Gold-catalyzed cyclizations: A comparative study of ortho,ortho'- substituted KITPHOS monophosphines with their biaryl monophosphine counterpart SPHOS

Article abstract of DOI:10.1002/adsc.201000879

Electrophilic gold(I) triflimide (trifluoromethanesulfonimide) complexes of electron-rich ortho,ortho'-disubstituted KITPHOS (11-dicyclohexylphosphino-12- phenyl-9,10-ethenoanthracene) monophosphines are efficient catalysts for intramolecular cycloisomeri

Full text of DOI:10.1002/adsc.201000879

FULL PAPERS
DOI: 10.1002/adsc.201000879
Gold-Catalyzed Cyclizations: A Comparative Study of
ortho,ortho’-Substituted KITPHOS Monophosphines with
their Biaryl Monophosphine Counterpart SPHOS
A. Stephen K. Hashmi,a,* Annette Loos,a Simon Doherty,b Julian G. Knight,b
Katharine J. Robson,b and Frank Romingera
a
Organisch-Chemisches Institut, Universitꢀt Heidelberg, Im Neuenheimer Feld 270, 69120 Heidelberg, Germany
Fax : (+49)-6221-54-4205; e-mail: hashmi@hashmi.de
School of Chemistry, Bedson Building, Newcastle University, Newcastle upon Tyne, NE17RU, U.K.
b
Received: November 22, 2010; Published online: March 10, 2011
Abstract: Electrophilic gold(I) triflimide (trifluoro- between a 1-alk
methanesulfonimide) complexes of electron-rich and 1,7-octadiyne, also formed a highly efficient cat-
ortho,ortho’-disubstituted KITPHOS (11- alyst for the same transformations. Monitoring of
dicyclohexylphosphino-12-phenyl-9,10-ethenoanthra- comparative catalyst testing between a KITPHOS-
cene) monophosphines are efficient catalysts for in- based gold(I) triflimide complex containing a coordi-
ACHTUNGTRENNyUNG nyl(dicyclohexylphosphine) oxide
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
tramolecular cycloisomerizations that afford phenols, nated tetrahydrothiophene and its counterpart coor-
3-acylindenes and methylene-oxazolines; compara- dinated solely by the triflimide anion revealed that
tive catalyst testing showed that these catalysts the former is an order of magnitude less efficient
either competed with or outperformed that based on than the latter, confirming that tetrahydrothiophene
SPHOS
[2-(2’,6’-dimethoxybiphenyl)dicyclohexyl- can be an effective catalyst inhibitor.
phosphine]. An electron-rich biarylmonophosphine
containing a single ortho-methoxy substituent, pre- Keywords: alkynes; amides; expoxides; gold; phos-
pared by rhodium-catalyzed [2+2+2]cycloaddition phane ligands; rhodium
Introduction
gold(I)-catalyzed cyclizations initiated by addition of
a nucleophile to a h2-coordinated alkyne or allene.[3]
Electron-rich biaryl and biaryl-like monophosphines Buchwald’s biarylmonophosphines such as 1 and 2
are emerging as a highly efficient class of ligand for a provided the lead ligand for this area and since their
host of transition metal-catalyzed transformations, introduction a number of alternative highly efficient
À
À
most notably palladium-catalyzed C C and C N systems such as pyrrole- and indolyl-based monophos-
[2]
bond formation[1] as well as C H activation but also phines 3, 4 and 5, respectively,[4,5] BippyPhos 6,[6] and
À
Figure 1. Biaryl monophosphines (1 and 2), pyrrole-based (3) and indolyl-based (4 and 5) phosphines and BippyPhos (6),
BI-DIME (7) and KITPHOS (8).
Adv. Synth. Catal. 2011, 353, 749 – 759
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A. Stephen K. Hashmi et al.
FULL PAPERS
Me-substituted KITPHOS monophosphines form effi-
cient catalysts for a host of intramolecular cyclizations
and that both compete with their SPHOS counterpart
across a range of substrates.
Results and Discussion
Figure 2. ortho,ortho’-disubstituted KITPHOS monophos-
phines 8a and 8b.
KITPHOS monophosphines 8a, b required for this
study were prepared in reasonable yield by reduction
most recently BI-DIME 7,[7] have been developed of the Diels–Alder adduct resulting from the corre-
using this basic design concept (Figure 1). To this end sponding 1-alkynylphosphine oxide and anthracene,
we have recently developed the biaryl-like KITPHOS following the previously reported procedure.[9]
class of monophosphine 8,[8] which is architecturally
Since the biaryl architecture of electron-rich mono-
similar to Buchwald’s biaryl monophosphines in that phosphines has also recently been constructed by rho-
the PR2 group is connected to a double bond, albeit dium-catalyzed [2+2+2]cycloaddition of tethered
not an aryl ring but an anthracene-derived bicyclic diynes with 1-alkynylphosphine oxides and sulfides,[12]
framework, and there is a proximal non-phosphine we also used this methodology to synthesize a new
containing aryl ring which can be systematically modi- electron-rich MeO-substituted Buchwald-type mono-
fied since it is derived from a 1-alkynylphosphine phosphine, 11. Slow addition of a slight excess of 1,7-
oxide. Encouragingly, our early studies showed that octadiyne to a solution of [Rh(cycloocta-1,5-diene)-
electron-rich KTPHOS monophosphines were highly
N
and
2-(dicyclohexylphosphin-
À
efficient ligands for palladium-catalyzed C C and
[8]
À
C N bond formation and that ortho,ortho’-substitu- for 48 h gave 10 in excellent yield, after purification
tion of the proximal aryl ring enhances catalyst per- by column chromatography. Reduction of 10 was
formance compared with the corresponding systems achieved in good yield by heating a toluene solution
based on their unsubstituted or monosubstituted containing chlorosilane, triethylamine and the oxide
counterparts.[9] Moreover, electron-rich KITPHOS at 1108C for 48 h to afford biarylmonophosphine 11
monophosphines either competed with or outper- (Scheme 1) The identity and purity of 11 has been es-
formed their biaryl-based counterparts in palladium- tablished using conventional spectroscopic and analyt-
catalyzed cross-coupling which prompted us to extend ical techniques.
