Gold(I)-catalyzed addition of thiols and thioacids to 3,3-disubstituted cyclopropenes

Article abstract of DOI:10.1021/jo300930c

Gold(I)-catalyzed reactions of thiols, thiophenols, and thioacids with 3,3-disubstituted cyclopropenes occur in a regioselective and chemoselective manner to produce either vinyl thioethers or primary allylic thioesters in good yields. A survey of commonly used gold(I) catalysts shows Echavarren's cationic gold(I) catalyst to be most tolerant of deactivation by sulfur. A novel digold with bridging thiolate complex is characterized by X-ray crystallography, shedding light on a possible deactivation pathway.

Full text of DOI:10.1021/jo300930c

Note
pubs.acs.org/joc
Gold(I)-Catalyzed Addition of Thiols and Thioacids to 3,3-
Disubstituted Cyclopropenes
Richard J. Mudd, Paul C. Young, James A. Jordan-Hore, Georgina M. Rosair, and Ai-Lan Lee*
Institute of Chemical Sciences, Heriot-Watt University, Edinburgh, EH14 4AS, United Kingdom
S
* Supporting Information
ABSTRACT: Gold(I)-catalyzed reactions of thiols, thiophenols,
and thioacids with 3,3-disubstituted cyclopropenes occur in a
regioselective and chemoselective manner to produce either vinyl
thioethers or primary allylic thioesters in good yields. A survey of
commonly used gold(I) catalysts shows Echavarren’s cationic
gold(I) catalyst to be most tolerant of deactivation by sulfur. A
novel digold with bridging thiolate complex is characterized by X-ray crystallography, shedding light on a possible deactivation
pathway.
hioethers are of academic and industrial importance
because the thioether linkage is present in many
(both primary and tertiary) are employed as nucleophiles with
catalyst 17, it is the vinyl thioethers 16c−e that are formed
exclusively and in good yields (entries 7−9). It is interesting to
note that reactions with aliphatic thiols are slower than with
thioacids or thiophenol (1−20 h vs <30 min), even though
aliphatic thiols are more nucleophilic, suggesting that some
degree of catalyst deactivation by sulfur is taking place.
To our delight, even thiols bearing pendant nucleophilic
groups react very selectively at the S-position (entries 10−12).
Furfuryl mercaptan, for example, reacts selectively at the thiol
end to produce solely 16f (entry 10), a result that was initially
very surprising, as furans are known to react with cyclopropenes
in a facile manner (<2 min with 0.01 mol % of 17).7e Similarly,
2-mercaptoethanol and 3-mercaptopropionic acid both react
selectively at the S-position (entries 11−12). These results
clearly indicate that thiols reduce the activity of gold(I) to an
extent that other usually reactive nucleophiles such as furans
and alcohols are now no longer reactive under these conditions,
allowing the thiol end of the nucleophile to react chemo-
selectively.
For comparison, the in situ formed N-heterocyclic carbene
(NHC) catalysts13 (IPr)AuSbF6 and (IPr)AuOTf as well as
PPh3AuSbF6 were investigated (entries 13−17). With thioacetic
acid, (IPr)AuSbF6 and PPh3AuSbF6 appear to be comparable to
PPh3AuNTf2 as a catalyst, although small amounts of 16b are
now formed (entries 13 and 15 vs. entry 2). Changing the
counterion ((IPr)AuOTf, entry 14) seems to have a larger
effect on the product distribution, forming predominantly 14b
but with an inseparable side product present. Since using
thiophenol as a nucleophile completely deactivates catalyst 12
(entry 3) but not catalyst 17 (entry 7), we were keen to
investigate how other catalysts compared. While 16c is
successfully produced using (IPr)AuSbF6 and PPh3AuSbF6,
∼60% of a cyclopropane side-product 1114 is also observed
T
pharmaceuticals, natural products and synthetic intermediates.1
Despite the importance of sulfur-containing molecules, the
formation of C−S bonds is not investigated as much as C−C,
C−O and C−N bonds. For example, reports using thiols as
nucleophiles with late transition metals are nowhere near as
numerous as with other nucleophiles, because sulfur is known
to deactivate/poison late transition metal catalysts.2 In the
burgeoning field of homogeneous gold-catalysis, for example,
successful reports of thiols as nucleophiles are relatively
scarce.3−6
One of the research efforts within our group is to explore the
diverse chemistry of gold-catalyzed reactions with cyclo-
propenes.7−9 While alcohols are excellent intermolecular
nucleophiles (Scheme 1),7a,c we found that reactions with N-
nucleophiles do not proceed to completion (max. 42% conv),
presumably due to catalyst deactivation by the N-nucleophile
(Scheme 1). We were thus very keen to see how S-
nucleophiles, known strong coordinators to gold,10 would
compare. Despite the initial presumption that S-nucleophiles
would fare worse than N-nucleophiles, we are pleased to report
that the reactions are in fact mild and facile, providing 4 or 5 in
good yields, regioselectivity and chemoselectivity (Scheme 1).
Following initial optimization studies (see the Supporting
Information), we proceeded to investigate a selection of
different thioacid and thiol nucleophiles (Table 1). While
thiobenzoic and thioacetic acids produce 14a and 14b
regioselectively as the major products (entries 1−2), the
more nucleophilic thiophenol and benzyl thiol fail to react
when PPh3AuNTf2 1211 is used as a catalyst, presumably due to
catalyst deactivation by these thiols (entries 3−4). Echavarren’s
catalyst 17,12 on the other hand, appears far more tolerant of
thiols; catalytic activity is observed in the presence of a wide
range of thiols (entries 5−12). However, when 17 is used as a
catalyst with thioacids as nucleophiles, the product distribution
changes, and the vinyl thioesters 16 begin to be observed as
side products (entries 5−6). In fact, when thiophenol and thiols
Received: May 15, 2012
Published: July 29, 2012
© 2012 American Chemical Society
7633
dx.doi.org/10.1021/jo300930c | J. Org. Chem. 2012, 77, 7633−7639

The Journal of Organic Chemistry
Note
Scheme 1. Comparison with O- and N-Nucleophiles
Table 1. Screen of Thiol Nucleophiles and Gold Catalysts
a
b
c
1
Determined by H NMR analysis. Unreacted starting material, 11, and other minor unidentified products observed in crude NMR. 16:1 E:Z.
d
e
f
g
>20:1 E:Z. (IPr) = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidine. Unidentified inseparable side-product present. 11 present in ∼60%.
(entries 16 and 17). Changing the counterion to a more
coordinating tosylate, however, changes the outcome of the
reaction, producing no desired product 16c at all (entry 18).
Thus, we conclude that among the catalysts investigated in this
study, it is the identity of the counterion rather than the ligand
that causes the complete deactivation of the gold catalyst in the
presence of thiophenol, with slightly more coordinating anions
Cyclopropenes 24 and 25, with ester as one of the substituents,
do not react under these conditions (entries 8−9, rt or 70 °C),
not even to form the previously reported gold-catalyzed
intramolecular rearrangement to butenolide.7a,g,9b These results
suggest that the gold catalyst in the presence of thiol is not
active enough to catalyze the ring-opening of less reactive7e
cyclopropenes 24 and 25.
