Ortho, ortho′-Substituted KITPHOS monophosphines: Highly efficient ligands for palladium-catalyzed C-C and C-N bond formation

Article abstract of DOI:10.1002/adsc.200900577

ortho, ortho′-Substitution of the phosphinoalkyne-derived aryl ring in KITPHOS (11-dicyclohexylphosphino-12-phenyl-9,10-ethenoanthracene) monophosphines enhances the performance of this class of ligand in palladium-catalyzed Suzuki-Miyaura cross-couplings and BuchwaldHartwig aminations, compared with their unsubstituted and mono-substituted counterparts. An alternative complementary synthesis of KITPHOS monophosphines has been developed and two new members of this family, 2,6-Me₂-KITPHOS [11-dicyclohexylphosphino-12-(2,6-dimethylphenyl)-9,10-ethenoanthracene] and 2,6-(MeO)₂-KITPHOS [11-dicyclohexylphosphino-12-(2,6-dimethoxyphenyl)-9,10-ethenoanthracene], have been prepared; palladium complexes of both are highly efficient catalysts for C - C and C - N bond formation with a range of electron-rich and electron-poor aromatic chlorides as well as heteroaryl chlorides.

Full text of DOI:10.1002/adsc.200900577

UPDATES
DOI: 10.1002/adsc.200900577
ortho,ortho’-Substituted KITPHOS Monophosphines: Highly
À
À
Efficient Ligands for Palladium-Catalyzed C C and C N
Bond Formation
Simon Doherty,a,* Julian G. Knight,a,* John P. McGrady,a Alexandra M. Ferguson,a
Nicholas A. B. Ward,a Ross W. Harrington,a and William Clegga
a
School of Chemistry, Bedson Building, Newcastle University, Newcastle upon Tyne, NE1 7RU, U.K.
Fax : (+44)-191-222-6929; e-mail: simon.doherty@newcastle.ac.ukj.g.knight@newcastle.ac.uk
Received: August 21, 2009; Published online: December 30, 2009
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200900577.
Abstract: ortho,ortho’-Substitution of the phos-
phinoalkyne-derived aryl ring in KITPHOS (11-di-
ACHTUNGTRENNUNGcyclohexylphosphino-12-phenyl-9,10-ethenoanthra-
loadings and the need to realize these goals continues
to fuel interest in the design and identification of new
catalysts.[7] In this regard, recent years have witnessed
a number of quite remarkable advances in catalyst de-
velopment which began in 1998 with the discovery
that electron-rich biarylmonophosphines form highly
ACHTUNGTRENNUNG
cene) monophosphines enhances the performance
of this class of ligand in palladium-catalyzed
Suzuki–Miyaura cross-couplings and Buchwald–
Hartwig aminations, compared with their unsubsti-
tuted and mono-substituted counterparts. An alter-
native complementary synthesis of KITPHOS
monophosphines has been developed and two new
members of this family, 2,6-Me2-KITPHOS [11-di-
cyclohexylphosphino-12-(2,6-dimethylphenyl)-9,10-
ethenoanthracene] and 2,6-(MeO)2-KITPHOS [11-
dicyclohexylphosphino-12-(2,6-dimethoxyphenyl)-
9,10-ethenoanthracene], have been prepared; palla-
dium complexes of both are highly efficient cata-
À
À
efficient catalysts for C C and C N bond formation
(Figure 1, 1-4).[8] While early catalysts suffered from
limited substrate scope and stability, mechanistic stud-
ies guided the design of more efficient ligands by indi-
cating that elimination of the ortho hydrogen atoms
on the lower non-phosphine-containing aryl ring
would improve catalyst activity and longevity.[9]
Indeed, ortho,orthoꢀ-substitution of this aryl ring re-
sulted in a marked improvement in performance such
that a catalyst based on SPHOS exhibited unprece-
dented scope, reaction rate and stability.[10] The effi-
ciency of these catalysts has been attributed to a com-
bination of factors; (i) their electron-rich character
which facilitates oxidative addition of the less reactive
aryl chlorides,[8b,11] (ii) their steric bulk which favours
formation of the active monophosphine complex
L1Pd(0);[12] and (iii) the absence of ortho hydrogens
which prevents the formation of palladacycles.[13] Ex-
perimental and computational studies have also estab-
lished that either a Pd-arene interaction with the ipso
carbon or a Pd-O interaction with an oxygen atom of
À
À
lysts for C C and C N bond formation with a
range of electron-rich and electron-poor aromatic