our studies to include gold-catalyzed cyclizations.[10]
With the intention of systematically evaluating the
While electrophilic Lewis acid gold(I) triflimide com- performance of KITPHOS monophosphines 8a and
plexes of electron-rich KITPHOS monophosphines 8b in gold(I)-catalyzed cyclizations, bis(trifluorome-
were shown to be an efficient catalyst for a range of thane)sulfonimide precursors 12a and b were pre-
cycloisomerizations to afford phenols, tetrahydropyr- pared in a one-pot two-step procedure involving reac-
ans, lactones and alkylidene-oxazolines, more recent tion of [(tht)AuCl] with the corresponding phosphine
studies have shown that catalysts based on diphenyl- followed by treatment of the resulting chloride com-
phosphino-substituted KITPHOS monophosphines plex with AgNTf2 at room temperature (Scheme 2);
outperformed their electron-rich dicyclohexylphosphi- both complexes were isolated as spectroscopically and
no counterparts for the cycloisomerization of a range analytically pure crystalline solids in excellent yield.
of propargylic amides.[11]
The same procedure was also used to prepare 13, the
We have now undertaken a systematic comparison corresponding gold(I) coordination complex of the
between the performance of ortho,ortho’-substituted Buchwald-type biarylmonophosphine 11, which was
KITPHOS monophosphines (Figure 2) and their isolated in 97% yield.
biaryl counterpart SPHOS in gold(I)-catalyzed cyclo-
isomerizations and herein disclose the details of this the performance of KITPHOS monophosphines 8a
study which has shown that ortho,ortho’-MeO and and 8b, the gold(I) complex of SPHOS[13] (Figure 3)
In order to undertake a meaningful comparison of
ACHTUNGTRENNUNG
Scheme 1. Synthesis of Buchwald-type biarylmonophosphine 11.
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Gold-Catalyzed Cyclizations: A Comparative Study of ortho,ortho’-Substituted KITPHOS Monophosphines
rable to those reported for gold(I) complexes of elec-
tron-rich biarylmonophosphines[16] and KITPHOS
monophosphines.[10a,11] Figure 4 also reveals that the
proximal aryl ring is orientated parallel and close to
1
À
the Au P bond such that there is a weak h -interac-
tion between the gold atom and the ipso carbon atom
of the aryl ring; the Au···Cipso distances of 3.187 ꢂ
(12a), 3.176(7) ꢂ (12b) and 3.133(7) ꢂ (14) are less
than the sum of the van der Waals radii and similar to
the Au···Cipso interactions reported for gold(I) com-
plexes of PCy2(o-biphenyl)[16c] and 11-(dicyclohexyl-
phosphino)-12-(2-methoxyphenyl)-9,10-dihydro-9,10-
ethenoanthracene.[11]
Scheme 2. Synthesis of KITPHOS gold(I) triflimide com-
plexes 12a and 12b.
With the intention of evaluating and comparing the
efficiency of gold(I) tetrahydrothiophene complexes
of KITPHOS monophosphines as precatalysts, 15a
and 15b were also prepared by treatment of a di-
chloromethane solution of (tht)AuCl and the corre-
sponding KITPHOS monophosphine with AgNTf2 at
room temperature (Scheme 3); the identify and purity
of both complexes have been established using con-
ventional spectroscopic and analytical techniques.
A single crystal X-ray structure determination of
15b (Figure 5) was also undertaken[15] to compare the
key structural features with those of {[2-(dicyclohexyl-
phosphino)-12-phenyl-9,10-dihydro-9,10-ethano-
Figure 3. Gold(I) triflimide complexes of 11 and SPHOS.
[SO3CF3].[11] The P(1) Au(1)
ACHTUNGTRENNUNG
À
À
U
T
À
À
for gold(I)-catalyzed transformations.[14]
2.2691(18) ꢂ and 2.327(2) ꢂ, respectively, are similar
À
As we have previously prepared and crystallograph- to those in [(PPh3)Au
(SMe2)]
R
ically characterized gold(I) complexes of a number of P(1) bond also lies parallel to the phenyl ring with a
unsubstituted and monosubstituted KITPHOS mono- Au(1)···Cipso distance of 3.185(7) ꢂ, which is similar to
phosphines, single-crystal X-ray analyses of 12a, 12b that of 3.147 ꢂ in {[2-(dicyclohexylphosphino)-12-
and 14 were undertaken to compare their key struc- phenyl-9,10-dihydro-9,10-ethanoanthracene]AuACHTUNGTRENNUNG(tht)}-
tural features;[15] perspective views of the molecular
structures are shown in Figure 4. In each case the
ACHTUNGTRENNUNG
gold atom clearly adopts a near linear geometry with and monosubstituted KITPHOS monophosphines are
À
À
P(1) Au(1) N(1) angles of 177.19(9)8 (12a), efficient ligands for gold(I)-catalyzed cycloisomeriza-
177.63(15)8 (12b) and 174.76(9)8 (14) while the Au
tions,[11] we chose the same transformations to investi-
À
P(1) bond lengths of 2.2208(9) ꢂ (12a), 2.2380(16) ꢂ gate the effect on catalyst performance of introducing
(12b) and 2.2374(8) ꢂ (14) are all similar and compa- ortho,ortho’-substituents on to the proximal aryl ring
Figure 4. Molecular structures of 12a, 12b and 14. Hydrogen atoms have been omitted for clarity.
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A. Stephen K. Hashmi et al.