Next, a similar screen was carried out with thiophenol as a
nucleophile to produce 16 (entries 10−17, Table 2). Pleasingly,
the reaction with thiophenol proceeds very cleanly and in good
yields with cyclopropenes 13, 18−19, 22−23 to produce 16
with excellent E-selectivity (entries 10−14). Interestingly,
benzyl substituents do not seem to be tolerated under these
conditions when thiophenol is used as a nucleophile (entries
15−16); a complex mixture of products is observed. We
suspect that this is a result of further reaction/decomposition of
the expected vinyl thioether products 16, which so happen to
be unstable when a combination of a benzyl substituent and an
arylthioether are present. Indeed, when cyclopropene 20 is
subjected to a different thiol (furfuryl mercaptan), the reaction
now proceeds to yield 16s (1H NMR analysis of the crude
mixture, entry 17), but product 16s decomposes upon
(NTf2 and OTs−) faring worse than the very weakly
−
−
coordinating SbF6 . From these results, 12 was chosen as the
optimal catalyst when thioacids are used as nucleophiles to form
14 selectively, while 17 was chosen as the optimal catalyst for
thiophenol and alkyl thiols to form 16 selectively.
Next, we proceeded to explore the cyclopropene substrate
scope. Thiobenzoic acid adds to a range of 3,3-disubstituted
cyclopropenes to produce allylic thioesters 14a, 14i−n in good
yields and generally good selectivity for the primary 14 (vs.
tertiary 15) allylic thioesters (entries 1−7, Table 2).15 As
expected, the E:Z ratio, where applicable, is good when the
substituents R1 and R2 are sterically different (e.g., entry 6), but
poor when they are sterically similar (entries 1, 3−4). Another
trend to note is that small amounts of 16 begin to be observed
when both substituents are bulky (entries 5 and 7).
7634
dx.doi.org/10.1021/jo300930c | J. Org. Chem. 2012, 77, 7633−7639

The Journal of Organic Chemistry
Note
Table 2. Cyclopropene Scope with Thiobenzoic Acid or Thiophenol As Nucleophile
a
b
c
d
e
f
Determined by 1H NMR analysis. ClCH2CH2Cl used as solvent, 70 °C. No reaction at rt. 24 + Complex mixture. Complex mixture. Product
decomposes upon purification.
Scheme 2. Plausible Mechanistic Pathways to 14 and 16
standing/purification, resulting in a low 27% yield. This result
suggests that a benzyl substituent on the cyclopropene is not an
inherent problem in the gold-catalyzed reaction, but the vinyl
thioethers 16 formed from it are unstable, thereby forming a
complex mixture of decomposition products.
thiophenol:17 were investigated by NMR. Both show almost
instantaneous conversion to a new complex [31P NMR
(CD2Cl2) 57.3 ppm for 17, 62.9 ppm for new complex],14
and recrystallization produces novel complex 28 (confirmed by
X-ray crystallography, Scheme 4). Isolated complex 28 provides
The proposed mechanism (Scheme 2) shows that 14 can be
obtained from thioacid/thiol attack at the C-1 position on
intermediate I,7g,9f,g followed by protodemetalation. The vinyl
thioether/ester 16 can be produced either via isomerization of
14 (path a), or SE′ directly16 from II (path b). A deuterium-
labeling study with deuterated thiophenol 27 resulted in D-
incorporation at the C-3 position only (Scheme 3), implying
Scheme 4. Novel Digold−Thiolate Complex 28
Scheme 3. Deuterium Studies
only 6% conversion to 16c when used as a catalyst, implying
that such species are not efficient precatalysts for the reaction,17
but may be a possible mode of deactivation in gold(I)-catalyzed
reactions with thiols.
In conclusion, we have shown that various thiol S-
nucleophiles react in a mild and facile manner to produce
either 14 or 16 in good yields and selectivities. Echavarren’s
catalyst 17 appears more tolerant of deactivation by thiols
compared to other gold(I) catalysts screened, and analysis of 17
in the presence of thiophenol led to the characterization of a
novel digold−thiolate species 28, which sheds light on a
that path b operates. Furthermore, when 14a is resubjected to
the reaction conditions, no isomerization to 16a is observed,
further implying that 16 must be formed through path b.
Finally, in order to shed light on the interaction between the
Au(I) catalyst and thiols, which causes the observed dampening
of catalyst activity, a 20:1 as well as a 1:1 mixture of
7635
dx.doi.org/10.1021/jo300930c | J. Org. Chem. 2012, 77, 7633−7639

The Journal of Organic Chemistry
Note
g, 6.57 mmol, 88%) as a colorless oil: νmax/cm−1 2958 m 2921 s 2853
possible mode of deactivation by thiols. Pleasingly, the
dampening of catalyst activity in the presence of thiols allows
for very chemoselective thiol additions in the presence of other
nucleophilic functional groups. We hope that our successful
results presented here and in particular our investigations into
the activity of various commonly used gold(I) catalysts will
open the door for more future work on gold-catalyzed C−S
bond formations.
1
m (C−H), 1629 w (CC) 1457 m (alkyl C−H bend); H NMR
(300 MHz, CDCl3) δ 7.28 (s, 2H), 1.47−0.97 (m, 20H), 0.87 (t, J =
6.9 Hz, 6H); 13C NMR (75 MHz, CDCl3) δ 120.1 (CH), 38.8 (CH2),
32.2 (CH2), 29.6 (CH2), 27.2 (CH2), 24.8 (C), 22.9 (CH2), 14.3
(CH3); HRMS (APCI-Orbitrap) m/z calcd for C15H29 [M + H]+
209.2264, found 209.2258.
Representative Procedure for Gold-Catalyzed Aniline
Additions to 3,3-Disubstituted Cyclopropenes to Form tert-
Allylic Amines 3. 4-Methoxy-N-(2-methyl-1-phenylbut-3-en-2-yl)-
aniline (3, R1 = Me, R2 = Bn, Ar = p-OMeC6H4). To a stirred solution
of cyclopropene 20 (17.3 mg, 0.12 mmol) and anisidine (12.3 mg,
0.10 mmol) in CH2Cl2 (1 mL, 0.1 M), catalyst 17 was added in one
portion (3.8 mg, 0.0051 mmol, 5 mol %). The resultant yellow
solution was stirred for 18 h, after which point it had become dark
yellow/brown. The mixture was then evaporated to dryness (1H NMR
analysis shows 42% conv), and the residue was purified by flash
column chromatography (petrol ether:EtOAc, 9:1) to give the title
compound as a yellow film (9 mg, 0.034 mmol, 34%): νmax/cm−1 3391
w (N−H) 2929 w (C−H), 1602 w (CC), 1508 s (Ar CC), 1234
EXPERIMENTAL SECTION
■
The gold(I)-catalyzed reactions were carried out without the need for
dry solvents or inert atmosphere, except for the deuterium labeling
study (Scheme 3). 3,3-Disubstituted cyclopropene substrates 18−25
were synthesized following previously reported procedures.7a,b,f,18
The following three-step procedure describes the synthesis of 13 via
29 and 30.
1,1-Dibromo-2,2-dihexylcyclopropane 29. A solution of
bromoform (2.4 mL, 26.5 mmol) in CH2Cl2 (0.6 mL) was added
dropwise over 30 min to a stirring mixture of aqueous sodium
hydroxide (5.8 mL, 10 M), alkyltrimethylammonium bromide (0.54
g), 7-methylenetridecane (2.59 g, 13.2 mmol) and CH2Cl2 (2.5 mL).
