Synthesis of 1,5-enynes by Broonsted acid catalyzed substitution of propargylic alcohols and one-pot synthesis of bicyclo[3.1.0]hexenes

Article abstract of DOI:10.1055/s-2007-983831

A practical air and moisture tolerant procedure for the preparation of 1,5-enynes from propargylic alcohols by the Bronsted acid catalyzed direct propargylic substitution of the hydroxy group with allylsilanes is described. Also, a straightforward sequent

Full text of DOI:10.1055/s-2007-983831

3252
PRACTICAL SYNTHETIC PROCEDURES
Synthesis of 1,5-Enynes by Brønsted Acid Catalyzed Substitution of
Propargylic Alcohols and One-Pot Synthesis of Bicyclo[3.1.0]hexenes
S
ynthesis of 1,5-E
o
nynes and
O
b
ne-Pot Synt
e
hesis of Bic
r
yclo[3.1
t
.0]hex
o
enes Sanz,*a Alberto Martínez,a Delia Miguel,a Julia M. Álvarez-Gutiérrez,a Félix Rodríguez*b
a
Departamento de Química, Área de Química Orgánica, Facultad de Ciencias, Universidad de Burgos,
Pza. Misael Bañuelos s/n, 09001-Burgos, Spain
Fax +34(947)258831; E-mail: rsd@ubu.es
b
Instituto Universitario de Química Organometálica ‘Enrique Moles’, Universidad de Oviedo,
C/ Julián Clavería 8, 33006-Oviedo, Spain
PSP
Fax +34(98)5103447; E-mail: frodriguez@uniovi.es
Received 12 March 2007
No98
Abstract: A practical air and moisture tolerant procedure for the preparation of 1,5-enynes from propargylic alcohols by the Brønsted acid
catalyzed direct propargylic substitution of the hydroxy group with allylsilanes is described. Also, a straightforward sequential catalytic
protocol for the synthesis of bicyclo[3.1.0]hexane derivatives, from readily available starting materials, is presented.
Key words: catalysis, allylations, alcohols, enynes, tandem reactions
OH
R3
PTS (5 mol%)
R1
Procedure 1
R3
SiMe3
+
MeCN, 20 °C
R1
R2
2a (R3 = H), 2b (R3 = Ph)
3
R2
1
OH
R1
H
R2
1
1)
PTS (5 mol%), MeCN, 20 °C
R1
Procedure 2
+
2) (PPh3)AuCl/AgSbF6 (5 mol%)
20–50 °C
R2
SiMe3
4
2a
Scheme 1
The development of novel methods for the direct substitu- highly desirable. In this context, we have recently found
tion of alcohols is one of the most challenging goals in or- that simple Brønsted acids like p-toluenesulfonic acid
ganic chemistry. For the substitution of propargylic (PTSA) catalyze the direct nucleophilic substitution of
alcohols, reactions have been traditionally carried out us- propargylic,7 as well as allylic and benzylic alcohols.8
ing the Nicholas protocol with some limitations (several
On the other hand, 1,5-enynes are useful substrates for
steps and a stoichiometric amount of [Co2(CO)8]).1 Very
several cycloisomerization processes.9 For example, the
recently, a few catalytic methodologies for the direct sub-
formation of interesting bicyclo[3.1.0]hexenes from 1,5-
stitution of propargylic alcohols, including allylation re-
enynes has been reported using platinum and gold com-
actions, have been reported in the presence of transition
plexes.10
metal complexes of ruthenium,2 rhenium,3 or gold,4 as
Herein, we describe a simple protocol for accessing 1,5-
enynes through a Brønsted acid catalyzed substitution re-
action of propargylic alcohols and allylsilanes (Procedure
1). Also, a straightforward procedure for the synthesis of
bicyclo[3.1.0]hexenes through a one-pot tandem se-
quence involving both, Brønsted acid and gold-catalyzed
reactions is reported (Procedure 2)11(Scheme 1).
well as other metal salts like BiCl3.5 Moreover, cations de-
rived from propargylic alcohols can be generated from the
corresponding alkoxides in the presence of BCl3 and fur-
ther allylated in situ.6 However, all these strategies are
limited by the syntheses and costs of the catalysts or by the
need for anhydrous conditions. Thus, the development of
efficient substitution reactions of propargylic alcohols us-
ing inexpensive reagents and mild conditions would be
As shown in Procedure 1, treatment of secondary propar-
gylic alcohols 1 with a slight excess (1.1 equiv) of the al-
lylsilanes 212 and 5 mol% of p-toluenesulfonic acid
(PTSA) in analytical grade acetonitrile (1 mL mmol–1) at
room temperature led to the formation of 1,5-enynes 3 in
SYNTHESIS 2007, No. 20, pp 3252–3256
x
x.
x
x
.