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Scheme 3. Synthesis of KITPHOS gold(I) triflimide complexes 15a and 15b.
obtained with 12c (entry 14). Cyclization of 2-alkyn-
AHCTUNGTREGUNyNN laryl epoxide 20 required 2 mol% catalyst which
gave good yields of 3-acylindene 21 after 8 h at room
temperature, for each catalyst tested.[19] There were
only minor differences in the performance of the cata-
lysts, 12b was more efficient than both 12a and 13
(entries 15–17), while that based on SPHOS was the
most efficient one (entry 18). Compound 12c once
more was comparable to 12a/12b (entry 19). Differen-
ces in catalyst performance were more marked for the
cyclization of 2-alkynylaryl epoxide 22 to afford 3-
acylindene 23 (entries 20–23). For example, 2 mol%
of 12a catalyzed the cyclization of 22 to give 23 in
64% yield after 54 h (60% after 30 h) whereas 12b
achieved a yield of only 48% after 30 h, which corre-
sponds to TONs of 32 and 24, respectively. Gratifying-
ly though, both KITPHOS-based catalysts were signif-
Figure 5. Molecular structure of 15b. Hydrogen atoms and
the bis(trifluoromethane)sulfonimide anion have been omit-
ted for clarity.
of KITPHOS. Parallel catalyst testing was also con- icantly more active than either 13 and 14 which ach-
ducted with the new electron-rich Buchwald-type ieved yields of only 39% and 34%, respectively. The
monophosphine and the performance of each catalyst mono-substituted KITPHOS 12c gave only 50% yield
was compared with that based on SPHOS, full details under these conditions (entry 24). Finally, cycloisome-
of which are listed in Table 1.
rization of tert-butyl-based propargylic amide 24 with
Our preliminary catalyst evaluation focused on the 0.1 mol% catalyst in dichloromethane at room tem-
cyclization of alkynyl-tethered furans 16 and 18 to perature gave excellent conversions to the corre-
afford phenols 17 and 19, respectively,[18] and qualita- sponding methylene-oxazoline 25, with no evidence
tively there are only very minor differences in the per- for the formation of its oxazole counterpart.[20] The
formance of each catalyst. For example, cyclization of performance of catalysts based on KITPHOS mono-
substrate 16 using 0.05 mol% catalyst gave good to phosphine 12b and SPHOS were essentially indistin-
excellent conversions with TONs ranging from 1720 guishable, the former giving a TON of 980 compared
to 1860 (entries 1–4), similar to those obtained previ- with 990 for the latter; both catalysts outperformed
ously with catalysts based on unsubstituted and mono- 12a and 13, which gave TONs of 900 and 870, respec-
substituted KITPHOS monophosphines like 12c tively (entries 25–28). The yield of 94% obtained with
(entry 5).[10a] A higher catalyst loading (0.1 mol%, en- 12c is slightly inferior to the yield from 12b
tries 6–9) was required for substrate 18 since there (entry 29).
was no evidence for conversion with 0.05 mol% cata-
The conversion of 2-alkynylaryl epoxide 20 as a
lyst. Under these conditions, although the yields were function of time for each of the catalysts under study
moderate to good they were consistently lower than was monitored by in situ IR spectroscopy (ReactIR)
those obtained with substrate 16. Interestingly, the under the same conditions as those used for the catal-
yields did not improve when the catalyst loading was ysis in Table 1, i.e., in C6D6 at room temperature
further increased to 0.25 mol%, rather, the yields using 2 mol% catalyst. The plot of yield against time
were marginally lower for each catalyst and the in Figure 6 clearly shows that, in the early stages of
TONs dropped from 660–730 to 232–272 (entries 10– the reaction, the kinetic profiles for all four catalysts
13). Again these values are quite similar to the values are essentially identical and corresponds to initial
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Gold-Catalyzed Cyclizations: A Comparative Study of ortho,ortho’-Substituted KITPHOS Monophosphines
Table 1. Gold(I)-catalyzed cyclizations with 12a–c, 13 and 14.
Entry
Reactant
Product[a]
Cat.
Cat. [mol%]
Solvent
Yield [%][b]
TON
1800
1
12a
0.05
CDCl3
90
2
3
4
5
16
16
16
16
17
17
17
17
12b
13
0.05
0.05
0.05
0.05
CDCl3
CDCl3
CDCl3
CDCl3
86
93
93
95
1720
1860
14
1860
12c[c]
1900[10a]
6
12a
0.1
CD2Cl2
71
710
7
8
9
10
11
12
13
14
18
18
18
18
18
18
18
18
19
19
19
19
19
19
19
19
12b
13
14
12a
12b
13
0.1
0.1
0.1
0.25
0.25
0.25
0.25
0.25
CD2Cl2
CD2Cl2
CD2Cl2
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
66
71
73
58
67
65
68
70
660
710
730
232
268
260
14
272
12c[c]
280[10a]
15
12a
2
C6D6
60
30
16
17
18
19
20
20
20
20
21
21
21
21
12b
13
2
2
2
2
C6D6
C6D6
C6D6
C6D6
67
64
75
69
33.5
32
14
37.5
12c[c]
35[10a]
20
12a
2
C6D6
64
32
21
22
23
24
22
22
22
22
23
23
23
23
12b
13
2
2
2
2
C6D6
C6D6
C6D6
C6D6
48
39
34
50
24
19.5
17
14
12c[c]
25[10a]
25
12a
0.1
CD2Cl2
90
900
26
27
28
29
24
24
24
24
25
25
25
25
12b
13
0.1
0.1
0.1
0.1
CD2Cl2
CD2Cl2
CD2Cl2
CD2Cl2
98
87
99
94
980
870
14
990
12c[c]
940[10a]
[a]
Reaction conditions: all catalysed reactions were performed at room temperature in an NMR tube.
The yield was determined by integration and comparison with an internal standard.
