Gold catalysis: Efficient 1,3-induction with diastereotopic homopropargyl alcohols in the phenol synthesis

Article abstract of DOI:10.1002/adsc.200900402

Furans with diastereotopic alkynyl groups were prepared and then converted to anellated phenols in gold-catalyzed reactions. In all cases a highly diastereoselective reaction was observed. The stereochemical outcome of the 1,3-induction could be assigned

Full text of DOI:10.1002/adsc.200900402

FULL PAPERS
DOI: 10.1002/adsc.200900402
Gold Catalysis: Efficient 1,3-Induction with Diastereotopic
Homopropargyl Alcohols in the Phenol Synthesis
a,
a
a
´
A. Stephen K. Hashmi, * Melissa Hamzic, Matthias Rudolph,
Martin Ackermann,a and Frank Romingera
Organisch-Chemisches Institut, Ruprecht-Karls-Universitꢀt Heidelberg, Im Neuenheimer Feld 270, 69120 Heidelberg,
Germany
a
Fax : (+49)-(0)6221-54-4205; phone: (+49)-(0)6221-54-8413; e-mail: hashmi@hashmi.de
Received: June 10, 2009; Revised: August 26, 2009; Published online: October 1, 2009
Abstract: Furans with diastereotopic alkynyl groups showing a cis-arrangement of the two alkyl substitu-
were prepared and then converted to anellated phe- ents on the benzoanellated cyclohexene ring.
nols in gold-catalyzed reactions. In all cases a highly
diastereoselective reaction was observed. The stereo-
chemical outcome of the 1,3-induction could be as- Keywords: alkynes; arenes; cobalt; furans; gold; ste-
signed by two independent crystal structure analyses, reoselectivity
Introduction
In homogeneous gold catalysis[1] the cycloisomeriza-
tion of w-alkynylfurans 1 to anellated phenols 2, the
first example of a substrate with the 1,6-enyne sub-
structure (shown in bold in Scheme 1) in a gold-cata-
lyzed cycloisomerization reaction, has proven to be
Figure 1. Substrates with diastereotopic alkynyl groups.
one of the most reliable and broadly applicable meth-
ods in this area. After the discovery of this useful
transformation in 2000,[2] mechanistic investigations[3]
and exploration of the synthetic scope of the reaction new bonds involve only sp2 centers), such stereoselec-
in the synthesis of different carbo- and heterocycles[4] tive conversions would demand heterotopic reacting
have dominated.
groups in the substrate. A substrate like 3, with identi-
So far, stereoselective reactions have not been in- cal length of the tether between the branching point
vestigated. Since the reacting sp and sp2 centers of the and the alkyne unit would fulfil this condition
alkyne and the furan do not form new stereocenters (Figure 1).
in the product 2 (with respect to the carbon atoms, all
Here we describe the synthesis and the gold-cata-
lyzed conversion of such substrates possessing two
diastereotopic alkynyl groups.
Results and Discussion
For the substrate synthesis we started with the furfu-
rals 4, the addition of Grignard compounds delivered
5, the latter was oxidized to the acylfurans 6
(Scheme 2).
As shown in Table 1, these reactions often gave ex-
cellent yields of the furfurols 5, but the yield of the
subsequent oxidation step could be as low as 34%
(entry 5). The oxidation of 5 to 6 was successful with
either MnO2 or Dess–Martin periodinane (DMP).
Scheme 1. The gold-catalyzed phenol synthesis.
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Table 1. Two-step route to the acylfurans 6.
Entry
1
4
5
Yield [%]
100
Oxidant
6
Yield [%]
4a: R1 =Me
5a: R1 =Me, R2 =c-Pr
MnO2
DMP
DMP
BaMnO4
MnO2
DMP
6a
73
–
95
–
–
2
3
5b: R1 =Me, R2 =i-Pr
99
99
6b
5c: R1 =Me, R2 =t-Bu
6c
88
MnO2
MnO2
DMP
–
54
34
4
5
5d: R1 =Me, R2 =n-Bu
5e: R2 =Me
100
58
6d
6e
4b: R1 =Ph
Table 2. Aldol condensation leading to 7 and Reformatsky
reaction providing 8.
Entry
6
7
Yield
[%]
8
Yield
[%]
1
2
3
4
5
6
7
8
6a: R1 =Me, R2 =c-Pr
6b: R1 =Me, R2 =i-Pr
6c: R1 =Me, R2 =t-Bu
6d: R1 =Me, R2 =n-Bu
6e: R1 =Ph, R2 =Me
6f: R1 =Ph, R2 =H
8a
56
7b 64
–
–
–
8d 47
7e
7g
78
48
8f
8g
80
97
6g: R1 =Me, R2 =Me
6h: R1 =Me, R2 =H
7h 36
Scheme 2. Synthesis of 6 from furfurals 4.
Nevertheless, this short sequence is a fast synthetic with the aldol condensation also good yields could be
route to 6. obtained (entry 5). Due to the different ester groups
For the further conversion of 6 we investigated two (Me or t-Bu), the results cannot be compared directly.
different routes. The aldol condensation with tert- For the substrate 6c, where the initial nucleophilic
butyl acetate provided the tert-butyl esters 7, the Re- attack must occur at a neopentylic carbonyl group,
formatsky reaction with methyl bromoacetate gave both reaction types failed completely (entry 3). The
the corresponding methyl esters 8 (Scheme 3).
low yield of 7h resulted from a significant portion of
The results from Table 2 show that the Reformat- aldol addition product which had not eliminated to
sky reaction might give better results (entry 7), but 7h.
Scheme 3. Aldol and Reformatsky route to the a,b-unsaturated esters 7 and 8.
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Gold Catalysis: Efficient 1,3-Induction with Diastereotopic Homopropargyl Alcohols
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Scheme 4. Transfer hydrogenation delivers 9.
Table 3. Hydrogenation of 7 and 8.
Entry
Substrate
Product
Yield [%]
1
2
3
4
5
6
7
8a: R1 =Me, R2 =c-Pr, R3 =Me
7b: R1 =Me, R2 =i-Pr, R3 =t-Bu
8d: R1 =Me, R2 =n-Bu, R3 =Me
7e: R1 =Ph, R2 =Me, R3 =t-Bu
8f: R1 =Ph, R2 =H, R3 =Me
7g: R1 =Me, R2 =Me, R3 =t-Bu
7h: R1 =Me, R2 =H, R3 =t-Bu
9a: R2 =n-Pr[a]
99
94
97
96
42
87
83
9b
9d
9e
9f
9g
9h
[a]
Additional hydrogenative ring opening.
The substrates 7 and 8 were then reduced to the strained cyclopropyl ring is also opened by a hydroge-
À
esters 9 with cyclohexene as the hydrogen transfer re- native C C bond cleavage to deliver 9a with an n-
agent and
(Scheme 4).
a
heterogeneous palladium catalyst propyl side chain.
The substrates 9 were subsequently converted to
Table 3 shows that with the exception of 9f the tertiary alcohols 10. Since the two-fold addition is
(entry 5) very good yields were obtained. In 8a the Pd a step-wise process, a propargyl ketone is the inter-
catalyst does not only hydrogenate the alkene, the mediate, and this intermediate might partially isomer-
ize to the corresponding allenyl ketone prior to addi-
tion of the second equivalent of propargylmagnesium
bromide – this ultimately can deliver the allenyl-prop-
argyl carbinol 11 as
a side-product (Scheme 5,
Table 4).[5]
A significant amount of this side-product is ob-
tained only in two cases (Table 4: 11d, entry 3 and
11h, entry 7), in one case a small amount (3%) could
be detected (11g, entry 6). For these three cases the
propargyl compound was difficult to separate from
allene 6, 10d/11d could not be separated but were
used as a mixture in the next step in which the allenic
substrate only delivered oligomeric/polymeric materi-
al which could easily be separated. The pair 10g/11g
behaved similarly, but due to the small percentage of
11g, the spectroscopic data for 10g could be assigned.
Scheme 5. Tertiary alcohols 10 and 11 by Grignard addition
to the ester group of 9.
Table 4. Grignard addition to the ester group of 9.
Entry
9
10
Yield [%]
11
Yield [%]
1
2
3
4
5
6
7
9a: R1 =Me, R2 =n-Pr, R3 =Me
9b: R1 =Me, R2 =i-Pr, R3 =t-Bu
9d: R1 =Me, R2 =n-Bu, R3 =Me
9e: R1 =Ph, R2 =Me, R3 =t-Bu
9f: R1 =Ph, R2 =H, R3 =Me
9g: R1 =Me, R2 =Me, R3 =t-Bu
9h: R1 =Me, R2 =H, R3 =t-Bu
10a: R1 =Me, R2 =n-Pr
10b: R1 =Me, R2 =i-Pr
10d: R1 =Me, R2 =n-Bu
10e: R1 =Ph, R2 =Me
10f: R1 =Ph, R2 =H
33
36
32
61
66
31
44
11a
11b
11d
11e
11f
11g
11h
–
–
32
–
–
10g: R1 =Me, R2 =Me
10h: R1 =Me, R2 =H
3
30
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Scheme 7. Preparation of a crystalline derivative of 13g.
Scheme 6. Gold-catalyzed conversion of substrates 10.
In the case of 10h/11h the constitutional isomers
could be separated. The other conversions of 9 pro-
vided clean 10.
The gold-catalyzed conversion of 10 now delivered
only one single diastereoisomer (Scheme 6). Neither
in the NMR spectra taken in situ during the transfor-
mation nor during the work-up or by GC, did we find
any evidence for the other diastereoisomer. Thus a
diastereoselectivity better than 99:1 can be assumed.
Figure 2. X-Ray crystal structure analysis of the dicobalthexa-
The yields are moderate to good and seem to carbonyl complex 1
4
.
depend on a complicated interplay of both R1 (proba-
bly influencing the electronic properties of the furan
ring and intermediates) and R2 (influencing the con- clohexane ring. In the solid state they occupy a
formation of the tether), a comparison of entries 4 pseudo-equatorial position, placing the hydroxy group
and 6 from Table 5 shows that even the remote at C-1 in an axial position.
phenyl group in 10e deminishes the yield, with the re-
Once we had obtained the crystal structure of 14 by
lated methyl derivative 10g a significantly higher yield functionalization of 13g, one of the products 13,
was obtained.
namely 13a, also crystallised over time (Figure 3).
For 13a the same relative configuration and a simi-
The assignment of the product to one of the two
possible structures 12 or 13, which is already provided lar conformation as in 14 is observed in the solid
in Table 5, was not easy. Intensive NMR studies gave state. Again the n-propyl group at C-10 and the prop-
no clear results, and initially none of the products was argyl group at C-8 are cis and in a pseudo-equatorial
crystalline. Thus we converted the product 13g to the position, the hydroxy group at C-8 is axial.
dicobalt hexacarbonyl complex, which indeed deliv-
These two structures independently show that this
ered a crystalline product 14 (Scheme 7). Single crys- 1,3-induction results in a cis-arrangement of the sub-
tals for a X-ray crystal structure analysis could be ob- stitutent and the unreacted propargyl group. On this
tained (Figure 2).[6]
basis the products from Table 5 were assigned to the
The methyl substitutent at C-6 and the side-chain diastereoisomer 13, the NMR spectroscopic data of
at C-1 (the former propargyl group) are cis on the cy- the products are in good agreement with the data of
the two products 13a and 13g, there is no evidence for
another relative configuration in any of the other
Table 5. Diastereoselective gold-catalyzed cycloisomeriza-
tion of 10.
