HgCl2-Catalyzed Benzylation of 1-Aryl-1-propynes

Full text of DOI:10.1021/jo972269f

J . Org. Chem. 1998, 63, 3497-3498
3497
Sch em e 1
HgCl2-Ca ta lyzed Ben zyla tion of
1-Ar yl-1-p r op yn es†
Shengming Ma* and Lisha Wang
Laboratory of Organometallic Chemistry, Shanghai Institute
of Organic Chemistry, Chinese Academy of Sciences, 354
Fenglin Lu, Shanghai 200032, People’s Republic of China
Received December 15, 1997
Formation of C-C bonds is one of the major objectives
in organic synthesis. Cross-coupling reaction between an
organometallic reagent (RMLn) and R′X (X ) leaving
group) with or without transition-metal catalysts is very
attractive because of the easy availability of both reac-
tants.1 C-H activation using strong bases (deprotona-
tion), halide-metal exchange, direct reaction of an alkyl
halide with a metal, carbometalation (including hydro-
metalation), and transmetalation are major pathways to
organometallic reagents (RMLn). Although alkylation of
1-(trimethylsilyl)-1-propyne using n-BuLi and an alky-
lating agent is well documented,2 the corresponding
lithiation of 1-phenyl-1-propyne was reported to be
problematic.3 During the course of our study on transi-
tion-metal-catalyzed intramolecular cyclization reaction,
the product from benzylation of 1-aryl-1-propyne was
desired. We wish to report here our newly developed
novel methodology for benzylation of 1-aryl-1-propynes.
As expected,3 lithiation of 1-phenyl-1-propyne at -78
°C and subsequent addition of benzyl bromide in THF
afforded the expected product 2a in <5% yield (Scheme
1). After screening several additives, it is interesting to
observe that lithiation of 1-phenyl-1-propyne in the pres-
ence of 1.5 mol % HgCl2 at -78 °C followed by the
addition of benzyl bromide gave the monobenzylation
product 2a in desirable 65% yield (Scheme 1). The
formation of dibenzylated product 3 was not observed.
This new method is general for benzylic alkylation of
1-aryl-1-propynes. Some results are summarized in
Table 1. Several points are noteworthy: (1) the yields
are from moderate to good; (2) both chlorides and
bromides are effective; (3) while the reactions of benzylic
halides with an electron-donating group on the aromatic
ring are high yielding, p-nitrobenzyl bromide did not
afford the expected product in decent yield; and (4)
regioisomers, e.g., 2f and 2g, were prepared cleanly just
by switching the corresponding substituents in the start-
ing alkynes and benzylic halides (compare entries 6 and
7, Table 1).
Ta ble 1. Ben zyla tion of 1-Ar y-l-p r op yn esa
a
Alkyne (1.0 mmol), HgCl2 (1.5 mol %), n-BuLi in n-heptane
b
(1.0 mmol), and benzylic halide (1.2 mmol) were used. Isolated
yield. c 1.4 equiv of n-BuLi was used.
sized by HMPA-mediated methylation of lithium pheny-
lacetylide with MeI in THF. However, the reaction
between lithium phenylacetylide and 2-phenylethyl bro-
mide/iodide in the presence of HMPA afforded only a
trace amount of the title compound 2a . The major
reaction was the elimination reaction of 2-phenylethyl
halides affording styrene. In both cases, halides are
recovered in large amounts (Scheme 2).
In conclusion, we have developed an efficient method-
ology for the benzylation of 1-aryl-1-propynes and a
convenient route to 1,4-diaryl-1-butynes, which are not
easily available from known methods. Due to the easy
availability of both starting compounds, wide scope,
simple operation, and high yield, this reaction will show
its utility in organic synthesis. The effect of HgCl2 in
this reaction and further synthetic applications are under
investigation in our laboratory.
From retrosynthetic analysis, compounds 2 might be
prepared by direct reaction of Ar′CH2CH2X with lithium
arylacetylide. Indeed, 1-phenyl-1-propyne was synthe-
† Dedicated to Professor Xiyan Lu on the occasion of his 70th
birthday.
(1) Trost, B. M., Fleming, I., Eds. Comprehensive Organic Synthesis;
Pergamon Press: Oxford, 1991; Vol. 3.
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Ireland, R. E.; Dawson, M. L.; Lipinski, C. A. Tetrahedron Lett. 1970,
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S0022-3263(97)02269-X CCC: $15.00 © 1998 American Chemical Society
Published on Web 04/30/1998