The structure of 12c is:
[b]
[c]
TOFs of 47 hÀ1 (12a), 33 hÀ1 (12b), 48 hÀ1 (13) and mately manifested in the vastly disparate yields of
50 hÀ1 (14). As the reaction progresses (>1 h) minor product. For instance, while the initial TOFs of 48 hÀ1
differences in activity begin to emerge, which is ulti- and 50 hÀ1 for catalyst 13 and 14, respectively, were
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Conclusions
Gold(I) triflimide complexes of electron rich ortho,or-
thoꢃ-disubstituted KITPHOS monophosphines are ef-
ficient catalysts for a range of intramolecular cycliza-
tions to afford phenols, 3-acylindenes and methylene-
oxazolines; in the majority of cases these catalysts
competed with that based on the corresponding or-
tho,orthoꢀ-substituted biarylmonophosphine SPHOS.
Moreover, an electron-rich biarylmonophosphine con-
taining a single ortho-MeO substituent, prepared via
rhodium-catalyzed [2+2+2]cycloaddition, also forms
a highly efficient catalyst for the same transforma-
tions and gives TONs that rival those obtained with
both ortho,orthoꢃ-substituted KITPHOS monophos-
phines as well as SPHOS. Comparative catalyst test-
ing has shown that a catalytic amount of tetrahydro-
thiophene acts as an inhibitor and slows the reaction
Figure 6. Kinetics of the conversion of 20 as determined by
in situ IR spectroscopy.
similar the yields of 58% and 75%, respectively, ob- by an order of magnitude compared to the corre-
tained after 5.5 h were markedly different; the former sponding system coordinated solely by the bis(trifluor-
is much closer to that of 59% obtained with 12b omethane)sulfonamide anion; this may well explain
which had an initial TOF of 33 hÀ1.
why many thioether- or thiol-containing substrates
In order to thoroughly evaluate the performance of fail to react in the presence of electrophilic gold(I)
15a and assess the influence of the coordinated tetra- catalysts. At this stage it is unclear how the substitu-
hydrothiophene on catalyst efficiency, parallel compa- tion pattern of the non-phosphine-containing aryl ring
rative catalyst testing was conducted using 2 mol% in biaryl and biaryl-like monophosphines affects cata-
12a and 15a for the cyclization of 2-alkynylaryl epox- lyst performance and further studies are currently un-
ide 20; the reaction was also monitored using Reac- derway to systematically explore what factors influ-
tIR. A plot of yield as a function of time for both cat- ence catalyst efficiency.
alysts (Figure 7) clearly shows the disparate perfor-
mance of these two systems with 12a giving 60% con-
version within in 8 h while 15a requires nearly 4 days
Experimental Section
to reach 62% conversion; the initial TOFs of 12a and
15a are 47 hÀ1 and 5 hÀ1, respectively. Since 15a is gen-
General Comments
erated by substitution of the coordinated triflimide
anion in 12a with tetrahydrothiophene it is reasonable
All manipulations involving air-sensitive materials were car-
to attribute the low activity of the former to the tht ried out using standard Schlenk line techniques under an at-
mosphere of nitrogen or argon in oven-dried glassware. Di-
chloromethane and 1,2-dichloroethane were distilled from
calcium hydride, toluene from sodium and hexane from
Na/K alloy under an atmosphere of nitrogen. 1,7-Octadiyne,
rac-BINAP and 2-dicyclohexylphosphino-2’,6’-dimethoxybi-
phenyl (SPHOS) were purchased from commercial suppliers
and used without further purification. 11-(Dicyclohexylphos-
phinoyl)-12-(2,6-dimethylphenyl)-9,10-dihydro-9,10-etheno-
which coordinates to gold more strongly than the tri-
flimide, i.e., low concentrations of tht inhibit cataly-
sis;[21] the corollary of this is that sulfur-containing
substrates may also inhibit/poison electrophilic Lewis
acid gold(I) complexes.
AHCTUNGTRENNUNG
anthracene (8a),[11] 11-(dicyclohexylphosphinoyl)-12-(2,6-di-
AHCTUNGTRENNUNG
methoxyphenyl)-9,10-dihydro-9,10-ethenoanthracene (8b),[11]
2-(dicyclohexylphosphinoylethynyl)anisole (9),[8] [RhCl(cy-
cloocta-1,5-diene)]2,[22] (tht)AuCl,[23] and substrates 15, 17,
1
19, 21 and 23 were prepared as previously described. H and
13C{1H} NMR spectra were recorded on JEOL LAMBDA-
500, ECS-400 or Bruker Avance 500 instruments. The first
multiplicity listed for 13C NMR refers to coupling with pro-
tons. If there were couplings with other heteroatoms (31P),
the multiplicity is listed separately after the muliplicity
based on protons. Thin-layer chromatography (TLC) was
carried out on aluminum sheets pre-coated with silica gel
60F 254 and column chromatography was performed using
Merck Kieselgel 60.
Figure 7. Comparison of the kinetics of the conversion of 20
catalyzed by 12a (gray line) and 15a (dark line).
