for organometallic reagents. DMSO has long been regarded
as an excellent polar solvent for a wide variety of organic
reactions6 but has been hitherto thought of as an unlikely
solvent for organozinc reactions.7
(ET)11 of CH3CN (46) is largely similar to those of DMF (43.8)
and DMSO (45.0). On the other hand, the donor numbers
(DN)12 of DMF (26.6) and DMSO (29.8) are higher values
than that of CH3CN (14.1). The highest DN solvent gave the
most excellent result.
The synthesis of substituted allenes has been extensively
studied,8 and the SN2′ reaction of propargyl electrophiles is
one of the important methods by which to achieve this.
However, the use of organiczinc reagent as nucleophiles for
this SN2′ reaction9 has been limited due to their poor
reactivity, and this has led to organozinc reagents being
employed for other modes of allene synthesis instead.10 To
clarify solvent effects on the reactivity of organozinc
reagents, the SN2′ reaction of propargyl electrophiles with
organozinc reagents was investigated using DMSO as a
solvent.
To examine further the scope and limitations of the procedure,
the reactions of other substrates were investigated. 3-Phenyl-
1-phenethylpropargyl mesylate (1a) and 3-butyl-1-phenethyl-
propargyl mesylate (1b) reacted smoothly to give corresponding
1,1,3-trisubstituted allenes 2a and 2b (Table 2, entries 1 and
2). Various substituents on the aromatic ring of the 3-arylpro-
pargyl mesylates (2c-h) were also compatible with this allene
synthesis. Substitution with an electron-donating methoxy group
is acceptable to the reaction, and the corresponding allene 2c
was obtained in good yield (Table 2, entry 3). However, yields
of allenes 2d,e were moderate when methyl-substituted sub-
strates 1d,e were utilized (Table 2, entries 4 and 5). The
tolerance of the alkoxycarbonyl group (1f), the cyano group
(1g), and the bromo substituent (1h) to the allene synthesis is
considered to be synthetically important (Table 2, entries 6-8).
The reaction of the substrate with terminal alkyne 1i was also
found to be successful, and 1,3-disubstituted allene 2i was
selectively obtained in high yield (Table 2, entry 9). It is
noteworthy that no deprotonation of the terminal alkyne was
observed during the reaction.10a,b The allenylsilyl compound
2j was obtained from the trimethylsilylated substrate 1j using
similar reaction conditions (Table 2, entry 10). The high
functional group tolerance of this allene synthesis using
organozinc reagents in DMSO is considered to offer sig-
nificant advantages over the use of conventional organome-
tallic nucleophiles.8b Lastly, di-n-butylzinc, prepared from
n-butyllithium and zinc chloride, can be used for the reaction,
allowing the corresponding allene 2k to be obtained quan-
titatively (Table 2, entry 11).
In our preliminary experiment, the reaction of diethylzinc
and 3-phenylpropargyl mesylate (1) in various organic solvents
was carried out at room temperature (Table 1). In nonpolar
Table 1. Solvent Effect on SN2′ Reaction of 1a
entry
solvent
ET
DN
time (h)
yield (%)b
1
2
3
4
5
6
CH2Cl2
toluene
THF
CH3CN
DMF
41.1
33.9
37.4
46.0
43.8
45.0
-
-
24
24
24
24
24
18
n.r.
n.r.
n.r.
n.r.
43
20.0
14.1
26.6
29.8
DMSO
90
a All reactions were carried out using 3-phenylpropargyl mesylate (1)
A functionalized alkylzinc halide has also been employed
for this allene synthesis, with ethoxycarbonylpropylzinc
bromide prepared using Rieke’s zinc13 having been reacted
with 1a in DMSO to give 3 in 57% yield (Scheme 1).
To examine the stereochemistry of allene formation, an
enantiomerically pure substrate was employed for the reaction.
The chiral propargyl mesylate 514 was prepared from (R)-(+)-
3-butyn-2-ol and reacted with LiCl-free dibutylzinc15 to give
chiral allene 6. The absolute configuration of 6 was determined
as (R) by converting 6 to the known chiral furanone 8,16 the
(0.3 mmol) and diethylzinc (0.6 mmol) at rt. b Isolated yield.
solvents such as CH2Cl2 and toluene, the reaction did not
proceed at all (Table 1, entries 1 and 2). In polar solvents such
as THF and CH3CN, failure to react was again observed (Table
1, entries 3 and 4). To our surprise, in polar and strongly donor
solvents such as DMF and DMSO, the SN2′ reaction was
dramatically promoted, and the target allene 2 was obtained
(Table 1, entries 5 and 6). The best result (90%) was observed
when DMSO was employed as solvent. The solvent polarlity
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Org. Lett., Vol. 10, No. 15, 2008