Gold(I)-catalyzed hydration of allenes

Article abstract of DOI:10.1016/j.tet.2008.10.113

A gold(I) N-heterocyclic carbene complex catalyzes the intermolecular hydration of allenes to form allylic alcohols in modest yield with selective delivery of water to the terminal carbon atoms of the allenyl moiety.

Full text of DOI:10.1016/j.tet.2008.10.113

Tetrahedron 65 (2009) 1794–1798
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Gold(I)-catalyzed hydration of allenes
*
Zhibin Zhang, Seong Du Lee, Aaron S. Fisher, Ross A. Widenhoefer
Department of Chemistry, Duke University, French Family Science Center, Durham, NC 27708-0346, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 1 August 2008
Received in revised form 15 October 2008
Accepted 23 October 2008
Available online 24 December 2008
A gold(I) N-heterocyclic carbene complex catalyzes the intermolecular hydration of allenes to form allylic
alcohols in modest yield with selective delivery of water to the terminal carbon atoms of the allenyl
moiety.
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
monosubstituted allenes with water led to competitive hydrative
dimerization and hydration initiated via attack of water at the in-
There has been considerable interest in the transition metal-
catalyzed hydration of alkenes as an alternative to acid-catalyzed or
heavy metal-mediated approaches to hydration, particularly as
a means to achieve anti-Markovnikov addition.1 However, effective
transition metal-catalyzed hydration of simple alkenes has not been
realized. Complexes of a number of transition metals including
Pt(II),2,3 Hg(II),3,4 Au(I),5 and Ru(II)6 catalyze the hydration of al-
kynes,7 but these methodsare noteffectiveforalkenes. Palladium(II)
salts promote the addition of water to ethylene and unactivated 1-
ternal allenyl carbon atom.15 Attack of water at the central carbon of
the allene is also observed in the Brønsted acid-catalyzed hydration
of allenes.16 Here we report the gold(I)-catalyzed hydration of
allenes to form allylic alcohols via selective attack of water at the
terminal allenyl carbon atoms.
2. Results and discussion
We have recently reported that a mixture of the gold(I)
N-heterocyclic carbene complex (1)AuCl [1¼1,3-bis(2,6-diisopro-
pylphenyl)imidazol-2-ylidine] and AgOTf catalyzes the inter-
molecular hydroalkoxylation of allenes with alcohols (Eq. 1),14 and
we considered that this catalyst system might also be effective
for the hydration of allenes. However, direct application of the
catalyst system employed for the intermolecular hydro-
alkoxylation of allenes met with modest success. Stirring a mix-
ture of 2,3-pentadienyl benzoate (2, 0.4 M), water (2 equiv), and
a catalytic 1:1 mixture of (1)AuCl and AgOTf in toluene at 23 ꢀC
for 24 h led to complete consumption of 2 to form a 1:1 mixture
of secondary allylic alcohols 3a and 3b in 33% combined yield
(Table 1, entry 1). Neither 3-propanonyl benzoate, resulting from
attack of water at the central allenyl carbon atom, nor 1-vinyl-1-
propenyl benzoate, formed via isomerization of 2,17 was detected
in the crude reaction mixture. Rather, the major byproducts of the
gold(I)-catalyzed hydration of 2 were bis(allylic) ethers formed
via sequential hydration/hydroalkoxylation. This observation
suggested that inefficient hydration of 2 was due, at least in part,
to the limited solubility of water in toluene. Indeed, gold(I)-cat-
alyzed hydration of 2 in water miscible solvents such as acetone,
THF, or dioxane led to significant increase in the yield of 3 (Table
1, entries 2–4). In a preparative-scale experiment, reaction of 2
(0.4 M) with water (2 equiv) and a catalytic 1:1 mixture of (1)AuCl
and AgOTf in dioxane at 23 ꢀC for 3 h led to isolation of 3a in 48%
yield and 3b in 25% yield (Table 2, entry 1). Control experiments
alkenes, but facile
b-hydride elimination leads to oxidation and
formation of ketones.8 Reports on platinum-catalyzed anti-Mar-
kovnikov hydration of 1-hexene9 have not been validated,10 and as
such transition metal-catalyzed alkene hydration has been re-
stricted to electron deficient alkenes such as maleate esters.11
(1)AuCl (5 mol %)
AgOTf (5 mol %)
Ph
+
Me
N
Ph
OH
i-Pr
toluene, rt, 1 h
96%
i-Pr
ð1Þ
Me
N
Ph
O
Ph
i-Pr
i-Pr
1
We became interested in the transition metal-catalyzed hydra-
tion of allenes, which are destabilized by w10 kcal/mol relative to
alkenes,12 as an entry point into the development of catalytic al-
kene hydration processes. Although a number of O–H nucleophiles
undergo efficient transition metal-catalyzed intermolecular addi-
tion across the C]C bond of an allene,13,14 water is not among
them. In
a lone example, the Ru(II)-catalyzed reaction of
* Corresponding author. Tel.: þ1 919 660 1533; fax: þ1 919 660 1605.