The mixture was allowed to stir vigorously at 35 °C overnight. The
reaction mixture was then diluted with water (30 mL), CH2Cl2 (40
mL) was added, and the layers were partitioned. The aqueous layer
was washed twice with CH2Cl2 (40 mL). The combined organic layers
were washed with brine (60 mL), dried over MgSO4 and concentrated
under reduced pressure. The resulting material was purified by flash
column chromatography (hexane), and the remaining bromoform was
evaporated under high vacuum (21 h, 35 °C) to yield the title
compound (4.33 g, 11.7 mmol, 89%) as a colorless oil: νmax/cm−1
2954 m 2925 s 2857 m (C−H), 1457 m (alkyl C−H bend); 1H NMR
(300 MHz, CDCl3) δ 1.73−1.19 (m, 22H), 0.95−0.83 (m, 6H); 13C
NMR (75 MHz, CDCl3) δ 40.3 (C), 35.1 (CH2), 34.4 (CH2), 33.3
(C), 31.9 (CH2), 29.5 (CH2), 26.3 (CH2), 22.8 (CH2), 14.2 (CH3);
HRMS (APCI-Orbitrap) m/z calcd for C15H29Br2 [M + H]+ 367.0631,
found 367.0627.
2-Bromo-1,1-dihexylcyclopropane 30. A solution of ethyl-
magnesium bromide (1.0 M in THF, 13 mL, 13 mmol) was added
over 1.5 h to a stirring solution of 1,1-dibromo-2,2-dihexylcyclopro-
pane (4.00 g, 10.9 mmol), Ti(OiPr)4 (0.33 mL, 1.09 mmol) and THF
(35 mL). The solution was allowed to stir for an additional 3 h at
room temperature. The reaction was quenched by slow addition of
water (35 mL), and then 20% aqueous sulfuric acid (80 mL) was
added, and the resulting mixture was stirred for 30 min. Diethyl ether
(70 mL) was added, and the layers were partitioned. The aqueous
layer was washed a further two times with diethyl ether (70 mL). The
combined organic layers were washed with saturated sodium
bicarbonate (90 mL) and brine (90 mL), dried over MgSO4 and
concentrated under reduced pressure. The crude material was purified
by flash column chromatography (pentane) to yield the title
compound (2.34 g, 8.09 mmol, 74%) as a colorless oil: νmax/cm−1
2956 m 2925 s 2857 m (C−H), 1458 m (alkyl C−H bend); 1H NMR
(300 MHz, CDCl3) δ 2.82 (dd, J = 7.6, 4.3 Hz, 1H), 1.58−1.14 (m,
20H), 0.97−0.81 (m, 7H,), 0.60 (dd, J = 6.0, 4.3 Hz, 1H); 13C NMR
(75 MHz, CDCl3) δ 35.5 (CH2), 33.3 (CH2), 32.0 (CH2), 32.0
(CH2), 30.3 (CH), 29.7 (CH2), 29.6 (CH2), 26.3 (CH2), 26.1 (CH2),
25.0 (C), 22.8 (CH2), 22.8 (CH2), 22.2 (CH2), 14.3 (CH3), 14.2
(CH3); HRMS (APCI-Orbitrap) m/z calcd for C15H30Br [M + H]+
289.1525, found 289.1518.
1
m (C−O−C); H NMR (400 MHz, CDCl3) δ 7.31−7.18 (m, 3H),
7.16−7.08 (m, 2H), 6.76−6.64 (m, 4H), 6.06 (dd, J = 17.5, 10.8 Hz,
1H), 5.20−5.10 (m, 2H), 3.73 (s, 3H), 3.40 (br s, 1H), 3.12 (d, J =
13.1 Hz, 1H), 2.81 (d, J = 13.1 Hz, 1H), 1.23 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 152.6 (C), 145.8 (CH), 140.2 (C), 137.1 (C), 130.9
(CH), 127.9 (CH), 126.5 (CH), 118.3 (CH), 114.3 (CH), 113.7
(CH2), 57.8 (C), 55.7 (CH3), 45.6 (CH2), 25.3 (CH3). HRMS
(APCI-Orbitrap) m/z calcd for C18H22ON [M]+ 268.1696, found
268.1691.
Representative Procedure for Gold-Catalyzed Thioacid
Additions to 3,3-Disubstituted Cyclopropenes to Form Allylic
Thioester 14. S-3-Hexylnon-2-enyl Benzothioate 14a. A solution of
thiobenzoic acid (7.5 μL, 8.7 mg, 0.064 mmol) and PPh3AuNTf2 (2:1
toluene complex, 2.3 mg, 0.0031 mmol) in CH2Cl2 (0.31 mL) was
added to a solution of 3,3-dihexylcycloprop-1-ene 13 (13 mg, 0.062
mmol) in CH2Cl2 (0.31 mL) at 25 °C and stirred for 10 min. The
solution was then concentrated under reduced pressure and filtered
through a plug of silica (hexane:Et2O, 10:1). The crude mixture was
then purified using flash column chromatography (hexane:Et2O, 50:1)
to yield a 9:1 ratio of 14a:15a (17.2 mg, 0.0496 mmol, 80%) as a clear
colorless oil: νmax/cm−1 2955 w (C−H), 2925 m (C−H), 2855 w (C−
1
H), 1662 s (CO); 1597 w, 1581 w, 1448 m (Ar CC); H NMR
(300 MHz, CDCl3) δ 8.06−7.40 (m, 5H), 5.31 (t, J = 7.7 Hz, 1H),
3.78 (d, J = 7.7 Hz, 2H), 2.19−2.09 (t, J = 7.5 Hz, 2H), 2.09−1.98 (t, J
= 7.4 H, 2H), 1.50 - 1.23 (m, 16H), 0.99 - 0.82 (m, 6H); 13C NMR
(75 MHz, CDCl3) δ 192.3 (C), 145.4 (C), 137.2 (C), 133.2 (CH2),
128.6 (CH), 127.2 (CH), 118.0 (CH), 36.9 (CH2), 31.8 (CH2), 31.8
(CH2), 30.3 (CH2), 29.7 (CH2), 29.1 (CH2), 28.6 (CH2), 27.9 (CH2),
27.2 (CH2), 22.6 (CH2), 22.6 (CH2), 14.1 (2 x CH3); HRMS (ESI-
Orbitrap) m/z calcd for C22H35OS [M + H]+ 347.2406, found
347.2403.
S-3-Hexylnon-2-enyl Ethanethioate 14b. Clear colorless oil (13.8
mg, 76%, 9:1 14b:15b): νmax/cm−1 2956 w (C−H), 2926 m (C−H),
2856 w (C−H), 1683 s (C−H); 1H NMR (300 MHz, CDCl3) δ 5.20
(t, J = 8.0 Hz, 1H), 3.57 (d, J = 8.0 Hz, 2H), 2.39−2.29 (s, 3H), 2.06
(t, J = 7.4 Hz, 2H), 2.00 (t, J = 7.4 Hz, 2H), 1.45−1.18 (m, 16H),
1.00−0.82 (m, 6H); 13C NMR (75 MHz, CDCl3) δ 196.3 (C), 145.1
(C), 118.1 (CH), 36.9 (CH2), 31.92 (CH2), 31.88 (CH2), 30.6 (CH3),
30.3 (CH2), 29.6 (CH2), 29.2 (CH2), 28.6 (CH2), 28.0 (CH2), 27.3
(CH2), 22.7 (CH2), (plus an overlapping peak), 14.3 (2 x CH3);
HRMS (APCI-Orbitrap) m/z calcd for C17H33OS [M + H]+ 285.2247,
found 285.2249.
