Gold-catalysis: Reactions of furandialkynes

Article abstract of DOI:10.1055/s-2008-1067227

Six furandialkynes were prepared and investigated in gold-catalyzed reactions. Only gold(III) chloride allowed a conversion of the furandialkynes into the corresponding phenol derivative and a further conversion of the ortho-alkynylfurans into benzofurans. Free hydroxy groups in the substrate led to competing hydroalkoxylations to give acylfurans or benzofuran spiroketals. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1067227

PAPER
2707
Gold-Catalysis: Reactions of Furandialkynes
Gold-Catalysis:
R
e
.
actions of Fu
S
randialkynestephen K. Hashmi,* Elisabeth Enns, Tanja M. Frost, Sascha Schäfer, Wolfgang Frey, Frank Rominger
Organisch-Chemisches Institut, Ruprecht-Karls-Universität Heidelberg, Im Neuenheimer Feld 270, 69120 Heidelberg, Germany
Fax +49(6221)544205; E-mail: hashmi@hashmi.de
Received 21 January 2008; revised 26 May 2008
reach full conversion and a significant amount of the in-
termediate 4 was still present when the conversion had
stopped due to catalyst deactivation.
Abstract: Six furandialkynes were prepared and investigated in
gold-catalyzed reactions. Only gold(III) chloride allowed a conver-
sion of the furandialkynes into the corresponding phenol derivative
and a further conversion of the ortho-alkynylfurans into benzo-
furans. Free hydroxy groups in the substrate led to competing hy-
droalkoxylations to give acylfurans or benzofuran spiroketals.
AuCl3 (3 mol%)
MeCN
NTs
O
NTs
Key words: alkynes, benzofurans, furans, gold, homogeneous ca-
talysis, spiro compounds
Pr
O
Pr
H
3
4 (23%)
+
Homogeneous gold-catalyzed reactions have recently at-
tracted much attention.1 One example of a previously un-
known reaction is the gold-catalyzed phenol synthesis,2–4
which added a new pathway to the family of enyne cyclo-
isomerization reactions. In these reactions a g-alkynyl fu-
ran 1, which contains a 1,6-enyne substructure (bold in 1),
delivers a phenol 2 (Scheme 1). The direct conversion of
1 into 2 was previously unknown and would otherwise
only have been possible by multi-step sequences. Apart
from the dihydroisoindole5–7 shown in Scheme 1, dihydro-
isobenzofurans,2,8,9 dihydroindanes,2,10,11 dihydroindoles,12
tetrahydroisoquinolines,13–17 tetrahydroquinolines,12 tet-
rahydronaphthalenes,10 dihydrobenzopyrans,8,18 chro-
manes,12 and dihydrobenzofurans12 could be synthesized.
Furthermore, good mechanistic insight into the mecha-
nism of this reaction could be obtained.19–21
NTs
H
O
Pr
5 (48%)
Scheme 2 Five new bonds formed in the gold-catalyzed synthesis
of benzofuran 5
We wanted to further explore the scope and limitations of
the reactions of such furandialkynes with new gold cata-
lysts that are now available since we expected a more ef-
ficient conversion to take place.
The synthesis of the substrates started from commercially
available 5-bromofurfural (6). The first alkynyl group was
conveniently introduced by a Sonogashira coupling
(Scheme 3), and three of the coupling products delivered
crystals suitable for crystal structure analysis (Figure 1).23
They all show the same syn-periplanar arrangement of the
formyl and the furan oxygen atoms; however, these simi-
larities are restricted to the molecular level, since 7c crys-
tallizes in a monoclinic lattice, 7g in an orthorhombic and
7h in a triclinic one.
AuI or AuIII
catalyst
NTs
O
NTs
R
R
O
H
1
2
Scheme 1 Four new bonds in the gold-catalyzed synthesis exempli-
fied with dihydroisoindole 2
The frequently used route shown in Scheme 3 was used to
deliver substrates 10. Thus imine 8, formed from aldehyde
7 and propargylamine, was reduced with sodium borohy-
dride to the secondary amine 9 and N-tosylated with tosyl-
chloride. As demonstrated previously,21 the sequence
from aldehyde 7 to the bis-alkyne 10 can efficiently be
done in a one-pot mode. In two of the reactions, two dif-
ferent products were obtained. The reduction of imine 8c
delivered the desired amine 9c, but the major product was
the desilylated terminal alkyne 9e. The silyl alkyne 9c and
the terminal alkyne 9e could be separated and were indi-
vidually converted into the corresponding tosylamides
10c and 10e. The tosylation of the amino alcohol 9a oc-
curred at the secondary amine to deliver alcohol 10a, but
In all these reactions, four bonds of the substrate are bro-
ken and four new bonds are formed to deliver the product.
There exists one singular example of an additional ring-
closure reaction that involved a second alkynyl group on
the furan ring in substrate 3 (Scheme 2). The benzofuran
5 was generated through the formation of a fifth bond, as
proven by control experiments with 4.5 Related cycliza-
tions of 2-alkynylphenols to benzofurans using different
transition-metal catalysts are known in the literature.22
However, the gold(III) chloride catalyzed reaction did not
SYNTHESIS 2008, No. 17, pp 2707–2718
x
x.
x
x
.
2
0
0
8
Advanced online publication: 13.08.2008
DOI: 10.1055/s-2008-1067227; Art ID: T01208SS
© Georg Thieme Verlag Stuttgart · New York

2708
A. S. K. Hashmi et al.
PAPER
a)
O
O
O
O
Br
R
6
7
a 89%
b 92%
c 85%
d 98%
g 96%
7–10:
a R = (CH2)3OH
b R = 1-cyclohexenyl
c R = TMS
b)
d R = CH2CH(OH)Me
e R = H
f R = (CH2)3OTs
g R = 4-(MeO)C6H4
O
N
R
8
a
7h R = n-Pr5
97%
b 100%
89%
d 100%
c
g
98%
c)
d)
O
O
NTs
NH
R
R
10
9
a 50% + f 18%
c 97%
d 87%
a 95%
b 80%
c 19%
Figure 1 Solid-state structures of the 5-alkynylfufurals 7c, 7g and
7h
e 66% (from 9e)
g 96%
d 30% (from 7d)
e 41% (from 7c)
g 95%
also at both the secondary amine and the primary alcohol
to deliver the bis-tosylate 10f. Tosylamide 10e delivered
crystals suitable for crystal structure analysis (Figure 2).23
The relative arrangement of the furyl group and the alky-
nyl group was found to be in a conformation typical for
this class of compounds.20
Scheme 3 Synthesis of the substrates 10a–f via the propargylamine
route. Reagents and conditions: (a) Pd2Cl2(PPh3)2, CuI, Et3N, THF,
r.t.; (b) propargylamine, MgSO4, CH2Cl2, r.t.; (c) NaBH4, MeOH, r.t.;
(d) DMAP (0.01 equiv), TsCl, Et3N, CH2Cl2, r.t.
With the seven substrates 10a–g in hand, we investigated
gold catalysis (Table 1). We started with the terminal
alkyne 10e, which surprisingly failed to convert with
Gagosz’s catalysts24 {[(Ph3P)Au]NTf2; entry 1}. Gold(III)
chloride only slightly changed the situation, with small
amounts of 14e and 15e being obtained, but with respect
to the yield this was a stoichiometric rather than a catalytic
reaction (entry 2). We then investigated the silylated
alkyne 10c and found that the gold(III) catalyst was rapid-
ly deactivated (black precipitate); [(Ph3P)Au]NTf2 effi-
ciently deprotected the alkyne (entries 3 and 4). The latter
reaction depends on the use of non-absolute solvents and
can be explained by the isolobal-analogy of LAu+ and
H+.1f So desilylation is much more effective than the phe-
nol synthesis. The 1,3-enyne side-chain in 10b delivered
both the phenol 14b and the benzofuran 15b (entry 5).
Again the catalyst was deactivated during the formation of
15b, thus some of the intermediate 14b could be isolated.
The overall low yield was probably caused by the high
sensitivity of the conjugated systems in both the starting
material and in the products. [(Ph3P)Au]NTf2 was inferior
to AuCl3 in these reactions (entry 6). The use of substrate
10d, bearing a free secondary hydroxy group, with AuCl3,
Figure 2 Solid-state structure of furandialkyne 10e
As an alternative, the condensation of 7 with tosylamide
was also tested (Scheme 4). After reduction of 11 with so-
dium borohydride, propargylation of the tosylamide 12
with propargyl bromide delivered 10.
In our hands, the sequence via 8 and 9 gave more reliable
results and was more convenient in experimental details
(for example the isolation of 11 from the dark sticky crude
product was not always trivial).
Synthesis 2008, No. 17, 2707–2718 © Thieme Stuttgart · New York

PAPER
Gold-Catalysis: Reactions of Furandialkynes
2709
the 5-position of the furan ring, and such substrates have
been shown to fail in the phenol synthesis.20
a)
O
O
O
NTs
Compound 10a, in which the hydroxy group is one carbon
further away from the alkyne than in 10d gave, in an un-
precedented reaction, the unique spiro-ketal 13. Again,
ring closure to form the five-membered ring is preferred
and the ketal center is formed in the homobenzylic posi-
tion rather than in benzylic position (entry 10). The sensi-
tivity of the ketal significantly reduced the yield during
the workup procedure; in situ monitoring by NMR
showed a selective reaction. Since [(Ph3P)Au]NTf2 did
not induce the conversion of the furandialkynes in the
sense of the phenol synthesis, entry 9 delivered no useful
results. Finally, placing a tosyl group on the hydroxy
function as in 10f, delivered 14f and 15f with AuCl3 (entry
12) but not with [(Ph3P)Au]NTf2 (entry 11).
R
R
7
11
b
d
c
b 48%
d 25%
c 76%
b)
O
NTs
7,11,12,10:
b R = 1-cyclohexenyl
c R = TMS
d R = CH2CH(OH)Me
e R = H
H
R
12
b 58%
d 79%
c 62%
e 18% (from 11c)
All ortho-alkynyl phenols obtained (14b, 14e and 14f)
readily cyclized to the benzofurans when subjected to 1
mol% of AuCl3; these cyclizations were quantitative as
shown by in situ NMR. Single crystals of the arylbenzo-
furan 15g suitable for X-ray crystallographic analysis
were also obtained (Figure 3).23
c)
O
NTs
The furandialkynes only gave phenols and benzofurans
with the gold(III) catalyst. Even with high catalyst load-
ings, full conversion into the benzofurans was not
reached; however, when the reaction mixture was subject-
ed to gold catalysts again, the ortho-alkynyl furans 14,
which were obtained as by-products, readily cyclized to
the benzofurans. The formation of the benzofurans 15 and
the spiroketal 13 proceeded with the formation of five
new bonds. While gold(I) phosphane complexes were
successful in the phenol synthesis with furan-
monoalkynes, they failed with the furandialkynes. Neigh-
boring hydroxy groups directed the regioselectivity of the
reaction, with intramolecular hydroalkoxylation of the
alkyne occurring faster than the intramolecular phenol
synthesis. Alkyl tosylates were tolerated in the phenol
synthesis.