2
0
0
7
Advanced online publication: 30.07.2007
DOI: 10.1055/s-2007-983831; Art ID: Z06107SS
© Georg Thieme Verlag Stuttgart · New York

PRACTICAL SYNTHETIC PROCEDURES
Synthesis of 1,5-Enynes and Bicyclo[3.1.0]hexenes
3253
high yields.13 Regarding the structure of the starting
alkynol 1, it is important to note that secondary benzylic
substrates are needed in order to achieve high conver-
sions. Thus, aryl (1a,b), functionalized aryl (1c–e), or het-
eroaryl alkynols (1f) gave the expected substitution
compounds 3 in generally short reaction times (Table 1).
Moreover, the R2 substituent of the starting alkyne can be
an aromatic (1a,e,f) or an aliphatic (1b–d) group. Regard-
ing the starting allylsilane, both 2a (R3 = H) and 2b
(R3 = Ph) gave similar results.
Table 2 One-Pot Synthesis of Bicyclo[3.1.0]hexenes 4 from
Alkynols 1
1) 2a (1.1 equiv)
H
OH
PTSA (5 mol%)
R1
MeCN, 20 °C
R1
2) (PPh3)AuCl/AgSbF6 (5 mol%)
R2
MeCN, 20–50 °C
R2
1
4
Alkynol R1
R2
Product
4a
Yield (%)a
1a
1b
1c
1d
1e
Ph
Ph
64
Ph
n-Bu
n-Bu
n-Bu
4b
82
Table 1 PTSA-Catalyzed Allylation of Alkynols 1 with Allylsi-
lanes 2
4-ClC6H4
3-BrC6H4
4c
52b
50b
61
Alkynol R1
R2
AllylsilaneProduct Yield (%)a
4d
1a
1b
1c
1d
1e
1f
Ph
Ph
2a
2a
2a
2a
2a
2a
2b
2b
3aa
3ba
3ca
3da
3ea
3fa
73
3-MeOC6H4
Ph
4e
a Isolated yields based on starting alkynol 1.
Ph
n-Bu
n-Bu
n-Bu
Ph
85
b The first step was carried out at reflux; ca. 20% of the symmetric
4-ClC6H4
3-BrC6H4
3-MeOC6H4
3-thienyl
Ph
62b
60b
74
ethers derived from the corresponding 1 were also generated.
In conclusion, we have developed a practical method for
the preparation of 1,5-enynes from propargylic alcohols
by the Brønsted acid catalyzed direct propargylic substi-
tution of the hydroxy group with allylsilanes. The reaction
is tolerant to air and moisture. This metal-free strategy
represents a clean, environmentally friendly, and synthet-
ically competitive alternative to the already established
use of metal complexes. Moreover, we have also devel-
oped a practical sequential catalytic protocol for the syn-
thesis of bicyclo[3.1.0]hexenes from easily available
starting materials. This procedure provides a clear exam-
ple of concurrent tandem catalysis with potential applica-
tion in diversity-oriented synthesis.
Ph
80
1b
1c
n-Bu
n-Bu
3bb
3cb
81c
86c
4-ClC6H4
a Isolated yields based on starting alkynol 1.
b Carried out at reflux; ca. 20% of the symmetric ethers derived from
the corresponding alkynol 1 were also isolated.
c Carried out at reflux. Obtained as a ca. 1:1 mixture of diastereoiso-
mers.
These results prompted us to develop a catalytic sequen-
tial reaction to synthesize complex organic molecules
from simple and readily available alkynols and allylsi-
lanes. Our attention was focused on the reported gold-cat-
alyzed cycloisomerization of enyne systems.10c
All reactions were carried out under air in oven-dried glassware
with magnetic stirring. NMR spectra were recorded in CDCl3 at 300
1
or 400 MHz for H NMR and 75.4 or 100.6 MHz for 13C NMR
(Varian Mercury-Plus 300 and Varian Inova 400). Chemical shifts
are reported in ppm relative to TMS. IR spectra were recorded on a
Nicolet Impact 410 (Software Omnic for Windows) spectrometer.
Low-resolution MS were recorded using a GC/MS combination of
the type HP 6890 and MSD 5973 with a HP-5MS column. HRMS
were recorded on a Micromass Autospec spectrometer (EI, 70 eV).
