomers in a 3:1 ratio, and this
relation did not change even after keeping 3f* for one week in
CDCl3 solution (Scheme 3a). Therefore, this mixture was used
for the programmed labelling experiments.
In summary, this work illustrates our initial results on the
synthesis of (alkynyl)dibenzothiophenium triflates and our efforts
to evaluate their potential and scope as electrophilic alkynylation
reagents. Moreover, a detailed mechanistic picture of their mode
of action in relation with their substitution pattern is provided.
Thus, α-attack of the nucleophile is observed for TIPS-
substituted (alkynyl)dibenzothiophenium salts, while for Ph-
substituted salts, attack at the β-position of the alkyne is most
probable. The application of these and other sulfonium salts in
the area of metal catalysis is currently under investigation in our
Acknowledgements
Support from the DFG (AL 1348/7-1 and INST 186/1237-1) is
gratefully acknowledged. We also thank our NMR department
for assistance.
Interestingly, when 3f* was made react with the three
nucleophiles of reference, the products obtained, 9*, 24* and 29*
invariably contain the higher labelled carbon still attached to the
silicon rest and with identical isotope ratio as in 3f* (Scheme 3b).
This result supports the operation of a divergent mechanism for
TIPS-substituted (alkynyl)dibenzothiophenium salts. In this case
an α-attack of the incoming nucleophiles is the most probable
reaction pathway (Scheme 3c).
Keywords: electrophilic alkynylation • transfer reagents •
isotopic labeling • sulfonium salts • alkynes
[1]
Acetylene Chemistry: Chemistry, Biology and Material Science, (Eds.: F.
Diederich, P. J. Stang, R. R. Tykwinski), Wiley-VCH, Weinheim, 2005.
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[2]
[3]
A
a) D. Seyferth, R. S. Marmor, P. Hilbert, J. Org. Chem., 1971, 36,
1379–1386; b) J. C. Gilbert, U. Weerasooriya, J. Org. Chem., 1982, 47,
1837–1845.
24%
α
13
76%
β
S
Me
TIPS
3Si
TIPS
38
a)
6
[4]
For a recent review on the synthesis and reactivity of haloacetylenes
see: a) W. Wu, H. Jiang, Acc. Chem. Res. 2014, 47, 2483-2504. For
selected recent examples: b) T. Ohmura, A. Kijima, Y. Komori, M.
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G. Zhu, Org. Biomol. Chem. 2014, 12, 2310-2321; c) J. Zhang, P. Li, L.
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F. M. Beringer, S. A. Galton, J. Org. Chem. 1965, 30, 1930-1934.
M. Ochiai, Y. Masaki, M. Shiro, J. Org. Chem. 1991, 56, 5511-5513.
V. V. Zhdankin, C. J. Kuehl, A. P. Krasutsky, J. T. Bolz, A. J. Simonsen,
J. Org. Chem. 1996, 61, 6547-6551.
TfO
O
3f*
(76/24)
c)
B
MeO
C
a)
3f*
b)
O
S
Ph
TIPS
O
MeO
O
S
N
75%
25%
24%
76%
[5]
[6]
[7]
24%
76%
TIPS
TIPS
9*
24*
Me
29*
[8]
a) M. Ochiai, M. Kunishima, Y. Nagao, K. Fuji, M. Shiro, E. Fujita, J. Am.
Chem. Soc. 1986, 108, 8281-8283; b) M. Ochiai, T. Ito, Y. Takaoka, Y.
Masaki, M. Kunishima, S. Tani, Y. Nagao, J. Chem. Soc. Chem.
Commun. 1990, 118-119.
R = Ph
S
Nu
Nu
S
1,2
S
Nu
[9]
M. D. Bachi, N. Bar-Ner, C. M. Crittell, P. J. Stang, B. L. Williamson, J.
Org. Chem. 1991, 56, 3912-3915.
both groups
can migrate
1,2
R
R
R
-attack
β
S-elimination
+ 1,2-shift
[10] a) D. Fernández-González, J. P. Brand, J. Waser, Chem. Eur. J. 2010,
16, 9457-9461; b) D. Fernández-González, J. P. Brand, R. Mondière, J.
Waser, Adv. Synth. Catal. 2013, 355, 1631-1639; c) R. Frei, J. Waser, J.
Am. Chem. Soc. 2013, 135, 9620-9623; d) R. Frei, M. D. Wodrich, D. P.
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16563-16573; e) C. C. Chen, J. Waser, Chem. Commun. 2014, 50,
12923-12926.
-addition
product
β
Nu
S
S
α
Nu
R = TIPS
β
R
R
Nu
Nu
Nu
plausible initial
ionic interaction
S
S
S
R
R
R
-attack
= dibenzothiophene
S
[11] a) J. P. Brand, J. Waser, Chem. Soc. Rev. 2012, 41, 4165-4179; b) J.
Waser, Synlett 2016, 27, 2761-2773.
S-elimination
α
α
-addition
product
[12] For a general monography in I(III) chemistry see: Hypervalent Iodine
Chemistry, V. V. Zhdankin; John Wiley &Sons, Ltd, 2014.
Scheme 3. Summary of isotopic labeling experiments. Reagents and
conditions: a) -50 °C→0 °C, 7 h., 85%; b) p-(methoxy)benzylthiol (1 equiv.),
Cs2CO3 (1 equiv.), CH2Cl2, rt; c) ketoester (1 equiv.), Cs2CO3 (1 equiv.),
CH2Cl2, 60°C; d) N-phenyl tosylamine (1 equiv.), Cs2CO3 (1 equiv.), CH2Cl2, rt.
[13] See ref. 12, Chapter 7, page 425: “The vast majority of organic λ3-
iodanes lack thermal stability and some of them are explosive”.
[14] a) G. Talavera, J. Peña, M. Alcarazo, J. Am. Chem. Soc. 2015, 137,
8704-8707; b) A. G. Barrado, A. Zieliński, R. Goddard, M. Alcarazo,
Angew. Chem. Int. Ed. 2017, 56, 13401-13405.
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