(non-crystalline) products 13b–13e. Only the sub-
strates 10f and 10h lack the furylic stereocenter and
thus deliver only racemic products 13f and 13h. These
simply provide another proof of the reaction principle
and the chemoselectivity for the phenol synthesis
even in the presence of the free hydroxy group and
the second alkyne.
Entry
10
Product
Yield [%]
1
2
3
4
5
6
7
10a: R1 =Me, R2 =n-Pr
10b: R1 =Me, R2 =i-Pr
10d: R1 =Me, R2 =n-Bu
10e: R1 =Ph, R2 =Me
10f: R1 =Ph, R2 =H
13a
13b
13d
13e
13f
13g
13h
46
87
67
50
87
67
66
The stereoselectivity-determining step is the forma-
À
tion of the first C C bond after coodination of the
10g: R1 =Me, R2 =Me
10h: R1 =Me, R2 =H
catalyst to a triple bond. The two transition states of
this selectivity-determining step, a 6-exo-dig cycliza-
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Gold Catalysis: Efficient 1,3-Induction with Diastereotopic Homopropargyl Alcohols
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the unprotected and protected substrate. This suggests
that the direct influence of the hydroxy group by co-
ordination is only a minor one.
Conclusions
Highly diastereoselective ring-closure reactions with
simple AuCl3 are possible when using diastereotopic
alkynyl groups in the phenol synthesis. The 1,3-cis po-
sition of the two side chains at the newly formed cy-
clohexenyl ring suggests a bis-equatorial position of
these groups in the transition state of the ring closure
step.
Figure 3. X-Ray crystal structure analysis of 13a.
Experimental Section
General Procedure A: For the Grignard Reaction
with Aldehydes
All reactions were carried out under a nitrogen atmosphere
in oven-dried glassware. The Grignard reagent (0.5–2M,
2 equiv.) was diluted in 20–30 mL Et2O, cooled to about
À108C. Aldehyde (1 equiv.) was then added slowly over
20 min with vigorous stirring. Then the temperature was al-
lowed to rise to +108C. A suspension formed which was hy-
drolyzed by pouring it into a solution of saturated cold am-
monium chloride. After phase separation the aqueous phase
was extracted with Et2O. The organic phase was dried over
MgSO4, filtered and the solvent was removed under reduced
pressure. Then the product was isolated by column chroma-
tography.
Figure 4. Competing transition states in the cyclization of
10.
tion, ultimately leading to the two diastereomers 12
and 13, are shown in Figure 4. Transition state A
would deliver the diastereomer 12, but the propargyl
group would be placed in an axial position. This prob-
ably is the reason for the selectivity for transition
state B, leading to diastereomer 13.
Another question is the possible participation of
the hydroxy group as an active volume, also coordi-
nating to the catalyst. In order to address this ques-
tion, we prepared substrate 15 with a TBDMS pro-
General Procedure B: For Oxidation with DMP or
MnO2
a) With DMP: The secondary alcohol (1 equiv.) was dis-
tecting group on the tertiary alcohol by protecting solved in 20 mL of dichloromethane and DMP (1.1 equiv.)
was added. The reaction was stirred at room temperature
for 3–5 h. The resulting suspension was filtered, the filtrate
was washed with dichloromethane. The solvent was re-
moved, the residue was purified by column chromatography.
b) With MnO2: The secondary alcohol (1 equiv.) was dis-
solved in 20 mL of dichloromethane or acetone, manganese
dioxide (15.5–20 equiv.) was added. The mixture was stirred
at room temperature for 3–5 h, then the suspension was
then filtered and the filtrate was washed with dichlorome-
thane or acetone. The solvent was removed and the residue
10g with TBDMSOTf. The gold-catalyzed cyclization
of 15 (Scheme 8) still delivered the same diastereomer
of 16, but with slightly reduced diastereoselectivity
(87:13).
The stereochemical assignment again was not trivi-
al, the deprotection of 16 to 13 failed even with
Bu4NF or CsF. Only the TBDMS-protection of 13a,
delivering 16, after two-fold silylation and subsequent
deprotection of the reactive silyl group on the phenol-
ic oxygen atom, finally proved that the same relative was purified by chromatography column.
configuration was formed in the conversion of both
General Procedure C: For the Reformatsky Reaction
Activated zinc (1.7 equiv.) was dissolved in 20–30 mL of ab-
solute toluene and a mixture of the ketone (1 equiv.) and
methyl bromoacetate (1.5 equiv.) in 10 mL toluene was
slowly added. After refluxing for 24 h, the reaction mixture
was hydrolyzed with 3N HCl. The organic layer was sepa-
rated, the aqueous phase was extracted with toluene and the
combined organic phasees were washed with water, dried
over MgSO4, filtered and the solvent removed under re-
Scheme 8. Preferred diastereomer formed with protected 15.
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duced pressure. The crude product was purified by column
chromatography.
(CDCl3, 300 MHz): d=0.87 (d, J=6.9 Hz, 3H), 1.04 (d, J=
6.9 Hz, 3H), 2.08 (m, J=6.9 Hz, 1H), 2.30 (s, 3H), 4.28 (m,
1H), 5.94 (d, J=3.0 Hz, 1H), 6.12 (d, J=3.0 Hz, 1H). These
data are in agreement with the literature.[7]
2,2-Dimethyl-1-(5-methylfuran-2yl)propan-1-ol (5c): Pre-
pared according to the general procedure A using 5-methyl-
furfural (1.00 g, 900 mL, 9.08 mmol,) in 10 mL absolute THF
and tert-BuLi (5.34 mL, 9.08 mmol). After the removal of
the solvent under vacuum the desired product 5c was ob-
General Procedure D: For the Transfer
Hydrogenation
All reactions were carried out under a nitrogen atmosphere
in oven-dried glassware. The unsaturated ester (1 equiv.)
was taken up in 10–20 mL of absolute methanol. Freshly dis-
tilled cyclohexene (20–40 equiv.) and Pd/C (5% of Pd or
l0% Pd) were added. The mixture was heated to reflux for
24 h. Then the reaction mixture was filtered over celite and
the solvent was removed under reduced pressure.
˜
tained; yield: 1.51 g (99%). IR (film): n=3449, 2995, 2871,
1666, 1561, 1479, 1464, 1365, 1219, 1062, 1018, 964, 785 cmÀ1
;
1H NMR (CDCl3, 300 MHz): d=0.91 (s, 9H), 2.23 (s, 3H),
4.24 (s, 1H), 5.86 (d, J=3.0 Hz, 1H), 6.03 (d, J=3.0 Hz,
1H); 13C NMR (CDCl3, 75.5 MHz): d=13.5 (q), 25.6 (q),
35.6 (s), 76.5 (d), 105.8 (d), 107.8 (d), 150.9 (s), 153.8 (s);
MS (EI, 70 eV): m/z (%)=168 (10) [M+], 111 (100) [M+À11
C6H7O2], 57 (10) [M+À11 C4H9]; anal. calcd. for C10H16O2
(168.12): C 71.39, H 9.59; found: C 68.47, H 9.23; HR-MS
(EI+): m/z=168.1158, calcd. for M+ =C10H16O2: 168.1224.
1-(5-Methylfuran-2-yl)pentan-1-ol (5d): Prepared accord-
ing to the general procedure A using the 5-methylfurfural
(1.40 mL, 13.6 mmol) in 2 mL absolute Et2O and butylmag-
nesium chloride (1.60 mL, 27.3 mmol). After removal of the
solvent under vacuum the desired product 5d was obtained;
General Procedure E: For the Grignard Reaction
with Propargylmagnesium Bromide
All reactions were carried out under a nitrogen atmosphere
in oven-dried glassware. Propargylmagnesium bromide
(4 equiv., 2.04M in diethyl ether) was dissolved in 5–10 mL
diethyl ether and cooled to À108C. The ester (1 equiv.) was
added over 15 min with vigorous stirring to the Grignard re-
agent, the temperature was controlled to be in the range
À108C to 08C. Then the cooling bath was removed and the
mixture was allowed to warm to room temperature. A sus-
pension was formed, after stirring overnight, the mixture
was hydrolyzed by pouring the reaction mixture in a cold sa-
turated solution of NH4Cl (30–50 mL). The layers were sep-
arated, the aqueous phase was extracted with diethyl ether
(2ꢂ20 mL), the combined organic phases were dried over
MgSO4, filtered and the solvent was removed under reduced
pressure. The crude product was purified by column chro-
matography.
1
yield: 3.36 g (100%). H NMR (CDCl3, 300 MHz): d=0.92
(t, J=7.3 Hz, 3H), 1.36 (m, J=7.3 Hz, 2H), 1.62 (m, 2H),
1.82 (m, 2H), 2.41 (s, 3H), 3.47 (q, 1H), 6.15 (dq, J=3.1 Hz,
1H), 7.08 (d, J=3.1 Hz, 1H). These data are in agreement
with the literature.[8]
1-(5-Phenylfuran-2-yl)ethanol (5e): Prepared according to
the general procedure A using 5-phenylfurfural (2.00 g,
11.6 mmol) in 10 mL absolute Et2O and methylmagnesium
bromide (1.98 g, 9.70 mL, 29.1 mmol). After removal of the
solvent under vacuum 5e was obtained; yield: 1.22 g (58%).
1H NMR (CDCl3, 300 MHz): d=1.57 (d, J=7.5 Hz, 3H),
4.15 (q, J=7.5 Hz, 1H), 6.20 (dd, J=3.1 Hz, 0.7 Hz, 1H),
6.61 (d, J=3.1 Hz, 1H), 7.25 (m, 1H), 7.37 (m, 2H), 7.66
(m, 2H). These data are in agreement with the literature.[8]
Cyclopropyl(5-methylfuran-2-yl)methanone (6a): Pre-
pared according to the general procedure Bb using alcohol
5a (1.68 g, 11.0 mmol) in 25 mL absolute dichloromethane
and MnO2 (14.9 g, 171 mmol). After 3 days the solvent was
removed under vacuum and 6a was obtained; yield: 1.21 g
General Procedure F: For Gold Catalysis
To a solution of dipropargyl Alcohol derivative in acetoni-
trile-d3 (650 mL) was added 5 mol% AuCl3. The progress of
1
the reaction was monitored by H NMR spectroscopy. Upon
completion, the reaction mixture was concentrated under
vacuum and the crude product was purified by column chro-
matography on silica gel.