E-mail address: rwidenho@chem.duke.edu (R.A. Widenhoefer).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.10.113

Z. Zhang et al. / Tetrahedron 65 (2009) 1794–1798
1795
Table 1
In comparison to 2, 1-aryl-2,3-butadienes 4 and 5 underwent
gold(I)-catalyzed hydration to form 6 and 7, respectively, in >60%
yield as single regioisomers resulting from attack of water at the
methyl-bound allenyl carbon atom (Table 2, entries 2 and 3).
Gold(I)-catalyzed hydration of enantiomerically enriched 4 (78%
ee) formed racemic 6, owing to the rapid racemization of 4 under
reaction conditions.14,18 The 1,3-dialkyl-substituted allene 8 also
underwent gold(I)-catalyzed hydration to form 9 in 54% yield (Ta-
ble 2, entry 4). Gold(I)-catalyzed hydration of the monosubstituted
allenes 10 and 11 and the 1,1-disubstituted allene 12 led to isolation
of primary allylic alcohols 13–15, respectively, as single regio- and
diastereoisomer, in modest yield (Table 2, entries 5–7). In com-
parison, hydration of the trisubstituted allene 16 led to isolation of
a 2.5:1 mixture of tertiary allylic alcohol 17a and secondary allylic
alcohol 17b, in 73% combined yield (Table 2, entry 8).
Effect of solvent on the hydration of 2 catalyzed by a mixture of (1)AuCl and AgOTf
(1)AuCl (5 mol %)
AgOTf (5 mol %)
Me
+ H2O
BzO
23 °C
100% convn
2
Me
OH
OH
BzO
+
BzO
Me
3a
3b
Entry
Solvent
Time (h)
Yielda (%)
3a/3b
1
2
3
4
Toluene
Acetone
THF
24
4
4
33
69
75
77
1:1
3:1
1:1
2:1
Dioxane
4
a
In summary, we have developed a gold(I)-catalyzed protocol for
the hydration of allenes to form (E)-allylic alcohols via selective
deliveryofwatertotheterminalallenyl carbonatom(s). Wecontinue
to work toward the development of more effective allene hydration
catalysts and toward the development of alkene hydration catalysts.
Combined yield of 3a and3b determined byGCanalysisof the crudereactionmixture.
revealed that both AgOTf and (1)AuCl were required for allene
hydration and that Brønsted acid played no role in allene hy-
dration (see Experimental section).
3. Experimental
Table 2
3.1. General methods
Hydration of allenes catalyzed by a mixture of (1)AuCl (5 mol %) and AgOTf (5 mol %)
in dioxane at 23 ꢀC
Reactions were performed under
a nitrogen atmosphere
Entry
Allene
Allylic alcohol(s)
Me
Yielda (%)
48
employing standard Schlenk and dry box techniques unless speci-
fied otherwise. NMR spectrawere obtained on Varian spectrometers
operating at 400 MHz for 1H NMR and 101 MHz for 13C NMR in CDCl3
at 25 ꢀC unless noted otherwise. IR spectra were obtained on
a Nicolet Avatar 360-FT IR spectrometer. Gas chromatography was
performed on a Hewlett–Pakard 5890 gas chromatography equip-
ped with a 15 m or 25 m polydimethylsiloxane capillary column and
FID detector. Column chromatography was performed employing
230–400 mesh silica gel (Silicycle). Catalytic reactions were per-
formed in sealed glass tubes under an atmosphere of dry nitrogen
unless noted otherwise. Elemental analyses were performed by
Complete Analysis Laboratories (Parsippany, NJ). Thin layer chro-
matography (TLC) was performed on silica gel 60 F254 (EMD Chem-
icals Inc.). Room temperature is 23 ꢀC. All solvents were purchased
from Aldrich or Acros in anhydrous form and used as received. All
reagents were purchased from major suppliers and used as received.
Tridec-7-yn-6-ol,19 o-nitrobenzenesulfonyl hydrazine,20 ethyl 3-
hexyl-3,4-pentadienoate,21 4-(4-(trifluoromethyl)phenyl)-3-butyn-
2-ol,22 2,3-pentadienyl benzoate (2),14 1-phenyl-1,2-butadiene (4),14
dimethyl 2-(2,3-butadienyl)malonate (10),14 and 1-(benzyloxy)-2-
(5-methyl-3,4-hexadienyl)benzene(16)14 wereprepared employing
the published procedures.