Flash column chromatographic purifications were carried out using
Merck Kieselgel 60 (230–400 mesh ASTM). Solvents used were
analytical grade (SDS). p-Toluenesulfonic acid monohydrate
(PTSA) reagent grade (98%) was purchased from Aldrich. Other
commercially available starting materials were purchased form
Acros, Fluka and Aldrich and used without further purification. The
starting propargylic alcohols 1 were synthesized as previously de-
scribed,7a by addition of the corresponding lithium acetylide to the
carbonyl derivative.
Thus, as shown in Procedure 2, the consecutive reaction
of propargylic alcohols 1 and the allyltrimethylsilane 2a
with PTSA (5 mol%) and an in situ formed cationic
gold(I) complex (5 mol%) led to the formation of bicyc-
lo[3.1.0]hexene derivatives 4 in moderate to high yields.
It should be remarked that this one-pot process does not
require any solvent change or the removal of the PTSA
prior to the addition of the gold catalyst.14 These reactions
were easily followed by GC-MS. When the PTSA-cata-
lyzed reaction of alkynols 1 with 2a, to give the interme-
diate enynes 3, was completed, the resulting mixture was
added to a preformed suspension of chloro(triphenylphos-
phine)gold and silver hexafluoroantimonate (5 mol%) in
MeCN. The cycloisomerization reaction is slow even at
PTSA-Catalyzed Allylation of Propargylic Alcohols; 1,5-
refluxing acetonitrile. Surprisingly, we have observed that Enynes 3 (Procedure 1)
The corresponding propargylic alcohol 1 (3 mmol) was dissolved in
the reactions are always completed when the solvent is re-
moved under reduced pressure using a water bath at ca. 50
°C. In this way, bicyclo[3.1.0]hexene derivatives 4 were
easily isolated after silica gel column chromatography
with hexanes (Table 2).
MeCN (3 mL). Then, silane 2 (3.3 mmol) and PTSA (28.5 mg, 0.15
mmol) were added. The mixture was stirred at r.t. or at reflux until
all the starting material was consumed (determined by TLC and
GC/MS analysis). The solvent was removed under reduced pressure
Synthesis 2007, No. 20, 3252–3256 © Thieme Stuttgart · New York

3254
R. Sanz et al.
PRACTICAL SYNTHETIC PROCEDURES
and the residue was purified by column chromatography (eluent:
hexane) affording the corresponding 1,5-enynes 3.
1H NMR (300 MHz, CDCl3): d = 7.52 (s, 1 H), 7.37–7.33 (m, 1 H),
7.30–7.25 (m, 1 H), 7.18 (t, J = 7.7 Hz, 1 H), 5.90–5.75 (m, 1 H),
5.09–5.00 (m, 2 H), 3.67–3.60 (m, 1 H), 2.48–2.41 (m, 2 H), 2.24
(td, J = 6.8, 2.0 Hz, 2 H), 1.58–1.36 (m, 4 H), 0.93 (t, J = 7.0 Hz, 3
H).
13C NMR (75.4 MHz, CDCl3): d = 144.6, 135.4, 130.7, 130.0,
129.8, 126.3, 122.5, 117.2, 84.5, 80.4, 43.0, 37.8, 31.2, 22.1, 18.6,
13.8.
1,3-Diphenyl-5-hexen-1-yne (3aa)
Obtained from alkynol 1a (0.62 g, 3 mmol) and silane 2a (0.38 g,
3.3 mmol), according to Procedure 1 at r.t. for 1 h, as a colorless oil
(0.51 g, 73%) after column chromatography (hexane); Rf = 0.28
(hexane).
IR (film): 3422, 3061, 3027, 2198, 1721, 1683, 1596, 1450, 915,
757, 694 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.60–7.20 (m, 10 H), 6.04–5.88
(m, 1 H), 5.20–5.08 (m, 2 H), 3.95 (t, J = 7.2 Hz, 1 H), 2.68–2.58
(m, 2 H).
MS (EI, 70 eV): m/z (%) = 292 (2, [M+ + 2]), 290 (2, [M+]), 251
(100), 249 (100), 169 (60), 155 (64), 141 (45), 128 (73), 115 (22).
HRMS (EI): m/z [M+ – C3H5] calcd for C13H14Br: 249.0279; found:
249.0268.
13C NMR (75.4 MHz, CDCl3): d = 141.5, 135.6, 131.8 (2 C), 128.6
(2 C), 128.3 (2 C), 127.9, 127.7, 127.0, 123.8, 117.2, 91.0, 83.9,
42.9, 38.7.
MS (EI, 70 eV): m/z (%) = 232 (1, [M+]), 191 (100).