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Gold-Catalyzed Cyclizations: A Comparative Study of ortho,ortho’-Substituted KITPHOS Monophosphines
6.91 (d, J=3.2 Hz, 1H, Ar-H), 6.97 (t, J=7.8 Hz, 1H, Ar-
Synthesis of Dicyclohexyl[3-(2-methoxyphenyl)-
5,6,7,8-tetrahydronaphthalen-2-yl]phosphine Oxide
(10)
H), 7.06 (dd, J=7.3, 1.9 Hz, 1H, Ar-H), 7.21, (br s, 1H, Ar-
H), 7.32 (d, J=8.2 Hz, 1H, Ar-H), 13C{1H} NMR
(125.8 MHz, CDCl3): d=23.2 (s, CH2), 23.4 (s, CH2), 26.5 (s,
Cy), 26.7 (s, Cy), 27.4 (s, Cy), 27.5 (s, 2ꢄCy), 27.6 (d, J=
13.2 Hz, Cy), 28.6 (d, J=5.7 Hz, Cy), 29.2 (s, CH2), 29.4 (s,
CH2), 29.9 (d, J=12.4 Hz, Cy), 30.2 (d, J=17.3 Hz, Cy), 30.7
(d, J=16.2 Hz, Cy), 33.7 (d, J=13.3 Hz, Cy), 35.2 (d, J=
14.3 Hz, Cy), 55.1 (s, OMe), 119.6 (s, Ar), 128.4 (s, Ar),
130.8 (d, J=5.8 Hz, Ar), 131.4 (d, J=18.1 Hz, Ar), 132.1 (s,
2 ꢄ Ar), 134.9 (d, J=6.7 Hz, Ar), 133.1 (d, J=2.9 Hz, Ar),
135.3 (s, Ar), 137.5 (s, Ar), 144.1 (d, J=30.2 Hz, Ar),156.6
(s, Ar); 31P{1H} NMR (202.5 MHz, CDCl3) d=À10.5; LR-
MS (ESI+): m/z=435 [M+H]+; HR-MS (ESI+): m/z=
435.2813, calcd. for [C29H40OP]: 435.2817 [M+H]+; anal.
calcd. for C29H39OP: C 80.15, H 9.05; found: C 80.43, H
9.37.
A flame-dried Schlenk flask was charged with [RhCl-
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ethane (40 mL). The mixture was heated to 808C and a solu-
tion of 1,7-octadiyne (370 mg, 3.5 mmol) in 1,2-dichloro-
ethane (20 mL) was added over 3 h using a syringe pump.
The reaction mixture was stirred at 808C for a further 48 h
after which time the solvent was removed under vacuum to
leave a crude brown solid, which was purified by column
chromatography eluting with ethyl acetate/methanol (100:4)
to afford 10 as an off-white solid; yield: 1.06 g (81%).
1H NMR (500.16 MHz, CDCl3): d=0.98–0.94 (m, 2H, Cy-
H), 1.32–1.1 (m, 8H, Cy-H), 1.72–1.42 (m, 12H, Cy-H), 1.81
(br 4H, CH2), 1.81 (br m, 2H, CH2), 2.75 (br, 2H, CH2),
3.74 (s, 3H, OCH3), 6.86 (d, J=4.1 Hz, 1H, Ar-H), 6.94 (d,
J=8.7 Hz, 1H, Ar-H), 6.97 (t, J=7.6 Hz, 1H, Ar-H), 7.04
(dd, J=7.6, 1.9 Hz, 1H, Ar-H), 7.36 (td, J=8.3, 1.9 Hz, 1H,
Ar-H),7.75 (d, J=11.4 Hz, 1H, Ar-H); 13C{1H} NMR
(125.8 MHz, CDCl3): d=22.9 (s, CH2), 23.2 (s, CH2), 25.7 (d,
J=2.9 Hz, Cy), 25.9 (d, J=13.1 Hz, Cy), 26.1 (d, J=3.8 Hz,
Cy), 26.5 (s, 2 x Cy), 26.6 (s, Cy), 26.7 (s, Cy), 26.7 (d, J=
3.0 Hz, Cy), 26.8 (d, J=2.9 Hz, Cy), 26.9 (d, J=2.9 Hz, Cy),
29.1 (s, CH2), 29.2 (s, CH2), 37.7 (d, J=20.9 Hz, Cy), 38.3 (d,
J=20.1 Hz, Cy), 55.4 (s, OMe), 110.3 (s, Ar), 119.7 (s, Ar),
127.4 (d, J=8.2 Hz, Ar), 129.4 (s, Ar), 130.7 (s, Ar), 130.9 (s,
Ar), 132.6 (d, J=9.6 Hz, Ar), 134.8 (d, J=6.7 Hz, Ar), 136.2
(d, J=9.6 Hz, Ar), 136.9 (d, J=8.6 Hz, Ar), 139.7 (s,
Ar),157.0 (s, Ar); 31P{1H} NMR (202.5 MHz, CDCl3): d=
48.2; LR-MS (ESI+): m/z=451 [M+H]+; HR-MS (ESI+):
m/z=451.2761, calcd. for [C29H40O2P]: 451.2766 [M+H]+;
anal. calcd. for C29H39O2P: C 77.30, H 8.72; found: C 77.68,
H 8.04.
General Procedure for the Synthesis of Gold(I)
Bis(trifluoromethane)sulfonimide Complexes
To a solution of (tht)AuCl (1 equiv.) in dichloromethane
(100 mmol/mL) was added phosphine ligand (1 equiv.) and
the resulting mixture stirred for 30 min, after which time the
solvent and tetrahydrothiophene were completely removed
under reduced pressure at room temperature to afford the
corresponding chloride complex. The solid was redissolved
in dichloromethane (100 mmol/mL) and AgNTf2 (1 equiv.)
was added. The reaction mixture was stirred in the dark for
an additional 45 min, the resulting suspension filtered
through a short pad of silica gel and the solvent removed
under reduced pressure at room temperature to afford a
white solid. The product was typically crystallized by slow
evaporation of a dichloromethane/pentane solution at room
temperature.