OBz
OBz
OH
3a
Me
1
OH
+
2
25
OBz
Me
3b
OH
Me
Ar
Me
Ar
2
3
Ar¼Ph (4)
6
7
64b
62
Ar¼p-C6H4CF3 (5)
OH
R
R
4
5
6
54
41
42
R
R
8 (R = n-pentyl)
9
E
E
E
E
HO
10 (E = CO2Me)
13
Me
Me
17
HO
17
3.2. Preparation of allenes
14
11
3.2.1. 1-(1,2-Butadienyl)-4-(trifluoromethyl)benzene (5)
OBn
OBn
Diethylazodicarboxylate (1.4 mL, 8.8 mmol) was added to a so-
lution of triphenylphosphine (2.3 g, 8.8 mmol) in THF (15 mL) at
ꢁ10 ꢀC over 1 min. The resulting solution was stirred at ꢁ10 ꢀC for
10 min, treated with a solution of 4-(4-(trifluoromethyl)phenyl)-3-
butyn-2-ol (1.45 g, 6.8 mmol) in THF (10 mL), stirred for 10 min,
and treated with a solution of o-nitrobenzenesulfonyl hydrazine
(1.9 g, 8.8 mmol) in THF (15 mL). The resulting mixture was stirred
between ꢁ10 ꢀC and 0 ꢀC for 2 h, warmed to room temperature, and
stirred overnight. The reaction mixture was cooled to 0 ꢀC, diluted
with Et2O, washed with ice water, dried (MgSO4), and concentrated.
The resulting residue was chromatographed (hexane) to give 5 as
7
36
n-hexyl
n-hexyl
HO
15
12
Ar
OH
Me
Me Me
17a
Ar
16 (Ar = 2-C6H4OBn)
8
73 (2.5:1)
+
Me
OH Me
Me
Ar
17b
a colorless oil, 74%. TLC (hexane): Rf¼0.69. 1H NMR:
d 7.54 (d,
a
Yield refers to isolated material of >95% purity.
b
J¼8.0 Hz, 2H), 7.38 (d, J¼8.0 Hz, 2H), 6.14–6.10 (m, 1H), 5.61
Employment of enantiomerically enriched 4 (78% ee) led to the formation of
racemic 6.
(quintet, J¼7.0 Hz, 1H), 1.81 (ddd, J¼1.2, 3.2, 7.2 Hz, 3H). 13C{1H}

1796
Z. Zhang et al. / Tetrahedron 65 (2009) 1794–1798
NMR:
d
207.1, 139.3, 128.8 (q, 2JC–F¼32.4 Hz), 126.9, 125.7 (q, 3JC–F
¼
temperature for 5 min, treated with a solution of 2 (37.6 mg,
4.0 Hz), 124.5 (q, 1JC–F¼271.9 Hz), 93.2, 90.2, 13.8. IR (neat, cmꢁ1):
2930, 1615, 1322, 1162, 1119, 1064, 1016, 875, 843, 754. HRMS calcd
(found) for C11H9F3 (Mþ): 198.0656 (198.0657).
0.20 mmol) and H2O (5.4 mg, 0.30 mmol) in 1,4-dioxane (0.3 mL),
and stirred at room temperature for 4 h. Column chromatogra-
phy of the crude reaction mixture (hexanes–EtOAc¼10:1/2:1)
gave (E)-4-hydroxy-2-pentenyl benzoate (3a, 19.8 mg, 48%) and
(E)-2-hydroxy-3-pentenyl benzoate (3b, 10.1 mg, 25%) as color-
less oils.
3.2.2. 6,7-Tridecadiene (8)
6,7-Tridecadiene (8)23 was synthesized from tridec-7-yn-6-ol
(0.30 g, 1.5 mmol) employing a procedure analogous to that used to
For 3a: TLC (hexanes–EtOAc¼5:1): Rf¼0.18. 1H NMR:
d 8.04–8.01
synthesize 5. Colorless oil, 37%. 1H NMR:
d
5.09–5.04 (m, 2H), 2.00–
(m, 2H), 7.55–7.51 (m, 1H), 7.43–7.39 (m, 2H), 5.83 (dqd, J¼1.2, 6.4,
15.6 Hz, 1H), 5.53 (qdd, J¼1.6, 6.4, 15.2 Hz, 1H), 4.46–4.41 (m, 1H),
4.34 (dd, J¼3.8, 11.2 Hz, 1H), 4.22 (dd, J¼7.2, 11.2 Hz, 1H), 2.36 (br s,
1.94 (m, 4H), 1.45–1.25 (m, 12H), 0.89 (t, J¼6.8 Hz, 6H). 13C{1H}
NMR:
d 204.0, 91.1, 31.6, 29.2, 29.1, 22.7, 14.3.
