Gold-catalyzed carboalkoxylations of 2-ethynylbenzyl ethers to form 1- and 2-indanones chemoselectively: Effects of ligands and solvents

Article abstract of DOI:10.1002/adsc.201300988

The selective syntheses of 1- and 2-indan-one compounds from 2-ethynylbenzyl ethers have been achieved with suitable catalysts and solvents. The highly acidic [tris(pentafluorophenyl)phos-phine]gold hexafluoroantimonate [(C₆F₅)₃AuSbF₆] in nitromethane (MeNO₂) preferably gives 1-indan-ones whereas [(ortho-biphenyl) di(tert-butyl)phosphine] gold triflimide [(tBu)₂(o-biphenyl) AuNTf₂] in dichloroethane tends to form 2-indanone derivatives. For 2-indanone products, we isolated two indenyl methyl ethers for deuterium labeling analyses, providing evidence for p-alkyne activation.

Full text of DOI:10.1002/adsc.201300988

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DOI: 10.1002/adsc.201300988
Gold-Catalyzed Carboalkoxylations of 2-Ethynylbenzyl Ethers to
form 1- and 2-Indanones Chemoselectively: Effects of Ligands
and Solvents
Chiou-Dong Wang,a Yi-Feng Hsieh,a and Rai-Shung Liua,*
a
Department of Chemistry, National Tsing-Hua University, Hsinchu, Taiwan, ROC
Fax : (+886)-3-571-1082; e-mail: rsliu@mx.nthu.edu.tw
Received: November 6, 2013; Published online: January 8, 2014
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201300988.
ꢀ
Abstract: The selective syntheses of 1- and 2-indan-
one compounds from 2-ethynylbenzyl ethers have
been achieved with suitable catalysts and solvents.
The highly acidic [tris(pentafluorophenyl)phos-
tion of various C X bonds (X=C, O, N), thus provid-
ing access to 1,2-difunctionalized molecules.[1] The
carboalkoxylation reactions of alkynes emerge as
ACHTUNGTRENNUNG
ꢀ
ꢀ
a thriving topic, which enable new C C and C O
bonds to be generated on to readily available alk-
A
ACHTUGNERTN(NUNG C6F5)3AuSbF6]
AHCTUNGTRENNUNG
ynes.[2–4] Toste and co-workers reported the carboalk-
A
ACHTUNGTRENoNUGN xylations of 2-alkynylbenzyl ethers, involving an ini-
A
tial 5-exo-dig attack of an ether at its gold p-alkyne to
generate a carbocation-like intermediate II, eventual-
ly giving 3-alkoxy-1H-indene 2 or 1-indanone prod-
ucts (Scheme 1).[4a] For these 2-alkynylbenzyl ethers,
we are aware of no instance to control the regioselec-
tive carboalkoxylation of their terminal alkyne ana-
logues 3 to form 1- or 2-indanones selectively. Such 1-
and 2-indanones are important structural motifs in
several naturally occurring compounds; representa-
tives include pterosin P,[5a–c] monachosorin A,[5a–c]
(+)-pauciflorol F,[5d,e] taiwaniaquinol B,[5f] gloeophyllol
C[5g] and caulerpal B[5h] that are depicted in Scheme 2.
in dichloroethane tends to form 2-indanone deriva-
tives. For 2-indanone products, we isolated two in-
denyl methyl ethers for deuterium labeling analyses,
providing evidence for p-alkyne activation.
Keywords: carboalkoxylations; 2-ethynylbenzyl
ethers; gold catalysis; 1-indanones; 2-indanones
The Au- and Pt-catalyzed electrophilic activations of The chemoselective formation of the two indanones
alkynes offer convenient tools to mediate the forma- from the same 2-alkynylbenzyl ethers is highly de-
Scheme 1. Chemoselectivities for carboalkoxylations.