R
10
b 86%
d 81%
e 84% (from 12e)
Scheme 4 Synthesis of the substrates 10b and 10e by the tosylamide
route. Reagents and conditions: (a) TsNH2, TiCl4, THF, CH2Cl2, 0 °C
to r.t.; (b) NaBH4, MeOH, r.t.; (c) propargyl bromide, Cs2CO3, ace-
tone, r.t.
delivered only a complex mixture in an unselective reac-
tion (entry 8). On the other hand, with [(Ph3P)Au]NTf2, a
highly selective addition of water to the alkyne was ob-
served (entry 7). Probably, the hydroxy group intramolec-
ularly attacked the coordinated alkyne to form a
dihydrofuran ring,22d this process being faster than the
phenol synthesis. Then water was added to the enol ether
to form a hemi-acetal, which opened to the hydroxyl ke-
tone 16. The latter compound 16 contains an acyl group in
Table 1 Gold-Catalyzed Conversion of the Furandialkynes 10a–g
Entry
1
Substrate
Solvent
CH2Cl2
Catalyst
Time (h)
24
Product, yield (%)
a
10e
5 mol% [(Ph3P)Au]NTf2
–
NTs
14e (13%)
15e (1%)
OH
2
3
10e
10c
CH2Cl2
CH2Cl2
15 mol% AuCl3
5 mol% AuCl3
2
+
NTs
O
a
24
–
Synthesis 2008, No. 17, 2707–2718 © Thieme Stuttgart · New York

2710
A. S. K. Hashmi et al.
PAPER
Table 1 Gold-Catalyzed Conversion of the Furandialkynes 10a–g (continued)
Entry
4
Substrate
Solvent
CH2Cl2
Catalyst
Time (h)
40
Product, yield (%)
10c
5 mol% [(Ph3P)Au]NTf2
O
NTs
10e (68%)
NTs
14b (13%)
OH
+
5
10b
CDCl3
5 mol% AuCl3
2
NTs
O
15b (62%)
a
6
7
10b
10d
CH2Cl2
CH2Cl2
5 mol% [(Ph3P)Au]NTf2
2 mol% [(Ph3P)Au]NTf2
24
2
–
O
NTs
O
O
H
16 (56%)
8
9
10d
10a
CH2Cl2
CH2Cl2
5 mol% AuCl3
24
24
complex mixture
5 mol% [(Ph3P)Au]NTf2
complex mixture
NTs
10
11
10a
10a
CHCl3
7 mol% AuCl3
20
24
O
O
13 (25%)
a
CH2Cl2
5 mol% [(Ph3P)Au]NTf2
–
OTs
NTs
14f (35%)
OH
+
12
10f
CDCl3
7 mol% AuCl3
24
NTs
15f (56%)
O
TsO
NTs
O
13
10g
CD2Cl2
5 mol% AuCl3
48
15g (81%)
MeO
a No conversion.
Synthesis 2008, No. 17, 2707–2718 © Thieme Stuttgart · New York

PAPER
Gold-Catalysis: Reactions of Furandialkynes
2711
mmol, 1.6 equiv) were added. The mixture was stirred at r.t. for 5 h
then filtered and concentrated under reduced pressure to deliver 8a.
Yield: 965 mg (97%); orange solid; mp 78–80 °C; Rf = 0.25 (hex-
anes–EtOAc, 2:1).
IR (film): 3197, 2942, 2227, 1650, 1513, 1308, 1052, 804, 674, 610
cm–1.
1H NMR (500 MHz, CDCl3): d = 1.73 (s, 1 H), 1.85 (quin,
J = 6.5 Hz, 2 H), 2.56 (t, J = 2.4 Hz, 1 H), 2.57 (t, J = 7.2 Hz, 2 H),
3.79 (t, J = 6.1 Hz, 2 H), 4.55 (t, J = 2.0 Hz, 2 H), 6.54 (d,
J = 3.4 Hz, 1 H), 6.78 (d, J = 3.6 Hz, 1 H), 8.38 (t, J = 1.6 Hz, 1 H).
13C NMR (125 MHz, CDCl3): d = 16.0 (t), 30.9 (t), 46.8 (t), 61.3 (t),
71.2 (s), 76.3 (d), 78.2 (s), 96.0 (s), 115.3 (d), 115.6 (d), 139.6 (s),
150.1 (d), 151.2 (s).
Figure 3 Solid-state structure of furandialkyne 15g
MS (EI, 70 eV): m/z (%) = 215 (100) [M+], 184 (25), 170 (14), 115
(20), 89 (14), 77 (17).
Commercially available chemicals (Aldrich, Fluka, Lancaster,
Strem and Merck) were used without further purification. THF and
Et2O were dried over Na/benzophenone prior to use. Et3N was dis-
tilled from LAH. CH2Cl2 was dried over Al2O3. Anhydrous DMF
was bought under a protecting atmosphere sealed with a crown cap
and used without further purification. If not indicated otherwise, all
reactions were carried out using Schlenk techniques under an atmo-
sphere of nitrogen. Purification was effected by column chromatog-
raphy on silica gel. Melting points were determined on a Büchi
SMP-20 melting point apparatus and are uncorrected. NMR spectra
were recorded at r.t. on Bruker ARX500, ARX300 or ARX250
spectrometers. Chemical shifts (d, ppm) were referenced to residual
solvent protons. Signal multiplicities are as follows: s (singlet), br s
(broad singlet), d (doublet), t (triplet), q (quartet), quint (quintet), m
(multiplet). The mutiplicities assigned to the 13C NMR data are
based on a combination of DEPT 135 and DEPT 90 spectra and are
defined as follows: s (quarternary C), d (CH), t (CH2), q (CH3). MS
spectra were recorded on Finnigan MAT 90 or Varian 711 instru-
ments. IR spectra were recorded on a Bruker Vector 22 spectrome-
ter.
Anal. Calcd for C13H13NO2: C, 72.54; H, 6.09; N, 6.51. Found: C,
71.77; H, 6.09; N, 6.35.
5-(5-Prop-2-ynylaminomethylfuran-2-yl)pent-4-yn-1-ol (9a)
8a (864 mg, 4.01 mmol, 1 equiv) was dissolved in MeOH (25 mL)
and NaBH4 (304 mg, 8.03 mmol, 2 equiv) was added in portions.
The mixture was stirred at r.t. for 2 h then concentrated under re-
duced pressure. Distilled H2O (5 mL) was added and the mixture
was extracted with CH2Cl2 (3 × 10 mL). The combined organic ex-
tracts were dried over MgSO4, filtered and concentrated under re-
duced pressure to deliver 9a.
Yield: 832 mg (95%); light-yellow oil; Rf = 0.26 (hexanes–EtOAc,
1:1).
IR (film): 3289, 2926, 1604, 1537, 1431, 1331, 1061, 794, 642 cm–1.
1H NMR (500 MHz, CDCl3): d = 1.67 (br s, 2 H), 1.85 (quin,
J = 6.44 Hz, 2 H), 2.25 (t, J = 2.52 Hz, 1 H), 2.56 (t, J = 6.94 Hz,
2 H), 3.43 (d, J = 2.52 Hz, 2 H), 3.79 (t, J = 6.30 Hz, 2 H), 3.85 (s,
2 H), 6.19 (d, J = 3.15 Hz, 1 H), 6.41 (d, J = 3.15 Hz, 1 H).
13C NMR (125 MHz, CDCl3): d = 16.0 (t), 31.0 (t), 37.2 (t), 44.7 (t),
61.5 (t), 71.5 (s), 71.9 (d), 81.4 (s), 93.9 (s), 108.6 (d), 114.7 (d),
136.8 (s), 153.4 (s).
MS (EI, 70 eV): m/z (%) = 217 (89) [M+], 188 (100), 163 (25), 145
(24), 106 (18), 91 (26), 77 (23).
HRMS (EI, 70 eV): m/z [M]+ calcd for C13H15NO2: 217.1103;
found: 217.1101.
5-(5-Hydroxypent-1-ynyl)furan-2-carbaldehyde (7a)
Pent-4-yn-1-ol (721 mg, 798 mL, 8.57 mmol, 1.5 equiv) and Et3N (2
mL) were dissolved in THF (5 mL) and the solution was degassed
(3×) and then stirred under nitrogen. 5-Bromofurfural (6; 1.0 g, 5.71
mmol, 1 equiv) and PdCl2(PPh3)2 (83.2 mg, 103 mmol, 1.8 mol%)
were added and, after 1 min, CuI (43.5 mg, 229 mmol, 4 mol%) was
added. The mixture was stirred at r.t. for 16 h then concentrated un-
der reduced pressure. The crude product was purified by flash chro-
matography on silica gel (hexanes–EtOAc, 2:1) to deliver 7a.
N-[5-(5-Hydroxypent-1-ynyl)furan-2-ylmethyl]-4-methyl-N-
prop-2-ynyl-benzenesulfonamide (10a) and Toluene-4-sulfonic
Acid 5-(5-{[Prop-2-ynyl(toluene-4-sulfonyl)amino]methyl}fu-
ran-2-yl)pent-4-ynyl Ester (10f)
9a (732 mg, 3.37 mmol, 1 equiv) was dissolved in CH2Cl2 (15 mL)
and Et3N (375 mg, 514 mL, 3.71 mmol, 1.1 equiv), DMAP (4.12 mg,
33.7 mmol, 0.01 equiv) and tosyl chloride (706 mg, 3.71 mmol, 1.1
equiv) were added. The mixture was stirred at r.t. for 22 h then di-
luted with H2O (15 mL) and the mixture was extracted with CH2Cl2
(3 × 10 mL). The combined organic extracts were dried over
MgSO4, filtered and concentrated under reduced pressure to give
the crude product, which was purified by flash chromatography on
silica gel (hexanes–EtOAc, 2:1) to deliver 10a and 10f.
Yield: 908 mg (89%); light-yellow solid; mp 55–57 °C; Rf = 0.10
(hexanes–EtOAc, 3:1).
IR (film): 3249, 2931, 2227, 1728, 1505, 1392, 1276, 962, 811, 761
cm–1.
1H NMR (500 MHz, CDCl3): d = 1.75 (s, 1 H), 1.88 (quin,
J = 6.6 Hz, 2 H), 2.61 (t, J = 6.9 Hz, 2 H), 3.80 (t, J = 6.1 Hz, 2 H),
6.61 (d, J = 3.6 Hz, 1 H), 7.21 (d, J = 3.5 Hz, 1 H), 9.57 (s, 1 H).
13C NMR (125 MHz, CDCl3): d = 16.1 (t), 30.7 (t), 61.3 (t), 70.7 (s),
98.0 (s), 116.1 (d, 2 C), 121.6 (d), 142.4 (s), 151.9 (s), 177.2 (s).
MS (EI, 70 eV): m/z (%) = 179 (12) [M+], 178 (100), 160 (16), 147
(48), 131 (24), 103 (28), 77 (31).
10a
Anal. Calcd for C10H10O3: C, 67.41; H, 5.66. Found: C, 67.39; H,
5.70.
Yield: 630 mg (50%); light-yellow oil; Rf = 0.26 (hexanes–EtOAc,
2:1).
5-(5-Prop-2-ynyliminomethylfuran-2-yl)pent-4-yn-1-ol (8a)
7a (827 mg, 4.64 mmol, 1 equiv) was dissolved in CH2Cl2 (15 mL),
then MgSO4 (2.00 g) and prop-2-ynylamine (409 mg, 509 mL, 7.43
IR (film): 3286, 1598, 1431, 1348, 1160, 1093, 1017, 893, 802, 663
cm–1.
1H NMR (500 MHz, CDCl3): d = 1.72 (br s, 1 H), 1.85 (quin,
J = 6.4 Hz, 2 H), 2.08 (t, J = 2.4 Hz, 1 H), 2.43 (s, 3 H), 2.56 (t,
Synthesis 2008, No. 17, 2707–2718 © Thieme Stuttgart · New York

2712
A. S. K. Hashmi et al.
PAPER
J = 7.0 Hz, 2 H), 3.79 (t, J = 6.1 Hz, 2 H), 4.04 (d, J = 2.4 Hz, 2 H),
4.39 (s, 2 H), 6.25 (d, J = 3.3 Hz, 1 H), 6.38 (d, J = 3.3 Hz, 1 H),
7.73 (d, J = 8.3 Hz, 2 H), 7.30 (d, J = 8.2 Hz, 2 H).
13C NMR (125 MHz, CDCl3): d = 16.0 (t), 21.6 (q), 31.0 (t), 36.4
(t), 42.9 (t), 61.5 (t), 71.2 (d), 74.1 (s), 76.4 (s), 94.2 (s), 110.9 (d),
114.8 (d), 127.7 (d, 2 C), 129.6 (d, 2 C), 135.9 (s), 137.7 (s), 143.7
(s), 149.0 (s).