HRMS (EI): m/z [M+] calcd for C18H16: 232.1252; found: 232.1261.
1-Methoxy-3-(1-phenylethynylbut-3-enyl)benzene (3ea)
Obtained from alkynol 1e (0.71 g, 3 mmol) and silane 2a (0.38 g,
3.3 mmol), according to Procedure 1 at r.t. for 1 h, as a pale yellow
oil (0.58 g, 74%) after column chromatography (hexane); Rf = 0.40
(hexane–EtOAc, 20:1).
1H NMR (300 MHz, CDCl3): d = 7.49–7.46 (m, 2 H), 7.33–7.29 (m,
4 H), 7.05–7.03 (m, 2 H), 6.85–6.81 (m, 1 H), 6.02–5.89 (m, 1 H),
5.18–5.10 (m, 2 H), 3.93 (t, J = 7.1 Hz, 1 H), 3.84 (s, 3 H), 2.63 (t,
J = 7.1 Hz, 2 H).
13C NMR (75.4 MHz, CDCl3): d = 160.0, 143.3, 135.8, 132.0 (2 C),
129.8, 128.5 (2 C), 128.1, 124.0, 120.3, 117.4, 113.8, 112.4, 91.1,
84.2, 55.5, 43.0, 38.9.
MS (EI, 70 eV): m/z (%) = 262 (9, [M+]), 221 (100), 189 (6), 178
(11), 152 (5).
(1-Allylhept-2-ynyl)benzene (3ba)
Obtained from alkynol 1b (0.56 g, 3 mmol) and silane 2a (0.38 g,
3.3 mmol), according to Procedure 1 at r.t. for 1 h, as a colorless oil
(0.54 g, 85%) after column chromatography (hexane); Rf = 0.48
(hexane).
IR (film): 2956, 2929, 2867, 2353, 1641, 1554, 917 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.47–7.25 (m, 5 H), 6.03–5.88 (m,
1 H), 5.19–5.09 (m, 2 H), 3.77 (tt, J = 7.1, 2.2 Hz, 1 H), 2.57 (t,
J = 7.2 Hz, 2 H), 2.36–2.28 (m, 2 H), 1.66–1.45 (m, 4 H), 1.01 (t,
J = 7.1 Hz, 3 H).
HRMS (EI): m/z [M+] calcd for C19H18O: 262.1358; found:
262.1368.
13C NMR (75.4 MHz, CDCl3): d = 142.2, 135.9, 128.4 (2 C), 127.6
(2 C), 126.6, 116.7, 83.8, 81.2, 43.2, 38.1, 31.3, 22.0, 18.6, 13.7.
MS (EI, 70 eV): m/z (%) = 212 (2, [M+]), 197 (2), 183 (2), 171
(100), 141 (11), 129 (45), 115 (27), 91 (37).
3-(1-Phenylethynylbut-3-enyl)thiophene (3fa)
Obtained from alkynol 1f (0.64 g, 3 mmol) and silane 2a (0.38 g, 3.3
mmol), according to Procedure 1 at r.t. for 1 h, as a pale yellow oil
(0.57 g, 80%) after column chromatography (hexane); Rf = 0.22
(hexane).
HRMS (EI): m/z [M+ – C3H5] calcd for C13H15: 171.1174; found:
IR (film): 3100, 2933, 2906, 2229, 1489, 1435, 917, 688 cm–1.
171.1160.
1H NMR (300 MHz, CDCl3): d = 7.56–7.50 (m, 2 H), 7.40–7.28 (m,
5 H), 7.21–7.17 (m, 1 H), 6.09–5.94 (m, 1 H), 5.27–5.15 (m, 2 H),
4.09 (t, J = 6.9 Hz, 1 H), 2.74–2.65 (m, 2 H).
13C NMR (75.4 MHz, CDCl3): d = 141.8, 135.4, 131.7 (2 C), 128.3
(2 C), 127.9, 127.1, 125.9, 123.6, 121.2, 117.3, 90.8, 83.3, 41.6,
33.8.
MS (EI, 70 eV): m/z (%) = 238 (4, [M+]), 197 (100), 152 (6).
HRMS (EI): m/z [M+] calcd for C16H14S: 238.0816; found:
1-(1-Allylhept-2-ynyl)-4-chlorobenzene (3ca)
Obtained from alkynol 1c (0.67 g, 3 mmol) and silane 2a (0.68 g, 6
mmol), according to Procedure 1 at reflux for 12 h, as a colorless oil
(0.46 g, 62%) after column chromatography (hexane); Rf = 0.41
(hexane).