144
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Gold-Catalyzed Carboalkoxylations of 2-Ethynylbenzyl Ethers
Scheme 2. Natural products bearing a 1- or 2-indanone moiety.
sired. The synthesis of 2-indanones is challenging be- dichloromethane (DCM), which yielded 1- and 2-in-
cause Au- and Pt-catalyzed carboalkoxylations of danones 5a and 6a in 48% and 37% yields, respective-
other terminal alkynes proceed preferably via 5-exo- ly; these indanones arose from a facile hydrolysis of
dig rather than 6-endo-dig cyclizations.[2h,4b] Herein, their precursors 2a and 4a catalyzed with a gold cata-
we report chemoselective syntheses of 1- and 2-inda- lyst. The chemoselectivity toward 1-indanone 5a was
nones with most ether substrates 3, as optimized by significantly improved with acidic
gold catalysts and reaction solvents. The electron-rich AgSbF6 and P(C6F5)3AuCl/AgSbF6, affording the de-
gold catalyst P(t-Bu)2(ortho-biphenyl) uNTf2 tends sired 5a in 70–72% yields, together with 2-indanone
to favor 2-indanone derivatives in toluene (or di- 6a in minor proportions (13–15%). A polar solvent
chloroethane) whereas the electron-deficient such as nitromethane enhanced the yield of 1-indan-
(C6F5)3AuSbF6 produces preferably 1-indanone one 5a to 87% if P(C6F5)3AuCl/AgSbF6 was used
products in MeNO2. (entry 4). We then sought electron-rich gold catalysts
Shown in Table 1 is the control of the regioselectivi- to improve the chemoselectivity towards 2-indanone
ty modulated by electron-deficient and electron-rich 6a. (t-Bu)2(o-biphenyl)AuCl/AgX (X=SbF6 and
gold catalysts, respectively. We first tested P(p- NTf2) gave preferably 2-indanone 6a in DCM with
PACTHNGUTREN(UNG OPh)3AuCl/
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUNG
P
N
N
ACHTUNGTRENNUNG
PACHTUNGTRENNUNG
[4a]
CF3C6H4)3AuCl/AgSbF6
on terminal alkyne 3a in satisfactory yields (82–85%, entries 5 and 6). The
Table 1. Catalyst-dependent chemoselectivity.
Entry
L
Y
Solvent
Time [hour]
Yields [%][b]
5a
6a
1
2
3
4
5
6
7
8
9
P(p-CF3C6H4)3
SbF6
SbF6
SbF6
SbF6
SbF6
NTf2
NTf2
NTf2
NTf2
NTf2
DCM
DCM
DCM
MeNO2
DCM
DCM
DCE
toluene
MeNO2
DCM
4
4
2
4
6
6
6
6
6
6
48
70
72
87
7
37
13
15
8
82
85
92
82
18
73
P
ACHTUNGTRENNUNG
PACHTUNGTRENNUNG
PACHTUNGTRENNUNG
P
G
P
G
5
P
E
trace
trace
75
P
T
PACHTUNGTRENNUNG
10
15
[a]
[3a]=0.1M.
[b]
[c]
Product yields are reported after purification from a silica column.
IPr=1,3-bis(diisopropylphenyl)imidazol-2-ylidene.
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Chiou-Dong Wang et al.
Table 2. Chemoselectivity over alkoxy and aryl substituents.
Entry
Substrates
Conditions A[b]
Conditions B[b]
5 [%]
3
R
Ar
t [h]
Yields [%][c]
t [h]
6 [%]
1
2
3
4
5
6
7
8
3b
3c
3d
3e
3f
3g
3h
3i
Et
Ph
Ph
Ph
Ph
6
6
5a (70)
5a (77)
–
5a (64)
5f (83)
5g (84)
5h (72)
5i (78)
6a (10)
6a (18)
–
6a (21)
6f (0)
6g (0)
6h (0)
6i (12)
8
8
8
8
5a (0)
5a (0)
5a (0)
5a (0)
5f (0)
5g (79)
5h (0)
5i (0)
6a (85)
6a (76)
6a (88)
6a (83)
6f (92)
6g (0)
n-butyl
allyl
benzyl
Me
Me
Me
24[d]
8
4-MeC6H4
4-MeOC6H4
4-ClC6H4
4-FC6H4
4
4
4
4
6
10
10
6
6h (73)
6i (88)
Me
[a]
[3]=0.1M, 5 mol% catalyst.