Cyclopropyl(5-methylfuran-2-yl)methanol (5a): Prepared
according to the general procedure A using 5-methylfurfural
(1.00 g, 0.91 mL, 9.08 mmol,) in 10 mL absolute Et2O and
˜
(73%). IR (film): n=3500, 3124, 3013, 2921, 2876, 1661,
1
1517, 1396, 1054, 799 cmÀ1; H NMR (CDCl3, 300 MHz): d=
cyclopropylmagnesium
bromide
(1.98 g,
27.2 mL,
0.91–0.97 (m, 2H), 1.15–1.20 (m, 2H), 2.38 (s, 3H), 2.43–
2.52 (m, 1H), 6.14 (d, J=3.4 Hz, 1H), 7.12 (d, J=3.4 Hz,
1H); 13C NMR (CDCl3, 75.5 MHz): d=10.9 (t, 2C), 14.0 (q),
16.9 (d), 108.8 (d), 118.4 (d), 152.0 (s), 157.5 (s), 188.5 (s);
MS (EI+): m/z (%)=150 (80) [M+], 109 (100)
[M+Àcyclopropyl].
13.6 mmol). After the solvent was removed under vacuum
the desired product 5a was obtained and used without fur-
˜
ther purification; yield: 1.81 g. IR (film): n=3375, 3085,
1
3006, 2923, 2880, 1564, 1433, 1220, 1021, 785 cmÀ1; H NMR
(CDCl3, 300 MHz): d=0.28–0.46 (m, 2H), 0.51–0.67 (m,
2H), 1.25–1.36 (m, 1H), 2.27 (s, 3H), 3.95 (d, J=8.3 Hz,
1H), 5.89 (d, J=3.0 Hz, 1H), 6.16 (d, J=3.0 Hz, 1H);
13C NMR (CDCl3, 75.5 MHz): d=2.5 (t), 3.3 (t), 13.6 (q),
16.0 (d), 72 (d), 106.0 (d), 106.8 (d), 151.8 (s), 154.3 (s); MS
(EI, 70 eV): m/z (%)=152 (70) [M+], 124 (100), 111 (90)
[M+Àcyclopropyl], 71 [M+ÀC4H7O].
2-Methyl-1-(5-methylfuran-2-yl)propan-1-one (6b): Pre-
pared according to the general procedure Ba using alcohol
5b (1.40 g, 9.05 mmol) in 25 mL absolute dichloromethane
and DMP (5.00 g, 11.8 mmol). After 24 h the solvent was re-
moved under vacuum and after work-up 6b was obtained;
yield: 1.30 g (95%). 1H NMR (CDCl3, 300 MHz): d=1.21
(d, J=6.8 Hz, 6H), 2.41 (s, 3H), 3.29 (m, J=6.9 Hz, 1H),
6.16 (dd, J=3.5 Hz, 0.9 Hz, 1H), 7.12 (d, J=3.4 Hz, 1H).
These data are in agreement with the literature.[9]
2-Methyl-1-(5-methylfuran-2-yl)propan-1-ol (5b): Pre-
pared according to the general procedure A using 5-methyl-
furfural (2.00 g, 19.8 mmol) in 10 mL absolute Et2O and iso-
propylmagnesium bromide (3.05 g, 14.8 mL, 29.7 mmol).
After removal of the solvent under vacuum the desired
product 5b was obtained; yield: 3.04 g (99%). 1H NMR
2-Methyl-1-(5-methylfuran-2-yl)propan-1-one (6c): Pre-
pared according to the general procedure Ba using alcohol
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Gold Catalysis: Efficient 1,3-Induction with Diastereotopic Homopropargyl Alcohols
FULL PAPERS
5c (1.50 g, 8.92 mmol) in 25 mL absolute dichloromethane
and DMP (4.90 g, 11.7 mmol). After 24 h the solvent was re-
moved under vacuum and after work-up 6c was obtained;
matography on silica gel furnished the alcohol 7b’ as an
orange oil; yield: 1.50 g (78%). Rf (petrol ether:ethyl ace-
˜
tate, 10:1)=0.25; IR (film): n=3484, 2969, 2935, 2879, 1707,
1
yield: 1.30 g (88%). IR (film): n=2971, 2932, 2875, 1661,
1604, 1347, 1252, 1229, 1152, 1026 cmÀ1; H NMR (CDCl3,
˜
1
1508, 1480, 1459, 1367, 1200, 1006, 905, 797 cmÀ1; H NMR
300 MHz): d=0.86 (t, J=7.1 Hz, 6H), 1.34 (s, 9H), 1.99 (m,
J=7.1 Hz, 1H), 2.23 (d, J=0.9 Hz, 3H), 2.58 (d, J=15.2 Hz,
1H,), 2.82 (d, J=15.2 Hz, 1H), 5.84 (dd, J=3.03 Hz, 0.9 Hz,
1H), 6.07 (d, J=3.0 Hz, 1H); 13C NMR (CDCl3, 125 MHz):
d=13.6 (q), 16.8 (q), 17.3 (q), 27.9 (q, 3C), 37.3 (d), 41.1 (t),
75.1 (s), 81.6 (s), 105.9 (d), 106.9 (d), 150.7 (s), 155.9 (s),
172.7 (s); MS (FAB+): m/z (%)=268 (29) [M+], 251 (100),
250 (65); HR-MS (FAB+): m/z=268.1642, calcd. for M+ =
C15H24O4: 268.1675.
b) Elimination to 7b: The racemic alcohol 7b’ (500 mg,
1.86 mmol) was dissolved in 15 mL THF, 25 mL of 3N HCl
were added and the mixture was stirred for 30 min at room
temperature. The mixture was diluted with 20 mL of Et2O,
the layers were separated and the organic layer was dried
with MgSO4. After filtration the solvent was removed under
reduced pressure. Purification by column chromatography
delivered 7b; yield: 298 mg (64%). Rf (petroleum ether:eth-
(CDCl3, 300 MHz): d=1.37 (s, 9H), 2.37 (s, 3H), 6.14 (dd,
J=3.5 Hz, 0.9 Hz, 1H), 7.15 (d, J=3.4 Hz, 1H); 13C NMR
(CDCl3, 125 MHz): d=14.0 (q), 27.2 (q, 3C), 42.9 (s), 108.3
(d), 119.6 (d), 151.0 (s), 156.0 (s), 194.4 (s); MS (EI+): m/z
(%)=166 (21) [M+], 110 (22), 109 (100) [M+ÀC6H5O2.];
HR-MS: (EI+): m/z=166.0981, calcd. for M+ =C10H14O2:
166.0994.
1-(5-Methylfuran-2-yl)pentan-1-one (6d): Prepared ac-
cording to the general procedure Bb using alcohol 5d
(3.36 g, 19.9 mmol) in 50 mL absolute dichloromethane and
MnO2 (15.0 g, 172 mmol). After removal of the solvent
under vacuum and the purification by column chromatogra-
phy 6d was obtained; yield: 1.81 g (54%). Rf (petrol ether:
1
ethyl acetate, 20:1)=0.15; H NMR (CDCl3, 300 MHz): d=
0.94 (t, J=7.3 Hz, 3H), 1.39 (m, J=7.3 Hz, 2H), 1.67 (m,
2H), 2.39 (s, 3H), 2.75 (t, 2H), 6.15 (dq, J=3.1 Hz, 1H),
7.08 (d, J=3.1 Hz, 1H). These data are in agreement with
the literature.[10]
1-(5-Phenylfuran-2-yl)ethanone (6e): Prepared according
to the general procedure Ba using alcohol 5e (1.22 g,
6.47 mmol) in 25 mL absolute dichloromethane and DMP
(3.02 g, 7.11 mmol). After 24 h the solvent was removed
under vacuum and 6e was obtained; yield: 405 mg (34%).
1H NMR (CDCl3, 300 MHz): d=2.56 (s, 3H), 6.81 (d, J=
3.2 Hz, 1H), 7.29 (d, J=3.1 Hz, 1H), 7.39–7.52 (m, 3H),
7.79–7.82 (m, 2H). These data are in agreement with the lit-
erature.[11]
˜
yl acetate; 100:1)=0.52; IR (film): n=2974, 2933, 1703,
1609, 1589, 1523, 1458, 1392, 1368, 1273, 1224, 1205, 1147,
1127, 1029, 878, 785, 750, 699 cmÀ1 1H NMR (CDCl3,
;
300 MHz): d=1.29 (d, J=7.0 Hz, 6H), 1.52 (s, 9H), 2.33 (s,
2H), 4.25 (m, J=7.0 Hz, 1H), 6.04 (d, J=3.1 Hz, 1H), 6.18
(s, 1H), 6.56 (d, J=3.1 Hz, 1H); 13C NMR (CDCl3,
125 MHz): d=13.7 (q), 21.4 (q), 27.1 (d), 28.3 (q, 3C), 79.8
(s), 107.8 (d), 112.6 (d), 113.7 (d), 150.8 (s), 151.7 (s), 153.0
(s), 166.5 (s); HR-MS: (FAB+): m/z=250.1579, calcd. for
M+ =C15H22O3: 250.1569.
Methyl (2E)-3-(5-methylfuran-2-yl)hept-2-enoate (8d):
Prepared according to the general procedure C using the
ketone 6d (433 mg, 2.61 mmol), methyl bromoacetate
(399 mg, 2.93 mmol) and zinc dust (170 mg, 2.61 mmol) in
toluene (20 mL). After removal of the solvent under
vacuum and purification by column chromatography the de-
sired product 8d was obtained; yield: 273 mg (47%). Rf
Methyl (2E)-3-cyclopropyl-3-(5-methylfuran-2-yl)prop-2-
enoate (8a): Prepared according to the general procedure C
using 6a (1.13 g, 7.53 mmol), methyl bromoacetate (1.73 g,
11.3 mmol) and zinc (840 mg, 12.8 mmol) in toluene 20 mL.
After removal of the solvent under vacuum 8a was ob-
˜
tained; yield: 810 mg (56%). IR (film): n=3012, 2953, 2928,
1
2855, 1721, 1437, 1255, 1199, 1171, 1023, 736 cmÀ1; H NMR
(petrol ether:ethyl acetate, 50:1)=0.11; IR (film): n=2953,
˜
(CDCl3, 300 MHz): d=0.73–0.78 (m, 2H), 0.93–0.99 (m,
2H), 2. 28 (s, 3H), 2.31–2.41 (m, 1H), 3.72 (s, 3H), 6.00 (d,
J=3.3 Hz, 1H,), 6.32 (d, J=1.4 Hz, 1H,), 6.57 (d, J=3.3 Hz,
1H); 13C NMR (CDCl3, 125 MHz): d=8.1 (t, 2C), 11.4 (d),
15.8 (q), 51.1 (q), 108.2 (d), 113.2 (d), 113.7 (d), 147.5 (s),
151.3 (s), 153.8 (s), 167.3 (s); MS (EI+): m/z (%)=206
(100) [M+], 178 (93) [M+ÀCH3O], 163 (37), 147 (41), 91
(54); HR-MS: (EI+): m/z=206.0943, calcd. for M+ =
C12H14O3: 206.0924.