IR (film): 3090, 2937, 2861, 2235, 1723, 1489, 1086 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.30–7.28 (m, 4 H), 5.91–5.75 (m,
1 H), 5.07–4.99 (m, 2 H), 3.65 (tt, J = 7.0, 2.2 Hz, 1 H), 2.44 (tt,
J = 7.0, 1.2 Hz, 2 H), 2.24 (td, J = 6.9, 2.2 Hz, 2 H), 1.58–1.36 (m,
4 H), 0.93 (t, J = 7.2 Hz, 3 H).
238.0819.
[1-(1-Phenylallyl)hept-2-ynyl]benzene (3bb)
13C NMR (75.4 MHz, CDCl3): d = 140.7, 135.4, 132.4, 129.0 (2 C),
128.5 (2 C), 117.1, 84.2, 80.7, 43.1, 37.5, 31.2, 22.1, 18.6, 13.8.
MS (EI, 70 eV): m/z (%) = 246 (2, [M+]), 205 (100), 189 (6), 163
(20), 149 (17), 125 (51), 115 (8).
HRMS (EI): m/z [M+ – C3H5] calcd for C13H14Cl: 205.0784; found:
205.0774.
Obtained as a ca. 1:1 mixture of diastereoisomers from alkynol 1b
(0.56 g, 3 mmol) and silane 2b (0.63 g, 3.3 mmol), according to Pro-
cedure 1 at reflux for 30 min, as a pale yellow oil (0.70 g, 81%) after
column chromatography (hexane); Rf = 0.35 (hexane).
IR (film): 3073, 3019, 2956, 2925, 2236, 1493, 1454, 921, 695 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.34–7.22 (m, 18 H), 7.19–7.15
(m, 2 H), 6.43–6.33 (m, 1 H), 6.23–6.13 (m, 1 H), 5.20–4.95 (m, 4
H), 4.09–4.02 (m, 2 H), 3.68–3.60 (m, 2 H), 2.35–2.30 (m, 2 H),
2.24–2.19 (m, 2 H), 1.65–1.33 (m, 8 H), 1.01 (t, J = 7.2 Hz, 3 H),
0.94 (t, J = 7.3 Hz, 3 H).
13C NMR (100.6 MHz, CDCl3): d = 142.4, 141.3, 140.9, 140.5,
139.4, 138.3, 128.9 (2 C), 128.6 (2 C), 128.4 (2 C), 128.3 (2 C),
128.2 (2 C), 128.1 (2 C), 128.0 (2 C), 127.8 (2 C), 126.8, 126.6,
126.5, 126.4, 116.9, 116.2, 85.6, 85.2, 80.2, 79.8, 57.2, 57.1, 44.6,
44.4, 31.2, 31.0, 22.0, 21.9, 18.7, 18.6, 13.8, 13.7.
1-(1-Allylhept-2-ynyl)-3-bromobenzene (3da)
Obtained from alkynol 1d (0.86 g, 3 mmol) and silane 2a (0.68 g, 6
mmol), according to Procedure 1 at reflux for 1 h, as a colorless oil
(0.52 g, 60%) after column chromatography (hexane); Rf = 0.36
(hexane).
IR (film): 3078, 2955, 2929, 2873, 2238, 2202, 1710, 1470, 1419,
1070 cm–1.
Synthesis 2007, No. 20, 3252–3256 © Thieme Stuttgart · New York

PRACTICAL SYNTHETIC PROCEDURES
Synthesis of 1,5-Enynes and Bicyclo[3.1.0]hexenes
3255
MS (EI, 70 eV): m/z (%) = 288 (24, [M+]), 259 (4), 245 (7), 231
(100), 184 (27), 129 (59), 115 (75), 91 (76).
IR (film): 3054, 3027, 2956, 2921, 2855, 1606, 1489, 1446, 1026,
750, 688 cm–1.
HRMS (EI): m/z [M+] calcd for C22H24: 288.1878; found: 288.1877.
H NMR (400 MHz, CDCl3): d = 7.42–7.37 (m, 2 H), 7.33–7.28 (m,
2 H), 7.23–7.18 (m, 1 H), 6.34 (t, J = 1.8 Hz, 1 H), 3.06 (ddd,
J = 16.9, 7.0, 1.8 Hz, 1 H), 2.71 (d, J = 16.9 Hz, 1 H), 1.77–1.68 (m,
1 H), 1.59–1.31 (m, 6 H), 0.94 (t, J = 7.0 Hz, 3 H), 0.83 (dd, J = 7.9,
3.6 Hz, 1 H), 0.28 (t, J = 3.8 Hz, 1 H).
13C NMR (100.6 MHz, CDCl3): d = 138.7, 136.8, 132.4, 128.4 (2
C), 126.8, 125.2 (2 C), 37.0, 36.6, 33.2, 30.9, 23.3, 23.0, 21.4, 14.3.