Conditions A: PACHTUNGTRENNUNG(C6F5)3AuSbF6/MeNO2; conditions B: PAHCTUNGTREN(NUGN t-Bu)2(ortho-biphenyl)AuNTf2/DCE.
Product yields are reported after separation on a silica column.
Starting 3d was recovered in 76%.
[b]
[c]
[d]
same reactions in dichloroethane (DCE) and toluene tion to form 1-indanone 5g exclusively with the two
produced 2-indanone exclusively (82–92%, entries 7 catalysts; this methoxy group tends to stabilize the
and 8). Surprisingly, use of nitromethane reversed the benzyl cation II, as depicted in Scheme 1.
chemoselectivity to afford mainly 1-indanone 5a in
75% yield (entry 9). IPrAuCl/AgNTf2 [IPr=1,3-bis- (X, Y) for benzyl ethers 7a–7k. For an electron-with-
ACHTUNGTRENNUNG(diisopropylphenyl)imidazol-2-ylidene] in DCM gave drawing group as in ethers 7a–7c (X=F, Cl, Br),
Table 3 shows the effects of the benzene subsituents
1- and 2-indanones 5a and 6a in 15% and 73% yields,
PACHTUNGTRENNUNG
respectively (entry 10).
Inspired by these preliminary results, we prepared 3–60% yields; in contrast, P
benzyl ethers 3b–3i to assess their substituent effects.
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
ty, using P
A), and
G
ACHTUGNERTN(NUNG C6F5)3AuSbF6,
PACHTUNGTRENNUNG
DCE (conditions B). As shown in Table 2, variable yields whereas PACHTUGNTRENNNUG
alkoxy groups as in ether substrates 3b–3e (R=ethyl, forded 2-indanones 9d–9f in 73–84% yields (en-
n-butyl, allyl, benzyl) showed distinguishable chemo- tries 4–6). Such a catalyst-dependent selectivity was
selectivity such that P
5a as major species (64–77%, entries 1, 2 and 4) group (X=Me, Y=H; X=H, Y=Me, t-Bu); the re-
whereas P(t-Bu)2(o-biphenyl)NTf2 afforded 2-indan- spective 1-indanones 8g–8i and 2-indanones 9g–9i
one 6a exclusively (>76%). In entry 3, no reaction were produced selectively with satisfactory yields (>
occurred for alloxy derivative 3d with 73%, entries 7–9). For benzyl ether 7j bearing a me-
(C6F5)3AuSbF6. An electron-rich 4-methylphenyl thoxy at the phenyl C-5 position, both catalysts gave
ACHTUNGNERTN(UNG C6F5)3AuSbF6 gave 1-indanone applicable to benzyl ethers 7g–7i bearing an alkyl
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
PACHTUNGTRENNUNG
group as in benzyl ether 3f was amenable to such a mixture of 1- and 2-indanones 8j and 9j in signifi-
a catalyst-dependent chemoselectivity to give 1- and cant portions (entry 10). For ether 7k bearing a C-4
2-indanones 5f and 6f in 83% and 92% yields, respec- methoxy group (entry 11), P
tively (entry 5). Nevertheless, 4-methoxyphenyl deriv- 1-indanone 8k in 87% yield, whereas P
ative 3g gave only 1-indanone 5g with 79–84% yields biphenyl)AuNTf2 delivered 1- and 2-indanones 8k
using the two catalysts (entry 6). For 4-chloro- and 4- and 9k in comparable yields (36–39%). With P(t-
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG
fluorophenyl derivatives 3h and 3i, we again observed Bu)2(ortho-biphenyl)AuNTf2, the majority of the
a distinct chemoselectivity with the two catalysts, af- benzyl ethers 7 in Table 3 gave 2-indanones 9a–9i as
fording indanones 5h, 5i and 6h, 6i, respectively, in the sole or major products; species 7k represented an
72–78% and 73–88% yields (entries 7 and 8). Most exception because its C-4 substituted methoxy group
benzyl ethers in Table 2 gave 1- or 2-indanones 5 and favored the formation of a benzyl cation II as depict-
6 selectively with satisfactory yields (>60%). 4-Meth- ed in Scheme 1. With P
ACHTNUGTNER(UNNG C6F5)AuSbF6, 1-indanone
ACHTUNGTRENNUNG
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Gold-Catalyzed Carboalkoxylations of 2-Ethynylbenzyl Ethers
Table 3. Substituent effects of the bridging benzenes.