1H), 1.71–1.69 (m, 3H). 13C{1H} NMR:
d 166.9, 133.3, 130.1, 129.8,
3.2.3. Henicosa-1,2-diene (11)
129.5,129.3,128.6, 71.1, 68.8,18.0. IR (neat, cmꢁ1): 3468, 2949,1712,
1602, 1449, 1376, 1271, 1115, 1068, 967, 710. Anal. Calcd (found) for
C12H14O3: C, 69.88 (69.76); H, 6.84 (6.79).
1-Icosyne (5.10 g, 50.0 mmol) was added to a suspension of
formaldehyde (1.55 g, 50.0 mmol), diisopropylamine (5.10 g,
50.0 mmol), and CuBr (1.44 g, 10.0 mmol) in dioxane (75 mL). The
mixture was refluxed for 20 h, cooled, and concentrated under vac-
uum. The residue was diluted with Et2O (150 mL), filtered through
silica gel, eluted with Et2O (150 mL), and the filtrate was concen-
trated under vacuum. Column chromatography of the residue (hex-
ane) gave 11 (3.43 g, 52%) as a white solid. TLC (hexane): Rf¼0.81. 1H
For 3b: TLC (hexanes–EtOAc¼5:1): Rf¼0.09. 1H NMR:
d 8.04–
8.02 (m, 2H), 7.55–7.51 (m, 1H), 7.43–7.39 (m, 2H), 5.90 (dd, J¼4.8,
16.0 Hz, 1H), 5.85 (td, J¼5.2, 15.6 Hz, 1H), 4.79 (dd, J¼1.0, 4.6 Hz,
2H), 4.37–4.31 (m, 1H), 1.89 (br s, 1H), 1.27 (d, J¼6.4 Hz, 3H). 13C{1H}
NMR: d 166.5, 138.6, 133.2, 130.3, 129.8, 128.5, 123.8, 68.1, 64.9, 23.3.
IR (neat, cmꢁ1): 3409, 2971, 1713, 1602, 1450, 1375, 1268, 1112, 1066,
967, 710. Anal. Calcd (found) for C12H14O3: C, 69.88 (69.76); H, 6.84
(6.94).
NMR:
d
5.06 (quintet, J¼6.8 Hz,1H), 4.61 (td, J¼3.2, 6.8 Hz, 2H), 2.03–
1.94 (m, 2H),1.48–1.10 (m, 32H), 0.87 (t, J¼6.8 Hz, 3H). 13C{1H} NMR:
d
208.7, 90.2, 74.6, 32.2, 30.0, 29.7, 29.6, 29.4, 29.3, 28.5, 22.9, 14.3. IR
The E-configuration of allylic alcohols was assigned on the basis
of the large vicinal C]C coupling constant of the allylic moiety in
the 1H NMR spectrum (3JHHz15.6 Hz).
(neat, cmꢁ1): 2956, 2915, 2848, 1956, 1467, 861, 841, 721, 562. HRMS
calcd (found) for C21H40 (Mþ): 292.3130 (292.3127).
3.2.4. 3-(2-Benzyloxyethyl)-1,2-nonadiene (12)
3.3.2. (E)-4-Phenyl-3-buten-2-ol (6)25
Ethyl 3-hexyl-3,4-pentadienoate (2.54 g, 12.9 mmol) was added
dropwise to a stirred suspension of LiAlH4 (0.63 g, 16.5 mmol) in
THF (100 mL) at 0 ꢀC. The reaction mixture was stirred for 4 h and
then treated sequentially with water (0.6 mL), NaOH 15% (1.25 mL),
and water (2 mL). The resulting mixture was filtered through a pad
of Celite and concentrated to give 3-hexyl-3,4-pentadien-1-ol (18)
as a colorless oil (1.93 g, 97%) that was used in the subsequent step
without further purification. Alcohol 18 (1.00 g, 5.94 mmol) was
added dropwise to a stirred suspension of NaH (171 mg, 7.14 mmol)
in DMF (50 mL) at 0 ꢀC, stirred for 30 min, and treated with benzyl
bromide (1.22 g, 7.14 mmol). The resulting suspension was warmed
to room temperature and stirred for 10 h. The reaction mixture was
cooled to 0 ꢀC, treated with water (50 mL), and extracted with
EtOAc (100 mL). The combined organic extracts were washed with
brine (75 mL), dried (MgSO4), and concentrated. The resulting
residue was chromatographed (hexanes–EtOAc¼30:1) to give 12 as
a colorless oil (0.67 g, 43%).