MS (EI, 70 eV): m/z (%) = 212 (23, [M+]), 170 (50), 155 (100), 141
(17), 115 (16), 91 (16).
HRMS (EI): m/z [M+] calcd for C16H20: 212.1565; found: 212.1570.
[1-(1-(4-Chlorophenyl)allyl)hept-2-ynyl]benzene (3cb)
Obtained as a ca. 1:1 mixture of diastereoisomers from alkynol 1c
(0.67g, 3 mmol) and silane 2b (0.63 g, 3.3 mmol), according to Pro-
cedure 1 at reflux for 12 h, as a pale yellow oil (0.83 g, 86%) after
column chromatography (hexane); Rf = 0.20 (hexane).
IR (film): 3074, 2954, 1647, 1483, 1102, 1015 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.44–7.08 (m, 18 H), 6.41–6.26
(m, 1 H), 6.13–6.09 (m, 1 H), 5.20–4.95 (m, 4 H), 4.07–3.96 (m, 2
H), 3.65–3.51 (m, 2 H), 2.31 (td, J = 6.7, 1.9 Hz, 2 H), 2.21 (td,
J = 6.7, 1.8 Hz, 2 H), 1.64–1.30 (m, 8 H), 0.99 (t, J = 7.2 Hz, 3 H),
0.94 (t, J = 7.1 Hz, 3 H).
13C NMR (75.4 MHz, CDCl3): d = 141.9, 140.9, 139.5, 139.1,
139.0, 138.1, 138.0, 132.4, 132.3, 129.9 (2 C), 129.7 (2 C), 128.8 (2
C), 128.3 (2 C), 128.1 (2 C), 128.0 (2 C), 127.9 (2 C), 126.7 (2 C),
117.2, 116.5, 85.9, 85.6, 79.6, 79.4, 57.1, 57.0, 44.0, 43.8, 31.1,
31.0, 22.1, 21.9, 18.6, 18.5, 13.8 (2 C).
1-Butyl-3-(4-chlorophenyl)bicyclo[3.1.0]hex-2-ene (4c)
Obtained from alkynol 1c (0.45 g, 2 mmol) and silane 2a (0.46 g, 4
mmol), according to Procedure 2, as a colorless oil (0.26 g, 52%) af-
ter column chromatography (hexane); Rf = 0.41 (hexane).
IR (film): 3036, 2921, 1609, 1483, 1091, 819 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.30–7.21 (m, 4 H), 6.31 (t,
J = 1.7 Hz, 1 H), 3.00 (ddd, J = 16.8, 7.0, 1.7 Hz, 1 H), 2.65 (d,
J = 16.8 Hz, 1 H), 1.74–1.63 (m, 1 H), 1.54–1.30 (m, 6 H), 0.92 (t,
J = 7.1 Hz, 3 H), 0.83 (dd, J = 7.9, 3.7 Hz, 1 H), 0.25 (t, J = 3.9 Hz,
1 H).
MS (EI, 70 eV): m/z (%) = 324 (8, [M+ + 2]), 322 (24, [M+]), 265
(100), 230 (23), 155 (28), 125 (68), 117 (91), 91 (45).
HRMS (EI): m/z [M ] calcd for C22H23Cl: 322.1488; found:
322.1517.
13C NMR (75.4 MHz, CDCl3): d = 137.6, 135.3, 133.1, 132.3, 128.4
(2 C), 126.4 (2 C), 37.0, 36.8, 33.1, 30.9, 23.4, 23.0, 21.5, 14.3.
MS (EI, 70 eV): m/z (%) = 246 (1, [M+]), 205 (100), 163 (19), 149
(17), 141 (10), 125 (45), 115 (9).
Tandem PTSA- and Gold-Catalyzed Reaction of Propargylic
Alcohols 1 and Allylsilane 2a; One-Pot Synthesis of Bicyc-
lo[3.1.0]hexenes 4 (Procedure 2)
HRMS (EI): m/z [M+] calcd for C16H19Cl: 246.1175; found:
246.1185.