Entry
Substrates
Conditions A[b]
Yields [%][c]
Conditions B[b]
Yields [%][c]
7
X
Y
t [h]
t [h]
1
2
3
4
5
6
7
8
7a
7b
7c
7d
7e
7f
7g
7h
7i
F
H
H
H
F
Cl
Br
H
Me
t-Bu
H
5
6
5
5
5
4
5
4
4
4
4
8a (48)
8b (33)
8c (71)
8d (82)
8e (87)
8f (86)
8g (85)
8h (92)
8i (82)
8j (27)
8k (87)
9a (42)
9b (60)
9c (3)
9d (0)
9e (0)
9f (0)
9g (0)
9h (0)
9i (0)
8
8
8
8
10
10
8
10
5
8a (0)
8b (0)
8c (0)
8d (0)
8e (0)
8f (0)
8g (0)
8h (0)
8i (0)
9a (70)
9b (89)
9c (80)
9d (84)
9e (79)
9f (73)
9g (82)
9h (73)
9i (90)
9j (60)
9k (39)
Cl
Br
H
H
H
Me
H
H
OMe
H
9
10
11
7j
7k
9j (33)
9k (0)
10
5
8j (20)
8k (36)
OMe
[a]
[7]=0.1M, 5 mol% catalyst.
[b]
[c]
Conditions A: PACHTUNGTRENNUNG(C6F5)3AuSbF6/MeNO2; conditions B: PAHCTUNGTREN(NUGN t-Bu)2(ortho-biphenyl)AuNTf2/DCE.
Product yields are reported after separation on a silica column.
ethers 7 except for those bearing X=F, Cl and OMe retained 66% deuterium content whereas d1-6a com-
(entries 1, 2 and 10). pletely lost deuterium. A small loss of deuterium con-
Electron-rich gold complexes react with acidic ter- tent for d1-5a is due to an equilibrium between p-
minal alkynes to form alkynylgold complexes reversi- alkyne and alkynylgold species [Eq. (1)].[6,7] We tested
bly [Eq. (1)],[6,7] the roles of p-alkynes and alkynyl- the reaction of d1-7b with (C6F5)3PAuCl/AgNTf2 in
gold species in the reaction chemoselectivity are un- wet DCE (4.0 equiv. H2O), giving 1-indanone (d1-8b)
clear. We performed deuterium labeling experiments and 2-indanone (d1-9a) comprising 84% and 0% deu-
using P(4-CF3C6H4)3AuSbF6 on benzyl ether d1-3a, af- terium contents. This information leads us to postu-
fording 1- and 2-indanones 5a and 6a in comparable late that 1-indanones are generated from p-alkyne
proportions [44–46% yields, Eq. (2)]. In the presence species because of the small deuterium loss, even
of added water (4 equiv.) in DCM, 1-indanone d1-5a though water is present in a large proportion
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Chiou-Dong Wang et al.
(4 equiv); the mechanism is essentially the same as led to 2-indanone 9b with ca. 30% deuterium loss
that postulated by Toste (Scheme 1).