A mixture of (1)AuCl (12.4 mg, 0.020 mmol) and AgOTf (5.1 mg,
0.020 mmol) in 1,4-dioxane (0.2 mL) was stirred at room temper-
ature for 5 min, treated with a solution of buta-1,2-dienylbenzene
(4) (52.1 mg, 0.40 mmol) and H2O (14.4 mg, 0.80 mmol) in 1,4-di-
oxane (0.3 mL), and stirred at room temperature for 3 h. Column
chromatography of the crude reaction mixture (hexanes–
EtOAc¼10:1/5:1) gave 6 (31.9 mg, 54%) as a colorless oil. TLC
(hexanes–EtOAc¼5:1): Rf¼0.20. 1H NMR:
d 7.36–7.19 (m, 5H), 6.53
(d, J¼16.0 Hz, 1H), 6.23 (ddd, J¼1.2, 6.4, 16.0 Hz, 1H), 4.50–4.42 (m,
1H), 1.80 (br s, 1H), 1.34 (dd, J¼1.2, 6.4 Hz, 3H). 13C{1H} NMR:
d
136.9, 133.8, 129.6, 128.8, 127.8, 126.6, 69.1, 23.6.
All remaining intermolecular hydration reactions were per-
formed employing a procedure analogous to that used to synthe-
size 6 unless noted otherwise.
3.3.3. (E)-4-(4-(Trifluoromethyl)phenyl)-3-buten-2-ol (7)
Colorless oil, 62%. TLC (CH2Cl2): Rf¼0.24. 1H NMR:
d 7.54 (d,
For 18:24 TLC (hexanes–EtOAc¼4:1): Rf¼0.17. 1H NMR:
d
4.78–
J¼8.4 Hz, 2H), 7.44 (d, J¼8.0 Hz, 2H), 6.59 (d, J¼16.0 Hz, 1H), 6.34
(dd, J¼6.0, 16.0 Hz, 1H), 4.50 (quintet, J¼6.4 Hz, 1H), 1.72 (br s, 1H),
4.64 (m, 2H), 3.73 (t, J¼6.2 Hz, 2H), 2.23–2.17 (m, 2H), 1.99–1.88 (m,
2H), 1.81 (s, 1H), 1.52–1.20 (m, 8H), 0.87 (t, J¼6.3 Hz, 3H). 13C{1H}
1.37 (d, J¼6.4 Hz, 3H). 13C{1H} NMR:
d 140.5, 136.4, 129.6 (q,
NMR:
d
205.6, 100.4, 76.3, 60.9, 35.4, 32.4, 31.8, 29.1, 27.5, 22.7, 14.2.
J¼32.4 Hz), 128.1, 126.8, 125.7 (q, J¼4.0 Hz), 124.4 (q, J¼271.9 Hz),
68.8, 23.6. IR (neat, cmꢁ1): 3359, 2976, 1616, 1414, 1322, 1163, 1119,
1066, 816. HRMS calcd (found) for C11H11F3O (Mþ): 216.0762
(216.0762).
IR (neat, cmꢁ1): 3395, 2955, 2926, 2856, 1716, 1457, 1378, 1175,
1029, 845, 724. HRMS: calcd (found) for C11H20O (Mþ): 168.1514
(168.1516).
For 12: TLC (hexanes–EtOAc¼4:1): Rf¼0.83. 1H NMR:
d 7.39–7.28
(m, 5H), 4.74–4.67 (m, 2H), 4.55 (s, 2H), 3.62 (t, J¼7.0 Hz, 2H), 2.35–
2.25 (m, 2H), 2.04–1.95 (m, 2H), 1.51–1.24 (m, 8H), 0.92 (t, J¼6.7 Hz,
3.3.4. (E)-Tridec-7-en-6-ol (9)
Colorless oil, 54%. TLC (hexanes–EtOAc¼8:1): Rf¼0.40. 1H NMR:
3H). 13C{1H} NMR:
d
205.9, 138.7, 128.4, 127.8, 127.6, 100.3, 75.8,
d
5.63 (dt, J¼6.8, 15.2 Hz, 1H), 5.44 (ddt, J¼1.2, 7.2, 15.2 Hz, 1H), 4.03
73.0, 68.9, 32.5, 32.3, 31.8, 29.1, 27.5, 22.8, 14.2. IR (neat, cmꢁ1):
2924, 2855, 1454, 1362, 1099, 844, 732, 696. HRMS calcd (found) for
C18H26O (Mþ): 258.1984 (258.1982).
(q, J¼6.8 Hz, 1H), 2.02 (q, J¼6.8 Hz, 2H), 1.60–1.20 (m, 15H), 0.88 (t,
J¼6.8 Hz, 6H). 13C{1H} NMR:
d 133.2, 132.5, 73.5, 37.5, 32.4, 32.0,
31.6, 29.1, 25.4, 22.8, 22.7, 14.3, 14.2. IR (neat, cmꢁ1): 2957, 2923,
2853, 1463, 1378, 1062, 969. HRMS calcd (found) for C13H26O (Mþ):
198.1984 (198.1977).