MS (EI, 70 eV): m/z (%) = 371 (49) [M+], 218 (23), 217 (27), 216
(100), 188 (14), 163 (28), 91 (62), 77 (12).
HRMS (EI, 70eV): m/z [M]+ calcd for C20H21NO4S: 371.1191;
found: 371.1197.
equiv) were dissolved in CH2Cl2 (20 mL) and THF (2 mL). The
mixture was cooled to 0 °C and TiCl4 (372 mg, 215 mL, 1.96 mmol,
0.5 equiv) dissolved in CH2Cl2 (0.8 mL) was added dropwise. The
mixture was stirred at r.t. for 16 h then diluted with sat. aq Na2CO3
(20 mL) and filtered over celite. The organic phase was separated,
washed with H2O (3 × 20 mL), dried over MgSO4, filtered and con-
centrated under reduced pressure. The crude product was purified
by flash chromatography on silica gel (hexanes–EtOAc, 15:1), then
the p-toluenesulfonamide was separated from the product by crys-
tallization from CH2Cl2 to give 11b.
Yield: 659 mg (48%); orange-brown crystals; mp 153–154 °C;
Rf = 0.41 (hexanes–CH2Cl2–EtOAc, 5:3:1).
IR (film): 2935, 2190, 1591, 1158, 1084, 1027, 805, 750, 669, 605
cm–1.
1H NMR (500 MHz, CDCl3): d = 1.64 (m, 4 H), 2.16 (m, 4 H), 2.43
(s, 3 H), 6.33 (m, 1 H), 6.66 (d, J = 3.8 Hz, 1 H), 7.29 (d,
J = 3.8 Hz, 1 H), 7.33 (d, J = 8.2 Hz, 2 H), 7.86 (d, J = 8.2 Hz, 2 H),
8.70 (s, 1 H).
13C NMR (75 MHz, CDCl3): d = 21.6 (t), 22.0 (q), 22.4 (t), 26.3 (t),
28.7 (t), 76.6 (s), 100.3 (s), 108.8 (d), 117.7 (d), 119.8 (s), 128.5 (d,
2 C), 130.2 (d, 2 C), 135.7 (s), 139.6 (d), 143.7 (s), 144.9 (s), 148.9
(s), 154.9 (d).
10f
Yield: 323 mg (18%); light-yellow oil; Rf = 0.42 (hexanes–EtOAc,
2:1).
IR (film): 597, 1433, 1349, 1160, 1094, 1015, 928, 813, 663, 618
cm–1.
1H NMR (500 MHz, CDCl3): d = 1.93 (quin, J = 6.6 Hz, 2 H), 2.08
(t, J = 6.6 Hz, 1 H), 2.43 (s, 6 H), 2.49 (t, J = 7.0 Hz, 2 H), 4.04 (d,
J = 2.6 Hz, 2 H), 4.17 (t, J = 6.0 Hz, 2 H), 4.39 (s, 2 H), 6.25 (d,
J = 3.2 Hz, 1 H), 6.34 (d, J = 3.2 Hz, 1 H), 7.29 (d, J = 8.2 Hz, 2 H),
7.34 (d, J = 8.2 Hz, 2 H), 7.73 (d, J = 8.2 Hz, 2 H), 7.80 (d,
J = 8.2 Hz, 2 H).
MS (EI, 70 eV): m/z (%) = 353 (100) [M+], 354 (22), 262 (8), 198
(23), 155 (6), 143 (20), 91 (36).
13C NMR (125 MHz, CDCl3): d = 15.8 (t), 21.6 (q, 2 C), 21.6 (q),
27.7 (t), 36.4 (t), 42.9 (t), 68.8 (t), 71.8 (d), 74.2 (s), 76.3 (s), 92.5
(s), 110.8 (d), 115.1 (d), 127.7 (d, 2 C), 127.9 (d, 2 C), 129.6 (d, 2
C), 129.9 (d, 2 C), 132.9 (s), 135.8 (s), 137.4 (s), 143.8 (s), 144.9
(s), 149.2 (s).
Anal. Calcd for C20H19NO3S: C, 67.97; H, 5.42; N, 3.96. Found: C,
67.35; H, 5.44; N, 3.81.
N-(5-Cyclohex-1-enylethynylfuran-2-ylmethyl)-4-methyl-
benzenesulfonamide (12b)
MS (EI, 70 eV): m/z (%) = 525 (18) [M+], 370 (100), 215 (8), 198
11b (622 mg, 1.76 mmol, 1 equiv) was dissolved in MeOH (45 mL)
and CH2Cl2 (15 mL). The mixture was cooled to 0 °C and NaBH4
(133 mg, 3.52 mmol, 2 equiv) was added in portions. The mixture
was stirred at 0 °C for 15 min and at r.t. for 3 h, then the mixture was
concentrated under reduce pressure and diluted with H2O (20 mL).
The aqueous phase was extracted with CH2Cl2 (3 × 10 mL) and the
combined organic extracts were dried over MgSO4, filtered and
concentrated under reduced pressure. The p-toluenesulfonamide
was separated from the product by crystallization from CH2Cl2 to
deliver 12b.
(15), 184 (24), 145 (20), 115 (12), 91 (94).
HRMS (EI, 70eV): m/z [M]+ calcd for C27H27NO6S2: 525.1280;
found: 525.1274.
5-Cyclohex-1-enylethynylfuran-2-carbaldehyde (7b)
1-Ethynylcyclohexene (607 mg, 672 mL, 5.71 mmol, 1 equiv) and
Et3N (3.5 mL) were dissolved in THF (6 mL), then the solution was
degassed (3×) and stirred under nitrogen. 6 (1.00 g, 5.71 mmol, 1
equiv) and PdCl2(PPh3)2 (83.2 mg, 103 mmol, 1.8 mol%) were add-
ed and, after 1 min, CuI (43.5 mg, 227 mmol, 4 mol%) was added.
The mixture was stirred at r.t. for 7 h then concentrated under re-
duced pressure to give the crude product, which was purified by
flash chromatography on silica gel (hexanes–EtOAc, 20:1) to deliv-
er 7b.
Yield: 365 mg (58%); orange solid; mp 155 °C; Rf = 0.51 (hexanes–
EtOAc, 3:1).
IR (film): 3250, 2922, 1597, 1434, 1317, 1156, 811, 721, 664, 612
cm–1.
Yield: 1.05 g (92%); orange-brown crystals; mp 46 °C; Rf = 0.39
(hexane–EtOAc–Et2O, 10:5:0.1).
1H NMR (300 MHz, CDCl3): d = 1.66 (m, 4 H), 2.22 (m, 4 H), 2.44
(s, 3 H), 4.17 (d, J = 6.0 Hz, 2 H), 4.72 (t, J = 5.0 Hz, 1 H), 6.08 (d,
J = 3.4 Hz, 1 H), 6.24 (m, 1 H), 6.34 (d, J = 3.4 Hz, 1 H), 7.29 (d,
J = 8.3 Hz, 2 H), 7.71 (d, J = 8.3 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 21.3 (q), 21.5 (t), 22.2 (t), 25.8 (t),
29.7 (t), 40.3 (t), 95.4 (s), 108.2 (s), 109.5 (d), 115.1 (d), 119.8 (s),
127.1 (d, 2 C), 129.7 (d, 2 C), 136.7 (s), 136.7 (s), 137.4 (d), 143.6
(s), 150.0 (s).
IR (film): 2934, 2859, 2825, 2365, 2329, 1678, 1500, 1388, 1347,
1022, 973, 806, 752 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.53–175 (m, 4 H), 2.05–2.28 (m,
4 H), 6.30–6.32 (m, 1 H), 6.62 (d, J = 3.7 Hz, 1 H), 7.23 (d,
J = 3.7 Hz, 1 H), 9.56 (s, 1 H).
13C NMR (75 MHz, CDCl3): d = 21.3 (t), 22.1 (t), 26.0 (t), 28.5 (t),
76.2 (s), 98.6 (s), 116.4 (d), 119.5 (s), 121.8 (d), 138.8 (d), 142.7 (s),
152.2 (s), 177.1 (d).
MS (EI, 70 eV): m/z (%) = 355 (45) [M+], 200 (28), 199 (100), 171
(10), 143 (7), 115 (6), 91 (15).
Anal. Calcd for C20H21NO3S: C, 67.58; H, 5.95; N, 3.94. Found: C,
67.01; H, 5.92; N, 3.72.
MS (EI, 70 eV): m/z (%) = 200 (100) [M+], 172 (16), 171 (39), 143
(15), 128 (23), 115 (18), 89 (5), 75 (14).
Anal. Calcd for C13H12NO2: C, 77.98; H, 6.04. Found: C, 77.58; H,
5.99.
N-(5-Cyclohex-1-enylethynylfuran-2-ylmethyl)-4-methyl-N-
prop-2-ynylbenzenesulfonamide (10b)
12b (829 mg, 2.33 mmol, 1 equiv) was dissolved in acetone (10 mL)
and K2CO3 (645 mg, 4.67 mmol, 2 equiv) and propargyl bromide
(1.39 g, 1.03 mL, 11.7 mmol, 5 equiv) were added. The mixture was
stirred at r.t. for 16 h, but starting material was still present. Thus,
Cs2CO3 (1.52 g, 4.67 mmol, 2 equiv) was added and the mixture
N-(5-Cyclohex-1-enylethynylfuran-2-ylmethylene)-4-methyl-
benzenesulfonamide (11b)
7b (785 mg, 3.92 mmol, 1 equiv), p-toluenesulfonamide (1.01 g,
5.88 mmol, 1.5 equiv) and Et3N (1.19 g, 1.63 mL, 11.8 mmol, 3
Synthesis 2008, No. 17, 2707–2718 © Thieme Stuttgart · New York

PAPER
Gold-Catalysis: Reactions of Furandialkynes
2713
was stirred for 3 h then concentrated under reduced pressure. The
crude product was purified by flash chromatography on silica gel
(hexanes–EtOAc, 3:1) to give 10b. The product was stable at
–20 °C.
J = 2.5 Hz, 2 H), 3.86 (s, 2 H), 6.22 (m, 2 H), 6.45 (d, J = 3.4 Hz,
1 H).
13C NMR (125 MHz, CDCl3): d = 21.4 (t), 22.2 (t), 25.8 (t), 28.8 (t),
37.2 (t), 44.8 (t), 71.8 (d), 76.9 (s), 81.5 (s), 95.1 (s), 108.9 (d, 2 C),
115.1 (d, 2 C), 120.0 (s), 136.1 (d), 137.0 (s), 153.8 (s).
Yield: 789 mg (86%); orange solid; mp 64–66 °C; Rf = 0.63 (hex-
anes–EtOAc, 3:1).
MS (EI, 70 eV): m/z (%) = 239 (100) [M+], 210 (90), 185 (62), 157
IR (film): 3288, 2924, 1596, 1327, 1157, 1018, 791, 730, 664, 619
cm–1.
(12), 128 (18), 115 (20), 91 (12), 77 (13).
Anal. Calcd for C16H17NO: C, 80.30; H, 7.16; N, 5.85. Found: C,
79.93; H, 7.23; N, 5.75.
1H NMR (500 MHz, CDCl3): d = 1.65 (m, 2 H), 1.67 (m, 2 H), 2.08
(t, J = 2.4 Hz, 1 H), 2.15 (m, 2 H), 2.20 (m, 2 H), 2.43 (s, 3 H), 4.05
(d, J = 2.5 Hz, 2 H), 4.42 (s, 2 H), 6.24 (m, 1 H), 6.27 (d,
J = 3.2 Hz, 1 H), 6.41 (d, J = 3.2 Hz, 1 H), 7.29 (d, J = 8.2 Hz, 2 H),
7.73 (d, J = 8.2 Hz, 2 H).