Synthesis of {[11-(Dicyclohexylphosphinoyl)-12-(2,6-
dimethylphenyl)-9,10-dihydro-9,10-ethenoanthra-
cene]AuACTHNUGTRNE(NUG CF3SO2)2N} (12a)
Synthesis of Dicyclohexyl[3-(2-methoxyphenyl)-
5,6,7,8-tetrahydronaphthalen-2-yl]phosphine (11)
A flame-dried Schlenk flask was charged with 10 (900 mg,
2.0 mmol), toluene (25 mL), and triethylamine (11.3 mL,
80.4 mmol). Trichlorosilane (2.02 mL, 20.1 mmol) was added
slowly and the mixture heated at 1108C for 3 days. The reac-
tion mixture was diluted with diethyl ether (40 mL) and
added slowly to a mixture of ice (15 g) and 20% aquous
NaOH (30 mL). After stirring vigorously at room tempera-
ture for 30 min, the organic layer was removed and the
aqueous phase extracted with diethyl ether (3ꢄ40 mL). The
organic fractions were combined, washed with saturated
NaHCO3 (2ꢄ30 mL), water (2ꢄ20 mL) and brine (2ꢄ
20 mL), dried over MgSO4, filtered and the solvent removed
under vacuum. The product was purified by column chroma-
tography eluting with hexane/ethyl acetate (9:1) to afford 11
as a spectroscopically pure colourless solid; yield: 644 mg
(74%). An analytically pure sample was obtained by slow
diffusion of a chloroform solution layered with methanol at
Compound 12a was prepared according to the procedure de-
scribed above from (tht)AuCl (33.5 mg, 105 mmol), 8a
(52.7 mg, 105 mmol) and AgNTf2 (40.5 mg, 105 mmol) and
isolated as a colourless powder; yield: 94.1 mg (95.7 mmol,
92%); mp decomp. at 273–2758C; 1H NMR (300 MHz,
CDCl3): d=1.01–1.44 (m, 10H), 1.52–2.01 (m, 10H), 1.68 (s,
6H), 2.24 (m, 2H), 5.16 (d, J=3.6 Hz, 1H), 5.44 (d, J=
5.3 Hz, 1H), 7.03–7.12 (m, 6H), 7.21 (m, 1H), 7.34 (m, 4H);
13C NMR (75 MHz, CDCl3): d=21.2 (q, 2C), 25.8 (t, 2C),
26.7 (t, d: JC,P =14.1 Hz, 2C), 26.8 (t, d: JC,P =13.0 Hz, 2C),
30.8 (t, d: JC,P =1.8 Hz, 2C), 30.9 (t, 2C), 35.9 (d, d: JC,P
=
37.3 Hz, 2C), 54.1 (d), 60.8 (d, d: JC,P =8.5 Hz), 119.4 (s, q:
1JC,F =323.4 Hz, 2C), 123.0 (d, 2C), 124.1 (d, 2C), 125.5 (d,
2C), 125.9 (d, 2C), 128.5 (d, 2C), 128.7 (d), 134.7 (s, 2C),
137.3 (s), 143.8 (s, d: JC,P =1.9 Hz, 2C), 144.5 (s, d: JC,P
=
2.0 Hz, 2C), 171.0 (s, d: JC,P =12.7 Hz) one quaternary C
could not be detected; 31P NMR (121 MHz, CDCl3): d=
33.04; IR (KBr): n=2930, 2853, 1627, 1459, 1396, 1350,
1333, 1198, 1141, 1060, 768, 744 cmÀ1; MS (FAB+): m/z=
981.2 [M]+, 701.3 [MÀNTf2]+; HR MS (FAB+): m/z=
701.2685, calcd. for [C36H41PAu]: 701.2611.
1
room temperature. H NMR (500.16 MHz, CDCl3): d=1.30–
0.99 (br m, 10H, Cy-H), 1.75–1.53 (br m, 12H, Cy-H), 1.85
(br m, 5H, CH2, Cy-H), 2.78 (br m, 2H, CH2), 2.83 (br, 2H,
CH2), 3.70 (s, 3H, OCH3), 6.89 (d, J=8.2 Hz, 1H, Ar-H),
Adv. Synth. Catal. 2011, 353, 749 – 759
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asc.wiley-vch.de
755

A. Stephen K. Hashmi et al.
FULL PAPERS
6H), 6.70 (d, J=8.5 Hz, 2H), 7.21 (m, 1H), 7.38–7.65 (m,
4H); 31P NMR (101 MHz, CDCl3): d=39.27.
Synthesis of {[11-(Dicyclohexylphosphinoyl)-12-(2,6-
dimethoxyphenyl)-9,10-dihydro-9,10-ethenoanthra-
cene]AuACHTUNGTRENNUNG(CF3SO2)2N} (12b)
Compound 12b was prepared according to the procedure
described above from (tht)AuCl (23.1 mg,72.0 mmol), 8b
