1
proton from 1a (R ) H) to produce HCtCMe, which is
these anions with 1a to afford MgBr
activation of Mg with Br(CH Br in THF followed by
reaction with 1a produced similar precipitates. On the other
hand, attempted preparation in Et O with and without the
Br) resulted in the
complete recovery of Mg.
To identify effective catalysts, the preparation of 2a in
2
as precipitates. Pre-
1
ultimately changed to BrMgCtCMe (6). On the other hand,
the role of the catalyst in the preparation of 2 (R * H) is
not clearly stated to the best of our knowledge. To avoid
the problem associated with recovery of the mercury catalyst,
2 2
)
1
2
pre-activation of Mg (with Br(CH
2 2
)
1
Rieke Mg was once used for the preparation of 2 (R )
5
TMS). Use of zinc and lithium reagents similar to 2 (R )
,6,7
8
Si(alkyl)
3
, alkyl)4 and the dianion, LiCtCCH
2
Li, has been
Et O was examined with a number of metal salts (2-5 mol
2
an alternative choice. These anions have been synthesized
by reaction of 1 with Zn, by lithiation of 2-alkynes with
t-BuLi,6 and by lithiation of propyne and allene (CH
%) from a stock room. While most of the common metal
salts placed in group 1 of Table 1 were ineffective,
4
,7
2
dCd
8
CH
2
) with nBuLi, respectively. On the other hand, several
metals have been shown to assist generation of 2 in Barbier-
type reactions. These methods, however, seem less attractive
9
Table 1. Results of the Metal Salts Attempted for Preparation
of 2a in Et O
2
a
because of the complicated operation to prepare Rieke Mg,
inconvenience in handling gaseous propyne and allene for
the preparation of 2-alkynes as well as for the direct lithiation,
low reactivity and product selectivity, or the narrow range
of electrophiles for Barbier-type reactions.
consumption
of Mgb
concn
of 2a (M)c
group
metal salts
1
CuCl2
NiCl2
HfCl4
ZrCl4
no
no
CoCl2
CeCl3
FeCl3
Bu3SnCl
Zn(OAc)2
Zn(acac) 2
no
no
no
In contrast to the above method, two recent reports have
1
described the preparation of 2a (R ) H) in the usual way
without a mercury catalyst.10 Due to the significance, we
reinvestigated the preparation and confirmed that the mercury
catalyst is indeed necessary. Instead, we found an environ-
Cp2TiCl2
TiCl4
Zn(OTf)2
no
2
Zn(OTs)2
ZnEt2
yes
yes
yes
0
0
1
mentally acceptable catalyst for the preparation of 2 (R )
3
ZnX (X ) Cl, Br, I)
0-0.52
2
H, TMS, alkyls). Herein, we describe the preparation of 2
and applications including the synthesis of 5,6-epoxyiso-
prostane phosphorylcholine and its acetylene derivative.
After confirmation of the successful preparation of 2a in
a
Preparation was examined with 1a (1.0 mL, 13 mmol), Mg (650 mg,
27 mg-atom), and a catalyst (2-5 mol %) in Et O (18 mL) at 0-5 °C for
2
b
1
-2 h. Mg turnings from Nacalai Tesque, Japan, were used for the
c
investigation. Determined by titration with methyl orange.
2
Et O (0.38 M by titration with methyl orange, 54% yield
based on 0.70 M for 100% conversion) by adding propargyl
bromide (1a) (1 mL scale) to Mg turnings (2 equiv) in the
consumption of Mg was observed with TiCl
though concentration of 2a by titration was almost 0 M. To
our delight, production of 2a was brought about with ZnX
group 3, Table 1). Further investigation with other zinc salts
was, however, unsuccessful (see the zinc salts listed in groups
4
(group 2),
presence of HgCl
solvent and the catalyst was briefly studied. In THF at 0-5
C (ca. 2 h), Mg was consumed smoothly with formation of
gray precipitates. Surprisingly, the concentration was almost
M by titration, which was consistent with the result that
an attempted reaction of the mixture (supernatant and
precipitates) with Ph(CH CHO (7) did not afford any
2
(0.2 mol %), the requirement of the
2
(
°
1
and 2).
0
2
Concentrations of 2a prepared with ZnX of group 3 are
summarized in Table 2. For the two catalyst quantities (2
2 2
)
alcoholic products. These results indicate a pathway to
quench anions 2a and/or 6. One possibility is a coupling of
Table 2. Concentration of 2a vs Quantity of ZnX
2
(
5) Paquette, L. A.; Han, Y.-K. J. Am. Chem. Soc. 1981, 103, 1831-
mol %
of ZnX2
1
1
835.
(
6) Daniels, R. G.; Paquette, L. A. Tetrahedron Lett. 1981, 22, 1579-
ZnCl2
ZnBr2
ZnI2
582.
(
7) (a) Corey, E. J.; Kirst, H. A. Tetrahedron Lett. 1968, 5041-5043.
b) Corey, E. J.; R u¨ cker, C. Tetrahedron Lett. 1982, 23, 719-726. (c)
Commercon, A.; Normant, J.; Villieras, J. J. Organomet. Chem. 1975, 93,
4
4
2
1
2
3
4
5
0.39
0.41
0.51
0.52
(
0.31
0.29
0
15-421. (d) Pearson, N. R.; Hahn, G.; Zweifel, G. J. Org. Chem. 1982,
7, 3364-3366. (e) Ma, S.; Zhang, A.; Yu, Y.; Xia, W. J. Org. Chem.
000, 65, 2287-2291.
0.35
a
0.49
(8) (a) Hooz, J.; Calzada, J. G.; McMaster, D. Tetrahedron Lett. 1985,
a
Mg turnings from Aldrich gave a similar result (0.48 M).
2
6, 271-274. (b) Hooz, J.; Cabezas, J.; Musmanni, S.; Calzada, J. Org.
Synth. 1990, 69, 120-127. (c) Cabezas, J.; Alvarez, L. X. Tetrahedron
Lett. 1998, 39, 3935-3958. (d) Lipshutz, B. H.; Lower, A.; Berl, V.; Schein,
K.; Wetterich, F. Org. Lett. 2005, 7, 4095-4097.
(9) For example: (a) Masuyama, Y.; Ito, A.; Fukuzawa, M.; Terada,
and 4 mol %), the highest concentrations (0.41 and 0.52 M,
respectively) were recorded with ZnBr and were slightly
better than that obtained above with HgCl (0.38 M). A
similar result was attained with Mg from a different company
see footnote a of Table 2). A somewhat lower concentration
K.; Kurusu, Y. Chem. Commun. 1998, 2025-2026. (b) Alcaide, B.;
Almendros, P.; Aragoncillo, C. Org. Lett. 2000, 2, 1411-1414. (c) Nair,
V.; Jayan, C. N.; Ros, S. Tetrahedron 2001, 57, 9453-9459. (d) Inoue,
M.; Nakada, M. Angew. Chem., Int. Ed. 2006, 45, 252-255.
2
2
(
10) (a) Oppolzer, W.; Flaskamp, E.; Bieber, L. W. HelV. Chim. Acta
001, 84, 141-145. (b) Schrock, R. R.; Duval-Lungulescu, M.; Tsang, W.
C. P.; Hoveyda, A. H. J. Am. Chem. Soc. 2004, 126, 1948-1949.
(
2
was recorded with 1 mol %. On the basis of these results,
3536
Org. Lett., Vol. 9, No. 18, 2007