(E/Z)-S-3-Methyldodec-2-enyl Benzothioate 14i. Clear colorless
oil (17.2 mg, 67%, 6:1 ratio 14i:15i and approximately 1.25:1 E:Z ratio
of 14i): νmax/cm−1 2923 s (C−H), 2853 m (C−H), 1661 s (CO),
1597 w, 1582 w, 1448 m (Ar CC); 1H NMR (300 MHz, CDCl3) δ
8.04 - 7.38 (m, 5H),, 5.39−5.30 (m, 1H), 3.76 (d, J = 8.1 Hz, 2H),
2.22−2.09 (m, (E) 2H), 2.09−1.98 (m, (Z) 2H′), 1.76 (s, 3H) 1.52−
1.16 (m, 14H), 0.98−0.82 (m, 3H); 13C NMR (75 MHz, CDCl3) δ
192.2 (2xC), 141.3 (C), 141.0 (C), 137.2 (C), 137.1 (C), 133.2
3,3-Dihexylcycloprop-1-ene 13.19 Potassium tert-butoxide (1.44
g, 12.8 mmol) was dissolved in DMSO (20 mL). 2-Bromo-1,1-
dihexylcyclopropane 30 (2.30 g, 7.95 mmol) was added dropwise over
15 min. The reaction mixture was allowed to stir overnight at 55 °C
and then quenched by addition of water (100 mL). Pentane (100 mL)
was added and the layers partitioned. The aqueous layer was washed
four times with pentane (50 mL). The combined organic layers were
washed three times with brine (50 mL), dried over MgSO4 and
concentrated under reduced pressure. The resulting material was
purified by flash column chromatography (pentane) to yield 13 (1.37
7636
dx.doi.org/10.1021/jo300930c | J. Org. Chem. 2012, 77, 7633−7639

The Journal of Organic Chemistry
Note
(2xCH), 128.6 (2x CH), 127.2 (2xCH), 118.6 (CH), 118.0 (CH),
40.1 (CH2), 39.6 (CH2), 31.9 (2xCH2), 31.9 (2xCH2), 29.6 (2xCH2),
29.4 (CH2), 29.2 (2xCH2), 28.1 (CH2), 27.7 (CH2), 27.3 (CH2), 27.1
(CH2), 23.5 (CH3), 22.7 (2xCH2), 16.2 (CH3), 14.1 (2xCH3); HRMS
(ESI-Orbitrap) m/z calcd for C20H31OS [M + H]+ 319.2090, found
319.2094.
(CH2); HRMS (ESI-Orbitrap) m/z calcd for C22H31OS [M + H]+
343.2090, found 343.2094.
Representative Procedure for Gold-Catalyzed Thiophenol
or Thiol Additions to 3,3-Disubstituted Cyclopropenes to
Form Vinyl Thioether 16. (E)-(3-Hexylnon-1-enyl)(phenyl)sulfane
16c. A solution of thiophenol (7 μL, 8.1 mg, 0.065 mmol) and catalyst
17 (2.5 mg, 0.0033 mmol) in CH2Cl2 (0.33 mL) was added to a
solution of 3,3-dihexylcycloprop-1-ene 13 (13.6 mg, 0.065 mmol) in
CH2Cl2 (0.32 mL) at 25 °C and stirred for 30 min. The solution was
then concentrated under reduced pressure and filtered through a plug
of silica (hexane:Et2O, 10:1). The crude mixture was then purified
using flash column chromatography (hexane:Et2O, 50:1) to yield (E)-
(3-hexylnon-1-enyl)(phenyl)sulfane 16c (15 mg, 0.047 mmol, 72%) as
a clear colorless oil: νmax/cm−1 2955 m (C−H), 2923 s (C−H), 2853
m (C−H), 1584 w, 1479 m, 1466 m (Ar CC); 1H NMR (300 MHz,
CDCl3) δ 7.41−7.12 (m, 5H), 6.10 (d, J = 14.9 Hz,1H), 5.79 (dd, J =
9.2, 14.9 Hz, 1H), 2.20−2.07 (m, 1H), 1.51−1.19 (m, 20H), 1.00−
0.83 (m, 6H); 13C NMR (75 MHz, CDCl3) δ 143.1 (CH), 137.0 (C),
129.9 (CH), 128.1 (CH), 125.9 (CH), 119.9 (CH), 43.8 (CH), 35.1
(CH2), 31.9 (CH2), 29.4 (CH2), 27.3 (CH2), 22.7 (CH2), 14.2
(CH3); HRMS (APCI-Orbitrap) m/z calcd for C21H35S [M + H]+
319.2454, found 319.2455.
(E/Z)-S-3-Methyl-5-phenylpent-2-enyl Benzothioate 14j. Clear
colorless oil (16.9 mg, 63%, mixture: 6:1 ratio 14j:15j and ∼1:1 E:Z
ratio of 14j): νmax/cm−1 2923 s (C−H), 2853 m (C−H), 1661 s (C
1
O), 1597 vw, 1581 w, 1447 m (Ar CC); H NMR (300 MHz,
CDCl3) δ 8.08−7.39 (m, 5H + 5H′ (E and Z)), 7.39−7.05 (m, 5H +
5H′), 5.41−5.33 (m, 1H + 1H′), 3.76 (d, J = 8.1 Hz, (Z) 2H), 3.70−
3.53 (d, J = 8.4 Hz, (E) 2H′), 2.88−2.66 (m, 2H + 2H′), 2.56 - 2.22
(m, 2H + 2H′), 1.93−1.69 (m, 3H + 3H′); 13C NMR (75 MHz,
CDCl3) δ 192.2 (C), 192.1 (C), 141.9 (C), 141.8 (C), 139.9 (C),
139.7 (C), 137.1 (C), 137.1 (C), 132.2 (2xCH), 128.6 (CH), 128.5
(CH), 128.4 (CH), 128.4 (2xCH), 128.3 (CH), 126.2 (2xCH), 124.9
(CH), 124.8 (CH), 119.9 (CH), 119.0 (CH), 40.4 (CH2), 33.3
(2xCH2), 33.1 (CH2), 27.2 (CH2), 26.9 (CH2), 22.5 (CH3), 16.5
(CH3); HRMS (ESI-Orbitrap) m/z calcd for C19H21OS [M + H]+
297.1308, found 297.1313.
(E/Z)-S-3-Methyl-4-phenylbut-2-enyl Benzothioate 14k. Clear
colorless oil (15.3 mg, 62%, 14:1 ratio 14k:15k and 1.7:1 E:Z ratio
of 14k): νmax/cm−1 3061 vw (C−H), 3026 w (C−H), 2914 w (C−H),
1657 s (CO), 1598 w, 1580 w, 1447 m (Ar CC); 1H NMR (300
MHz, CDCl3) δ 8.08−7.40 (m, 5H + 5H′), 7.40−7.11 (m, 5H + 5H′),
5.59−5.43 (m, 1H + 1H′), 3.90 (d, J = 8.1 Hz, (Z) 2H), 3.81 (d, J =
7.7 Hz, (E) 2H′), 3.54 (s, (Z) 2H), 3.36 (s, (E) 2H′), 1.79−1.66 (6H,
m, 3H + 3H′); 13C NMR (75 MHz, CDCl3) δ 192.1 (C), 192.1 (C),
139.7 (C), 139.5 (C), 139.2 (C), 139.0 (C), 137.1 (C), 137.1 (C),
133.3 (CH), 133.3 (CH), 128.9 (CH), 128.7 (CH), 128.6 (CH),
128.5 (CH), 128.3 (CH), 127.3 (CH), 127.2 (CH), 126.2 (CH),
126.1 (CH), 120.5 (CH) (plus overlapping peaks), 46.0 (CH2), 37.9
(CH2), 27.3 (CH2), 27.3 (CH2), 23.4 (CH3), 16.1 (CH3); HRMS
(ESI-Orbitrap) m/z calcd for C18H19OS [M + H]+ 283.1151, found
283.1155.