2927, 2871, 2768, 1708, 1651, 1586, 1524, 1457, 1432, 1377,
1340, 1306, 1275, 1223, 1188, 1161, 1124, 1025, 963, 870,
631 cmÀ1
;
1H NMR (CDCl3, 300 MHz): d=0.94 (t, J=
7.3 Hz, 3H), 1.39 (m, J=7.3 Hz, 2H), 1.50 (m, 2H), 2.31 (s,
3H), 2.86 (t, 2H), 3.72 (s, 3H), 6.05 (dq, J=3.1 Hz, 1H),
6.25 (s, 1H), 6.54 (d, J=3.1 Hz, 1H); 13C NMR (CDCl3,
125 MHz): d=13.9 (q), 17.5 (q), 23.1 (t), 28.4 (t), 32.5 (t),
50.9 (t), 108.4 (d), 109.7 (d), 112.8 (d), 147.9 (s), 152.3 (s),
154.5 (s), 167.4 (s); MS: (EI+, 70 eV): m/z (%)=222 (35)
[M+], 191 (31), 180 (100), 161 (27), 122 (52), 105 (9), 77 (9),
43 (18); HR-MS (EI+, 70 eV): m/z=222.1236, calcd. for
C13H18O3: 222.1256.
tert-Butyl (2E)-3-(5-phenylfuran-2-yl)but-2-enoate (7e):
To LDA (1.73 mL, 2.99 mmol) in absolute THF (20 mL)
under an atmosphere of nitrogen at À788C tert-butylacetic
acid (290 mg, 2.5 mmol) was added dropwise. After 1 h 5-
phenyl-2-acetylfuran 6e (429 mg, 2.30 mmol) was added and
the mixture was stirred for 1 h at À788C. Then the reaction
mixture was allowed to gradually warm to room tempera-
ture and stirred for another hour. The reaction mixture was
quenched with 50 mL 2M HCl and diluted with 30 mL
ether. After two extractions with ether (30 mL each) the
combined organic phases were dried with MgSO4, filtered,
tert-Butyl
(2E)-4-Methyl-3-(5-methylfuran-2-yl)pent-2-
enoate (7b)
a) tert-Butyl 3-hydroxy-4-methyl-3-(5-methylfuran-2-yl)pen-
tanoate (7b’): Under nitrogen tert-butylacetic acid (840 mg,
7.23 mmol) was added dropwise to LDA (4.30 mL,
8.55 mmol) in absolute THF (20 mL) at À788C. After 1 h,
6b (1.00 g, 6.58 mmol) was added and the mixture was
stirred for 1 h at À788C. Then the reaction mixture was al-
lowed to gradually warm to room temperature and stirred at
that temperature for another hour. The reaction mixture
was quenched with 50 mL 2M HCl and diluted with 30 mL
ether. After two extractions with ether (30 mL each) the
combined organic phases were dried with MgSO4, filtered,
and the solvent was removed under vacuum. Column chro-
Adv. Synth. Catal. 2009, 351, 2469 – 2481
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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2475

A. Stephen K. Hashmi et al.
FULL PAPERS
and the solvent was removed under vacuum. Column chro-
matography on silica gel furnished 7e as an orange solid;
yield: 512 mg (78%); mp 80–858C. Rf (petrol ether:ethyl
(6), 91 (12), 77 (16), 43 (35); anal. calcd. for C10H12O3
(180.20): C 66.65, H 6.71; found: C 66.63, H 6.68.
(E)-tert-Butyl 3-(5-methylfuran-2-yl)acrylate (7h): To
LDA (9.00 g, 51.5 mmol) in absolute THF (70 mL) under an
atmosphere of nitrogen at À788C tert-butylacetic acid
(5.06 g, 43.6 mmol) was added dropwise. After 1 h 5-methyl-
2-furfural (4.36 g, 39.6 mmol) was added and stirred was
continued for 1 h at À788C. Then the reaction mixture was
allowed to gradually warm to room temperature and stirred
for another hour. The reaction mixture was quenched with
50 mL 2M HCl solution and diluted with 30 mL ether. After
two extractions with ether (30 mL each) the combined or-
ganic phases were dried with MgSO4, filtered, and the sol-
vent was removed under vacuum. Column chromatography
on silica gel furnished 7h as a yellow oil; yield: 3.05 g
(36%). Rf (petrol ether:ethyl acetate, 20:1and then 3:1)=
˜
acetate,10:1)=0.52; IR (film): n=2958, 2930, 2859, 1702,
1619, 1482, 1450, 1392, 1367, 1288, 1207, 1148, 1101, 1073,
1
1028, 761, 691 cmÀ1; H NMR (CDCl3, 300 MHz): d=1.50 (s,
9H), 2.47 (d, J=1.1 Hz, 3H), 6.1 (d, J=1.3 Hz, 1H), 6.77
(d, J=1.3 Hz, 1H), 7.31–7.75 (m, 6H, Ph, 1Furan);
13C NMR (CDCl3, 125 MHz): d=14.6 (q), 28.2 (q, 3C), 80.1
(s), 107.1 (d), 113.6 (d), 114.5 (d), 140.4 (d), 124.1 (d), 124.5
(d), 128.5 (d), 129.2 (d, 2C), 130.5 (s), 140.9 (s), 154.6 (s),
155.3 (s), 166.6 (s); HR-MS (EI+): m/z=284.1390, calcd. for
M+ =C18H20O3: 284.1412.
Methyl (2E)-3-(5-phenylfuran-2-yl)prop-2-enoate (8f):
Prepared according to the general procedure C using 6f
(2.00 g,
11.6 mmol),
methyl
bromoacetate
(2.13 g,
˜
0.50; IR (film): n=2975, 2356, 1701, 1635, 1307, 1150,
13.9 mmol) and zinc (840 mg, 12.8 mmol) in toluene
(20 mL). After removal of the solvent under vacuum and
purification by column chromatography 8f was obtained;
yield: 2.10 g (80%). Rf (petrol ether:ethyl acetate, 10:1)=
1
631 cmÀ1; H NMR (CDCl3, 300 MHz): d=1.50 (s, 9H), 2.31
(s, J=0.8 Hz, 3H), 6.04 (dd, J=3.2 Hz, 0.8 Hz, 1H), 6.16
(dd, J=15.7 Hz, 0.8 Hz, 1H), 6.45 (dd, J=3.2 Hz, 0.8 Hz,
1H), 7.25 (d, J=15.7 Hz, 1H); 13C NMR (CDCl3, 125 MHz):
d=13.8 (q), 28.2 (q, 3C), 80.0 (s), 108.6 (d), 115.7 (d), 116.1
(d), 130.1 (d), 149.7 (s), 155.0 (s), 166.7 (s); MS (70 eV): m/z
(%)=208 (19) [M+], 152 (100), 135 (38), 110 (21), 77 (10),
57 (10), 43 (17).
1
0.21; H NMR (CDCl3, 300 MHz): d=3.81 (s, 3H), 6.05 (d,
J=2.5 Hz, 1H), 6.39 (d, J=15.5 Hz, 1H), 6.5 (d, J=2.5 Hz,
1H), 7.24–7.41 (m, 6H, Ph and HC=C). These data are in
agreement with the literature.[12]
(E)-tert-Butyl 3-(5-methylfuran-2-yl)but-2-enoate (7g): To
LDA (3.76 g, 20.9 mmol) in absolute THF (30 mL) under an
atmosphere of nitrogen at À788C tert-butylacetic acid
(2.06 g, 17.7 mmol) was added dropwise. After 1 h 6g
(2.00 g, 16.1 mmol) was added and stirring was continued
for 1 h at À788C. Then the reaction mixture was allowed to
gradually warm to room temperature and stirred for another
hour. The reaction mixture was quenched with 50 mL 2M
HCl and diluted with 30 mL ether. After two extractions
with ether (30 mL each) the combined organic phases were
dried with MgSO4, filtered, and the solvent was removed
under vacuum. Column chromatography on silica gel fur-
nished 7g as a yellow oil; yield: 1.70 g (48%). Rf (petrol
Methyl 3-(5-methylfuran-2-yl)hexanoate (9a): Prepared
according to the general procedure D using of 8a (540 mg,
2.61 mmol) in absolute MeOH (10 mL) and cyclohexene
(10.6 mL, 104 mmol) and 5% Pd/C (320 mg). After 24 h the
solution was filtered over celite and the solvent was re-
moved under vacuum. After purification 9a was obtained;
yield: 540 mg (99%). Rf (petrol ether:ethyl acetate, 10:1)=
˜
0.52; IR (film): n=2957, 2913, 2973, 1739, 1437, 1274, 781,
1
746, 669 cmÀ1; H NMR (CDCl3, 300 MHz): d=0.86 (t, J=
7.3 Hz, 3H), 1.18–1.39 (m, 2H), 1.51–1.63 (m, 2H), 2.21 (s,
3H), 2.55 (dq, J=15.3 Hz, 7.4 Hz, 1H), 3.10–3.20 (m, 1H),
3.62 (s, 3H), 5.79 (d, J=3.0 Hz, 1H), 5.85 (d, J=3.0 Hz,
1H); 13C NMR (CDCl3, 125 MHz): d=13.5 (q), 13.9 (q),
20.2 (t), 35.4 (d), 36.0 (t), 39.2 (t), 51.5 (q), 105.5 (d), 106.0
(d), 150.5 (s), 155.4 (s), 172.8 (s); MS (EI+): m/z (%)=210
(50) [M+], 167 (100) [M+ÀC3H7], 151 (19), 137 (87), 125
(53), 95 (51), 91 (21); HR-MS: (EI+): m/z=210.1256,
calcd. for M+ =C12H18O3: 210.1263.
˜
ether:ethyl acetate, 50:1and then 10:1)=0.26; IR (film): n=
2978, 1704, 1624, 1367, 1349, 1283, 1255, 1207, 1128, 885,
1
799, 741, 676 cmÀ1; H NMR (CDCl3, 300 MHz): d=1.50 (s,
9H), 2.31 (s, 3H), 2.38 (d, J=1.3 Hz, 3H), 6.03 (dq, J=
3.3 Hz, 1.3 Hz, 1H), 6.23 (d, J=1.3 Hz, 1H), 6.50 (d, J=
3.3 Hz, 1H); 13C NMR (CDCl3, 125 MHz): d=14.5 (q), 28.3
(q, 3C), 79.8 (s), 110.7 (d), 111.8 (d), 114.5 (d), 140.8 (s),
143.6 (d), 154.6 (s), 166.6 (s); MS (EI+, 70 eV): m/z (%)=
208 (16) [M+], 152 (100), 135 (46), 124 (19), 108 (20), 77
(15), 57 (20), 41 (14), 29 (10).