[eqs. (5) and (6)].[9]
In the carboalkoxylation of terminal alkynes, a teth-
The deuterium experiment in Eq. (4) suggests the
ered ether typically attacks the alkyne C-2 carbon, as intermediacy of gold p-alkynes to form 2-indanone
exemplified by 1-indanone products.[2h,3c,d,4] The for- products. Alkynylgold species in Eq. (1) enable a com-
mation of 2-indanones 6 and 9 from benzyl ethers 3 plete exchange between the alkynyl proton of initial
and 7 remains mechanistically unclear. We attempted d1-7b and H2O.[6,7] To balance the deuterium mass of
to isolate their enol ether precursors to seek the solu- species d1-4a, d1-4a’ and unreacted d1-7b in Eq. (4),
tion. As shown in Eq. (4), a brief reaction (1.5 h) be- external H2O with 0.16 equiv. provided the proton
tween deuterated d1-7b and P
ACHTUNGERTN(NUNG t-Bu)2(ortho-biphenyl)- source. Hence, the alkynylgold activation is expected
ACHTUNGTRENNUNG
uNTf2 (5 mol%) in freshly distilled DCM (288C, to give indenyl methyl ethers 4a and 4a’ with deuteri-
1.5 h) led to a 70% conversion, from which two in- um contents of less than 68%, but the resulting major
denyl methyl ethers d1-4b and d1-4b’ were isolated in ether 4a’ has a large deuterium content of ca. 94%.
15% and 50% yields, together with unreacted d1-7b in Accordingly, we postulate a 6-endo-dig cyclization for
1
29% recovery. H NMR analysis revealed that major the initial p-alkyne species A to form the oxonium-
enol ether d1-4b’ contained 94% deuterium content like species B, subsequently producing benzyl cation
(Y=0.47D) whereas minor ether d1-4b had 55% deu- C (Scheme 3). An intramolecular cyclization of this
terium content (X=0.55D), slightly higher than that benzyl cation is expected to give gold carbenes D that
(Z=0.43D) of unreacted d1-7b. With P
biphenyl)AuBARF {BARF=B[3,5-(CF3)2C6H3]4} in alize the different deuterium contents of ethers 4b
(t-Bu)2(ortho- undergo a complete 1,2-deuterium shift.[10] To ration-
ACHTUNGTRENNUNG
N
ACHTUNGTRENNUNG
dry DCM (288C, MS 4ꢁ, 2 h), species d1-7a provided and 4b’ [Eq. (4)], we envisage that the two non-aro-
only enol ether d1-4b containing 90% deuterium con- matic protons of species D are sufficiently acidic to
tents [X=0.90D, Eq. (5)]. Notably, enol ethers d1-4b cause its dissociation, giving gold containing enol
and d1-4b’ underwent no interconversion to each ethers E and E’, respectively. Subsequent protode-
other in the presence of P
G
ACHTUNGTRENaNUNG urations of species E and E’ afford indenyl methyl
in freshly distilled DCM (288C, 4 h), in which we ob- ethers E and E’; the former loses significant deuteri-
served no deuterium loss for both d1-4b and d1-4b’.[8] um content whereas species E’ retains the same deu-
The two ethers remained intact upon treatment with terium content.
P
G
The proposed mechanism is based on deuterium
12 h) because no Brønsted acid was present in this analyses of two isolable indenyl methyl ethers 4b and
system.[8] Treatment of enol ethers d1-4b and d1-4b’ 4b’ [eq. (4)]; we devised another experiment to sup-
with p-TSA (10 mol%) in wet DCE (4 equiv. H2O) port this mechanism (Scheme 4). We prepared d1-3a
bearing a benzylic deuterium; its gold-catalyzed car-
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Gold-Catalyzed Carboalkoxylations of 2-Ethynylbenzyl Ethers
Scheme 3. A p-alkyne route to 2-indanones.