(E)-Benzyl(3-hexylnon-1-enyl)sulfane 16d. Clear colorless oil
(17.3 mg, 81%): νmax/cm−1 2955 m (C−H), 2925 s (C−H), 2853
m (C−H), 1602 w, 1494 w, 1453 m (Ar CC); 1H NMR (300 MHz,
CDCl3) δ 7.46−7.18 (m, 5H), 5.84 (d, J = 15.0 Hz, 1H), 5.43 (dd, J =
9.0, 15.0 Hz, 1H), 3.99−3.81 (m, 2H), 2.04−1.88 (m, 1H), 1.44−1.01
(m, 20H), 0.91 (t, J = 6.8 Hz, 6H); 13C NMR (75 MHz, CDCl3) δ
137.0 (CH), 136.9 (CH), 127.7 (CH), 127.4 (CH), 125.9 (CH),
120.0 (CH), 42.7 (CH), 36.7 (CH2), 34.3 (CH2), 30.8 (CH2), 28.4
(CH2), 26.1 (CH2), 21.7 (CH2), 13.1 (CH2); HRMS (APCI-
Orbitrap) m/z calcd for C22H37S [M + H]+ 333.2610, found 333.2613.
(E)-tert-Butyl(3-hexylnon-1-en-1-yl)sulfane 16e. Clear colorless oil
(18.1 mg, 84%): νmax/cm−1 2956 m 2925 s 2854 s (C−H), 1601 w
1
(CC); H NMR (300 MHz, CDCl3) δ 5.98 (d, J = 14.8 Hz, 1H),
5.63 (dd, J = 14.8, 9.2 Hz, 1H), 2.10−1.93 (m, 1H), 1.32 (s, 9H),
1.47−1.08 (m, 20H), 0.87 (t, J = 6.7 Hz, 6H); 13C NMR (75 MHz,
CDCl3) δ 143.8 (CH), 119.1 (CH), 44.0 (CH), 43.7 (C), 35.4 (CH2),
32.0 (CH2), 30.9 (CH3), 29.5 (CH2), 27.4 (CH2), 22.8 (CH2), 14.3
(CH3). HRMS (APCI-Orbitrap) m/z calcd for C19H39S [M + H]+
299.2767, found 299.2771.
(E/Z)-S-3-Benzyl-4-methylpent-2-enyl Benzothioate 14l. Clear
colorless oil (14.8 mg, 73%, 13:2:1 ratio 14l:15l:16l and 1:3 E:Z
ratio of 14l): νmax/cm−1 3060 vw (C−H), 3025 vw (C−H), 2960 w
(C−H), 2927 w (C−H), 2870 vw (C−H), 1660 s (CO), 1598 w,
1
1580 w, 1447 m (Ar CC); H NMR (300 MHz, CDCl3) δ 8.04−
(E)-2-(((3-Hexylnon-1-en-1-yl)thio)methyl)furan 16f. Yellow oil
7.43 (m, 5H + 5H′), 7.37−7.14 (m, 5H + 5H′), 5.58 (t, J = 7.9 Hz,
1H′ (E)), 5.10 (t, J = 8.1 Hz, 1H (Z)), 3.87−3.79 (m, 2H + 2H′), 3.60
(s, 2H′(E)), 3.36 (s, 2H (Z)), 3.11−2.99 (m, 1H (Z)), 2.32−2.21 (m,
1H′ (E)), 1.07 (d, J = 6.9 Hz, 6H (Z)), 1.02 (d, J = 6.9 Hz, 6H′ (E));
13C NMR (75 MHz, CDCl3) δ 192.1 (C), 192.0 (C), 149.4 (C), 148.3
(C), 140.1 (C), 139.7 (C), 137.3 (C), 137.1 (C), 133.3 (CH), 133.3
(CH), 131.0 (CH), 129.4 (CH), 128.2 (CH), 127.2 (CH), 126.0
(CH), 126.0 (CH), 119.8 (CH), 118.3 (CH), (plus overlapping
peaks), 38.1 (CH2), 35.3 (CH2), 34.0 (CH), 29.3 (CH), 27.5 (CH2),
26.6 (CH2), 21.9 (CH3), 21.4 (CH3); HRMS (ESI-Orbitrap) m/z
calcd for C20H23OS [M + H]+ 311.1464, found 311.1470.
(20.3 mg, 86%): νmax/cm−1 2957 m 2922 s, 2854 m (C−H), 1594 w
1
(CC), 1503 m, 1458 m (Ar CC) 1010 s (C−O−C); H NMR
(300 MHz, CDCl3) δ 7.34 (dd, J = 1.9, 0.8 Hz, 1H), 6.29 (dd, J = 3.2,
1.9 Hz, 1H), 6.18 (dd, J = 3.2, 0.8 Hz, 1H), 5.84 (d, J = 15.0 Hz, 1H),
5.45 (dd, J = 15.0, 9.2 Hz, 1H), 3.83 (s, 2H), 2.03−1.90 (m, 1H),
1.45−1.07 (m, 20H), 0.88 (t, J = 6.8 Hz, 6H); 13C NMR (75 MHz,
CDCl3) δ 151.6 (C), 142.2 (CH), 138.9 (CH), 120.8 (CH), 110.5
(CH), 107.6 (CH), 43.9 (CH), 35.4 (CH2), 32.0 (CH2), 30.2 (CH2),
29.6 (CH2), 27.3 (CH2), 22.8 (CH2), 14.3 (CH3). HRMS (APCI-
Orbitrap) m/z calcd for C20H35OS [M + H]+ 323.2403, found
323.2405.
(E)-S-3-(3-(Adamantan-1-yl)but-2-enyl Benzothioate 14m. Clear
colorless oil (15.8 mg, 78%, 10:1 14m:15m): νmax/cm−1 2900 s (C−
H), 2847 m (C−H), 1660 s (CO); 1596 vw, 1581 vw, 1447 m (Ar
CC); 1H NMR (300 MHz, CDCl3) δ 8.06−7.40 (m, 5H), 5.34 (t, J
= 7.8 Hz, 1H), 3.79 (d, J = 7.8 Hz, 2H), 2.03 (br-s, 3H), 1.79−1.60
(m, 15H); 13C NMR (75 MHz, CDCl3) δ 192.4 (C), 149.1 (C), 137.2
(CH), 133.2 (CH), 128.6 (CH), 127.2 (CH), 115.3 (CH), 40.7
(CH2) 38.0 (C), 37.0 (CH2), 36.9 (CH2), 28.6 (CH), 27.7 (CH2),
11.9 (CH3); HRMS (ESI-Orbitrap) m/z calcd for C21H27OS [M +
H]+ 327.1777, found 327.1781.