(38.6 mg, 72.0 mmol) and AgNTf2 (28.3 mg, 72.0 mmol) and
isolated as a colourless powder; yield: 62.1 mg (61.2 mmol,
85%); mp decomp. at 265–2678C; 1H NMR (300 MHz,
CDCl3): d=1.00–1.45 (m, 12H), 1.58–1.72 (m, 4H), 1.86 (m,
4H), 2.18 (m, 2H), 3. 47 (s, 6H), 5.05 (d, J=3.4 Hz, 1H),
5.34 (d, J=5.6 Hz, 1H), 6.57 (d, J=6.6 Hz, 2H), 7.02 (m,
4H), 7.24–7.34 (m, 5H); 13C NMR (75 MHz, CDCl3): d=
25.8 (t, d: JC,P =1.2 Hz, 2C), 26.7 (t, d: JC,P =13.9 Hz, 4C),
Synthesis of {Dicyclohexyl
9,10-dihydro-9,10-ethenoanthracen-11-yl]-phosphan-
yl}(tetrahydrothiophene)[bis(trifluorometh-
ACHTUNGTNER[NUNG 12-(2,6-dimethylphenyl)-
AHCTUNGTRENNUNG
ane)sulfonimido]gold (15a)
Compound 8a (100 mg, 200 mmol), (tht)AuCl (64.1 mg,
200 mmol) and AgNTf2 (77.6 mg, 200 mmol) were suspended
in dichloromethane (3 mL) and stirred for 30 min. The reac-
tion mixture was filtered through silica gel and the solvent
removed under reduced pressure at room temperature to
afford 15a as a colourless solid; yield: 200 mg(187 mmol,
94%); mp decomp. at 217–2198C; 1H NMR (500 MHz,
CDCl3): d=1.06–1.47 (m, 10H), 1.57–1.65 (m, 2H), 1.71 (s,
6H), 1.72–1.88 (m, 6H), 1.91–1.98 (m, 2H), 2.04 (m, 4H),
2.46 (m, 2H), 3.12 (m, 4H), 5.15 (d, J=3.6 Hz, 1H), 5.52 (d,
J=5.1 Hz, 1H), 7.03–7.11 (m, 6H), 7.23 (t, J=7.5 Hz, 1H),
7.32 (d, J=6.7 Hz, 2H), 7.41 (d, J=7.5 Hz, 2H); 13C NMR
(125 MHz, CDCl3): d=21.3 (q, 2C), 25.7 (t, 2C), 26.5 (t, d:
30.1 (t, 2C), 30.6 (t, d: JC,P =2.8 Hz, 2C), 35.4 (d, d: JC,P
=
37.4 Hz, 2C), 54.3 (d, d: JC,P =4.1 Hz), 54.9 (q, 2C), 60.4 (d,
1
d: JC,P =8.4 Hz), 104.5 (d, 2C), 119.4 (s, q: JC,F =323.8 Hz,
2C), 122.5 (d, 2C), 123.8 (d, 2C), 124.8 (d, 2C), 125.6 (d,
2C), 128.9 (s), 130.2 (d), 131.0 (s), 144.0 (s, d: JC,P =2.0 Hz,
2C), 145.0 (s, d: JC,P =2.0 Hz, 2C), 156.7 (s, 2C), 164.8 (s, d:
J
C,P =11.4 Hz); 31P NMR (121 MHz, CDCl3): d=35.78; IR
(KBr): n=2929, 2852, 1586, 1472, 1449, 1351, 1332, 1252,
1199, 1138, 1114, 766, 741 cmÀ1; MS (FAB+): m/z=1013.4
[M]+, 733.3 [MÀNTf2]+; HR-MS (FAB+): m/z=1013.1690,
calcd. for [C38H41O6NF6PS2Au]: 1013.1683, m/z=733.2532,
calcd. for [C36H41O2PAu]: 733.2519.
J
C,P =14.5 Hz, 2C), 26.6 (t, d: JC,P =13.0 Hz, 2C), 31.0 (t,
2C), 31.0 (t, 2C), 31.3 (t, 2C), 35.4 (d, d: JC,P =34.1 Hz, 2C),
38.9 (t, 2C), 54.3 (d, d: JC,P =2.3 Hz), 60.5 (d, d: JC,P
=
8.4 Hz), 118.9 (s, q: JC,F =321.8 Hz, 2C), 123.4 (d, 2C), 123.8
(d, 2C), 125.7 (d, 2C), 126.0 (d, 2C), 128.4 (d, 2C), 128.7
(d), 134.0 (s, d: JC,P =47.0 Hz), 136.0 (s, 2C), 138.9 (s, d:
Synthesis of {[Dicyclohexyl(3-(2-methoxyphenyl)-
5,6,7,8-tetrahydronaphthalen-2-yl)phosphine]-
AuACHTUNGTRENNUNG(CF3SO2)2N} (13)
J
C,P =7.8 Hz), 143.8 (s, 2C), 144.2 (s, 2C), 170.7 (s, d: JC,P =
12.8 Hz); 31P NMR (202 MHz, CDCl3): d=38.22; IR (KBr):
n=2931, 2854, 1629, 1476, 1460, 1351, 1194, 1142, 1059, 769,
744 cmÀ1
;
MS (FAB+): m/z=789.4 [MÀNTf2]+, 701.4
Compound 13 was prepared according to the procedure de-
scribed above from (tht)AuCl (64.2 mg, 200 mmol), 11
(86.9 mg, 200 mmol) and AgNTf2 (77.6 mg, 200 mmol) and
isolated as a colourless powder; yield: 176 mg (193 mmol,
76%); mp 103–1058C; 1H NMR (500 MHz, CDCl3): d=
[MÀNTf2Àtht] +; HR-MS (FAB+): m/z=701.2624, calcd. for
[C36H41PAu]: 701.2611.