3498 J . Org. Chem., Vol. 63, No. 10, 1998
Notes
with saturated NaCl, drying over MgSO4, and chromatography
on silica gel (petroleum ether) afforded 267 mg (65%) of 2a :
liquid; 1H NMR δ 2.65 (t, J ) 7.39 Hz, 2 H), 2.90 (t, J ) 7.39
Hz, 2 H), 7.10-7.50 (m, 10 H); 13C NMR 21.833, 35.370, 89.572,
96.298, 124.046, 127.700, 128.292, 128.516, 128.642, 131.666,
Sch em e 2
132.434, 140.808; MS m/e 206 (M+, 100); IR (neat) 2226 cm-1
.
Anal. Calcd for C16H14: C, 93.16; H, 6.84. Found: C, 92.75; H,
7.08.
The following compounds were prepared similarly.
1-P h en yl-4-(4′-m eth oxylp h en yl)-1-bu tyn e (2b): liquid;
yield 61%; 1H NMR δ 2.58 (t, J ) 7.32 Hz, 2 H), 2.82 (t, J )
7.32 Hz, 2 H), 3.70 (s, 3 H), 6.75 (d, J ) 8.55 Hz, 2 H), 7.15 (d,
J ) 8.55 Hz, 2 H), 7.15∼7.40 (m, 5 H); MS m/e 236 (M+, 12.08),
121 (100); IR (neat) 2346 cm-1
. Anal. Calcd for C17H16O: C,
86.40; H, 6.82. Found: C, 86.59; H, 6.92.
1-P h en yl-4-(4′-m eth ylp h en yl)-1-bu tyn e (2c): liquid; yield
71%; 1H NMR δ 2.30 (s, 3 H), 2.65 (t, J ) 7.49 Hz, 2 H), 2.85 (t,
J ) 7.49 Hz, 2 H), 6.95-7.40 (m, 9 H); MS m/e 220 (M+, 27.37),
Exp er im en ta l Section
105 (100); IR (neat) 2252 cm-1
.
Anal. Calcd for C17H16
: C,
Ma ter ia ls. n-BuLi (from Fluka, 2.7 M in n-heptane), phe-
nylacetylene (from Fluka), 1-(chloromethyl)naphthalene (from
TCI), 1-bromonaphthalene (from TCI), and 4-methoxybenzyl
chloride (from Aldrich) are commercially available and used as
it is. 4-Methylbenzyl bromide, 2-bromobenzyl bromide, and
3-chlorobenzyl bromide were prepared from the BPO-catalyzed
benzylic bromination reactions of the corresponding methyl-
substituted arenes with NBS in CCl4.4
1-Naphthylacetylene was prepared by the Pd(PPh3)4-catalyzed
coupling reaction of ethynylzinc chloride with 1-iodonaphthalene
in THF at room temperature in 73% yield.5 The 1H NMR data
were the same as reported in ref 6.
1-Phenyl-1-propyne and 1-(1′-naphthyl)-1-propyne were pre-
pared according to a published procedure7 in 90% and 63% yield,
respectively. After the addition of MeI and HMPA, the reaction
was carried out at room temperature and under reflux, respec-
tively. The 1H NMR data were the same as reported in refs 8
and 9.
HgCl2-Catalyzed Ben zylation of 1-Ar yl-1-pr opyn es. Syn -
th esis of 1,4-Dip h en yl-1-bu tyn e (2a ). Typ ica l P r oced u r e.
To a solution of 1-phenyl-1-propyne (232 mg, 2.0 mmol) and
HgCl2 (8 mg, 1.5 mol %) in THF (5 mL) was added n-BuLi (2.7
M in n-heptane, 0.74 mL, 2.0 mmol) at -78 °C. After 1 h, benzyl
bromide (2.4 mmol) was added at -78 °C, and the reaction was
allowed to warm to room temperature naturally. After 4 h at
room temperature, the reaction was quenched with saturated
NH4Cl. Extracting with petroleum ether (60-90 °C), washing
92.68; H, 7.32. Found: C, 93.06; H, 7.12.
1-P h en yl-4-(3′-ch olor op h en yl)-1-bu tyn e (2d ): liquid; yield
65%; 1H NMR δ 2.65 (t, J ) 7.39 Hz, 2 H), 2.95 (t, J ) 7.39 Hz,
2 H), 6.95-7.60 (m, 9 H); MS m/e 242 (M+(37Cl), 10.08), 240 (M+-
(
C
35Cl), 27.19), 115 (100); IR (neat) 2228 cm-1; HRMS calcd for
16H13Cl(35Cl) 240.0704, found 240.0703.
1-P h en yl-4-(2′-br om op h en yl)-1-bu tyn e (2e): liquid; yield
70%; 1H NMR δ 2.75 (t, J ) 7.40 Hz, 2 H), 3.05 (t, J ) 7.40 Hz,
2 H), 7.02-7.60 (m, 9 H); MS m/e 286 (M+(81Br), 0.62), 284 (M+-
(
79Br), 0.78), 205 (100); IR (neat) 2318 cm-1
.
Anal. Calcd for
C16H13Br: C, 67.39; H, 4.59. Found: C, 66.92; H, 4.60.
1
1-P h en yl-4-n a p h th yl-1-bu tyn e (2f): liquid; yield 79%; H
NMR δ 2.85 (t, J ) 7.53 Hz, 2 H), 3.45 (t, J ) 7.63 Hz, 2 H),
7.10-8.25 (m, 12 H); MS m/e 256 (M+, 29.59), 141 (100); IR (neat)
2228 cm-1. Anal. Calcd for C20H16: C, 93.71; H, 6.29. Found:
C, 93.74; H, 6.72.
1-Na p h th yl-4-p h en yl-1-bu tyn e (2g): solid; mp 49-51 °C;
yield 73%; 1H NMR δ 2.85 (t, J ) 7.26 Hz, 2 H), 3.05 (t, J )
7.26 Hz, 2 H), 7.10-8.20 (m, 12 H); MS m/e 256 (M+, 50.39),
165 (100); IR (neat) 2225 cm-1
.
Anal. Calcd for C20H16
: C,
93.71; H, 6.29. Found: C, 93.92; H, 6.48.
Ack n ow led gm en t. We thank the NNSF of China
and Laboratory of Organometallic Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of
Sciences, for financial support.
1
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Su p p or tin g In for m a tion Ava ila ble: The H NMR spec-
trum of compound 2d (1 page). This material is contained in
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J O972269F