(E)-2-((3-Hexylnon-1-en-1-yl)thio)ethanol 16g. Clear colorless oil
(17.1 mg, 82%): νmax/cm−1 3400−3200 br. w (O−H), 2955 m, 2921 s,
2854 s (C−H), 1606 w (CC); 1H NMR (300 MHz, CDCl3) δ 5.79
(d, J = 15.0 Hz, 1H), 5.51 (dd, J = 15.0, 9.1 Hz, 1H), 3.81−3.71 (m,
2H), 2.83 (t, J = 5.9 Hz, 2H), 2.12−1.90 (m, 2H), 1.40−1.08 (m,
20H), 0.87 (t, J = 6.7 Hz, 6H); 13C NMR (75 MHz, CDCl3) δ 139.2
(CH), 120.4 (CH), 60.7 (CH2), 43.9 (CH), 36.5 (CH2), 35.3 (CH2),
32.0 (CH2), 29.5 (CH2), 27.4 (CH2), 22.8 (CH2), 14.3 (CH3). HRMS
(APCI-Orbitrap) m/z calcd for C17H35OS [M + H]+ 287.2403, found
287.2406.
S-3,3-Dicyclohexylallyl Benzothioate 14n. Clear colorless oil (19.7
mg, 94%, 7:1 ratio of 14n:16n): νmax/cm−1 2922 s (C−H), 2849 m
(E)-3-((3-Hexylnon-1-en-1-yl)thio)propanoic Acid 16h. Clear
colorless oil (16.5 mg, 73%): νmax/cm−1 3100−2700 br. w (O−H),
1
(C−H), 1660 s (CO), 1597 vw, 1581 w, 1447 m (Ar CC); H
1
2956 m 2924 s 2854 s (C−H), 1711 s (CO), 1604 w (CC); H
NMR (300 MHz, CDCl3) δ 8.04−7.40 (m, 5H),, 5.37−5.25 (t, J = 8.1
Hz, 1H), 3.83 (d, J = 8.1 Hz, 2H), 2.01−0.98 (m, 22H); 13C NMR (75
MHz, CDCl3) δ 192.5 (C), 155.6 (C), 137.2 (C), 133.2 (CH), 128.7
(CH), 127.2 (CH), 115.8 (CH), 40.9 (CH), 40.52 (CH), 34.7 (CH2),
31.0 (CH2), 27.1 (CH2), 27.0 (CH2), 26.6 (CH2), 26.3 (CH2), 26.1
NMR (300 MHz, CDCl3) δ 10.78−9.74 (br s, 1H), 5.80 (d, J = 15.0
Hz, 1H), 5.46 (dd, J = 15.0, 9.1 Hz, 1H), 2.88 (t, J = 7.0 Hz, 2H), 2.69
(t, J = 7.0 Hz, 2H), 2.08−1.91 (m, 1H), 1.41−1.10 (m, 20H), 0.87 (t, J
= 6.7 Hz, 6H); 13C NMR (75 MHz, CDCl3) δ 178.2 (C), 139.0 (CH),
7637
dx.doi.org/10.1021/jo300930c | J. Org. Chem. 2012, 77, 7633−7639

The Journal of Organic Chemistry
Note
120.5 (CH), 43.9 (CH), 35.4 (CH2), 34.5 (CH2), 32.0, (CH2) 29.5
(CH2), 27.6 (CH2), 27.4 (CH2), 22.8 (CH2), 14.3 (CH3). HRMS
(ESI-Orbitrap) m/z calcd for C18H33O2S [M − H]− 313.2207, found
313.2198.
MHz, CDCl3) δ 7.35−7.27 (m, 4H), 7.23−7.14 (m, 1H), 6.07 (d, J =
14.9 Hz, 1H), 5.76 (dd, J = 14.9, 9.2 Hz, 1H, from nondeuterated),
5.76 (d, J = 14.9 Hz, 1H), 2.17−2.06 (m, 1H, from nondeuterated),
1.47−1.13 (m, 20H), 0.89 (t, J = 6.6 Hz, 6H); 13C NMR (100 MHz,
CDCl3) δ 143.13 (CH nondeuterated), 143.10 (CH deuterated),
137.1 (C), 129.0 (CH), 128.3 (CH), 126.0 (CH), 120.09 (CH
nondeuterated), 120.07 (CH deuterated), 43.9 (CH nondeuterated),
43.4 (t, J = 19.1 HZ, CD), 35.3 (CH2 nondeuterated), 35.2 (CH2
deuterated), 32.0 (CH2), 29.5 (CH2), 27.5 (CH2 nondeuterated), 27.4
(CH2 deuterated), 22.8 (CH2), 14.3 (CH3). HRMS (EI-ion trap) m/z
calcd for C21H33DS [M]+ 319.2439, found 319.2434.
Complex 28. Thiophenol (2.8 mg, 2.7 μL, 0.026 mmol) was added
to a solution of catalyst 17 (20 mg, 0.026 mmol) in CH2Cl2 (0.70
mL). Single crystals were grown from slow evaporation of the CH2Cl2
solution: mp 184 °C (decomposes); νmax/cm−1 2951 m 2886 w (C−
H), 1577 m 1469 m 1440 m (Aromatic CC); 1H NMR (300 MHz,
CD2Cl2) δ 7.93−7.84 (m, 2H), 7.62−7.45 (m, 6H), 7.35−7.16 (m,
11H), 7.15−7.09 (m, 4H), 1.37 (d, J(1H−31P) = 15.8 Hz, 36H); 13C
NMR (75 MHz, CD2Cl2) δ 149.8 (d, J(13C−31P) = 14.2 Hz, C), 143.3
(d, J(13C−31P) = 6.7 Hz, C), 134.4 (CH), 133.73 (d, J(13C−31P) = 7.6
Hz, CH), 133.72 (CH), 131.7 (CH), 129.9 (CH), 129.7 (CH), 129.3
(CH), 129.2 (CH), 128.5 (CH), 128.1 (CH), 128.0 (CH), 127.8 (C),
127.5 (CH), 125.8 (d, J(13C−31P) = 44.3 Hz, C), 38.5 (d, J(13C−31P)
= 23.7 Hz, C), 31.3 (d, J(13C−31P) = 6.9 Hz, CH3); 31P NMR (121
MHz, CD2Cl2) δ 62.87. Crystal Data: C46H59Au2F6P2SSb, M =
1335.61, monoclinic, a = 24.6918(3) Å, b = 13.08924(15) Å, c =
29.3558(4) Å, β = 90.7654(11)°, V = 9486.84(19) Å3, T = 120.01(10),
space group Cc (no. 9), Z = 8, μ(Cu Kα) = 17.388, 77919 reflections
measured, 19283 unique (Rint = 0.0447), which were used in all
calculations. The final wR2 was 0.0820 (all data) and R1 was 0.0313
(>2σ(I)).
(E)-(3-Methyldodec-1-enyl)(phenyl)sulfane 16o. Clear colorless oil
(14.9 mg, 84%): νmax/cm−1 2970 s (C−H), 2922 s (C−H), 1583 w,
1
1454 m, 1439 m (Ar CC); H NMR (300 MHz, CDCl3) δ 7.26−
7.39 (m, 5H), 6.05−6.21 (d, J = 15.0 Hz, 1H), 5.84 - 6.02 (dd, J =
15.0, 7.9 Hz, 1H), 2.21−2.41 (m, 1H), 1.16−1.44 (m, 16H), 1.01−
1.13 (d, J = 6.6 Hz, 3H), 0.82−0.98 (t, J = 6.6 Hz, 3H); 13C NMR (75
MHz, CDCl3) δ 143.8 (CH), 136.8 (C), 128.9 (CH), 128.3 (CH),
125.9 (CH), 119.0 (CH), 37.6 (CH), 36.8 (CH2), 31.9 (CH2), 29.7
(CH2), 29.7 (CH2), 29.7 (CH2), 29.4 (CH2), 27.4 (CH2), 22.7 (CH2),
20.4 (CH3), 14.2 (CH3); HRMS (APCI-Orbitrap) m/z calcd for
C19H31S [M + H]+ 291.2141, found 291.2142.