13C NMR (125 MHz, CDCl3): d = 21.4 (t), 21.6 (q), 22.2 (t), 25.8
(t), 28.7 (t), 36.4 (t), 42.9 (t), 74.1 (s), 76.5 (d), 76.6 (s), 95.3 (s),
111.1 (d), 115.2 (d), 119.9 (s), 127.8 (d, 2 C), 129.5 (d, 2 C), 135.9
(s), 136.5 (d), 137.8 (s), 143.7 (s), 149.4 (s).
5-Trimethylsilanylethynylfuran-2-carbaldehyde (7c)
Trimethylsilylacetylene (1.22 mL, 842 mg, 8.57 mmol, 1.5 equiv)
and Et3N (2 mL) were dissolved in THF (5 mL). The solution was
degassed (5×) and stirred under nitrogen. 6 (1.00 g, 5.71 mmol, 1
equiv) and PdCl2(PPh3)2 (92.4 mg, 114 mmol, 2 mol%) were added.
After 1 min of stirring, CuI (43.5 mg, 229 mmol, 4 mol%) was add-
ed, then the mixture was stirred at r.t. for 2 h then concentrated un-
der reduced pressure. The crude product was purified by flash
chromatography on silica gel (hexanes–EtOAc, 10:1) to give of 7c.
MS (EI, 70 eV): m/z (%) = 355 (45) [M+], 200 (28), 199 (100), 171
(10), 143 (7), 115 (6), 91 (15).
Yield: 933 mg (85%); light-yellow crystals; mp 52–54 °C; Rf = 0.42
(hexane–EtOAc–Et2O, 10:5:0.1).
Anal. Calcd for C23H23NO3S: C, 67.58; H, 5.95; N, 3.94. Found: C,
67.01; H, 5.92; N, 3.72.
IR (film): 3321, 3132, 3091, 2961, 2854, 2154, 1671, 1493, 1384,
1260, 1200, 1026, 962, 847, 764 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.24 (s, 9 H), 6.69 (d, J = 3.7 Hz,
1 H), 7.18 (d, J = 3.7 Hz, 1 H), 9.58 (s, 1 H).
13C NMR (75 MHz, CDCl3): d = –0.5 (q, 3 C), 92.9 (s), 103.9 (s),
117.4 (d), 121.0 (d), 141.6 (s), 152.3 (s), 177.4 (d).
(5-Cyclohex-1-enylethynylfuran-2-ylmethylene)prop-2-ynyl-
amine (8b)
7b (100 mg, 499 mmol, 1 equiv) was dissolved in CH2Cl2 (15 mL),
then MgSO4 (1.00 g) and prop-2-ynylamine (41.3 mg, 51.4 mL, 749
mmol, 1.5 equiv) were added. The mixture was stirred at r.t. for 2 d,
but there was still starting material present. Thus further prop-2-
ynylamine (171 mL, 138 mg, 2.50 mmol, 5 equiv) was added. The
mixture was stirred for a further 2 d, filtered and concentrated under
reduced pressure. The crude product was purified by flash chroma-
tography on silica gel (hexanes–EtOAc, 3:1) to give 8b.
MS (EI, 70 eV): m/z (%) = 192 (36) [M+], 178 (14), 177 (100), 88
(3).
Anal. Calcd for C10H12O2Si: C, 62.46; H, 6.29. Found: C, 62.46; H,
6.27.
Yield: 119 mg (quantitative); orange-brown solid; mp 44–45 °C;
Rf = 0.68 (hexanes–EtOAc, 3:1).
Prop-2-ynyl(5-trimethylsilanylethynylfuran-2-ylmethyl-
ene)amine (8c)
IR (film): 3266, 2932, 2197, 1645, 1511, 1346, 968, 917, 819, 652
cm–1.
1H NMR (500 MHz, CDCl3): d = 1.63 (m, 4 H), 2.16 (m, 4 H), 2.55
(t, J = 2.4 Hz, 1 H), 4.55 (t, J = 2.2 Hz, 2 H), 6.26 (m, 1 H), 6.58 (d,
J = 3.6 Hz, 1 H), 6.79 (d, J = 3.6 Hz, 1 H), 8.39 (t, J = 2.0 Hz, 1 H).
13C NMR (125 MHz, CDCl3): d = 21.4 (t), 22.1 (t), 25.8 (t), 28.5 (t),
46.8 (t), 76.6 (d), 76.7 (s), 78.2 (s), 97.0 (s), 115.5 (d), 115.9 (d),
119.8 (s), 137.1 (d), 139.8 (s), 150.1 (s), 151.5 (d).
7c (100 mg, 520 mmol, 1 equiv) was dissolved in CH2Cl2 (5 mL),
and MgSO4 (1.50 g) and prop-2-ynylamine (143 mg, 178 mL, 2.60
mmol, 5 equiv) were added. The mixture was stirred at r.t. for 24 h,
then filtered and concentrated under reduced pressure to give the
crude product as a light-yellow solid. Purification by flash chroma-
tography on silica gel (hexanes–EtOAc, 5:1) gave 8c.
Yield: 106 mg (88%); light-pink solid; mp 35–36 °C; Rf = 0.64
(hexanes–EtOAc, 5:1).
MS (EI, 70 eV): m/z (%) = 237 (100) [M+], 238 (17), 210 (13), 141
(5), 128 (8), 115 (10), 91 (3), 77 (4).
IR (film): 3275, 2960, 2153, 1643, 1504, 1250, 996, 840, 761, 645
cm–1.
HRMS (EI, 70 eV): m/z [M]+ calcd for C16H15NO: 237.1154; found:
237.1137.
1H NMR (500 MHz, CDCl3): d = 0.24 (s, 9 H), 2.56 (t, J = 2.4 Hz,
1 H), 4.56 (t, J = 2.1 Hz, 2 H), 6.65 (d, J = 3.5 Hz, 1 H), 6.78 (d,
J = 3.5 Hz, 1 H), 8.40 (t, J = 1.9 Hz, 1 H).
(5-Cyclohex-1-enylethynylfuran-2-ylmethyl)prop-2-ynylamine
(9b)
13C NMR (125 MHz, CDCl3): d = 0.0 (q, 3 C), 47.3 (t), 77.1 (d), 78.5
(s), 94.1 (s), 102.3 (s), 115.4 (d), 117.5 (d), 139.5 (s), 150.5 (d),
152.2 (s).
8b (84.9 mg, 358 mmol, 1 equiv) was dissolved in MeOH (5 mL)
and NaBH4 (27.1 mg, 716 mmol, 2 equiv) was added in portions.
The mixture was stirred at r.t. for 2 h then concentrated under re-
duced pressure and H2O (5 mL) was added. After extraction with
CH2Cl2 (3 × 5 mL), the combined organic extracts were dried over
MgSO4, filtered and concentrated under reduced pressure to deliver
9b.
(5-Ethynylfuran-2-ylmethyl)prop-2-ynylamine (9e) and Prop-
2-ynyl(5-trimethylsilanylethynylfuran-2-ylmethyl)amine (9c)
8c (971 mg, 4.23 mmol, 1 equiv) was dissolved in MeOH (25 mL)
and cooled to 0 °C, then NaBH4 (480 mg, 12.7 mmol, 3 equiv) was
added in portions. The mixture was stirred at 0 °C for 30 min and at
r.t. for 2 h then concentrated under reduced pressure. A mixture of
CH2Cl2–H2O (1:1, 20 mL) was added and the aqueous phase was
extracted with CH2Cl2 (2 × 10 mL). The combined organic extracts
were dried over MgSO4, filtered and concentrated under reduced
pressure. The crude product was purified by flash chromatography
on silica gel (hexanes–EtOAc, 10:1) to deliver 9e and 9c.
Yield: 68.5 mg (80%); yellow oil; Rf = 0.34 (hexanes–EtOAc, 3:1).
IR (film): 3291, 2929, 1534, 1435, 1347, 1191, 1103, 1015, 634
cm–1.
1H NMR (500 MHz, CDCl3): d = 1.61 (m, 3 H), 1.66 (m, 2 H), 2.13
(m, 2 H), 2.19 (m, 2 H), 2.24 (t, J = 2.3 Hz, 1 H), 3.43 (d,
Synthesis 2008, No. 17, 2707–2718 © Thieme Stuttgart · New York

2714
9e
A. S. K. Hashmi et al.
PAPER
equiv) were added. The mixture was stirred at r.t. for 16 h then di-
luted with H2O (5 mL) and the aqueous phase was extracted with
CH2Cl2 (3 × 5 mL). The combined organic extracts were dried over
MgSO4, filtered and concentrated under reduced pressure. The
crude product was purified by flash chromatography on silica gel
(hexanes–EtOAc, 5:1) to deliver 10c.
Yield: 278 mg (41%); yellow oil; Rf = 0.23 (hexanes–EtOAc, 3:1).
IR (film): 3292, 2333, 1434, 1290, 1159, 814, 721, 664, 655 cm–1.
1H NMR (500 MHz, CDCl3): d = 1.62 (s, 1 H), 2.25 (t, J = 2.4 Hz,
1 H), 3.39 (s, 1 H), 3.44 (d, J = 2.4 Hz, 2 H), 3.87 (s, 2 H), 6.22 (d,
J = 3.2 Hz, 1 H), 6.58 (d, J = 3.3 Hz, 1 H).
13C NMR (125 MHz, CDCl3): d = 37.2 (t), 44.7 (t), 71.9 (d), 74.0
(d), 81.4 (s), 81.8 (s), 108.6 (d), 117.0 (d), 135.6 (s), 154.7 (s).
MS (EI, 70 eV): m/z (%) = 159 (31) [M+], 130 (79), 119 (22), 105
(100), 94 (31), 77 (51).
Yield: 198 mg (97%); colorless solid; mp 106–107 °C; Rf = 0.68
(hexanes–EtOAc, 3:1).
IR (film): 3289, 2958, 2158, 1346, 1162, 1092, 1019, 839, 659, 583
cm–1.
1H NMR (500 MHz, CDCl3): d = 0.25 (s, 9 H), 2.08 (t, J = 2.5 Hz,
1 H), 2.43 (s, 3 H), 4.04 (d, J = 2.5 Hz, 2 H), 4.41 (s, 2 H), 6.26 (d,
J = 3.3 Hz, 1 H), 6.50 (d, J = 3.4 Hz, 1 H), 7.30 (d, J = 8.2 Hz, 2 H),
7.23 (d, J = 8.2 Hz, 2 H).
13C NMR (125 MHz, CDCl3): d = 0.0 (q, 3 C), 21.9 (q), 36.8 (t), 43.2
(t), 74.5 (d), 76.7 (s), 94.2 (s), 100.3 (s), 111.2 (d), 116.9 (d), 128.1
(d, 2 C), 129.9 (d, 2 C), 136.1 (s), 137.6 (s), 144.0 (s), 150.2 (s).
Anal. Calcd for C10H9NO: C, 75.45; H, 5.70; N, 8.80. Found: C,
74.18; H, 5.80; N, 8.56.
9c
Yield: 187 mg (19%); yellow oil; Rf = 0.36 (hexanes–EtOAc, 3:1).
IR (film): 3299, 2362, 2152, 1251, 850 cm–1.
1H NMR (500 MHz, CDCl3): d = 0.24 (s, 9 H), 1.62 (s, 1 H), 2.24
(t, J = 2.3 Hz, 1 H), 3.42 (d, J = 2.4 Hz, 2 H), 3.86 (s, 2 H), 6.20 (d,
J = 3.3 Hz, 1 H), 6.54 (d, J = 3.3 Hz, 1 H).
13C NMR (125 MHz, CDCl3): d = 0.0 (q, 3 C), 37.5 (t), 45.03 (t),
72.2 (d), 81.7 (s), 94.6 (s), 99.9 (s), 109.0 (d), 116.8 (d), 136.8 (s),
154.6 (s).
MS (EI, 70 eV): m/z (%) = 385 (23) [M+], 386 (8), 231 (21), 230
(100), 202 (41), 177 (24), 149 (8), 91 (33).