Scheme 4. Additional labeling experiment.
boalkoxylation in dry DCE (288C, MS 4ꢁ) also af- dig cyclization.[2h,3c,d,4] Our rationalization on the cata-
forded two indenyl methyl ethers 4a and 4a’ in 45% lyst-dependent selectivity is highly speculative; we en-
and 41% yields, respectively. Enol ether d1-4a was visage that the strongly acidic gold complex
fully deuterated at its benzylic position, indicating
that the key F!G transformation was irreversible be- the p-alkyne C-2 carbon that can be stabilized by the
(t-
PACHTNUGTRENN(UG C6F5)3AuSbF6 generates a new positive charge on
cause of a facile deauration step F!d1-4a. The other neighboring benzene group. For the less acidic P
ACHTUNGTRENNUNG
enol ether d1-4a’ had only 36% deuterium content Bu)2(ortho-biphenyl)AuNTf2, the charge distribution
(X=0.18D), indicative of a protodeauration of spe- of the p-alkyne is affected by the intrinsic property of
cies G with an external proton source. In contrast the alkyne itself, in which the C-1 carbon is more
with transformation D!d1-4b (Scheme 2), we postu- electron-deficient than the C-2 carbon if benzene is
lated a direct deauration for transformation F!d1-4a considered to be a withdrawing group. Accordingly,
because the olefin moiety of d1-4a contained no deu- this C-1 regioselectivity is particularly favored by an
terium that would be expected to be present in solu- electron-deficient benzene, compatible with our ob-
tion in a small proportion. Without a chloro substitu- servation (Table 2, entries 1 and 2). We remain uncer-
ꢀ ꢀ
ent, we envisage that the Au C H proton of species tain about the reason for the solvent effects that sig-
F is insufficiently acidic to induce a dissociation of the nificantly affect the chemoselectivity.
proton.
Most of the 2-alkynylbenzyl ethers can deliver 1- of 1- and 2-indanones from most 2-ethynylbenzyl
and 2-indanone products using P(C6F5)3AuSbF6 and ethers optimized with gold catalysts and solvents.
(t-Bu)2(ortho-biphenyl)AuNTf2, in MeNO2 and DCE Highly acidic P(C6F5)3AuSbF6 in MeNO2 preferably
respectively. The mechanism of 2-indanones involves gives 1-indanones whereas electron-rich (t-
a 6-endo-dig cyclization rather than a typical 5-exo- Bu)2(ortho-biphenyl)AuNTf2 in DCE tends to form 2-
In this work, we have reported selective syntheses
AHCTUNGTRENNUNG
P
N
ACHTUNGTRENNUNG
PACHTUNGTRENNUNG
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Chiou-Dong Wang et al.
Acknowledgements
The authors wish to thank the National Science Council,
Taiwan for supporting this work.
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Experimental Section
General Procedure for Synthesis of 3-Phenyl-2,3-
dihydro-1H-inden-1-one (5a)
To a wet nitromethane solution (2.5 mL) of ClAuPACHTUNRGTNEUNG(C6F5)3
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(13.8 mg, 5 mol%) and AgSbF6 (6.0 mg, 5 mol%) was added
a nitromethane solution (1 mL) of 1-ethynyl-2-(methoxy-
ACHTUNGTRENNUNG(phenyl)methyl)benzene (3a, 78 mg, 0.35 mmol) at 288C.
The reaction mixture was stirred for 4 h before it was con-
centrated and eluted through a silica column to afford com-
pound 5a (yield: 63 mg, 87%) and compound 6a (yield:
6 mg, 8%) as a colorless oil. IR (neat): n=3086 (w), 1672
1
(s), 1533 cmꢀ1 (m); H NMR (400 MHz, CDCl3): d=7.81 (d,
J=7.6 Hz, 1H), 7.56 (t, J=7.2 Hz, 1H), 7.41 (t, J=7.6 Hz,
1H), 7.33~7.22 (m, 4H), 7.12 (d, J=7.2 Hz, 2H), 4.57 (dd,
J=8.0, 3.6 Hz, 1H), 3.22 (dd, J=19.2, 8.0 Hz, 1H), 2.68 (dd,
J=19.2, 4.0 Hz, 1H); 13C NMR (100 MHz, CDCl3): d=
206.0, 157.9, 143.6, 136.7, 125.1, 128.9, 127.8, 127.6, 127.0,
126.8, 123.4, 46.8, 44.4; HR-MS: m/z=208.0884, calcd. for
C15H12O: 208.0888.