Methyl (2E)-3-(5-methylfuran-2-yl)but-2-enoate (8g): Pre-
pared according to the general procedure C using 6g (1.00 g,
8.06 mmol), methyl bromoacetate (1.37 g, 8.94 mmol) and
zinc (530 mg, 8.06 mmol) in toluene (20 mL). After the re-
sidual solvent was concentrated under vacuum the desired
product 8g was obtained; yield: 1.40 g (97%); mp 858C. IR
tert-Butyl
4-methyl-3-(5-methylfuran-2-yl)pentanoate
(9b): Prepared according to the general procedure D using
7b (90 mg, 359 mmol) in absolute MeOH (10 mL) and cyclo-
hexene (0.7 mL, 7.19 mmol) and 5% Pd/C (38.3 mg). After
24 h the solution was filtered over celite and the solvent was
removed under vacuum. After purification 9b was obtained;
yield: 85.0 mg (94%). Rf (petrol ether:ethyl acetate, 10:1)=
˜
0.42; IR (film): n=3626, 3105, 3006, 2958, 2934, 2874, 1726,
1707, 1606, 1568, 1433, 1329, 1207, 1256, 1224, 1208, 1183,
1
1142, 1024, 842 cmÀ1; H NMR (CDCl3, 300 MHz): d=0.82
(d, J=7.0 Hz, 3H), 0.87 (d, J=7.0 Hz ,3H), 1.33 (s, 9H),
1.87 (m, J=6.8 Hz, 1H), 2.21 (s, 3H), 2.47 (m, 2H), 2.97 (m,
1H), 5.79 (s, 1H), 5.83 (d, J=3.0 Hz, 1H); 13C NMR
(CDCl3, 125 MHz): d=13.5 (q), 19.5 (q), 20.2 (q), 27.9 (q,
3C), 31.2 (d), 37.2 (t), 42.1 (d), 80.1 (s), 105.5 (d), 106.5 (d),
150.1 (s), 172.1 (s); HR-MS (FAB+): m/z=252.1716, calcd.
for M+ =C15H24O3: 252.1725.
˜
(film): n=2948, 2362, 1708, 1618, 1587, 1526, 1433, 1364,
1288, 1165, 1100, 1026, 750, 633 cmÀ1 1H NMR (CDCl3,
;
300 MHz): d=2.35 (s, 3H), 2.42 (s, 3H), 3.73 (s, 3H), 6.06
(dq, J=3.1 Hz, 0.9 Hz, 1H), 6.31 (s, 1H), 6.54 (d, J=3.1 Hz,
1H); 13C NMR (CDCl3, 125 MHz): d=13.9 (q), 14.6 (q),
51.0 (q), 108.4 (d), 110.4 (d), 112.9 (d), 142.6 (s), 152.8 (s),
154.5 (s), 167.9 (s); MS (EI+, 70 eV): m/z (%)=180 (100)
[M+], 165 (17), 150 (10), 149 (88), 138 (14), 122 (16), 105
Methyl 3-(5-methylfuran-2-yl)heptanoate (9d): Prepared
according to the general procedure D using 8d (100 mg, 449
2476
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ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2009, 351, 2469 – 2481

Gold Catalysis: Efficient 1,3-Induction with Diastereotopic Homopropargyl Alcohols
FULL PAPERS
mmol) in absolute MeOH (10 mL) and cyclohexene
(1.00 mL, 8.99 mmol) and 10% Pd/C (30.6 mg). After 24 h
the solution was filtered over celite and the solvent was re-
moved under vacuum to deliver 9d; yield: 130 mg (97%). IR
104.3 (d), 105.6 (d), 150.4 (s), 157.1 (s), 171.5 (s); anal.
calcd. for C13H20O3 (224.30): C 69.61, H 8.99; found: C
70.09, H 9.14.
tert-Butyl-3-(5-methylfuran-2-yl)propanoate (9h): Pre-
pared according to the general procedure D using of the un-
saturated ester 7h (500 mg, 2.40 mmol) in absolute MeOH
(10 mL) and cyclohexene (5.00 mL, 48.0 mmol) and 5% Pd/
C (150 mg). After 24 h the solution was filtered over celite
and the residual solvent was concentrated under vacuum to
afford the desired product 9h; yield: 420 mg (83%). IR
˜
(film): n=2953, 2927, 2871, 2768, 1708, 1651, 1586, 1524,
1506, 1457, 1432, 1377, 1340, 1310, 1276, 1249, 1188, 1161,
1124, 1025, 963, 909, 870, 849, 707, 631 cmÀ1 1H NMR
;
(CDCl3, 300 MHz): d=0.70 (t, J=7.3 Hz, 3H), 1.07 (m, J=
7.3 Hz, 2H), 1.13 (m, 2H), 1.41 (m, 2H), 2.08 (s, 3H), 2.38
(dd, J=15.3 Hz, 7.1 Hz, 1H), 2.44 (dd, J=15.3 Hz, 7.1 Hz,
1H), 2.99 (m, 1H), 3.48 (s, 3H), 5.66 (dq, J=3.0 Hz, 1.0 Hz,
1H), 5.71 (d, J=3.0 Hz, 1H); 13C NMR (CDCl3, 125 MHz):
d=13.6 (q), 14.0 (q), 22.5 (t), 29.2 (t), 33.4 (t), 35.5 (d), 39.0
(t), 51.6 (q), 105.6 (d), 105.7 (d), 155.4 (s), 154.5 (s), 172.9
(s).
tert-Butyl 3-(5-phenylfuran-2-yl)butanoate (9e): Prepared
according to the general procedure D using 7e (452 mg,
1.51 mmol) in absolute MeOH (10 mL) and cyclohexene
(3.23 mL, 31.8 mmol) and 5% Pd/C (96 mg). After 24 h the
solution was filtered over celite and the solvent was re-
moved under vacuum to afford 9e; yield: 560 mg (97%). IR
˜
(film): n=2997, 2924, 1728, 1570, 1453, 1391, 1366, 1254,
1217, 1148, 1022, 958, 847, 781 cmÀ1 1H NMR (CDCl3,
;
300 MHz): d=1.44 (s, 9H), 2.24 (d, J=1.0 Hz, 3H), 2.53 (t,
J=7.5 Hz, 2H), 2.86 (t, J=7.5 Hz, 2H), 5.83 (dd, J=3.1 Hz,
1.0 Hz, 1H), 5.86 (dd, J=3.1 Hz, 1H); 13C NMR (CDCl3,
125 MHz): d=13.5 (q), 23.7 (t), 28.1 (q, 3C), 34.4 (t), 82.1
(s), 104.3 (d), 105.7 (d), 150.5 (s), 152.6 (s), 171.9 (s); MS
(EI+, 70 eV): m/z (%)=210 (13) [M+], 211 (5), 157 (5), 154
(35), 111 (9), 95 (100), 57 (22), 28 (16); anal. calcd. for
C12H18O3 (210.28): C 68.54, H 8.63; found. C 68.42, H 8.46.
6-(5-Methylfuran-2-yl)-4-prop-2-yn-1-ylnon-1-yn-4-ol
˜
(film): n=2976, 1729, 1452, 1368, 1288, 1257, 1208, 1151,
(10a): Prepared according to the general procedure E using
9a (480 mg, 228 mmol) and the Grignard reagent (4.50 mL,
9.12 mmol). After removal of the solvent under vacuum and
after purification it was possible to obtain 10a; yield: 188 mg
(33%). Rf (petrol ether:ethyl acetate, 10:1)=0.29; IR (film):
1
1023, 789, 760, 692 cmÀ1; H NMR (CDCl3, 300 MHz): d=
1.32 (d, J=7.0 Hz, 3H), 1.40 (s, 9H), 2.39 (dd, J=15.0 Hz,
8.0 Hz, 1H), 2.66 (dd, J=15.0 Hz, 8.0 Hz, 1H), 3.34 (m, J=
7.0 Hz, 1H), 6.09 (dd, J=3.4 Hz, 1.2 Hz, 1H), 6.56 (d, J=
3.4 Hz, 1H), 7.21 (t, J=7.6 Hz, 1H), 7.4 (t, J=7.7 Hz,
1.6 Hz, 2H), 7.62 (d, J=7. 5 Hz, 2H); 13C NMR (CDCl3,
125 MHz): d=19.1 (q), 28.2 (q, 3C), 30.8 (d), 42.0 (t), 80.6
(s), 105.9 (d), 106.4 (d), 123.7 (d, 2C), 127.3 (d), 129.0 (d,
2C), 131.5 (s), 152.6 (s), 159.3 (s), 171.5 (s); HR-MS
(FAB+): m/z=286.1574, calcd. for M+ =C18H22O3: 286.1569.
Methyl 3-(5-phenylfuran-2-yl)propanoate (9f): Prepared
according to the general procedure D using 8f (2.07 g,
9.06 mmol) in absolute MeOH (10 mL) and cyclohexene
(18.5 mL, 181 mmol) and 5% Pd/C (670 mg). After 24 h the
solution was filtered over celite and the solvent was re-
moved under vacuum to afford 9f; yield: 877 mg (42%). IR
˜
n=3295, 2958, 2934, 2871, 2120, 1769, 1052, 985, 854, 648.
cmÀ1 1H NMR (CDCl3, 300 MHz): d=0.85 (t, J=7.3 Hz,
;
3H), 1.12–1.29 (m, 2H), 1.43–1.65 (m, 2H), 1.91–1.09 (m,
6H), 2.23 (s, 3H), 2.38 (m, 2H), 2.81–2.91 (m, 1H), 5.82 (d,
J=3.0 Hz, 1H), 5.90 (d, J=3.0 Hz, 1H); 13C NMR (CDCl3,
125 MHz): d=13.5 (q), 13.9 (q), 20.3 (t), 29.6 (t), 29.8 (t),
34.2 (d), 38.4 (t), 41.9 (t), 71.1 (d), 71.3 (d), 72.9 (s), 80.2 (s),
80.3 (s), 105.9 (d), 106.3 (d), 150.6 (s), 156.1 (s); MS (EI+,
70 eV): m/z (%)=230 (18) [M+], 191 (29), 173 (24), 109
(100), 43 (21), 39 (9); HR-MS (ESI+): m/z=281.1512, calcd.
for [M+Na+]=C17H22ONa: 281.1517.
7-Methyl 6-(5-methylfuran-2-yl)-4-prop-2-yn-1-yloct-1-yn-
4-ol (10b): Prepared according to the general procedure E
using 9b (80.0 mg, 320 mmol) and propargylmagnesium bro-
mide (600 mL, 950 mmol). After removal of the solvent
under vacuum and purification by column chromatography
10b was obtained; yield: 30 mg (36%). Rf (petrol ether:ethyl
˜
(film): n=2949, 2171, 2042, 1995, 1739, 1595, 1548, 1487,
1437, 1202, 1023 cmÀ1; H NMR (CDCl3, 300 MHz): d=2.76
1
(t, J=7.8 Hz, 2H), 3.07 (t, J=7.9 Hz, 2H), 3.74 (s, 3H), 6.14
(d, J=3.2 Hz, 1.18 Hz, 1H), 6.57 (d, J=3.2 Hz, 1H), 7.27 (t,
J=6.3 Hz, 1H), 7.38 (m, 2H), 7.64 (m, 2H); 13C NMR
(CDCl3, 125 MHz): d=21.1(t), 32.6 (t), 51.8 (q), 105.7 (d),
107.6 (d), 123.4 (d), 127.0 (d), 128.6 (d), 129.0 (d), 131.0 (s),
152.7 (s), 153.8 (s), 173.0 (s); anal. calcd. for C14H14O3
(230.26): C 73.03, H 6.13; found: C 74.18 , H 6.34; HR-MS
(ESI+): m/z=253.0835, calcd. for [M+ +Na]=C14H14O:
230.0841.
tert-Butyl-3-(5-methylfuran-2-yl)butanoate (9g): Prepared
according to the general procedure D using of 7g (1.00 g,
4.52 mmol) in absolute MeOH (50 mL) and cyclohexene
(9.10 mL, 89.9 mmol) and 5% Pd/C (310 mg). After 24 h,
the solution was filtered over celite and the solvent was re-
moved under vacuum to deliver 9g; yield: 884 mg (87%). IR
˜
acetate, 10:1)=0.26; IR (film): n=3548, 3530, 3299, 2959,
2323, 2873, 1562, 1466, 1436, 1386, 1370, 1337, 1278, 1221,
1164, 1066, 1022, 951, 783 cmÀ1
;
1H NMR (CDCl3,
300 MHz): d=0.81 (d, J=6.9 Hz, 3H), 0.95 (d, J=6.9 Hz,
3H), 2.0–2.1 (m, 2H), 2.24 (s, 3H), 2.34 (m, 2H), 2.39 (t, J=
2.8Hz, 2H), 2.68 (m, 1H), 5.84 (d, J=2.9 Hz, 1H), 5.92 (d,
J=3.0 Hz, 1H); 13C NMR (CDCl3, 125 MHz): d=13.6 (q),
19.6 (q), 20.6 (q), 29.66 (t), 29.7 (d), 32.0 (d), 33.2 (t), 40.3
(d), 71.3 (d, 2C), 72.9 (s), 80.3 (s), 80.3 (s), 105.8 (d), 107.1
8d), 150.6 (s), 155.4 (s); HR-MS: (EI+): m/z=258.1602,
calcd. for M+ =C17H22O2: 258.1620.