Anal. Calcd for C20H23NO3SSi: C, 62.30; H, 6.01; N, 3.63. Found:
C, 62.19; H, 6.15; N, 3.52.
5-(4-Hydroxypent-1-ynyl)furan-2-carbaldehyde (7d)
Pent-4-yn-2-ol (420 mg, 5.00 mmol, 1.9 equiv), 6 (460 mg, 2.63
mmol, 1 equiv), PdCl2(PPh3)2 (92.2 mg, 132 mmol, 5 mol%) and
CuI (50.2 mg, 264 mmol, 10 mol%) were dissolved in degassed di-
ethylamine (8 mL). The solution was stirred under nitrogen at 55 °C
for 5.5 h, then the mixture was concentrated under reduced pressure
and purified by flash chromatography on silica gel (hexanes–
EtOAc, 3:1) gave 7d.
MS (EI, 70 eV): m/z (%) = 231 (39) [M+], 230 (30), 204 (10), 202
(100), 187 (18), 177 (33), 176 (21), 151 (12).
Anal. Calcd for C13H17NOSi: C, 67.49; H, 7.41; N, 6.05. Found: C,
67.28; H, 7.50; N, 5.80.
N-(5-Ethynylfuran-2-ylmethyl)-4-methyl-N-prop-2-ynyl-
benzenesulfonamide (10e)
Yield: 459 mg (98%); brown solid; mp 29–30 °C; Rf = 0.45 (hex-
anes–EtOAc, 3:1).
9e (225 mg, 1.41 mmol, 1 equiv) was dissolved in CH2Cl2 (10 mL),
and Et3N (157 mg, 215 mL, 1.55 mmol, 1.1 equiv), DMAP (1.72 mg,
14.1 mmol, 0.01 equiv) and tosylchloride (296 mg, 1.55 mmol, 1.1
equiv) were added. The mixture was stirred at r.t. for 16 h, diluted
with H2O (5 mL) and the aqueous phase was extracted with CH2Cl2
(3 × 5 mL). The combined organic extracts were dried over MgSO4,
filtered and concentrated under reduced pressure to give the crude
product, which was purified by flash chromatography on silica gel
(hexanes–EtOAc, 10:1 with a small amount of CH2Cl2 then pure
CH2Cl2) to give 10e.
IR (film): 3371, 2971, 2227, 1669, 1504, 1387, 1114, 1062, 766
cm–1.
1H NMR (300 MHz, CDCl3): d = 1.35 (d, J = 6.2 Hz, 3 H), 1.87–
1.97 (br s, 1 H), 2.62 (dd, J = 17.0, 6.2 Hz, 1 H), 2.68 (dd, J = 17.0,
5.5 Hz, 1 H), 4.11 (sext, J = 5.0 Hz, 1 H), 6.66 (d, J = 3.7 Hz, 1 H),
7.22 (d, J = 3.7 Hz, 1 H), 9.60 (s, 1 H).
13C NMR (125 MHz, CDCl3): d = 22.8 (q), 30.1 (t), 66.3 (d), 72.5
(s), 95.0 (s), 116.6 (d), 121.5 (d), 142.1 (s), 152.2 (s), 177.4 (d).
MS (EI, 70 eV): m/z (%) = 178 (23) [M+], 134 (100), 105 (38), 77
Yield: 292 mg (66%); light-yellow solid; mp 75 °C; Rf = 0.58 (hex-
anes–EtOAc, 3:1).
(28), 45 (50).
IR (neat): 3284, 2926, 1596, 1521, 1428, 1344, 1328, 1216, 1200,
1157, 1132, 1089, 1064, 1019, 970, 923, 889, 812, 796, 766, 702,
679, 664, 654, 541 cm–1.
Anal. Calcd for C10H10O3: C, 67.41; H, 5.66. Found: C, 67.16; H,
5.79.
1H NMR (300 MHz, CDCl3): d = 2.09 (t, J = 2.4 Hz, 1 H), 2.43 (s,
3 H), 3.37 (s, 1 H), 4.05 (d, J = 2.4 Hz, 2 H), 4.42 (s, 2 H), 6.28 (d,
J = 3.3 Hz, 1 H), 6.54 (d, J = 3.3 Hz, 1 H), 7.29 (d, J = 8.2 Hz, 2 H),
7.72 (d, J = 8.2 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 21.9 (q), 36.8 (t), 43.1 (t), 73.9 (s),
74.5 (d), 76.6 (d), 82.3 (s), 111.1 (d), 117.3 (d), 128.0 (d, 2 C), 129.9
(d, 2 C), 136.1 (s), 136.6 (s), 144.1 (s), 150.6 (s).
5-(5-Prop-2-ynyliminomethylfuran-2-yl)pent-4-yn-2-ol (8d)
7d (1.60 g, 8.96 mmol, 1 equiv) was dissolved in CH2Cl2 (20 mL),
then MgSO4 (1.60 g) was added, followed by prop-2-ynylamine
(496 mg, 9.00 mmol, 1 equiv). The mixture was stirred at r.t. for 12
h then filtered and concentrated under reduced pressure to deliver
8d.
Yield: 1.93 g (quant); brown solid; mp 64–66 °C; Rf = 0.20 (hex-
anes–EtOAc, 1:1).
MS (EI, 70 eV): m/z (%) = 313 (13) [M+], 39 (10), 51 (12), 65 (13),
77 (13), 91 (33), 105 (35), 130 (37), 158 (100), 159 (11).
IR (film): 3291, 2971, 2903, 2226, 1643, 1512, 1306, 1114, 1020,
976, 940, 796, 639 cm–1.
Anal. Calcd for C17H15NO3S: C, 65.16; H, 4.82; N, 4.47. Found: C,
64.68; H, 4.89; N, 4.35.
1H NMR (500 MHz, CD2Cl2): d = 1.29 (d, J = 6.2 Hz, 3 H), 1.95–
2.15 (br s, 1 H), 2.59 (t, J = 2.4 Hz, 1 H), 2.59 (dd, J = 17.0, 6.3 Hz,
1 H), 2.64 (dd, J = 17.0, 5.4 Hz, 1 H), 4.00–4.07 (m, 1 H), 4.50 (t,
J = 2.2 Hz, 2 H), 6.59 (d, J = 3.5 Hz, 1 H), 6.79 (d, J = 3.5 Hz, 1 H),
8.33 (t, J = 2.0 Hz, 1 H).
4-Methyl-N-prop-2-ynyl-N-(5-trimethylsilanylethynylfuran-2-
ylmethyl)benzenesulfonamide (10c)
9c (152 mg, 655 mmol, 1 equiv) was dissolved in CH2Cl2 (10 mL),
and Et3N (72.9 mg, 99.9 mL, 721 mmol, 1.1 equiv), DMAP (800 mg,
6.55 mmol, 0.01 equiv) and tosylchloride (137 mg, 721 mmol, 1.1
Synthesis 2008, No. 17, 2707–2718 © Thieme Stuttgart · New York

PAPER
Gold-Catalysis: Reactions of Furandialkynes
2715
13C NMR (125 MHz, CD2Cl2): d = 22.9 (q), 30.5 (t), 47.5 (t), 66.7
(d), 73.0 (s), 76.4 (d), 79.0 (s), 93.8 (s), 115.6 (d), 116.5 (d), 139.6
(s), 150.6 (d), 152.1 (s).
MS (EI, 70 eV): m/z (%) = 215 (80) [M+], 171 (100), 144 (22), 132
(42), 115 (24), 104 (12), 77 (13), 45 (27).
MS (ESI): m/z (%) = 238 (100) [M + Na]+, 216 (79) [M + H]+, 198
(2), 172 (8).
HRMS (ESI): m/z [M + H]+ calcd for C13H14NO2: 216.1019; found
5-[(4-Methoxyphenyl)ethynyl]-2-furaldehyde (7g)
4-Methoxyacetylene (2.86 g, 21.7 mmol, 1.5 equiv) and Et3N (6
mL) were dissolved in THF (30 mL) and the solution was degassed
(3×) and then stirred under nitrogen. 5-Bromofurfural (6; 2.50 g,
14.5 mmol, 1 equiv) and PdCl2(PPh3)2 (183 mg, 260 mol, 1.8 mol%)
were added and, after 1 min, CuI (110 mg, 587 mol, 4 mol%) was
added. The mixture was stirred at r.t. for 24 h then concentrated un-
der reduced pressure and the crude product was purified by flash
chromatography on silica gel (hexanes–EtOAc, 2:1) to deliver 7g.
216.1024.
Yield: 3.12 g (96%); light-yellow solid; mp 73 °C; Rf = 0.55 (hex-
anes–EtOAc, 2:1).
5-(5-Prop-2-ynylaminomethylfuran-2-yl)pent-4-yn-2-ol (9d)
8d (179 mg, 8.34 mmol, 1 equiv) was dissolved in MeOH (5 mL),
and NaBH4 (34.0 mg, 9.00 mmol, 1.1 equiv) was added in portions.
The mixture was stirred at r.t. for 1 h then the reaction was quenched
by adding H2O (5 mL) and sat. aq NH4Cl (5 mL). The mixture was
extracted with CH2Cl2 (3 × 10 mL) and the combined organic layers
were dried over Na2SO4, filtered and concentrated under reduced
pressure. Purification by flash chromatography on silica gel (hex-
anes–EtOAc, 3:1) gave 9d.
IR (KBr): 3441, 3103, 2965, 2839, 2208, 1669, 1607, 1568, 1523,
1464, 1389, 1351, 1299, 1255, 1175, 1032, 961, 833, 813, 780, 735
cm–1.
UV/Vis (CH2Cl2): λmax (log λ) = 262 (3.84), 300 (4.07), 320 (4.31),
348 nm (4.22).
1H NMR (300 MHz, CD3CN): d = 3.85 (s, 3 H), 6.88 (d, J = 3.7 Hz,
1 H), 7.00 (d, J = 9.0 Hz, 2 H), 7.40 (d, J = 3.7 Hz, 1 H), 7.57 (d,
J = 9.0 Hz, 2 H), 9.58 (s, 1 H).
Yield: 141 mg (78%); yellow oil; Rf = 0.09 (hexanes–EtOAc, 1:1).
13C NMR (125 MHz, CDCl3): d = 56.2 (q), 77.9 (s), 97.2 (s), 113.6
(s), 115.5 (d), 117.9 (d), 123.8 (d), 134.4 (d), 142.5 (s), 153.5 (s),
162.0 (s), 178.4 (d).
IR (film): 3281, 2917, 1716, 1451, 1262, 1093, 1065, 938, 791, 704
cm–1.
1H NMR (300 MHz, CDCl3): d = 1.27 (d, J = 6.2 Hz, 3 H), 1.60–
1.95 (br s, 2 H), 2.28 (t, J = 2.5 Hz, 1 H), 2.54 (dd, J = 17.1, 6.6 Hz,
1 H), 2.63 (dd, J = 17.1, 5.4 Hz, 1 H), 3.40 (d, J = 2.4 Hz, 2 H), 3.81
(s, 2 H), 3.85–4.06 (m, 1 H), 6.19 (d, J = 3.3 Hz, 1 H), 6.45 (d,
J = 3.3 Hz, 1 H).
13C NMR (128 MHz, CD2Cl2): d = 22.9 (q), 30.5 (t), 37.6 (t), 45.2
(t), 66.8 (d), 71.9 (d), 73.5 (s), 82.2 (s), 91.7 (s), 108.9 (d), 115.6 (d),
136.9 (s), 154.7 (s).
MS (EI, 70 eV): m/z (%) = 226 (100) [M+], 211 (12), 169 (34), 126
(12), 113 (7).
HRMS (EI, 70 eV): m/z [M+] calcd for C14H10O3: 226.0630; found:
226.0654.
Anal. Calcd for C14H10O3: C, 74.33; H, 4.46. Found: C, 74.21; H,
4.42.
N-[(E)-{5-[(4-Methoxyphenyl)ethynyl]-2-furyl}methyl-
ene]prop-2-yn-1-amine (8g)
MS (EI, 70 eV): m/z (%) = 217 (48) [M+], 188 (100), 172 (41), 144
(38), 118 (73), 68 (56), 45 (58).