To a mixture of the corresponding propargylic alcohol 1 (2 mmol)
and PTSA (19 mg, 0.1 mmol) in MeCN (2 mL), was added allyltri-
methylsilane 2a (0.25 g, 2.2 mmol or 0.46 g, 4 mmol for the reac-
tions carried out at reflux). The mixture was stirred at r.t. or at reflux
until all the starting material was consumed (determined by TLC
and GC/MS analysis). The resulting solution was transferred via a
pipette – assisted with MeCN (0.5 mL) – to a flask containing a pre-
formed mixture of (PPh3)AuCl (49.5 mg, 0.1 mmol) and AgSbF6
(34.3 mg, 0.1 mmol). After stirring for 30 min at r.t., the solvent was
removed under reduced pressure (20 mmHg) at 50 °C (water bath)
until dryness. The residue was purified by column chromatography
(eluent: hexane), affording the corresponding bicyc-
lo[3.1.0]hexenes 4.
3-(3-Bromophenyl)-1-butylbicyclo[3.1.0]hex-2-ene (4d)
Obtained from alkynol 1d (0.57 g, 2 mmol) and silane 2a (0.46 g, 4
mmol), according to Procedure 2, as a colorless oil (0.29 g, 50%) af-
ter column chromatography (hexane); Rf = 0.59 (hexane).
IR (film): 3057, 2950, 2924, 1588, 1552, 1475 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.49 (t, J = 1.8 Hz, 1 H), 7.32–
7.24 (m, 2 H), 7.13 (t, J = 7.8 Hz, 1 H), 6.34 (t, J = 1.7 Hz, 1 H),
2.99 (ddd, J = 16.8, 7.0, 1.7 Hz, 1 H), 2.64 (d, J = 16.8 Hz, 1 H),
1.76–1.64 (m, 1 H), 1.52–1.29 (m, 6 H), 0.91 (t, J = 7.1 Hz, 3 H),
0.82 (dd, J = 7.9, 3.7 Hz, 1 H), 0.24 (t, J = 3.9 Hz, 1 H).
1,3-Diphenylbicyclo[3.1.0]hex-2-ene (4a)
13C NMR (75.4 MHz, CDCl3): d = 139.0, 137.4, 134.1, 129.9,
129.5, 128.2, 123.8, 122.7, 36.9, 36.8, 33.0, 30.9, 23.4, 23.0, 21.5,
14.3.
MS (EI, 70 eV): m/z (%) = 292 (17, [M + 2]), 290 (17, [M+]), 250
(35), 248 (35), 235 (20), 233 (20), 168 (36), 154 (100), 128 (10).
HRMS (EI): m/z [M+] calcd for C16H19Br: 290.0670; found:
290.0679.
Obtained from alkynol 1a (0.42 g, 2 mmol) and silane 2a (0.25 g,
2.2 mmol), according to Procedure 2, as a white solid (0.30 g, 64%)
after column chromatography (hexane); mp 46–48 °C; Rf = 0.28
(hexane).
IR (KBr): 3054, 3027, 2910, 2826, 1602, 1505, 750 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.50–7.45 (m, 2 H), 7.39–7.20 (m,
8 H), 6.66–6.64 (m, 1 H), 3.26 (ddd, J = 16.9, 7.0, 1.9 Hz, 1 H), 2.86
(d, J = 16.9 Hz, 1 H), 2.02–1.95 (m, 1 H), 1.66 (dd, J = 8.2, 4.1 Hz,
1 H), 0.81 (t, J = 4.4 Hz, 1 H).
13C NMR (100.6 MHz, CDCl3): d = 142.6, 139.9, 136.4, 131.0,
128.5 (2 C), 128.4 (2 C), 127.2, 126.5 (2 C), 125.8, 125.4 (2 C),
39.9, 37.1, 26.9, 25.3.
3-(3-Methoxyphenyl)-1-phenylbicyclo[3.1.0]hex-2-ene (4e)
Obtained from alkynol 1e (0.48 g, 2 mmol) and silane 2a (0.25 g,
2.2 mmol), according to Procedure 2, as a colorless oil (0.32 g,
61%) after column chromatography (hexane); Rf = 0.21 (hexane).
IR (film): 3057, 2910, 2839, 1598, 1576, 1494, 1293, 1048, 852
cm–1.
MS (EI, 70 eV): m/z (%) = 232 (100, [M+]), 217 (33), 202 (21), 189
(8), 153 (14), 141 (14), 115 (12), 91 (12).
HRMS (EI): m/z [M+] calcd for C18H16: 232.1252; found: 232.1258.