General Procedure for Synthesis of 1-Phenyl-1H-
inden-2(3H)-one (6a)
To a wet 1,2-dichloroethane solution 2.5 (mL) of ClAuPACTHNUTRGNEUNG(t-
Bu)2(ortho-biphenyl) (9.3 mg, 5 mol%) and AgNTf2 (6.8 mg,
5 mol%) was added a 1,2-dichloroethane solution (1 mL) of
1-ethynyl-2-[methoxyACTHNUGRTENUNG(phenyl)methyl]benzene (3a, 78 mg,
0.35 mmol) at 288C. The reaction mixture was stirred for 6 h
before it was concentrated and eluted through a silica
column to afford compound 6a as colorless oil; yield: 67 mg
(92%). IR (neat): n=3084 (w), 1768 (s), 1542 cmꢀ1 (m);
1H NMR (400 MHz, CDCl3): d=7.39~7.25 (m, 6H), 7.18 (d,
J=7.2 Hz, 1H), 7.10 (d, J=8.4 Hz, 2H), 4.67 (s, 1H), 3.66
(s, 2H); 13C NMR (100 MHz, CDCl3): d=213.9, 141.3, 138.1,
137.2, 128.8, 128.4, 128.0, 127.8, 127.3, 126.0, 124.8, 59.7,
43.0; HR-MS: m/z=208.0887, calcd. for C15H12O: 208.0888.
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150
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Gold-Catalyzed Carboalkoxylations of 2-Ethynylbenzyl Ethers
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nylacetylene (20 mol%) in wet DCE, giving 2-indanone
product d1-9b with 70% deuterium content (X=Y=
0.35D). No deuterium loss was observed for recovered
d1-4b. We observed a similar phenomenon for the other
enol ether d1-4b’.
[9] A partial loss of deuterium contents of 2-indanone d1-
9b from starting d1-4b and d1-4b’ [Eqs. (5) and (6)] indi-
cates that two equilibrium states (d1-4b/F and d1-4b’/F)
likely occur before 2-indanone 9b is produced. This
phenomenon reveals a risk of obtaining low enantiose-
lectivity in the carboalkoxylation of 2-ethynylbenzyl
ethers with chiral gold catalysts. In contrast, 1-indanone
products avoid this process; see ref.[4b]
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[8] In catalytic carboalkoxylations, we envisage that the
Brønsted acid is generated from the p-alkyne/s-acety-
lide equilibrium to facilitate the hydrolysis of enol
ethers 4b and 4b’. To test this hypothesis, d1-4b was
treated with PACHTUNGTRENNUNG(t-Bu)2(ortho-biphenyl)AgNTf2 and phe-
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[12] A large deuterium loss of d1-6a and d1-9b [Eqs. (2) and
3] is not due to the proton exchange of 2-indanone
products with water in the presence of gold catalyst.
Partial deuterium loss was observed for formation of
enol ether d1-4b [Eq. (4)]0, and also for the hydrolysis
of two enol ethers d1-4b and d1-4b’ [Eqs. (5) and (6)
and ref.[9]]. We do not rule out the possibility that
water[13] increases the concentration of alkynylgold spe-
cies H to assist the proton dissociation of key inter-
Adv. Synth. Catal. 2014, 356, 144 – 152
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151

COMMUNICATIONS
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mediate D, thus resulting in a large deuterium loss for
resulting enol ether d1-4b.
152
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Adv. Synth. Catal. 2014, 356, 144 – 152