6-(5-Methylfuran-2-yl)-4-prop-2-yn-1-yldec-1-yn-4-ol
˜
(film): n=2973, 2929, 1727, 1569, 1456, 1362, 1286, 1251,
(10d): Prepared according to the general procedure E using
9d (120 mg, 535 mmol) and Grignard reagent (1.05 mL,
2.14 mmol). After removal of the solvent in vacuum it was
possible to obtain a 1:1 mixture of 10d and 11d; yield:
92 mg (63%). These could not be separated. Rf (petrol
1220, 1149, 1027, 952, 843, 782 cmÀ1 1H NMR (CDCl3,
;
300 MHz): d=1.26 (d, J=6.5 Hz, 1H), 1.43 (s, 9H), 2.24 (s,
3H), 2.33 (dd, J=14.9 Hz, 8.2 Hz, 1H), 2.60 (dd, J=
14.9 Hz, 8.2 Hz, 1H), 3.24 (m, 1H), 5.82 (dq, J=3.1 Hz,
1H), 5.85 (d, J=3.1 Hz, 1H); 13C NMR (CDCl3, 125 MHz):
d=13.5 (q), 18.8 (q), 28.1 (q, 3C), 30.3 (d), 41.9 (t), 80.3 (s),
˜
ether:ethyl acetate, 3:1)=0.36; IR (film): n=3299, 2925,
2857, 2359, 1956, 1567, 1524, 1506, 1457, 1432, 1377, 1340,
Adv. Synth. Catal. 2009, 351, 2469 – 2481
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2477

A. Stephen K. Hashmi et al.
FULL PAPERS
1310, 1219, 1188, 1161, 1124, 1021, 963, 909, 889, 849, 707,
631 cmÀ1.
24.2 mg, 3:7 mixture, thus the spectroscopic data of 11h
could be obtained when substracting the signals of pure
10h) was obtaimed.
4-[2-(5-Phenylfuran-2-yl)propyl]hepta-1,6-diyn-4-ol (10e):
Prepared according to the general procedure E using 10e
(561 mg, 1.96 mmol) and propargylmagnesium bromide
(5.40 mL, 5.88 mmol). After removal of the solvent under
vacuum and purification by column chromatography 10e
was obtained; yield: 352 mg (61%). Rf (petrol ether:ethyl
10h: Rf (petrol ether:ethyl acetate, 7:1)=0.23; IR (film):
˜
n=3292, 2921, 2858, 1615, 1569, 1430, 1383, 1270, 1217,
1074, 1020, 995, 983, 947, 862, 781, 632 cmÀ1 1H NMR
;
(CDCl3, 300 MHz): d=2.05 (m, 2H), 2.09 (t, J=2.6 Hz,
2H), 2.25 (d, J=1.2 Hz, 3H), 2.55 (dd, J=16.6 Hz, 2.6 Hz,
4H), 2.73 (m, 2H), 5.84 (dq, J=3.1 Hz, 1.2 Hz, 1H), 5.88 (d,
J=3.1 Hz, 1H); 13C NMR (CDCl3, 125 MHz): d=13.5 (q),
22.2 (t), 29.6 (t, 2C), 36.4 (t), 71.6 (s), 71.8 (d, 2C), 80.0 (s,
2C), 105.5 (d), 105.9 (d), 150.5 (s), 153.7 (s); MS (EI+,
70 eV): m/z (%)=216 (7) [M+], 177 (18), 159 (15), 135 (4),
96 (8), 95 (100), 77 (4), 43 (27), 32 (13), 28 (54), 18 (9); HR-
MS (EI+, 70 eV): m/z=216.1151, calcd. for C14H16O2:
216.1144.
˜
acetate, 5:1)=0.25; IR (film): n=3302, 3053, 2974, 1546,
1265, 1021, 790, 738, 704, 651 cmÀ1 1H NMR (CDCl3,
;
300 MHz): d =1.35 (d, J=6.9 Hz, 3H), 1.94 (dd, J=15.2 Hz,
4.74 Hz, 1H), 2.06 (t, 2H), 2.26 (dd, J=15.2 Hz, 4.7 Hz,
1H), 2. 50 (m, 4H), 3.16 (m, J=7.0 Hz, 1H), 6.11 (s, 1H),
6.5 (s, 1H), 7.20 (t, J=7. 7 Hz, 1H), 7.33 (t, J=7.7 Hz, 2H),
7.60 (d, J=7.7 Hz, 2H); 13C NMR (CDCl3, 125 MHz): d=
21.9 (q), 29.0 (d), 29.5 (t), 29.7 (t), 43.4 (t), 71.4 (d), 71.5 (d),
72.9 (s), 96.8 (s), 97.3 (s), 105.7 (d), 106.3 (d), 123.3 (d),
123.4 (d), 126.9 (d), 126.9 (d), 128. 6 (d, 2C), 131. 0 (s),
152.3 (s), 159.5 (s); HR-MS (FAB+): m/z=292.1467, calcd.
for [M+]=C20H20O2: 292.1463.
4-(2-(5-Phenylfuran-2-yl)ethyl)hepta-1,6-diyn-4-ol (10f):
Prepared according to the general procedure E using 9f
(870 mg, 3.78 mmol) and propargylmagnesium bromide
(5.80 mL, 11.3 mmol). After removal of the solvent under
vacuum and purification by column chromatography 10f
was obtained; yield: 701 mg (66%). Rf (petrol ether:ethyl
11h: Rf (petrol ether:ethyl acetate, 7:1)=0.23; 1H NMR
(CDCl3, 300 MHz): d=2.05 (m, 2H), 2.09 (t, 1H), 2.24 (s,
3H), 2.52 (dd, 2H), 2.73 (m, 2H), 4.98 (d, J=6.7 Hz, 2H),
5.36 (t, J=6.7 Hz, 1H), 5.83 (dq, J=3.1 Hz, 1H), 5.86 (d,
J=3.1 Hz, 1H); 13C NMR (CDCl3, 125 MHz): d=13.5 (q),
22.7 (t), 32.0 (t), 38.3 (t), 72.5 (d), 80.01 (s), 96.71 (s), 105.9
(d), 105.4 (d), 150.4 (s), 153.8 (s), 206.03 (s); C14H16O2 (216.
28).
2-Methyl-5-propyl-7-prop-2-yn-1-yl-5,6,7,8-tetrahydro-
naphthalene-1,7-diol (13a): Prepared according to the gener-
al procedure F using 10a (50.0 mg, 119 mmol) in acetonitrile-
d3 and AuCl3 (2.93 mg, 9.39 mmol, 5 mol%). After removal
of the solvent under vacuum 13a was obtained as an orange
oil; yield: 23.0 mg (46%). Rf (pentane:ethyl acetate=
˜
acetate, 5:1)=0.16; IR (film): n=3543, 3292, 2920, 2120,
1967, 1594, 1486, 1447, 1285, 1075, 1019, 964, 891, 760 cmÀ1
;
1H NMR (CDCl3, 300 MHz): d=2.05 (m, 2H), 2.09 (m,
2H), 2.53 (m, 4H), 2.78 (m, 2H), 6.04 (d, 1H, J=3.1 Hz),
6.47 (d, 1H, J=3.1 Hz), 7.15 (m, 1H), 7.29 (m, 2H), 7.57
(m, 2H); 13C NMR (CDCl3, 125 MHz): d=22.4 (t), 35.9 (t,
2C), 36.22 (t), 71.9 (d, 2C), 72.5 (s), 79.78 (s, 2C), 105.89 (d),
107.14 (d), 123.40 (d, 2C), 126.7 (d), 128.62 (d, 2C), 131.08
(s), 152.48 (s), 154.43 (s); anal. calcd. for C19H18O2 (278.13):
C 81.99, H 6.52; found: C 80.53 , H 6.52; HR-MS (ESI+):
m/z=301.1199, calcd. for [M+]=C19H18NaO2: 301.1204.
4-[2-(5-Methylfuran-2-yl)propyl]hepta-1,6-diyn-4-ol (10g):
Prepared according to the general procedure E using 9g
(554 mg, 2.47 mmol) and propargylmagnesium bromide
(3.61 mL, 7.40 mmol). After removal of the solvent under
vacuum and purification by column chromatography 10g
(yield:158 mg, 31%) and 11g (yield:17 mg) were obtained.
10g: Rf (petrol ether:ethyl acetate, 7:1)=0.25; IR (film):
˜
10:3)=0.25; IR (film): n=3412, 3271, 2955, 2932, 2870,
1
1631, 1493, 1464, 1303, 1226, 1037, 803, 647 cmÀ1; H NMR
(CDCl3, 300 MHz): d=0.93 (t, J=7.3 Hz, 3H), 1.22–1.45
(m, 2H), 1.49–1.62 (m, 2H), 1.68 (s, 1H), 1.84–2.11 (m, 2H),
1.92–1.95 (m, 1H), 2.12 (t, J=2.6 Hz, 2H), 2.18 (s, 3H), 2.54
(t, J=2.5 Hz,1H), 2.80 (dd, J=16.9 Hz, 1H), 3.05 (s, 1H),
6.86 (d, J=8.0 Hz, 1H), 6.95 (d, J=8.0 Hz, 1H); 13C NMR
(CDCl3, 125 MHz): d=14.4 (q), 15.5 (q), 19.4 (t), 33.6 (d),
33.7 (t) 35.1 (t), 37.7 (t), 38.6 (t), 69.7 (d), 71.7 (s), 80.4 (s),
118.1 (d), 119.6 (s), 120.3 (s), 128.1 (d), 138.6 (s), 151.75 (s);
HR-MS (ESI+): m/z=281.1512, calcd. for [M+Na+]=
C17H22ONa: 281.1514.