3.3. Hydration products
3.3.1. (E)-4-Hydroxy-2-pentenyl benzoate (3a) and (E)-2-hydroxy-
3-pentenyl benzoate (3b)
A mixture of (1)AuCl (6.2 mg, 0.010 mmol) and AgOTf (2.6 mg,
0.010 mmol) in 1,4-dioxane (0.2 mL) was stirred at room
3.3.5. (E)-Dimethyl 2-(4-hydroxy-2-butenyl)malonate (13)
Colorless oil, 41%. TLC (hexanes–EtOAc¼1:5): Rf¼0.51. 1H NMR:
d
5.72 (ttd, J¼0.8, 5.2, 15.6 Hz, 1H), 5.63 (ttd, J¼0.8, 6.8, 15.6 Hz, 1H),
4.07–4.04 (m, 2H), 3.71 (s, 6H), 3.42 (t, J¼7.4 Hz, 1H), 2.62 (dt, J¼0.8,

Z. Zhang et al. / Tetrahedron 65 (2009) 1794–1798
1797
7.0 Hz, 2H), 1.53 (br s, 1H). 13C{1H} NMR:
d
169.4, 132.6, 127.6, 63.4,
3.4. Control experiments
52.8, 51.7, 31.6. IR (neat, cmꢁ1): 3378, 2955, 1731, 1437, 1343, 1231,
1157, 1096, 974, 851. HRMS calcd (found) for C9H12O4 (MþꢁH2O):
184.0736 (184.0738).
OBn
conditions
+
H2O
Me
2
3.3.6. (E)-2-Henicosen-1-ol (14)
White solid, (42%). TLC (hexane): Rf¼0.25. 1H NMR:
d
5.69 (td,
OH
OH
+
OBn
OBn
J¼6.4, 15.6 Hz, 1H), 5.55 (td, J¼6.4, 15.2 Hz, 1H), 3.90 (dd, J¼1.2,
Me
Me
3a
3b
6.0 Hz, 2H), 2.03 (q, J¼6.8 Hz, 2H), 1.50–1.00 (m, 33H), 0.88 (t,
J¼6.4 Hz, 3H). 13C{1H} NMR:
d 135.1, 126.5, 70.9, 32.5, 32.2, 29.9,
29.7, 29.6, 29.4, 29.3, 22.9, 14.3. IR (neat, cmꢁ1): 2955, 2917, 2871,
2848, 1712, 1471, 1462, 1375, 1360, 1260, 1166, 1118, 1064, 1019, 965,
803, 719, 599. HRMS calcd (found) for C21H42O (Mþ): 310.3236
(310.3240).
(1) Treatment of water (5.4 mg, 0.30 mmol) and 2 (37.6 mg,
0.20 mmol) with (1)AuCl (5 mol %) in dioxane (0.5 mL) at 23 ꢀC
for 40 h led to no consumption of 2 as determined by GC
analysis of the crude reaction mixture versus decane internal
standard.
(2) Treatment of water (5.4 mg, 0.30 mmol) and 2 (37.6 mg,
0.20 mmol) with 1 (5 mol %) and AgOTf (5 mol %) in dioxane
(0.5 mL) at 23 ꢀC for 40 h led to no consumption of 2 as de-
termined by GC analysis of the crude reaction mixture versus
decane internal standard.
(3) Treatment of water (5.4 mg, 0.30 mmol) and 2 (37.6 mg,
0.20 mmol) with 1 (5 mol %) and HOTf (5 mol %) in dioxane
(0.5 mL) at 23 ꢀC for 40 h led to no consumption of 2 as de-
termined by GC analysis of the crude reaction mixture versus
decane internal standard.
(4) Treatment of water (5.4 mg, 0.30 mmol) and 2 (37.6 mg,
0.20 mmol) with HOTf (10 mol %) in dioxane (0.5 mL) at 23 ꢀC
for 40 h led to no consumption of 2 as determined by GC
analysis of the crude reaction mixture versus decane internal
standard.