1.10–1.48 (m, 10H), 1.55–2.15 (m, 16H), 2.72–2.88 (m, 4H), Synthesis of {Dicyclohexyl
ACHTUNGTRENNUNG
3.74 (s, 3H), 6.94 (d, J=4.4 Hz, 1H), 6.98–7.08 (m, 3H),
7.36 (d, 11.0 Hz, 1H), 7.44 (t, J=7.2 Hz, 1H); 13C NMR
(125 MHz, CDCl3): d=22.8 (t), 23.0 (t), 25,7 (t), 25.8 (t),
26.5 (t, d: JC,P =14.6 Hz), 26.6 (t, d: JC,P =13.0 Hz), 26.8 (t, d:
phosphanyl}(tetrahydrothiophene)
ane)sulfonimido]gold (15b)
ACHTUNGTREN[NUNG bis(trifluorometh-
Compound 8b (107 mg, 200 mmol), (tht)AuCl (64.1 mg,
200 mmol) and AgNTf2 (77.6 mg, 200 mmol) were suspended
in dichloromethane (3 mL) and stirred for 1 h. The reaction
mixture was filtered through silica gel and the solvent was
removed under reduced pressure at room temperature to
afford 15b as a colourless solid; yield: 209 mg (190 mmol,
95%); mp decomp. at 177–1798C; 1H NMR (500 MHz,
CDCl3): d=1.00–1.50 (m, 12H), 1.63–1.94 (m, 7H), 2.06 (bs,
4H) 2.27–2.42 (m, 3H), 3.17 (bs, 4H), 3.49 (s, 6H), 5.02 (d,
J=3.2 Hz, 1H), 5.36 (d, J=4.9 Hz, 1H), 6.59 ( d, J=8.2 Hz,
2H), 7.03 (m, 4H), 7.23–7.40 (m, 5H); 13C NMR (125 MHz,
CDCl3): d=25.8 (t, 2C), 26.6 (t, d: JC,P =14.3 Hz, 2C), 26.6
(t, d: JC,P =12.6 Hz, 2C), 30.2 (t, 2C), 31.0 (t, 2C), 30.8 (t,
2C), 34.9 (d, d: JC,P =34.6 Hz, 2C), 39.1 (t, 2C), 54.3 (q,
2C), 55.6 (d), 60.2 (d, d: JC,P =9.0 Hz), 104.3 (d, 2C), 120.1
(s, q: JC,F =321.6 Hz, 2C), 122.7 (d, 2C), 123.8 (d, 2C), 125.0
(d, 2C), 125.4 (d, 2C), 128.9 (s), 130.9 (d), 131.0 (s), 143.7 (s,
2C), 144.7 (s, 2C), 157.4 (s, d: JC,P =1.5 Hz, 2C), 165.3 (s);
31P NMR (202 MHz, CDCl3): d=41.10; IR (KBr): n=2929,
2852, 1618, 1472, 1351, 1333, 1252, 1196, 1142, 1114, 1059,
767, 738 cmÀ1; MS (FAB+): m/z=821.3 [MÀNTf2]+, 733.3
[MÀNTf2Àtht]+; HR-MS (FAB+): m/z=821.2914, calcd. for
J
C,P =14.0 Hz), 26.9 (t, d: JC,P =13.7 Hz), 29.3 (t), 29.3 (t),
29.8 (t), 30.6 (t), 31.0 (t), 31.2 (t, d: JC,P =3.1 Hz), 36.6 (d, d:
C,P =35.3 Hz), 36.9 (d), 55.2 (q), 110.1 (s), 111.5 (d), 118.3
J
(s), 120.8 (s), 120.8 (s), 121.0 (d), 129.9 (d), 130.9 (d), 133.6
(d, JC,P =8.2 Hz), 137.0 (s), 141.5 (d), 156.5 (s), the CF3
carbon signals could not be detected; 31P NMR (202 MHz,
CDCl3): d=43.76; IR (KBr): n=2930, 2853, 1633, 1351,
1332, 1202, 1139, 1060, 744 cmÀ1; MS (FAB+): m/z=911.1
[M]+, 631.3 [MÀNTf2]+; HR-MS (FAB+): m/z=911.1542,
calcd. for [C31H39O5NF6PS2Au]: 911.1577; m/z=631.2430,
calcd. for [C29H39OPAu]: 631.2404.
Synthesis of {[2-Dicyclohexylphosphino-2’,6’-dimeth-
oxybiphenyl]AuACHTUNGTRENNUNG(CF3SO2)2N} (14)
Compound 14 was prepared according to the procedure de-
scribed above from (tht)AuCl (96.2 mg, 300 mmol),
2
(123 mg, 300 mmol) and AgNTf2 (116.4 mg, 300 mmol) and
isolated as a colourless powder; yield: 263 mg (293 mmol,
98%). The proton NMR data are entirely consistent with
the literature data for this compound.[4] 1H NMR (250 MHz,
CDCl3): d=1.10–1.42 (m, 10H), 1.59–2.23 (m, 12H), 3.69 (s,
756
asc.wiley-vch.de
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2011, 353, 749 – 759

Gold-Catalyzed Cyclizations: A Comparative Study of ortho,ortho’-Substituted KITPHOS Monophosphines
[C40H49O2PAuS]: 821.2856; m/z=733.2540, calcd. for
[C36H41O2PAu]: 733.2499.
Acknowledgements
We gratefully acknowledge Johnson Matthey for generous
loans of rhodium trichloride and Umicore AG & Co. KG for
the donation of tetrachloroauric acid.
Procedure for Gold-Catalyzed Cyclization of 16 to
Afford Phenol 17
An NMR tube was charged with substrate 16 (46.5 mg,
200 mmol) and 1,3,5-tri-tert-butylbenzene (2 mg) as internal
standard and CDCl3 (0.5 mL) and a reference spectrum of
the resulting solution was recorded. The corresponding
amount of gold complex (0.1 mmol, 0.05 mol%) was added
using a 1 wt% solution in CDCl3 and the reaction monitored
by 1H NMR spectroscopy. The yield was determined by inte-
gration and comparison with the internal standard.
References
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Afford Indene 21
To an NMR tube charged with 4.0 mmol (2 mol%) gold com-
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hexamethylbenzene as internal standard per 0.5 mL C6D6
1
and the reaction monitored by H NMR spectroscopy. The
yield was determined by integration and comparison with
the internal standard.
Procedure for Gold-Catalyzed Cyclization of 22 to
Afford Indene 23
To an NMR tube charged with 4.0 mmol (2 mol%) gold com-
plex dissolved in 100 mL of C6D6 was added 0.5 mL of a
standard solution containing 46.9 mg (200 mmol) of substrate
22 and 2 mg hexamethylbenzene as internal standard per
1
0.5 mL C6D6. The reaction was monitored by H NMR spec-
troscopy and the yield determined by integration and com-
parison with the internal standard.
Procedure for Gold-Catalyzed Cyclization of 24 to
Afford Methylene-oxazoline 25
Substrate 24 (20.9 mg, 150 mmol) and dioxane (2 mL) as in-
ternal standard were dissolved in 0.5 mL CD2Cl2 in an NMR
tube and a reference spectrum of the resulting solution was
recorded. The corresponding amount of gold complex
(0.15 mmol, 0.1 mol%) was added using a 0.3 wt% solution
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in CD2Cl2. The reaction was monitored by H NMR spec-
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Adv. Synth. Catal. 2011, 353, 749 – 759
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
757

A. Stephen K. Hashmi et al.
FULL PAPERS
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