HRMS (EI, 70 eV): m/z [M]+ calcd for C13H15NO2: 217.1103;
found: 217.1103.
7g (3.00 g, 13.4 mmol, 1 equiv) was dissolved in CH2Cl2 (20 mL),
then MgSO4 (6.00 g) and prop-2-ynylamine (2.36 g, 22.8 mmol, 3.2
equiv) were added. The mixture was stirred at r.t. for 72 h then fil-
tered and concentrated under reduced pressure to deliver 8g.
N-[5-(4-Hydroxypent-1-ynyl)furan-2-ylmethyl]-4-methyl-N-
prop-2-ynylbenzenesulfonamide (10d)
Yield: 3.43 g (98%); orange solid; mp 92 °C; Rf = 0.55 (hexanes–
EtOAc, 2:1).
9d (477 mg, 2.19 mmol, 1 equiv) was dissolved in CH2Cl2 (9 mL)
and Et3N (211 mg, 291 mL, 2.19 mmol, 0.9 equiv) and tosylchloride
(397 mg, 2.09 mmol, 0.9 equiv) were added. The mixture was
stirred at r.t. for 12 h, then quenched with H2O (20 mL). The aque-
ous phase was extracted with CH2Cl2 (3 × 10 mL), then the com-
bined organic layers were dried over MgSO4, filtered and
concentrated under reduced pressure. Purification by flash chroma-
tography on silica gel (hexanes–EtOAc, 2:1) gave 10d.
IR (KBr): 3257, 3101, 3083, 2842, 2811, 2539, 2208, 1647, 1606,
1571, 1523, 1498, 1350, 1306, 1291, 1265, 1249, 1183, 1149, 1113,
1021, 979, 960, 840, 834, 811 cm–1.
UV/Vis (CH2Cl2): λmax (log ε) = 264 (4.00), 328 (4.43), 348 nm
(4.31).
1H NMR (300 MHz, CD3CN): d = 2.76 (t, J = 2.5 Hz, 1 H), 3.81 (s,
3 H), 4.45 (t, J = 2.1 Hz, 2 H), 6.76 (d, J = 3.6 Hz, 1 H), 6.91 (d,
J = 3.6 Hz, 1 H), 6.95 (d, J = 9.0 Hz, 2 H), 7.50 (d, J = 9.0 Hz, 2 H),
8.33 (t, J = 1.9 Hz, 1 H).
Yield: 672 mg (87%); colorless oil; Rf = 0.10 (hexanes–EtOAc,
2:1).
13C NMR (75 MHz, CD3CN): d = 47.8 (t), 56.2 (q), 76.7 (d), 78.5
(s), 79.9 (s), 95.7 (s), 114.3 (s), 115.4 (d), 116.6 (d), 117.7 (d), 134.1
(d), 139.8 (s), 151.3 (d), 153.1 (s), 161.6 (s).
MS (EI, 70 eV): m/z (%) = 263 (100) [M+], 236 (17), 223 (12), 169
(24), 151 (12).
HRMS (EI, 70 eV): m/z [M+] calcd for C14H10O3: 263.0946; found:
263.0964.
IR (film): 3287, 2971, 1597, 1536, 1348, 1160, 1092, 892, 665 cm–1.
1H NMR (500 MHz, CDCl3): d = 1.31 (d, J = 6.2 Hz, 3 H), 1.90–
2.20 (br s, 1 H), 2.07 (t, J = 2.5 Hz, 1 H), 2.42 (s, 3 H), 2.57 (dd,
J = 17.0, 6.5 Hz, 1 H), 2.63 (dd, J = 17.0, 5.3 Hz, 1 H), 4.00–4.08
(m, 1 H), 4.04 (d, J = 2.4 Hz, 2 H), 4.39 (s, 2 H), 6.26 (d,
J = 3.3 Hz, 1 H), 6.41 (d, J = 3.3 Hz, 1 H), 7.29 (d, J = 8.2 Hz, 2 H),
7.72 (d, J = 8.4 Hz, 2 H).
13C NMR (125 MHz, CDCl3): d = 21.7 (q), 22.6 (q), 30.1 (t), 36.5
(t), 43.0 (t), 66.5 (d), 73.2 (s), 74.3 (d), 76.4 (d), 91.3 (s), 111.0 (d),
115.4 (d), 127.9 (d, 2 C), 129.7 (d, 2 C), 135.9 (s), 137.5 (s), 143.9
(s), 149.4 (s).
MS (EI, 70 eV): m/z (%) = 371 (39) [M+], 222 (50), 215 (100), 171
(81), 119 (51), 118 (78), 91 (80).
Anal. Calcd for C17H13NO2: C, 77.55; H, 4.98; N, 5.32. Found: C,
74.94; H, 4.90; N, 5.25.
N-({5-[(4-Methoxyphenyl)ethynyl]-2-furyl}methyl)prop-2-yn-
1-amine (9g)
8g (3.00 g, 11.4 mmol, 1 equiv) was dissolved in MeOH (40 mL),
and NaBH4 (863 mg, 22.8 mmol, 2 equiv) was added in portions.
The mixture was stirred at r.t. for 16 h then distilled H2O (30 mL)
HRMS (EI, 70 eV): m/z [M]+ calcd for C20H21NO4S: 317.1191;
found: 317.1192.
Synthesis 2008, No. 17, 2707–2718 © Thieme Stuttgart · New York

2716
A. S. K. Hashmi et al.
PAPER
was added. After extraction with CH2Cl2 (3 × 40 mL) the combined
organic extracts were dried over MgSO4, filtered and concentrated
under reduced pressure to deliver 9g.
Yield: 46 mg (25%); colorless solid; mp 151 °C; Rf = 0.40 (hex-
anes–EtOAc, 3:1).
IR (film): 2855, 1600, 1460, 1345, 1096, 983, 922, 804, 661, 620
cm–1.
Yield: 832 mg (95%); orange solid (melting point slightly above
r.t.); Rf = 0.16 (hexanes–EtOAc, 1:1).
1H NMR (500 MHz, CDCl3): d = 2.05 (m, 2 H), 2.22 (m, 1 H), 2.37
(m, 1 H), 2.40 (s, 3 H), 3.24 (d, J = 2.3 Hz, 2 H), 4.11 (q,
J = 7.5 Hz, 1 H), 4.01 (m, 1 H), 4.55 (m, 4 H), 6.65 (d, J = 7.4 Hz,
1 H), 7.03 (d, J = 7.5 Hz, 1 H), 7.23 (d, J = 8.2 Hz, 2 H), 7.75 (d,
J = 8.2 Hz, 2 H).
13C NMR (125 MHz, CDCl3): d = 21.5 (t), 24.0 (q), 36.6 (t), 38.2
(t), 51.2 (t), 53.9 (t), 68.8 (s), 114.2 (s), 117.3 (s), 119.5 (d), 124.1
(s), 125.1 (d), 127.6 (d), 129.8 (d), 133.8 (s), 137.1 (s), 143.6 (s),
152.4 (s).
IR (film): 3294, 2930, 2837, 2209, 1608, 1593, 1544, 1503, 1463,
1441, 1288, 1249, 1177, 1148, 1107, 1029, 832, 792 cm–1.
UV/Vis (CH2Cl2): λmax (log λ) = 262 (5.24), 286 (5.48), 302 (5.63),
310 (5.53), 322 nm (5.56).
1H NMR (300 MHz, CDCl3): d = 1.59 (s, 1 H), 2.23 (t, J = 2.4 Hz,
1 H), 3.42 (d, J = 2.4 Hz, 2 H), 3.79 (s, 3 H), 3.86 (s, 2 H), 6.22 (d,
J = 3.3 Hz, 1 H), 6.52 (d, J = 3.3 Hz, 1 H), 6.84 (d, J = 8.9 Hz, 2 H),
7.42 (d, J = 8.9 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 37.2 (t), 44.8 (t), 55.3 (q), 71.9 (d),
78.3 (s), 81.5 (d), 93.29 (s), 108.9 (d), 114.1 (d), 114.4 (s), 115.4 (d),
133.0 (d), 136.8 (s), 154.1 (s), 160.0 (s).
MS (EI, 70 eV): m/z (%) = 371 (100) [M+], 372 (25), 216 (43), 215
(86), 186 (3), 159 (51), 132 (8), 91 (42).
Anal. Calcd for C20H21NO4S: C, 64.67; H, 5.70; N, 3.77. Found: C,
63.96; H, 5.71; N, 3.84.
MS (EI, 70 eV): m/z (%) = 265 (100) [M+], 236 (57), 225 (29), 211
(90), 200 (22), 182 (12), 169 (18), 168 (17), 139 (18), 126 (17).
HRMS (EI, 70 eV): m/z [M+] calcd for C17H15NO2: 265.1103;
found: 265.1130.
Gold-Catalyzed Reaction of 10b
10b (21.3 mg, 54.1 mmol) was dissolved in CDCl3 (1 mL) in an
NMR tube and 1H NMR spectra were measured. Then AgCl3 (821
mg, 2.71 mmol, 5 mol%) was added and the reaction was monitored
Anal. Calcd for C17H15NO2: C, 76.96; H, 5.70; N, 5.28. Found: C,
76.81; H, 5.74; N, 5.26.
1
by H NMR spectroscopy. After 2 h a mixture of 5-cyclohex-1-
enylethynyl-2-(toluene-4-sulfonyl)-2,3-dihydro-1H-isoindol-4-ol
(14b) and 2-cyclohex-1-en-1-yl-7-[(4-methylphenyl)sulfonyl]-7,8-
dihydro-6H-furo[2,3-e]isoindole (15b) and the substrate 10b was
observed. The mixture was concentrated under reduced pressure
and purified by flash chromatography on silica gel (hexanes–
EtOAc, 10:1) to deliver 14b and 15b.
N-({5-[(4-Methoxyphenyl)ethynyl]-2-furyl}methyl)-4-methyl-
N-(prop-2-yn-1-yl)benzenesulfonamide (10g)
9g (2.00 g, 7.54 mmol, 1 equiv) was dissolved in CH2Cl2 (20 mL),
then Et3N (839 mg, 8.29 mmol, 1.1 equiv), DMAP (9 mg, 75 mol,
0.01 equiv) and tosylchloride (1.58 g, 8.29 mmol, 1.1 equiv) were
added. The mixture was stirred at r.t. for 2 h then diluted with H2O
(20 mL). The aqueous phase was extracted with CH2Cl2 (3 × 10
mL) and the combined organic extracts were dried over MgSO4, fil-
tered and concentrated under reduced pressure. The crude product
was purified by flash chromatography on silica gel (hexanes–
EtOAc, 2:1) to deliver 10g.
14b
Yield: 2.70 mg (13%); colorless solid; mp 147–149 °C; Rf = 0.58
(hexanes–EtOAc, 3:1).
IR (film): 3403, 2922, 2854, 1587, 1447, 1318, 1153, 1104, 811,
664 cm–1.
1H NMR (500 MHz, CDCl3): d = 1.62 (m, 2 H), 1.68 (m, 2 H), 2.15
(m, 2 H), 2.21 (m, 2 H), 2.41 (s, 3 H), 4.59 (s, 2 H), 4.60 (s, 2 H),
5.81 (s, 1 H), 6.23 (m, 1 H), 6.66 (d, J = 7.9 Hz, 1 H), 7.19 (d,
J = 7.9 Hz, 1 H), 7.31 (d, J = 8.2 Hz, 2 H), 7.77 (d, J = 8.3 Hz, 2 H).
13C NMR (125 MHz, CDCl3): d = 21.4 (t), 21.5 (q), 22.2 (t), 25.8
(t), 29.2 (t), 51.5 (t), 54.2 (t), 79.4 (s), 98.9 (s), 109.2 (s), 114.3 (d),
112.0 (s), 121.9 (s), 127.6 (d, 2 C), 129.9 (d, 2 C), 131.4 (d), 133.8
(s), 136.6 (d), 138.6 (s), 143.7 (s), 151.2 (s).