The reaction was also carried out on a larger 1.11 mmol scale to
give a clear colorless oil (256 mg, 78%).
(E)-(3-Methyl-5-phenylpent-1-enyl)(phenyl)sulfane 16p. Clear
colorless oil (23.2 mg, 90%): νmax/cm−1 2969 s (C−H), 2922 s (C−
H), 1594 w, 1582 m, 1494 m, 1478 m, 1453 m, 1439 m (Ar CC);
1H NMR (300 MHz, CDCl3) δ 7.44−7.12 (m, 10H), 6.25−6.12 (d, J
= 15.0 Hz, 1H), 5.95 (dd, J = 8.1, 15.0 Hz, 1H), 2.78−2.56 (m, 2H),
2.43−2.29 (m, 1H), 1.71 (q, J = 7.6 Hz, 2H), 1.20−1.04 (d, J = 7.0 Hz,
3H); 13C NMR (75 MHz, CDCl3) δ 142.4 (CH), 142.3 (C), 136.5
(C), 129.0 (CH), 128.5 (CH) 128.4 (CH) 128.4 (CH) 129.2 (CH)
125.8 (CH) 120.11 (CH), 38.5 (CH2), 37.2 (CH), 33.7 (CH2), 20.48
(CH3); HRMS (APCI-Orbitrap) m/z calcd for C18H21S [M + H]+
269.1358, found 269.1361.
(E)-(3-(3-(Adamantan-1-yl)but-1-enyl)(phenyl)sulfane 16q. Clear
colorless oil (15.7 mg, 76%): νmax/cm−1 2946 m (C−H), 2925 s (C−
1
H), 2847 m (C−H), 1582 w, 1478 m, 1438 m (Ar CC); H NMR
(300 MHz, CDCl3) δ 7.43−7.25 (m, 5H), 6.16−5.93 (m, 2H), 2.09−
1.94 (m, 3H), 1.98−1.84 (m, 1H), 1.83−1.46 (m, 12H), 1.07−0.93
(m, 3H); 13C NMR (75 MHz, CDCl3) δ 140.7 (CH) 137.0 (C), 128.9
(CH), 128.2 (CH), 125.9 (CH), 120.0 (CH), 48.7 (CH), 39.9 (CH2),
37.2 (CH2), 34.9 (C), 28.7 (CH), 13.8 (CH3); HRMS (APCI-
Orbitrap) m/z calcd for C20H27S [M + H]+ 299.1828, found 299.1830.
(E)-(3,3-Dicyclohexylprop-1-enyl)(phenyl)sulfane 16r. Clear color-
less oil (10.8 mg, 56%): νmax/cm−1 2928 s (C−H), 2850 m (C−H),
1583 w, 1478 w, 1447 m (Ar CC); 1H NMR (300 MHz, CDCl3) δ
7.39−7.26 (m, 5H), 6.08−5.95 (d, J = 15.0 Hz, 1H), 5.88 - 5.73 (dd, J
= 10.4, 15.0 Hz, 1H), 1.86−0.78 (m, 23H); 13C NMR (75 MHz,
CDCl3) δ 139.2 (CH) 137.0 (C), 128.9 (CH), 128.1 (CH), 125.8
(CH), 121.1 (CH), 55.7 (CH), 37.7 (CH), 32.0 (CH2), 31.0 (CH2),
29.7 (CH2), 26.7 (CH2), 26.6 (CH2); HRMS (APCI-Orbitrap) m/z
calcd for C21H31S [M + H]+ 315.2141, found 315.2146.
(E)-2-(((3-Methyl-4-phenylbut-1-en-1-yl)thio)methyl)furan 16s.
Clear colorless oil (7.1 mg, 27%): νmax/cm−1 3026 w 2959 m 2923
m (C−H), 1601 m (CC), 1497 m 1453 m (Ar CC) 1010 s (C−
O−C); 1H NMR (300 MHz, CDCl3) δ 7.35 (dd, J = 1.9, 0.8 Hz, 1H),
7.31−7.06 (m, 5H), 6.29 (dd, J = 3.2, 1.9 Hz, 1H), 6.12 (dd, J = 3.2,
0.8 Hz, 1H), 5.86 (d, J = 15.2 Hz, 1H), 5.68 (dd, J = 15.1, 6.9 Hz, 1H),
3.79 (s, 2H), 2.71−2.40 (m, 3H), 0.98 (d, J = 6.4 Hz, 3H); 13C NMR
(75 MHz, CDCl3) δ 151.4 (C), 142.2 (CH), 140.4 (C), 137.8 (CH),
129.4 (CH), 128.3 (CH), 126.0 (CH), 120.7 (CH), 110.6 (CH),
107.7 (CH), 43.5 (CH2), 39.3 (CH), 29.9 (CH2), 19.8 (CH3). HRMS
(APCI-Orbitrap) m/z calcd for C16H19OS [M + H]+ 259.1151, found
259.1151.
ASSOCIATED CONTENT
* Supporting Information
NMR spectra, initial optimization studies, X-ray data for
compound 28. This material is available free of charge via the
Internet at http://pubs.acs.org.
■
S
AUTHOR INFORMATION
Corresponding Author
*E-mail: A.Lee@hw.ac.uk.
Notes
■
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The authors would like to thank EPSRC (PCY) and the
Leverhulme Trust (JAJH, F/00 276/O) for funding and the
EPSRC National Mass Spectrometry Services (Swansea) for
analytical services. Johnson Matthey is gratefully acknowledged
for a loan of gold salts. We thank Ursula D. Paul for preliminary
work with N-nucleophiles.
REFERENCES
■
(1) For example, see: (a) Clayden, J.; MacLellan, P. Beilstein J. Org.
Chem. 2011, 7, 582. (b) Robertson, F.; Wu, J. Org. Lett. 2010, 12, 2668
and references cited therein.
(2) Kondo, T.; Mitsudo, T.-A. Chem. Rev. 2000, 100, 3205.
(3) Review on gold-catalyzed C-heteroatom bond forming reactions:
(E)-(3-Deutero-3-hexylnon-1-en-1-yl)(phenyl)sulfane 26. Deuter-
ated thiophenol 2720 (77% D-incorporation, 7.4 μL, 7.9 mg, 0.072
mmol) was added via syringe to a solution of catalyst 17 (2.9 mg,
0.0038 mmol) in dry CH2Cl2 (0.42 mL). The resulting solution was
transferred immediately to a solution of cyclopropene 13 in dry
CH2Cl2 (0.30 mL) via syringe. The reaction was stirred at 25 °C for 30
min under argon, and then the mixture was filtered through a short
plug of silica using 10:1 hexane:diethyl ether to yield the product as a
́
Corma, A.; Leyva-Perez, A.; Sabater, M. J. Chem. Rev. 2011, 111, 1657
and references cited therein for general reviews on gold catalysis.
(4) Intramolecular; with allenes: (a) Morita, N.; Krause, N. Angew.