3.3.7. (Z)-3-(2-(Benzyloxy)ethyl)-2-nonen-1-ol (15)
Colorless oil, 36%. TLC (hexanes–EtOAc¼5:1): Rf¼0.30. 1H
NMR:
d
7.32–7.20 (m, 5H), 5.63 (t, J¼7.6 Hz, 1H), 4.46 (s, 2H), 3.97
(dd, J¼5.6, 7.6 Hz, 2H), 3.44 (t, J¼6.0 Hz, 2H), 2.40 (t, J¼5.6 Hz, 1H),
2.35 (t, J¼6.0 Hz, 2H), 1.95 (t, J¼6.8 Hz, 2H), 1.39–1.15 (m, 8H), 0.83
(t, J¼6.8 Hz, 3H). 13C{1H} NMR:
d 141.8, 137.8, 128.7, 128.1, 126.1,
73.4, 67.8, 58.1, 36.7, 31.9, 30.9, 29.3, 28.0, 22.8, 14.3. IR (neat,
cmꢁ1): 3370, 2954, 2925, 2855, 1496, 1465, 1454, 1415, 1361, 1097,
1002, 735, 697. HRMS calcd (found) for C18H28O2 (MþꢁH2O):
258.1984 (258.1986). The Z-configuration of allylic alcohol (Z)-15
was unambiguously assigned through NOE analysis. Irradiation of
proton Ha led to enhancement of Hb but no enhancement of Hd,
and irradiation of Hc led to enhancement of Hd but no enhance-
ment of Hb.
(Z)-15
3.5. Identification of byproducts from the reaction of water
with 2
O
b
a
A mixture of (1)AuCl (18.6 mg, 0.030 mmol) and AgOTf (7.7 mg,
0.030 mmol) in dioxane (0.2 mL) was stirred at room temperature
for 5 min, treated with a solution of 2 (112.8 mg, 0.6 mmol) and
water (16.2 mg, 0.9 mmol) in dioxane (0.3 mL), and stirred at room
temperature for 4 h. GC analysis of the crude reaction mixture
revealed formation of a w1:1 mixture of 3a and 3b (GC retention
times¼2.72 and 2.52 min, respectively) that accounted for 33% of
the reaction mixture. The remainder of the reaction mixture con-
sisted of a 1.5:1.5:1:1 mixture of four compounds that eluted at 7.24
Me
HO
d
Hc
3.3.8. Hydration of 1-(benzyloxy)-2-(5-methyl-3,4-hexadienyl)-
benzene (16)
A mixture of (1)AuCl (6.2 mg, 0.010 mmol) and AgOTf (2.6 mg,
0.010 mmol) in 1,4-dioxane (0.2 mL) was stirred at room temper-
ature for 5 min, treated with a solution of 16 (55.7 mg, 0.20 mmol)
and H2O (5.4 mg, 0.30 mmol) in 1,4-dioxane (0.3 mL), and stirred at
room temperature for 9 h. Column chromatography of the crude
reaction mixture (hexanes–EtOAc¼10:1/5:1) gave a 2.5:1 mixture
of (E)-6-(2-(benzyloxy)phenyl)-2-methyl-3-hexen-2-ol (17a) and
1-(2-(benzyloxy)phenyl)-5-methyl-4-hexen-3-ol (17b) (43.2 mg,
73%) as a colorless oil. TLC (hexanes–EtOAc¼5:1): Rf¼0.28. 1H NMR
(1)AuCl (5 mol %)
AgOTf (5 mol %)
Me
+ H2O
BzO
23 °C, toluene
24 h
2
Me Me
OBz
BzO
3a +
(17a): 7.46–6.89 (m, 9H), 5.68 (td, J¼6.4, 15.6 Hz, 1H), 5.58 (dd,
J¼0.8,15.6 Hz,1H), 5.09 (s, 2H), 2.77 (t, J¼7.2 Hz, 2H), 2.35 (td, J¼6.8,
8.8 Hz, 2H), 1.43 (br s, 1H), 1.27 (s, 6H). 1H NMR (17b):
7.46–6.89
d
O
19
+
OBz
d
Me
(m, 9H), 5.20 (d, J¼8.8 Hz, 1H), 5.08 (s, 2H), 4.33 (q, J¼7.2 Hz, 1H),
BzO
3b +
Me
O
2.84–2.66 (m, 2H), 1.94–1.67 (m, 2H), 1.71 (s, 3H), 1.62 (s, 3H), 1.44
20
(br s, 1H). 13C{1H} NMR (both 17a and 17b):
d 156.7, 156.6, 138.5,
137.7, 137.5, 135.2, 130.9, 130.8, 130.3, 130.2, 128.7, 128.6, 128.2,
128.0, 127.9, 127.3, 127.25, 127.23, 127.20, 127.0, 121.1, 120.8, 111.9,
111.8, 70.7, 70.1, 69.9, 68.4, 38.1, 32.7, 30.6, 29.9, 26.5, 25.9, 18.4. IR
(neat, cmꢁ1): 3350, 2969, 1596, 1494, 1451, 1377, 1236, 1112, 1022,
970, 746, 695. HRMS calcd (found) for C20H24O2 (Mþ): 296.1776
(296.1774).
(1)AuCl (5 mol %)
OH
AgOTf (5 mol %)
Me
+
OBz
20
BzO
Me
23 °C
3a
2
Scheme 1.