5-Isopropyl-2-methyl-7-(propyl-2-ynyl)-5,6,7,8-tetrahydro-
naphthalene-1,7-diol (13b): Prepared according to the gener-
al procedure F using 10b (30.0 mg, 120 mmol) in acetonitrile-
d3 and AuCl3 (1.8 mg, 12 mmol, 5 mol%). After removal of
the solvent under vacuum 13b was obtained as a brown oil;
yield: 27 mg (87%). Rf (petrol ether:ethyl acetate=10:1)=
˜
n=3293, 2965, 2921, 2858, 1957, 1710, 1614, 1566, 1435,
1362, 1280, 1219, 1069, 1019, 940, 852, 781, 633 cmÀ1
;
1H NMR (CDCl3, 300 MHz): d=1.32 (d, J=7.2 Hz, 3H),
1.94 (dd, J=14.7 Hz, 4.5 Hz, 1H), 2.09 (t, J=2.4 Hz, 2H),
2.18 (dd, J=14.7 Hz, 4.5 Hz, 1H), 2.25 (s, 3H), 2.55 (dd, J=
15.7 Hz, 2.4 Hz, 4H), 3.0 (m, J=7.2 Hz, 4.5 Hz, 1H), 5.84
(dq, J=3.1 Hz, 1.2 Hz, 1H), 5.88 (d, J=3.1 Hz, 1H);
13C NMR (CDCl3, 125 MHz): d=13.5 (q), 21.9 (q), 28.9 (t),
29.6 (t), 29.9(t), 71.4 (d, 2C), 73.0 (s), 80.2 (d, 2C), 104.9 (d),
105.9 (d), 150.5 (s), 157.7 (s); MS (EI+, 70 eV): m/z (%)=
230 (18) [M+], 191 (29), 173 (24), 109 (100), 43 (21), 39 (9);
anal. calcd. for C15H18O2 (230.30): C 78.23, H 7.88; found: C
77.76, H 8.00.
˜
0.05; IR (film): n=3416, 3303, 2958, 2928, 2871, 1462, 1422,
1308, 1227, 1194, 1091, 1057, 954 cmÀ1 1H NMR (CDCl3,
;
300 MHz): d=0.59 (d, J=6.7 Hz, 3H), 1.04 (d, J=6.7 Hz,
3H), 1.59 (m, 2H), 1.89 (m, 1H), 2.18 (s, 3H), 2.29 (t, J=
2.6 Hz, 1H), 2.47 (m, 1H), 2.50 (d, J=2.6 Hz, 2H), 2.90 (dd,
J=16.5 Hz, 2.80 Hz, 1H), 2.99 (dd, J=16.5 Hz, 2.8 Hz, 1H),
6.8 (d, J=7.7 Hz, 1H), 6.96 (d, J=7.7 Hz, 1H); 13C NMR
(CDCl3, 125 MHz): d=15.7 (q), 20.9 (q), 29.3 (t), 30.8 (q),
34.3 (d), 35.3 (d), 36.1 (t), 39.8 (t), 70.0 (d), 71.8 (s), 80.9 (s),
119.0 (d), 119.4 (s), 121.5 (d), 128.4 (s), 138.5 (s), 152.2 (s);
MS (FAB+, 70 eV): m/z (%)=258 (24) [M+], 241 (31), 217
(27), 201 (19), 176 (23), 154 (100), 137, 136 (100), 107 865);
HR-MS (FAB+): m/z=258.1606, calcd. for [M+]=C17H27O2:
258.1620.
4-[2-(5-Methylfuran-2-yl)ethyl]hepta-1,6-diyn-4-ol (10h):
Prepared according to the general procedure E using 9h
(400 mg, 1.90 mmol) and Grignard reagent (7.00 mL,
7.60 mmol). After removal of the solvent in vacuum 10h
(yield: 182 mg, 44%) and a mixture of 10h and 11h (yield:
2478
asc.wiley-vch.de
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2009, 351, 2469 – 2481

Gold Catalysis: Efficient 1,3-Induction with Diastereotopic Homopropargyl Alcohols
FULL PAPERS
˜
5-Butyl-2-methyl-7-prop-2-yn-1-yl-5,6,7,8-tetrahydronaph-
thalene-1,7-diol (13d): Prepared according to the general
procedure F using 10d (40.0 mg, 147 mmol as a 1:1 mixture
with 40 mg 11d) in acetonitrile-d3 and AuCl3 (2.23 mg, 7.39
mmol, 5 mol%). After removal of the solvent under vacuum
and purification 13d was obtained as a brown oil; yield:
27.0 mg (67%). Rf (pentane:ethyl acetate:dichlorome-
dichloromethane=3:1:2)=0.25; IR (film): n=3534, 3294,
2996, 2926, 2871, 2360, 2244, 2117, 1577, 1493, 1461, 1420,
1380, 1328, 1226, 1133, 1096, 1021, 909, 893, 870, 807, 732,
696, 650, 635, 591 cmÀ1 1H NMR (CDCl3, 300 MHz): d=
;
1.35 (d, J=7.1 Hz, 3H), 1.5 (t, J=2.7 Hz, 1H), 1.94 (bs,
OH), 2.03 (dd, J=5.7 Hz, 2.7 Hz, 1H), 2.07 (dd, J=5.7 Hz,
2.7 Hz, 1H), 2.13 (t, J=2.7 Hz, 1H), 2.20 (s, 3H), 2.54 (t,
J=2.7 Hz, 2H), 2.73 (d, J=16.9 Hz, 1H), 2.90 (d, J=
16.9 Hz, 1H), 3.15 (m, 1H), 6.88 (d, J=8.0 Hz, 1H), 6.97 (d,
J=8.0 Hz, 1H); 13C NMR (CDCl3, 125 MHz): d=15.6 (q),
21.1 (q), 28.9 (d), 33.8 (t), 35.4 (t), 42.0 (t), 69.7 (d), 71.8 (s),
80.4 (s), 118.5 (s), 120.2 (d), 120.6 (s), 128.2 (d), 139.7 (s),
151.7 (s); MS (EI+, 70 eV): m/z (%)=230 (30) [M+], 191
(30), 173 (100), 158 (13), 148 (14), 121 (9), 77 (5), 53 (6);
HR-MS (EI+, 70 eV): m/z=230.1304, calcd. for C15H18O2:
230.1307.
2-Methyl-7-prop-2-yn-1-yl-5,6,7,8-tetrahydronaphthalene-
1,7-diol (13h): Prepared according to the general procedure
F using 10h (20.0 mg, 92.5 mmol) in acetonitrile-d3 and
AuCl3 (1.47 mg, 4.63 mmol, 5 mol%). After removal of the
solvent under vacuum and purification the desired phenol
13h was obtained as brown solid; yield: 13.2 mg (66%); mp
858C. Rf (pentane:ethyl acetate:dichloromethane=3:1:2)=
˜
thane=3:1:2)=0.29; IR (film): n=3534, 3291, 2929, 2859,
2218, 2142, 1578, 1492, 1460, 1421, 1378, 1310, 1226, 1101,
1
1051, 814, 698 cmÀ1; H NMR (CDCl3, 300 MHz): d=0.94 (t,
J=7.0 Hz, 3H), 1.26–1.40 (m, 4H), 1.55 (m, 1H), 1.66 (m,
1H), 1.92 (m, 2H), 2.11 (dd, J=5.7 Hz, 2.7 Hz, 1H), 2.14
(dd, J=5.7 Hz, 2.7 Hz, 1H), 2.23 (s, 3H), 2.54 (t, J=2.7 Hz,
1H), 2.73 (d, J=16.9 Hz, 1H), 2.98 (d, J=16.9 Hz, 1H),
3.09 (m, 1H), 6.91 (d, J=8.0 Hz, 1H), 7.01 (d, J=8.0 Hz,
1H); 13C NMR (CDCl3, 125 MHz): d=14.1 (t), 15.6 (q), 23.1
(t), 28.4 (d), 33.7 (t), 33.8 (t), 35.1 (t), 35.2 (t), 38.6 (t), 69.8
(d), 71.8 (s), 80.4 (s), 118.8 (s), 119.6 (d), 120.4 (s), 128.2 (d),
138.7 (s), 151.8 (s).
5-Methyl-2-phenyl-7-prop-2-yn-1-yl-5,6,7,8-tetrahydronap-
thalene-1,7-diol (13e): Prepared according to the general
procedure F using 10e (50.0 mg, 170 mmol) in acetonitrile-d3
and AuCl3 (2.6 mg, 17 mmol, 5 mol%). After removal of the
solvent under vacuum and purification 13e was obtained as
a brown oil; yield: 25.2 mg (50%). Rf (pentane:ethyl ace-
˜
0.10; IR (film): n=3290, 2927, 2360, 2341, 1581, 1494, 1462,
1422, 1381, 1322, 1226, 1183, 1041, 1008, 964, 874, 755, 744,
˜
ACHTUNGTRENNUNG
605 cmÀ1 1H NMR (CDCl3, 300 MHz): d=1.80 (m, 2H),
;
;
2.06 (t, J=2.5 Hz, 1H), 2.14 (s, 3H), 2.45 (dd, J=2.5 Hz,
2H), 2.72 (m, 1H), 2.75 (m, 2H), 2.96 (m, 1H), 4.50 (bs,
1H), 6.60 (d, J=8.1 Hz, 1H), 6.85 (d, J=8.1 Hz, 1H);
13C NMR (CDCl3, 125 MHz): d=15.5 (q), 26.0 (t), 32.1 (t),
32.8 (t), 35.3 (t), 69.8 (d), 71.8 (s), 80.2 (s), 119.6 (s), 120.2
(d), 120.6 (s), 128.1 (d), 134.3 (s), 151.9 (s); MS (EI+,
70 eV): m/z (%)=216 (63)[M+], 217 (10), 198 (32), 178 (2),
177 (75), 159 (100), 135 (4), 91 (18), 77 (9), 39 (2), 28 (2);
anal. calcd. for C14H16O2 (216.28): C 77.75, H 7.46; found: C
77.52, H 7.55.
tert-Butyldimethyl{4-[2-(5-methylfuran-2-yl)propyl]hepta-
1,6-diyn-4-yloxy}silane (15): 260 mg (1.13 mmol) 10g were
dissolved in 5 mL DCM and cooled to 08C. After the addi-
tion of 520 mL (2.26 mmol) TBDMSOTf and 526 mL
(4.52 mmol) lutidine, the solution was stirred for 2 d at room
temperature. After the addition of 5 mL H2O, the aqueous
phase was extracted three times with 5 mL dichloromethane.
The combined organic phases were dried over MgSO4, fil-
tered and the solvent was removed under vacuum. After pu-
rification by column chromatography (SiO2, hexanes), 15
was obtained as a colourless oil; yield: 317 mg (920 mmol,
1H NMR (CDCl3, 300 MHz): d=1.36 (d, J=6.8 Hz, 3H),
1.52 (s, 1H), 1.88 (bs, OH), 2.06 (dd, J=5.8, 2.6 Hz, 1H),
2.17 (t, J=2.5 Hz, 1H), 2.54 (t, J=2.7 Hz, 2H), 2.73 (dd, J=
17.9, 2.60 Hz, 2H), 2.98 (dd, J=17.9, 2.6 Hz, 1H), 3.15 (m,
J=6.8 Hz, 1H), 6.99 (d, J=7.5 Hz, 1H), 7.08 (d, J=7.8 Hz,
1H), 7.33–7.51 (m, 5H); 13C NMR (CDCl3, 125 MHz): d=
21.15 (q), 22.8 (d), 34.3 (t), 36.0 (t), 42.3 (t), 69.8 (d), 71.9
(s), 80.8 (s), 119.0 (d), 121.4 (s), 125. 3 (s), 127.6 (d), 128.2
(d), 129.5 (d, 2C), 129.9 (d, 2C), 137.9 (s), 142.3 (s), 150.6
(s); MS (FAB+, 70 eV): m/z (%)=292 (52) [M+], 275 (70),
249 (37), 235 (100), 233 (38), 221 (39), 202 (19), 178 (20);
HR-MS (FAB+): m/z=292.1440, calcd. for [M+]=C20H20O2:
292.1463.