Chem., Int. Ed. 2006, 45, 1897. For mechanistic study, see: (b) Ando,
K. J. Org. Chem. 2010, 75, 8516.
(5) Intermolecular; with dienes: (a) Brouwer, C.; Rahaman, R.; He,
C. Synlett 2007, 11, 1785. With allenes: (b) Menggenbateer, M. N.;
Ferrara, G.; Nishina, N.; Jin, T.; Yamamoto, Y. Tetrahedron Lett. 2010,
51, 4627. See also: (c) Arcadi, A.; Di Giuseppe, G. B. S.; Marinelli, F.
colorless oil (4.9 mg, 0.047 mmol, 65%), with approximately 49% D-
1
incorporation by H NMR, and MS data indicates 55%
10% D-
incorporation: νmax/cm−1 2955 m 2923 s 2854 s (C−H), 2163 w (C-
1
D), 1679 w (CC), 1584 m 1479 m (Ar CC); H NMR (300
7638
dx.doi.org/10.1021/jo300930c | J. Org. Chem. 2012, 77, 7633−7639

The Journal of Organic Chemistry
Note
Green Chem. 2003, 5, 64. Using heterogenized gold complexes:
(d) Corma, A.; Gonzal
Catal., A 2010, 375, 49.
́ ́
ez-Arellano; Iglesias, M.; Sanchez, F. Appl.
(6) For examples of other low-valent sulfur (i.e., thioethers; for thiols,
see refs 4 and 5) employed as nucleophiles in gold-catalyzed reactions,
see: (a) Nakamura, I.; Sato, T.; Yamamoto, Y. Angew. Chem., Int. Ed.
2006, 45, 4473−4475. (b) Peng, L.; Zhang, X.; Zhang, S.; Wang, J. J.
Org. Chem. 2007, 72, 1192. (c) Davies, P. W.; Albrecht, S. J.-C. Chem.
Commun. 2008, 238. (d) Davies, P. W.; Albrecht, S. J.-C. Synlett. 2012,
23, 70. For examples where thioethers are generated as products, see:
(e) Shapiro, N. D.; Toste, F. D. J. Am. Chem. Soc. 2007, 129, 4160.
(f) Li, G.; Zhang, L. Angew. Chem., Int. Ed. 2007, 46, 5156. (g) Davies,
P. W.; Albrecht, S. J.-C. Angew. Chem., Int. Ed. 2009, 48, 8372.
(7) (a) Bauer, J. T; Hadfield, M. S; Lee, A.-L. Chem. Commun. 2008,
6405. (b) Hadfield, M. S.; Lee, A.-L. Org. Lett. 2010, 12, 484.
(c) Hadfield, M. S.; Bauer, J. T.; Glen, P. E.; Lee, A.-L. Org. Biomol.
Chem. 2010, 8, 4090. (d) Heuer-Jungemann, A.; McLaren, R. G.;
Hadfield, M. S.; Lee, A.-L. Tetrahedron 2011, 67, 1609. (e) Hadfield,
M. S.; Lee, A.-L. Chem. Commun. 2011, 47, 1333. (f) Young, P. C.;
Hadfield, M. S.; Arrowsmith, L.; Macleod, K. M.; Mudd, R. J.; Jordan-
Hore, J. A.; Lee, A.-L. Org. Lett. 2012, 14, 898. (g) Hadfield, M. S.;
Haller, L. J.; Lee, A.-L.; Macgregor, S. A.; O’Neill, J. A. T.; Watson, A.
̈
M. Org. Biomol. Chem. 2012, 10, 4433.
(8) Recent reviews on cyclopropene chemistry: (a) Zhu, Z.-B.; Wei,
Y.; Shi, M. Chem. Soc. Rev. 2011, 40, 5534. (b) Marek, I.; Simaan, S.;
Masarwa, A. Angew. Chem., Int. Ed. 2007, 46, 7364. (c) Rubin, M.;
Rubina, M.; Gevorgyan, V. Chem. Rev. 2007, 107, 3117.
(9) For other gold(I)-catalyzed reactions with cyclopropenes, see:
(a) Zhu, Z.-B.; Shi, M. Chem.Eur. J. 2008, 14, 10219. (b) Li, C.;
Zeng, Y.; Wang, J. Tetrahedron Lett. 2009, 50, 2956. (c) Li, C.; Zeng,
Y.; Feng, J.; Zhang, Y.; Wang, J. Angew. Chem., Int. Ed. 2010, 49, 6413.
(d) Miege, C.; Meyer; Cossy, J. Org. Lett. 2010, 12, 4144. (e) Seraya,
E.; Slack, E.; Ariafard, A.; Yates, B. F.; Hyland, C. J. T. Org. Lett. 2010,
12, 4768. (f) Seidel, G.; Mynott, R; Furstner, A. Angew. Chem., Int. Ed.
̈
2009, 48, 2510. (g) Benitez, D.; Shapiro, N. D.; Tkatchouk, E.; Wang,
Y.; Goddard, W. A., III; Toste, F. D. Nat. Chem. 2009, 1, 482.
(h) Miege, C.; Meyer; Cossy, J. Chem.Eur. J. 2012, 18, 7810.
Reviews: (i) Miege, F.; Meyer, C.; Cossy, J. Beilstein J. Org. Chem.
2011, 7, 717. (j) Lu, B.-L.; Dai, L.; Shi, M. Chem. Soc. Rev. 2012, 41,
3318.
(10) For example, see: (a) Jadzinsky, P. D.; Calero, G.; Ackerson, C.
J.; Bushnell, D. A.; Kornberg, R. D. Science 2007, 318, 430. (b) Negishi,
Y.; Tsukida, T. J. Am. Chem. Soc. 2003, 125, 4046.
(11) Mez
(12) Nieto-Oberhuber, C.; Lop
́
ailles, N.; Richard, L.; Gagosz, F. Org. Lett. 2005, 7, 4133.
́
ez, S.; Munoz, M. P.; Cardenas, D. J.;
́
̃
Bunuel, E.; Nevado, C.; Echavarren, A. M. Angew. Chem., Int. Ed. 2005,
̃
44, 6146.
(13) For a review on applications of NHC−Au complexes, see:
Marion, N; Nolan, S. P. Chem. Soc. Rev. 2008, 37, 1776.
(14) See the Supporting Information for further information.
(15) The ratio of primary to tertiary allylic thioester (14:15) does not
seem to change over time (monitored between 10 and 120 min),
suggesting that they do not isomerize under these conditions.
(16) For other examples of SE′ of allylgold(I) intermediates, see ref 7f
and (a) Hashmi, A. S. K.; Schuster, A. M.; Litters, S.; Rominger, F.;
Pernpointer, M. Chem.Eur. J. 2011, 17, 5661. For related SE′
dealkylation, see: (b) Uemura, M.; Watson, I. D. G.; Katsukawa, M.;
Toste, F. D. J. Am. Chem. Soc. 2009, 131, 3464.
(17) Use of complex 28 in place of 17 results in only 6% of 16c with
the major product being 11. A control without any gold shows full
conversion to 11 with no 16c, implying that 28 does catalyze the
reaction to 16c but not very efficiently.
(18) Rubin, M.; Gevorgyan, V. Synthesis 2004, 5, 796.
(19) Nakamura, I; Bajracharya, G. B.; Yamamoto, Y. J. Org. Chem.
2003, 68, 2297.
(20) Shono, T.; Matsumura, Y.; Tsbata, K. Chem. Lett. 1979, 9, 1051.
7639
dx.doi.org/10.1021/jo300930c | J. Org. Chem. 2012, 77, 7633−7639