1798
Z. Zhang et al. / Tetrahedron 65 (2009) 1794–1798
(19a), 7.42 (19b), 7.48 (20a), and 7.55 (20b) min (Scheme 1). Col-
umn chromatography of the crude reaction mixture (hexanes–
EtOAc¼15:1/10:1) gave one fraction that contained a 1:1 mixture
of 19a and 19b (27 mg, 23% yield) and a second fraction that con-
tained a 1:1 mixture of 20a and 20b (18 mg, 15% yield). 1H NMR
analysis of 19 and 20 was consistent with diastereomeric mixtures
of regioisomeric diallyl ether derivatives (see below). No parent ion
peak was observed for either 19 or 20 via EIMS owing to facile
fragmentation about the allylic C–O bonds. Rather, key fragments
observed in the EIMS were m/z¼273.1 (MþꢁOBz) and 189.1
[MþꢁOCH(Me)C(H)]C(H)CH2OBz] (see below).
References and notes
1. Haggins, J. Chem. Eng. News 1993, May 31, 23–27.
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The assignment of 20 was supported through independent
synthesis (Scheme 1).
A
mixture of (1)AuCl (2.2 mg,
3.6ꢂ10ꢁ3 mmol) and AgOTf (0.9 mg, 3.6ꢂ10ꢁ3 mmol) in dioxane
(0.2 mL) was stirred at room temperature for 5 min, treated with
a solution of 2 (13.5 mg, 0.072 mmol) and 3a (15 mg, 0.072 mmol)
in dioxane (0.3 mL), and stirred at room temperature for 12 h.
Column chromatography of the crude reaction mixture (hexanes–
CH2Cl2¼1:1/1:2) gave 20 (5 mg, 18%) as a 1:1 mixture of di-
astereomers. The GC and 1H NMR spectra of 20 formed from
regioselective hydroalkoxylation of 2 with 3a14 were identical to
those of 20 isolated from the gold(I)-catalyzed hydration of 2.
For 19: 1H NMR:
d 8.07–8.03 (m, 4H), 7.59–7.53 (m, 2H), 7.47–
7.41 (m, 4H), 5.90–5.70 (m, 4H), [4.83 (d, J¼5.2 Hz), 4.80 (d,
J¼4.4 Hz), 1:1, 4H], [4.06 (q, J¼6.4 Hz), 4.00 (q, J¼6.4 Hz), 1:1, 2H],
[1.25 (d, J¼6.4 Hz), 1.24 (d, J¼6.8 Hz), 1:1, 6H]. The EIMS displayed
12. Padwa, A.; Filipkowski, M. A.; Meske, M.; Murphree, S. S.; Watterson, S. H.; Ni,
Z. J. Org. Chem. 1994, 59, 588–596.
13. (a) Patil, N. T.; Pahadi, N. K.; Yamamoto, Y. Can. J. Chem. 2005, 83, 569–573; (b)
Kim, I. S.; Krische, M. J. Org. Lett. 2008, 10, 513–515; (c) Schulz, M. J.; Teles, H.
(BASF AG). WO-A1 9721648, 1997; Chem. Abstr. 1997, 127, 121499.
14. Zhang, Z.; Widenhoefer, R. A. Org. Lett. 2008, 10, 2079–2081.
15. Saito, S.; Dobashi, N.; Wakatsuki, Y. Chem. Lett. 2005, 34, 504–505.
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three
major
peaks
at
m/z¼273.1
[MþꢁOBz],
189.1
[MþꢁOCH(Me)C(H)]C(H)CH2OBz], and 105.0 [OBz].
For 20: 1H NMR:
d 8.07–8.02 (m, 4H), 7.59–7.49 (m, 2H), 7.46–
7.36 (m, 4H), 5.90–5.70 (m, 3H), [5.45 (qdd, J¼2.0, 7.2, 15.6 Hz), 5.40
(qdd, J¼2.0, 7.2, 15.6 Hz), 1:1, 1H], 4.81 (m, 1H), 4.72 (d, J¼5.6 Hz,
1H), [4.37–4.11 (m), 4.04 (q, J¼6.8 Hz) 1:1, 4H], [1.74 (dd, J¼1.6,
6.4 Hz), 1.70 (dd, J¼1.6, 6.8 Hz), 1:1, 3H], [1.26 (dd, J¼1.6, 6.8 Hz),
1.26 (m), 1:1, 3H]. The EIMS displayed two major peaks at m/z
¼189.1 [MþꢁOCH(Me)C(H)]C(H)CH2OBz] and 105.0 [OBz].
Acknowledgements
Acknowledgment is made to the NSF (CHE-0555425), NIH (GM-
080422), and Johnson & Johnson for support of this research.