1H NMR (300 MHz, CDCl3): d = 7.42–7.21 (m, 6 H), 7.10 (d,
J = 7.7 Hz, 1 H), 7.30 (s, 1 H), 6.85 (d, J = 8.2 Hz, 1 H), 6.68 (s, 1
H), 3.87 (s, 3 H), 3.27 (dd, J = 16.9, 7.0 Hz, 1 H), 2.87 (d, J = 16.9
Hz, 1 H), 2.05–1.95 (m, 1 H), 1.71–1.65 (m, 1 H), 0.83 (td, J = 4.3,
2.2 Hz, 1 H).
1-Butyl-3-phenylbicyclo[3.1.0]hex-2-ene (4b)
Obtained from alkynol 1b (0.38 g, 2 mmol) and silane 2a (0.25 g,
2.2 mmol), according to Procedure 2, as a colorless oil (0.35 g,
82%) after column chromatography (hexane); Rf = 0.42 (hexane).
Synthesis 2007, No. 20, 3252–3256 © Thieme Stuttgart · New York

3256
R. Sanz et al.
PRACTICAL SYNTHETIC PROCEDURES
13C NMR (75.4 MHz, CDCl3): d = 159.7, 142.5, 139.7, 137.9,
131.4, 129.4, 128.4 (2 C), 126.4 (2 C), 125.8, 118.0, 112.5, 111.1,
55.3, 39.8, 37.1, 26.9, 25.2.
MS (EI, 70 eV): m/z (%) = 262 (100, [M+]), 247 (20), 231 (18), 215
(21), 202 (16), 171 (11), 153 (11), 121 (13), 115 (14).
HRMS (EI): m/z [M+] calcd for C19H18O: 262.1358; found:
262.1351.
(7) (a) Sanz, R.; Martínez, A.; Álvarez-Gutiérrez, J.-M.;
Rodríguez, F. Eur. J. Org. Chem. 2006, 1383. (b) Sanz, R.;
Martínez, A.; Miguel, D.; Álvarez-Gutiérrez, J.-M.;
Rodríguez, F. Org. Lett. 2007, 9, 727.
(8) Sanz, R.; Martínez, A.; Miguel, D.; Álvarez-Gutiérrez, J.-
M.; Rodríguez, F. Adv. Synth. Catal. 2006, 348, 1841.
(9) Zhang, L.; Sun, J.; Kozmin, S. A. Adv. Synth. Catal. 2006,
348, 2271.
(10) (a) Mamane, V.; Gress, T.; Krause, H.; Fürstner, A. J. Am.
Chem. Soc. 2004, 126, 8654. (b) Harrak, Y.; Blaszykowski,
C.; Bernard, M.; Cariou, K.; Mainetti, E.; Mouries, V.;
Dhimane, A. L.; Fensterbank, L.; Malacria, M. J. Am. Chem.
Soc. 2004, 126, 8656. (c) Luzung, M. R.; Markham, J. P.;
Toste, F. D. J. Am. Chem. Soc. 2004, 126, 10858.
(d) Nishibayashi, Y.; Yoshikawa, M.; Inada, Y.; Hidai, M.;
Uemura, S. J. Am. Chem. Soc. 2004, 126, 16066.
(11) Concurrent tandem catalysis constitutes a significant
challenge for synthetic chemists and presents a number of
opportunities to improve chemical transformations, see:
Wasilke, J.-C.; Obrey, S. J.; Baker, R. T.; Bazan, G. C.
Chem. Rev. 2005, 105, 1001.
(12) For the preparation of 2b, see: Hayashi, T.; Kabeta, K.;
Hamachi, I.; Kumada, M. Tetrahedron Lett. 1983, 24, 2865.
(13) In some cases, and when refluxing conditions are required,
competitive formation of the corresponding symmetric ether
is observed (ca. 20% isolated yield).
(14) Some interesting processes in which different transition-
metal catalysts work in the same medium have been
reported. However, in most cases, the reaction conditions
have to be changed. See, for instance: (a) Jeong, N.; Seo, S.
D.; Shin, J. Y. J. Am. Chem. Soc. 2000, 122, 10220.
(b) Son, S. U.; Park, K. H.; Chung, Y. K. J. Am. Chem. Soc.
2002, 124, 6838.
Acknowledgment
We gratefully thank Junta de Castilla y León (BU012A06) and Mi-
nisterio de Educación y Ciencia and FEDER (CTQ2004-08077-
C02-02/BQU) for financial support. A.M. and D.M. are grateful to
MEC for FPU predoctoral fellowships. J.M.A.-G. and F.R. are
grateful to MEC and Fondo Social Europeo (‘Ramón y Cajal’ con-
tracts).
References
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Synthesis 2007, No. 20, 3252–3256 © Thieme Stuttgart · New York