MS (EI, 70 eV): m/z (%) = 393 (66) [M+], 394 (17), 238 (42), 237
(100), 209 (30), 180 (5), 156 (5), 91 (29).
HRMS (EI, 70 eV): m/z [M]+ calcd for C23H23NO3S: 393.1399;
Yield: 3.05 g (96%); colorless solid; mp 94 °C; Rf = 0.45 (hexanes–
EtOAc, 2:1).
IR (KBr): 3291, 3279, 3128, 2972, 2921, 2841, 2208, 1606, 1596,
1543, 1503, 1352, 1337, 1292, 1252, 1160, 1091, 1022, 892, 812,
800, 749, 664, 580, 550 cm–1.
UV/Vis (CH2Cl2): λmax (log ε) = 284 (4.32), 294 (4.38), 302 (4.45),
310 (4.35), 322 nm (4.36).
1H NMR (300 MHz, CD3CN): d = 2.38 (2 s, 4 H), 3.08 (s, 3 H),
4.00 (d, J = 2.5 Hz, 2 H), 4.40 (s, 2 H), 6.36 (d, J = 3.3 Hz, 1 H),
6.58 (d, J = 3.4 Hz, 1 H), 6.94 (d, J = 9.0 Hz, 2 H), 7.36 (d, J = 8.0
Hz, 2 H), 7.46 (d, J = 9.0 Hz, 2 H), 7.72 (d, J = 8.4 Hz, 2 H).
13C NMR (75 MHz, CD3CN): d = 21.6 (q), 37.4 (t), 44.1 (t), 56.1
(q), 75.4 (d), 77.4 (d), 78.5 (s), 94.3 (s), 112.4 (d), 114.5 (s), 115.3
(d), 116.8 (d), 128.5 (d), 130.6 (d), 133.9 (d), 136.8 (s), 138.2 (s),
145.2 (s), 151.1 (s), 161.4 (s).
HRMS (ESI): m/z [M + Na+] calcd for C24H21NNaO4S: 442.10835;
found: 442.10816.
found: 393.1391.
15b
Yield: 13.2 mg (62%); colorless solid; mp 173–175 °C; Rf = 0.68
(hexanes–EtOAc, 3:1).
IR (film): 2937, 2860, 1432, 1343, 1154, 1073, 1012, 813, 665, 619
cm–1.
1H NMR (500 MHz, CDCl3): d = 1.68 (m, 2 H), 1.78 (m, 2 H), 2.27
(m, 2 H), 2.35 (m, 2 H), 2.39 (s, 3 H), 4.79 (s, 2 H), 4.85 (s, 2 H),
6.47 (s, 1 H), 6.58 (m, 1 H), 6.96 (d, J = 8.0 Hz, 1 H), 7.30 (d,
J = 8.1 Hz, 2 H), 7.37 (d, J = 7.9 Hz, 1 H), 7.79 (d, J = 8.2 Hz, 2 H).
13C NMR (125 MHz, CDCl3): d = 21.5 (q), 22.1 (t), 22.3 (t), 24.9
(t), 25.4 (t), 51.4 (t), 54.2 (t), 100.2 (d), 116.7 (d), 118.4 (s), 120.5
(d), 126.6 (d), 126.9 (s), 127.6 (d, 2 C), 128.9 (s), 129.8 (d, 2 C),
129.8 (d), 132.8 (s), 133.9 (s), 143.7 (s), 148.8 (s), 157.9 (s).
Anal. Calcd for C24H21NO4S: C, 68.72; H, 5.05; N, 3.34. Found: C,
68.68; H, 5.13; N, 3.23.
Gold-Catalyzed Reaction of 10a
10a (583 mg, 1.57 mmol) was dissolved in CDCl3 (5 mL) and AgCl3
(33.3 mg, 110 mmol, 7 mol%) was added. The mixture was stirred
at r.t. for 2 d then concentrated under reduced pressure. The crude
product was purified by flash chromatography on silica gel (hex-
anes–EtOAc, 3:1 then EtOAc) to deliver 5-(5-hydroxypent-1-ynyl)-
2-(toluene-4-sulfonyl)-2,3-dihydro-1H-isoindol-4-ol (13).
Synthesis 2008, No. 17, 2707–2718 © Thieme Stuttgart · New York

PAPER
Gold-Catalysis: Reactions of Furandialkynes
2717
MS (EI, 70 eV): m/z (%) = 393 (51) [M+], 394 (14), 238 (35), 237
(d, J = 8.0 Hz, 1 H), 7.32 (d, J = 8.3 Hz, 2 H), 7.77 (d, J = 8.2 Hz,
(100), 209 (23), 180 (4), 156 (7), 91 (29).
2 H).
HRMS (EI, 70 eV): m/z [M]+ calcd for C23H23NO3S: 393.1399;
found: 393.1400.
13C NMR (125 MHz, CDCl3): d = 21.5 (q), 51.5 (t), 54.2 (t), 77.5
(d), 84.8 (s), 107.3 (s), 114.5 (d), 122.3 (s), 127.6 (d, 2 C), 129.9 (d,
2 C), 132.0 (d), 133.7 (s), 139.8 (s), 143.8 (s), 152.4 (s).
Gold-Catalyzed Reaction of 10c
MS (ESI): m/z (%) = 336 (100) [M + Na]+, 354 (7), 372 (74), 383
10c (73.4 mg, 190 mmol) was dissolved in CH2Cl2 (5 mL) and
[(Ph3P)Au]NTf2 (7.04 mg, 9.52 mmol, 5 mol%) was added. The
mixture was stirred at r.t. for 2 d then concentrated under reduced
pressure and the crude product was purified by flash chromatogra-
phy on silica gel (hexanes–EtOAc, 5:1) to deliver N-(5-ethynylfu-
ran-2-ylmethyl)-4-methyl-N-prop-2-ynylbenzenesulfonamide (10e;
40.3 mg, 68%) as a colorless solid. For characteristic data, see the
synthesis of 10e above.
(12), 388 (8).
HRMS (ESI): m/z [M + Na]+ calcd for C17H15NNaO3S: 336.0665;
found: 336.0659.
HRMS (EI, 70 eV): m/z [M]+ calcd for C17H15NO3S: 313.0773;
found: 313.0767.
15e
Yield: 0.70 mg (1%); light-brown solid; mp 115–127 °C; Rf = 0.43
(hexanes–EtOAc, 3:1).
Gold-Catalyzed Reaction of 10d
10d (100 mg, 269 mmol) was dissolved in CH2Cl2 (10 mL) and
[(Ph3P)Au]NTf2 (3.98 mg, 5.39 mmol, 2 mol%) was added. The
mixture was stirred for 2 h, then concentrated under reduced pres-
sure and the crude product was purified by flash chromatography on
silica gel (hexanes–EtOAc, 2:1) to deliver of N-[5-(4-hydroxypen-
tanoyl)furan-2-ylmethyl]-4-methyl-N-prop-2-ynylbenzenesulfon-
amide (16).
IR (film): 3408, 2923, 2855, 1599, 1442, 1315, 1149, 1097, 814,
665, 583 cm–1.
1H NMR (500 MHz, CDCl3): d = 2.41 (s, 3 H), 4.60 (s, 2 H), 4.61
(s, 2 H), 5.55 (d, J = 1.5 Hz, 1 H), 5.73 (d, J = 1.6 Hz, 1 H), 6.73 (d,
J = 7.8 Hz, 1 H), 7.20 (d, J = 7.8 Hz, 1 H), 7.32 (d, J = 8.1 Hz, 2 H),
7.78 (d, J = 8.0 Hz, 2 H).
13C NMR (125 MHz, CDCl3): d = 21.5 (q), 51.6 (t), 54.1 (t), 114.5
(d), 118.1 (d), 123.6 (s), 123.9 (s), 127.6 (d, 2 C), 129.6 (d), 129.9
(d, 2 C), 133.6 (s), 135.4 (s), 139.7 (s), 143.8 (s), 147.9 (s).
Yield: 58.6 mg (56%); yellow solid; mp 70–72 °C; Rf = 0.12 (hex-
anes–EtOAc, 2:1).
IR (film): 3548, 3257, 2971, 2924, 1668, 1517, 1330, 1160, 1092,
817, 729, 659, 579 cm–1.
MS (ESI): m/z (%) = 336 (100) [M + Na]+, 352 (6) [M + Na]+, 368
(4), 649 (3) [2 × M + Na]+.
1H NMR (500 MHz, CDCl3): d = 1.24 (d, J = 6.2 Hz, 3 H), 1.80 (m,
2 H), 1.90 (m, 1 H), 2.11 (t, J = 2.5 Hz, 1 H), 2.44 (s, 3 H), 2.92 (t,
J = 7.3 Hz, 2 H), 3.87 (m, 1 H), 4.10 (d, J = 2.5 Hz, 2 H), 4.50 (s,
2 H), 6.47 (d, J = 3.2 Hz, 1 H), 7.14 (d, J = 3.2 Hz, 1 H), 7.31 (d,
J = 8.2 Hz, 2 H), 7.74 (d, J = 8.2 Hz, 2 H).
13C NMR (125 MHz, CDCl3): d = 21.6 (q), 23.7 (q), 32.9 (t), 34.8
(t), 37.0 (t), 43.3 (t), 67.5 (d), 74.4 (s), 76.1 (s), 111.8 (d), 117.9 (d),
127.7 (d, 2 C), 129.7 (d, 2 C), 135.6 (s), 144.0 (s), 152.6 (s), 153.8
(s), 189.6 (s).
HRMS (ESI): m/z [M + Na]+ calcd for C17H15NNaO3S: 336.0665;
found: 336.0661.
HRMS (EI, 70 eV): m/z [M]+ calcd for C17H15NO3S: 313.0773;
found: 313.0767.
Gold-Catalyzed Reaction of 10f
10f (226 mg, 430 mmol) was dissolved in CHCl3 (5 mL) and AgCl3
(9.13 mg, 30.1 mmol, 7 mol%) was added. The mixture was stirred
at r.t. for 24 h then concentrated under reduced pressure and the
crude product was purified by flash chromatography on silica gel
(hexanes–EtOAc, 5:1→4:1→3:1→EtOAc) to deliver toluene-4-
sulfonic acid 5-[4-hydroxy-2-(toluene-4-sulfonyl)-2,3-dihydro-1H-
isoindol-5-yl]pent-4-ynyl ester (14f) and 3-{7-[(4-methylphe-
nyl)sulfonyl]-7,8-dihydro-6H-furo[2,3-e]isoindol-2-yl}propyl 4-
methylbenzenesulfonate (15f).
MS (ESI): m/z (%) = 372 (49), 412 (100) [M + Na]+, 428 (15) [M +
K]+, 801 (2) [2 × M + Na]+.
HRMS (EI, 70 eV): m/z [M]+ calcd for C20H23NO5S: 389.1297;
found: 389.1291.
HRMS (ESI): m/z [M + Na]+ calcd for C20H23NNaO5S: 412.1189;
found: 412.1190.
Anal. Calcd for C20H23NO5S: C, 61.68; H, 5.95; N, 3.60. Found: C,
61.46; H, 6.02; N, 3.50.
14f
Yield: 80.1 mg (35%); brown solid; mp 68–70 °C; Rf = 0.18 (hex-
anes–EtOAc, 3:1).
Gold-Catalyzed Reaction of 10e
IR (film): 3412, 2851, 1597, 1449, 1319, 1151, 1097, 927, 810, 663
cm–1.
10e (56.7 mg, 181 mmol) was dissolved in CH2Cl2 (5 mL) and
AgCl3 (8.23 mg, 27.1 mmol, 15 mol%) was added. The mixture was
stirred at r.t. for 2 h, then concentrated under reduced pressure and
the crude product was purified by flash chromatography on silica
gel (hexanes–EtOAc, 3:1) to deliver 5-ethynyl-2-(toluene-4-sulfo-
nyl)-2,3-dihydro-1H-isoindol-4-ol (14e), 7-(toluene-4-sulfonyl)-
7,8-dihydro-6H-1-oxa-7-azaindacene (15e) and 10e (26.2 mg,
46%).