2-Phenyl-7-prop-2-yn-1-yl-5,6,7,8-tetrahydronaphthalene-
1,7-diol (13f): Prepared according to the general procedure
F using 10f (20.0 mg, 72.5 mmol) in acetonitrile-d3 and AuCl3
(1.1 mg, 3.63 mmol, 5 mol%). After removal of the solvent
under vacuum and purification 13 f was obtained as a brown
oil; yield: 17.2 mg (87%). Rf (pentane:ethyl acetate:di-
1
chloromethane=3:1:2)=0.27; H NMR (CDCl3, 300 MHz):
d=1.82 (m, 1H), 1.94 (m, 1H), 2.07 (t, J=2.5 Hz, 1H), 2.48
(dd, J=2.5 Hz, 2H), 2.65–3.0 (m, 4H), 4.50 (bs, 1H), 5.27
(bs, 1H), 6.74 (d, J=7.8 Hz, 1H), 7.03 (d, J=7.8 Hz, 1H),
7.33 (m, 2H), 7.40 (m, 3H); 13C NMR (CDCl3, 125 MHz):
d=26.1 (t), 32.4 (t), 32.7 (t), 35.5 (t), 69.7 (d), 71.82 (s), 80.3
(s), 120.7 (d), 121.3 (d), 123.4 (d), 125.0 (d), 127.9 (d), 128.6
(s), 129.5 (d), 136.5 (s), 137.2 (s), 150.4 (s); HR-MS (ESI+):
m/z=301.1199, calcd. for [M+Na+]=C19H18O2Na: 301.1204.
2,5-Dimethyl-7-prop-2-yn-1-yl-5,6,7,8-tetrahydronaptha-
lene-1,7-diol (13g): Prepared according to the general proce-
dure F using 10g and 11g (50.0 mg, 217 mmol containing ad-
ditional 10% 11g) in acetonitrile-d3 and AuCl3 (3.30 mg, 10.9
mmol, 5 mol%). After removal of the solvent under vacuum
and purification the desired phenol 13g was obtained as
brown oil; yield: 33.3 mg (67%). Rf (pentane:ethyl acetate:-
˜
81%). Rf (PE)=0.11. IR (film): n=3310, 2957, 2929, 2886,
2857, 2249, 2121, 1472, 1462, 1255, 1222, 1111, 1061, 1018,
990, 940, 910, 836, 815, 776, 736, 643 cmÀ1; H NMR (CDCl3,
1
250 MHz): d=0.15 (s, 3H), 0.17 (s, 3H), 0.91 (s, 9H), 1.26
3
2
3
(d, J=7.0 Hz, 3H), 1.86 (dd, J=14.4 Hz, J=4.4 Hz, 1H),
4
4
1.99 (t, J=2.7 Hz, 1H), 2.03 (t, J=2.7 Hz, 1H), 2.20–2.29
4
2
4
(m, 4H), 2.38 (d, J=2.7 Hz, 2H), 2.38 (dd, J=16.4 Hz, J=
2.7 Hz, 1H), 2.51 (dd, 2J=16.4 Hz, 4J=2.7 Hz, 1H), 2.99–
3.11 (m, 1H), 5.79–5.86 (m, 2H). 13C NMR (CDCl3,
126 MHz): d=À1.99 (q), À1.97 (q), 13.65 (q), 18.66 (s),
22.70 (q), 26.08 (q, 3 C), 28.89 (d), 29.70 (t), 31.42 (t), 44.84
(t), 70.95 (d), 71.38 (d), 76.61 (s), 81.29 (s), 81.39 (s), 104.64
(d), 105.87 (d), 150.16 (s), 158.39 (s); HR-MS (ESI+): m/z=
383.1809, calcd. for C21H32KO2Si: 383.1809.
Adv. Synth. Catal. 2009, 351, 2469 – 2481
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asc.wiley-vch.de
2479

A. Stephen K. Hashmi et al.
FULL PAPERS
7-(tert-Butyldimethylsilyloxy)-2,5-dimethyl-7-(prop-2-
ynyl)-5,6,7,8-tetrahydronaphthalen-1-ol (16): 110 mg (319
mmol) 15 were dissolved in 3 mL CH3CN and the solution
was cooled to 08C. After the addition of 2.90 mg (9.57
mmol) AuCl3 the starting material was fully converted after
10 min. Analysis of the crude mixture by GCMS, showed a
dr of 87:13 (the same dr was measured during a test reaction
at room temperature as well). Purification of the crude
product by column chromatography (SiO2, PE:EA, 100:1)
afforded the major diastereoisomer 16a (yield: 62.0 mg, 180
mmol, 56%) and the minor diastereoisomer 16b (yield:
10.1 mg, 29.0 mmol, 9%), both as yellow oils.
16.4, 2.7 Hz, 1H), 2.82 (d, J=17.0, 1H), 2.98 (dd, J=17.0,
2.7 Hz, 1H), 3.05–3.13 (m, 1H), 6.89 (d, J=7.9 Hz, 1H),
6.97 (d, J=7.9 Hz, 1H); 13C NMR (CDCl3, 75 MHz): d=
À3.36 (q), À2.56 (q), À2.41 (q), À2.25 (q), 17.73 (q), 18.29
(s), 18.31 (s), 21.46 (q), 25.86 (q, 3 C), 26.39 (q, 3C), 29.69
(d), 34.31 (t), 36.90 (t) ,43.67 (t), 70.94 (d), 73.44 (s), 81.67
(s), 119.66 (d), 125.10 (s), 125.91 (s), 128.36 (d), 140.09 (s),
151.65 (s); HR-MS (ESI+): m/z=481.2939, calcd. for
C27H46NaO2Si2: 481.2934.
The compound from the previous experiment was depro-
tected to furnish 16a as follows: 51.5 mg (116 mmol) 17 were
dissolved in 3 mL THF and cooled to 08C. After the addi-
tion of 73.2 mg (232 mmol) TBAF·3H2O, the reaction was
stirred for 5 min. 5 mL H2O were added and the solution
was extracted three times with dichloromethane (5 mL).
After drying over MgSO4 and filtration, the solvent was re-
moved under vacuum. Column chromatography on silica
(PE:EA, 50:1) afforded 16a as a yellow oil; yield: 38.3 mg
Major diastereoisomer 16a: Rf (PE:EA, 50:1)=0.11. IR
˜
(film): n=3559, 3310, 2955, 2929, 2856, 2249, 2120, 1463,
1359, 1328, 1308, 1254, 1224, 1178, 1112, 1067, 979, 908, 836,
807, 774, 735, 637 cmÀ1 1H NMR (CDCl3, 250 MHz): d=
;
À0.24 (s, 3H), 0.11 (s, 3H), 0.74 (s, 9H), 1.33 (d, J=6.9 Hz,
3H), 1.52–1.62 (m, 1H), 1.96–2.04 (m, 1H), 2.06 (t, J=
2.7 Hz, 1H), 2.23 (s, 3H), 2.56–2.57 (m, 2H), 2.83 (d, J=
17.3, 1H), 2.92 (d, J=17.3 Hz, 1H), 3.06–3.18 (m, 1H), 4.57
(s, 1H), 6.85 (d, J=7.9 Hz, 1H), 6.96 (d, J=7.9 Hz, 1H);
13C NMR (CDCl3, 126 MHz): d=À3.18 (q), À2.18 (q), 15.68
(q), 18.43 (s), 21.13 (q), 25.84 (q, 3 C), 29.26 (d), 34.27 (t),
35.13 (t), 43.44 (t), 71.14 (d), 73.08 (s), 81.51 (s), 118.52 (d),
119.18 (s), 120.86 (s), 127.93 (d), 140.55 (s), 151.51 (s); HR-
MS (ESI+): m/z=367.2064, calcd. forC21H32NaO2Si:
367.2069.
1
(111 mmol, 96%). Rf (PE:EA, 50:1)=0.11; H NMR (CDCl3,
250 MHz): d=À0.24 (s, 3H), 0.11 (s, 3H), 0.74 (s, 9H), 1.33
(d, J=6.9 Hz, 3H), 1.52–1.62 (m, 1H), 1.96–2.04 (m, 1H),
2.06 (t, J=2.7 Hz, 1H), 2.23 (s, 3H), 2.56–2.57 (m, 2H), 2.83
(d, J=17.3, 1H), 2.92 (d, J=17.3 Hz, 1H), 3.06–3.18 (m,
1H), 4.57 (s, 1H), 6.85 (d, J=7.9 Hz, 1H), 6.96 (d, J=
7.9 Hz, 1H). These data are in accordance with the data of
16a obtained in the cyclization of 15.
Minor diastereoisomer 16b: Rf (PE:EA, 50:1)=0.07. IR
˜
(film): n=3541, 3310, 2956, 2928, 2856, 2249, 2120, 1714,
1490, 1462, 1359, 1257, 1113, 1067, 1008, 979, 909, 836, 822,
Acknowledgements
1
807, 774, 735 cmÀ1; H NMR (CDCl3, 500 MHz): d=À0.26
(s, 3H), 0.09 (s, 3H), 0.71 (s, 9H), 1.30 (d, J=6.9 Hz, 3H),
1.52–1.54 (m, 1H), 1.95–1.99 (m, 1H), 2.05 (t, J=2.5 Hz,
1H), 2.12 (s, 3H), 2.49–2.57 (m, 2H), 2.77 (d, J=17.2 Hz,
1H), 2.89 (d, J=17.2 Hz, 1H), 3.04–3.12 (m, 1H), 4.51 (s,
1H), 6.64 (d, 8.5 Hz, 1H), 7.05 6 (d, J=8.5 Hz, 1H);
13C NMR (CDCl3, 126 MHz): d=À3.11 (q), À2.14 (q), 11.38
(q), 18.34 (s), 21.40 (q), 25.79 (q, 3 C), 29.09 (d), 34.33 (t),
39.11 (t), 43.45 (t), 71.09 (d), 73.52 (s), 81.54 (s), 112.91 (d),
121.52 (s), 124.56 (d), 133.78 (s), 134.58 (s), 151.26 (s); HR-
MS (ESI+): m/z=383.1803, calcd. for C21H32KO2Si:
383.1809.
This work was supported by Umicore AG & Co. KG and by
the Deutsche Forschungsgemeinschaft (HA 1932/10-1).
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G
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ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2009, 351, 2469 – 2481

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Adv. Synth. Catal. 2009, 351, 2469 – 2481
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2481