Davinia Fernꢀndez Gonzꢀlez et al.
UPDATES
induction will be very useful in the future to develop 1-[(Trimethylsilyl)ethynyl]-1,2-benziodoxol-3(1H)-one
a truly general and highly enantioselective alkynyla- (TMS-EBX, 1a)
tion method.
Trimethylsilyl triflate (5.54 mL, 30.7 mmol, 1.1 equiv.) was
added to a suspension of 2-iodosylbenzoic acid (7.36 g,
2
8.0 mmol, 1 equiv.) in CH Cl (85 mL) at room tempera-
2 2
ture. The resulting yellow mixture was stirred for 1 h, fol-
lowed by the dropwise addition of bis(trimethylsilyl)acety-
lene (6.98 mL, 30.7 mmol, 1.1 equiv.). The resulting suspen-
sion was stirred for 6 h at room temperature, during this
time a white solid was formed. A saturated solution of
Experimental Section
General Remarks
See Supporting Information for general experimental details
as well as procedures for the preparation and characteriza-
tion of all precursors and products.
NaHCO was then added and the mixture was stirred vigo-
3
rously until completely solubilization of the white solid. The
two layers were separated and the combined organic ex-
tracts were washed with saturated NaHCO , dried over
3
MgSO , filtered and evaporated under reduced pressure.
4
Recrystallization from acetonitrile (5 mL) afforded 1a as
Alkynylation Reactions
a colourless solid; yield: 7.17 g (20.8 mmol, 74%); mp
1
General procedure for alkynylation using TBAF: A solution
of substrate (1.0 equiv.) and alkynylbenziodoxolone reagent
(dec.): 143–1458C. H NMR (400 MHz, CDCl ): d=8.42
3
(dd, J=6.4, 1.9 Hz, 1H, ArH), 8.19 (m, 1H, ArH), 7.78 (m,
1
3
(
5
1.3 equiv.) in dried THF (60 mM) was stirred at À788C for
2H, ArH), 0.32 [s, 9H, Si ACHTUNEGRTNNUNG( CH )]; C NMR (100 MHz,
3
min under nitrogen. After this period of time, TBAF (1M
CDCl ): d=166.4, 134.9, 132.6, 131.7, 131.4, 126.1, 117.2,
3
in THF, 1.3 equiv.) was added and the mixture was vigorous-
ly stirred at À788C. The reaction was monitored by TLC
analysis (PET/EtOAc, 4:1, UV and p-anisaldehyde) and was
complete at À788C in the indicated time, or was slowly al-
lowed to warm up to 108C during the indicated time. The
reaction mixture was quenched with deactivated silica gel
and the solvent was evaporated under reduced pressure.
The product was purified via flash chromatography (SiO2,
hexane/EtOAc) with the indicated solvent ratio.
General procedure for catalytic phase-transfer alkynyla-
tion: A solution of saturated base solution (0.2M) was
added to a solution of phase-transfer catalyst (10 mol%)
and alkynylbenziodoxolone reagent (1.3 equiv.) in toluene
115.4, 64.2, À0.5; IR: n=3389 (w), 2967 (w), 1617 (s), 1609
(s), 1562 (m), 1440 (w), 1350 (m), 1304 (w), 1254 (w), 1246
À1
(w), 1112 (w), 1008 (w), 852 (s), 746 (m), 698 (m), 639 cm
(m).
Acknowledgements
EPFL and SNF (grant numbers 200021_119810 and
200020_134550) are acknowledged for financial support. Dr.
Rꢀgis Mondiꢁre is acknowledged for the DSC studies on
EBX reagents.
(
50 mM). The mixture was stirred at 08C for 5 min under ni-
trogen. After this period of time, the substrate (1.0 equiv.)
was added and the biphasic mixture was vigorously stirred
at 08C. The reaction was monitored by TLC analysis (PET/
EtOAc 4:1, UV and p-anisaldehyde). After the indicated References
time, the reaction mixture was quenched with water and the
aqueous layer was extracted with CH Cl . The combined or-
[1] F. Diederich, P. J. Stang, R. R. Tykwinsky, Acetylene
2
2
ganic layers were recollected, dried over MgSO , filtered
Chemistry: Chemistry, Biology, and Material Science,
Wiley-VCH, Weinheim, 2005.
4
and concentrated under reduced pressure. The crude prod-
uct was purified via silica gel flash chromatography (SiO2,
hexane/EtOAc) with the indicated solvent ratio.
General procedure for catalytic phase-transfer alkynyla-
tion using Maruokaꢀs catalyst: A saturated base solution
[2] a) F. Alonso, I. P. Beletskaya, M. Yus, Chem. Rev. 2004,
104, 3079; b) E. Jimenez-Nunez, A. M. Echavarren,
Chem. Commun. 2007, 333; c) J. F. Lutz, Angew. Chem.
2007, 119, 1036; Angew. Chem. Int. Ed. 2007, 46, 1018;
d) S. M. Abu Sohel, R. S. Liu, Chem. Soc. Rev. 2009, 38,
2269.
(
0.2M) was added to a solution of phase-transfer catalyst
(
3 mol%) and alkynylbenziodoxolone reagent (1.3 equiv.) in
xylene (50 mm). The mixture was stirred at 08C for 5 min
under nitrogen. After this period of time, the substrate
[3] B. M. Trost, A. H. Weiss, Adv. Synth. Catal. 2009, 351,
963.
(
1.0 equiv.) was added and the biphasic mixture was vigo-
[4] J. P. Brand, J. Waser, Chem. Soc. Rev. 2012, 41, 4165.
[5] A. S. Kende, P. Fludzinski, J. H. Hill, W. Swenson, J.
Clardy, J. Am. Chem. Soc. 1984, 106, 3551.
[6] a) M. G. Moloney, J. T. Pinhey, E. G. Roche, J. Chem.
Soc. Perkin Trans. 1 1989, 333; b) C. J. Parkinson, T. W.
Hambley, J. T. Pinhey, J. Chem. Soc. Perkin Trans.
1 1997, 1465.
rously stirred at 08C. The reaction was monitored by TLC
analysis (PET/EtOAc 4:1, UV and p-anisaldehyde) and was
complete at 08C in the indicated time, or was slowly allowed
to warm up to 108C during the indicated time. The reaction
mixture was quenched with water and the aqueous layer ex-
tracted with CH Cl . The combined organic layers were rec-
2
2
ollected, dried over MgSO , filtered and concentrated under
reduced pressure. The crude product was purified via silica
[7] a) M. Ochiai, T. Ito, Y. Takaoka, Y. Masaki, M. Kunish-
ima, S. Tani, Y. Nagao, J. Chem. Soc. Chem. Commun.
1990, 118; b) M. D. Bachi, N. Barner, C. M. Crittell,
P. J. Stang, B. L. Williamson, J. Org. Chem. 1991, 56,
4
gel flash chromatography (SiO , hexane/EtOAc) with the in-
2
dicated solvent ratio.
8
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Adv. Synth. Catal. 0000, 000, 0 – 0
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