1H NMR (500 MHz, CDCl3): d = 1.94 (quin, J = 6.2 Hz, 2 H), 2.40
(s, 6 H), 2.59 (t, J = 6.7 Hz, 2 H), 4.21 (t, J = 5.7 Hz, 2 H), 4.59 (d,
J = 2.0 Hz, 4 H), 6.08 (s, 1 H), 6.64 (d, J = 7.8 Hz, 1 H), 7.12 (d,
J = 7.9 Hz, 1 H), 7.31 (ddd, J = 8.7, 1.6, 0.8 Hz, 4 H), 7.78 (ddt,
J = 11.9, 8.4, 1.8 Hz, 4 H).
13C NMR (125 MHz, CDCl3): d = 15.9 (t), 21.5 (q), 21.6 (q), 27.7
(t), 51.6 (t), 54.2 (t), 68.5 (t), 75.4 (s), 95.1 (s), 108.8 (s), 114.2 (d),
122.2 (s), 127.6 (d, 2 C), 127.9 (d, 2 C), 129.9 (d, 2 C), 129.9 (d, 2
C), 131.8 (s), 132.8 (s), 133.7 (s), 143.7 (s), 145.0 (s), 151.9 (s).
MS (EI, 70 eV): m/z (%) = 525 (0.2) [M+], 353 (7), 246 (15), 197
(36), 172 (47), 124 (18), 107 (24), 91 (100).
HRMS (EI, 70 eV): m/z [M]+ calcd for C27H27NO6S2: 525.1280;
found: 525.1283.
14e
Yield: 7.50 mg (13%); light-brown solid; mp 162–164 °C; Rf = 0.40
(hexanes–EtOAc, 3:1).
IR (film): 3384, 3262, 2853, 1446, 1148, 1103, 1027, 814, 667, 575
cm–1.
1H NMR (500 MHz, CDCl3): d = 2.41 (s, 3 H), 3.45 (s, 1 H), 4.60
(s, 2 H), 4.61 (s, 2 H), 5.85 (s, 1 H), 6.69 (d, J = 8.0 Hz, 1 H), 7.26
Synthesis 2008, No. 17, 2707–2718 © Thieme Stuttgart · New York

2718
15f
A. S. K. Hashmi et al.
PAPER
2005, 3, 387. (e) Hashmi, A. S. K. Angew. Chem. Int. Ed.
2005, 44, 6990; Angew. Chem. 2005, 117, 7150.
(f) Hashmi, A. S. K.; Hutchings, G. Angew. Chem. Int. Ed.
2006, 45, 7896; Angew. Chem. 2006, 118, 8064.
(g) Hashmi, A. S. K. Chem. Rev. 2007, 107, 3180.
(2) Hashmi, A. S. K.; Frost, T. M.; Bats, J. W. J. Am. Chem. Soc.
2000, 122, 11553.
(3) Martín-Matute, B.; Cardenas, D. J.; Echavarren, A. M.
Angew. Chem. Int. Ed. 2001, 40, 4754; Angew. Chem. 2001,
113, 4890.
(4) Méndez, M.; Munoz, M. P.; Nevade, C.; Cárdenas, D. J.;
Echavarren, A. M. J. Am. Chem. Soc. 2001, 123, 10511.
(5) Hashmi, A. S. K.; Frost, T. M.; Bats, J. W. Org. Lett. 2001,
3, 3769.
(6) Hashmi, A. S. K.; Frost, T. M.; Bats, J. W. Catal. Today
2002, 72, 19.
(7) Hashmi, A. S. K.; Kurpejovic, E.; Frey, W.; Bats, J. W.
Tetrahedron 2007, 63, 5879.
(8) Hashmi, A. S. K.; Wölfle, M.; Ata, F.; Hamzic, M.; Salathé,
R.; Frey, W. Adv. Synth. Catal. 2006, 348, 2501.
(9) Hashmi, A. S. K.; Wölfle, M.; Teles, J. H.; Frey, W. Synlett
2007, 1747.
Yield: 127 mg (24%); greenish solid; mp 66–67 °C; Rf = 0.31 (hex-
anes–EtOAc, 3:1).
IR (film): 2847, 2360, 1597, 1439, 1324, 1158, 1095, 924, 811, 666
cm–1.
1H NMR (250 MHz, CDCl3): d = 2.06 (m, 2 H), 2.39 (s, 3 H), 2.44
(s, 3 H), 2.81 (t, J = 7.2 Hz, 2 H), 4.08 (t, J = 6.0 Hz, 2 H), 4.71 (d,
J = 1.8 Hz, 2 H), 4.79 (d, J = 1.8 Hz, 2 H), 6.30 (s, 1 H), 6.98 (d,
J = 7.9 Hz, 1 H), 7.31 (m, 5 H), 7.76 (d, J = 8.2 Hz, 2 H), 7.80 (d,
J = 8.2 Hz, 2 H).
13C NMR (62 MHz, CDCl3): d = 21.3 (q), 21.5 (q), 24.2 (t), 26.8 (t),
51.1 (t), 53.9 (t), 68.9 (t), 103.0 (d), 116.6 (d), 118.3 (s), 120.1 (d),
127.5 (d, 2 C), 127.6 (d, 2 C), 127.7 (s), 129.7 (d, 2 C), 129.7 (d, 2
C), 132.3 (s), 132.7 (s), 133.6 (s), 143.5 (s), 144.7 (s), 148.9 (s),
157.3 (s).
MS (EI, 70 eV): m/z (%) = 524 (0.5) [M+], 353 (12), 246 (19), 197
(90), 170 (23), 124 (23), 91 (100).
Anal. Calcd for C27H27NO6S2: C, 61.69; H, 5.18; N, 2.66. Found: C,
61.31; H, 5.21; N, 2.67.
2-(4-Methoxyphenyl)-7-[(4-methylphenyl)sulfonyl]-7,8-dihy-
dro-6H-furo[2,3-e]isoindole (15g)
(10) Hashmi, A. S. K.; Ding, L.; Fischer, P.; Bats, J. W.; Frey, W.
Chem. Eur. J. 2003, 9, 4339.
10g (100 mg, 238 mol) was dissolved in CD2Cl2 (0.6 mL) in an
NMR tube and AgCl3 (3.6 mg, 12 mmol, 5 mol%) was added. After
1 d the product precipitated as a white solid. After 2 d, no further
reaction was observed. The crude product was purified by recrystal-
lisation from MeCN to deliver 15g.
(11) Hashmi, A. S. K.; Grundl, L. Tetrahedron 2005, 61, 6231.
(12) Hashmi, A. S. K.; Rudolph, M.; Bats, J. W.; Frey, W.;
Rominger, F.; Oeser, T. Chem. Eur. J. 2008, 14, in press.
(13) Hashmi, A. S. K.; Weyrauch, J. P.; Rudolph, M.;
Kurpejovic, E. Angew. Chem. Int. Ed. 2004, 43, 6545;
Angew. Chem. 2004, 116, 6707.
(14) Hashmi, A. S. K.; Blanco, M. C.; Kurpejovic, E.; Frey, W.;
Bats, J. W. Adv. Synth. Catal. 2006, 348, 709.
(15) Hashmi, A. S. K.; Haufe, P.; Schmid, C.; Rivas Nass, A.;
Frey, W. Chem. Eur. J. 2006, 12, 5376.
Yield: 81 mg (81%); colorless needles; mp 181 °C (decomp.).
IR (KBr): 1613, 1507, 1464, 1434, 1345, 1327, 1305, 1273, 1255,
1177, 1158, 1107, 1027, 823, 424, 670, 602, 552, 537 cm–1.
UV/Vis (CH2Cl2): λmax (log ε) = 250 (3.64), 282 (3.79), 298 (4.12),
306 (4.24), 3.14 (4.33), 3.28 nm (4.23).
(16) Hashmi, A. S. K.; Salathé, R.; Frey, W. Chem. Eur. J. 2006,
12, 6991.
1H NMR (300 MHz, DMSO-d6): d = 2.33 (s, 3 H), 3.81 (s, 3 H),
4.66 (s, 2 H), 4.86 (s, 2 H), 7.05 (d, J = 9.0 Hz, 2 H), 7.11 (d, J = 8.0
Hz, 1 H), 7.26 (s, 1 H), 7.40 (d, J = 8.0 Hz, 2 H), 7.50 (d, J = 8.0 Hz,
1 H), 7.80 (d, J = 3.9 Hz, 2 H), 7.83 (d, J = 4.6 Hz, 2 H).
13C NMR (75 MHz, DMSO-d6): d = 20.9 (q), 50.9 (t), 53.8 (t), 55.3
(q), 100.3 (d), 114.4 (d), 114.5 (s), 117.7 (d), 118.1 (s), 120.6 (d),
122.1 (s), 126.3 (d), 127.5 (d), 128.8 (d), 129.9 (s), 132.7 (s), 132.9
(s), 143.7 (s), 155.6 (s), 159.8 (s).
(17) Hashmi, A. S. K.; Ata, F.; Kurpejovic, E.; Huck, J.; Rudolph,
M. Top. Catal. 2007, 44, 245.
(18) Hashmi, A. S. K.; Rudolph, M.; Siehl, H.-U.; Tanaka, M.;
Bats, J. W.; Frey, W. Chem. Eur. J. 2008, 14, 3703.
(19) Hashmi, A. S. K.; Rudolph, M.; Weyrauch, J. P.; Wölfle, M.;
Frey, W.; Bats, J. W. Angew. Chem. Int. Ed. 2005, 44, 2798;
Angew. Chem. 2005, 117, 2858.
(20) Hashmi, A. S. K.; Weyrauch, J. P.; Kurpejovic, E.; Frost, T.
M.; Miehlich, B.; Frey, W.; Bats, J. W. Chem. Eur. J. 2006,
12, 5806.
HRMS (ESI): m/z [M + Na+] calcd for C24H21NNaO4S: 442.10835;
found: 442.10824.
(21) Hashmi, A. S. K.; Kurpejovic, E.; Wölfle, M.; Frey, W.;
Bats, J. W. Adv. Synth. Catal. 2007, 349, 1743.
(22) (a) Monteiro, N.; Balme, G. Synlett 1998, 746. (b) Yoshida,
M.; Morishita, Y.; Fujita, M.; Ihara, M. Tetrahedron 2005,
61, 4381. (c) Li, X.; Chianese, A. R.; Vogel, T.; Crabtree, R.
H. Org. Lett. 2005, 7, 5437. (d) Belting, V.; Krause, N. Org.
Lett. 2006, 8, 4489.
(23) CCDC 631589 (7c), 687063 (7g), 631588 (7h), 631590
(10e) and 687064 (15g) contain the supplementary
crystallographic data for this paper. These data can be
obtained online free of charge or from the Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge
CB2 1EZ, UK; fax: +44(1223)336033; or
Anal. Calcd for C24H21NO4S: C, 67.41; H, 5.66. Found: C, 67.39; H,
5.70.
Acknowledgment
This work was supported by the Fonds der Chemischen Industrie
and by the Deutsche Forschungsgemeinschaft (HA 1932/9-1).
References
(1) (a) Dyker, G. Angew. Chem. Int. Ed. 2000, 39, 4237; Angew.
Chem. 2000, 112, 4407. (b) Hashmi, A. S. K. Gold Bull.
2003, 36, 3. (c) Hashmi, A. S. K. Gold Bull. 2004, 37, 51.
(d) Krause, N.; Hoffmann-Röder, A. Org. Biomol. Chem.
deposit@ccdc.cam.ac.uk
(24) Gagosz, F. Org. Lett. 2005, 7, 4129.
Synthesis 2008, No. 17, 2707–2718 © Thieme Stuttgart · New York