chlorides as well as heteroaryl chlorides.
Keywords: aryl chlorides; Buchwald–Hartwig ami-
nations; electron-rich species; KITPHOS biaryl-like
monophosphines; Suzuki–Miyaura coupling
À
À
Palladium-catalyzed C C and C N bond formation is the methoxy group on the non-phosphine-containing
an exceptionally powerful tool that has found wide- aromatic ring stabilizes intermediate complexes,
spread use in many areas of organic chemistry,[1] par- which increases catalyst life time.[14]
ticularly in the synthesis of important intermediates
Since their introduction, ortho,ortho’-substituted
and building blocks for fine chemicals[2] and pharma- biarylmonophosphines have proven to be the ligand
ceuticals.[3] Ideally, an efficient catalyst should have of choice for a number of challenging transformations
broad substrate scope and be capable of activating including the Negishi coupling of secondary alkylzinc
chloride-, tosylate- or mesylate-based electrophiles[4] halides with aryl bromides to give excellent ratios of
as well as sterically hindered[5] and heteroaryl part- secondary to primary coupling products,[15] palladium-
ners,[6] under mild conditions at very low catalyst catalyzed direct arylation of heteroarenes with tosy-
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Simon Doherty et al.
UPDATES
Figure 1. Biarylphosphines (1–4), pyrrole-based (5) and indolyl-based (6, 7) phosphines and BippyPhos (8).
lates and mesylates,[16] palladium-catalyzed Hiyama
cross-coupling of aryl arenesulfonates and mesylates
with arylsilanes,[17] selective monoarylation of acetate
esters and aryl methyl ketones using aryl chlorides,[18]
and highly selective monoarylation of primary amines
using aryl chlorides.[19] As palladium-catalyzed C C
and C N bond formation are pivotal transformations
À
À
in both academia and industry, the biaryl motif has
been used as the basic design concept to develop a
Figure 2. Retrosynthesis of KITPHOS monophosphines.
number of alternative highly efficient ligands, for ex-
ample cataCXiumꢂ P-ligands 5, indolyl-based mono-
phosphines 6 and 7, and BippyPhos 8, introduced by
Beller,[20] Kwong,[21] and Singer,[22] respectively C C and C N coupling, compared with the corre-
À
À
(Figure 1).[23]
Biarylmonophosphines 1–4 are typically prepared monosubstituted counterparts.
sponding systems based on their unsubstituted or
in a highly modular straightforward one-pot protocol
Although multistep, the synthesis of KITPHOS
involving addition of an aryl-Grignard to an in situ monophosphines is modular in that the steric bulk
generated benzyne followed by trapping of the result- and basicity of the phosphino group can be modified
ing biaryl-metal intermediate with an appropriate in a systematic manner, as can the substitution pattern
chlorophosphine.[24] However, more recently, the of the aryl rings since they are introduced through the
biaryl architecture of electron-rich monophosphines alkynylphosphine oxide and anthracene. Taking a
has also been constructed using cycloaddition meth- lead from the pioneering work of Buchwald,[9,10] we
odology, including Diels–Alder cycloaddition-elimina- became interested in establishing whether ortho,or-
tion between 1-alkynylphosphine oxides and various tho’-substitution of the alkynylphosphine-derived aro-
1,3-dienes[25] and rhodium-catalyzed [2+2+2]cyclo- matic ring in KITPHOS monophosphines would
addition of tethered diynes with 1-alkynylphosphine effect a similar positive influence on catalyst perfor-
sulfides and oxides.[26] We have recently applied this mance and as such identified 14a and b as suitable
approach to the Diels–Alder cycloaddition between targets (Scheme 2). In the first instance, alkynylphos-
1-alkynylphosphine oxides and anthracene to develop phine oxides 12a and b were prepared according to
an architecturally distinct family of electron-rich the procedure outlined in Scheme 1a. While the palla-
biaryl-like monophosphines, KITPHOS (11-dicyclo- dium-catalyzed Sonogoshira coupling between 2-iodo-
hexylphosphino-12-phenyl-9,10-ethenoanthracenes)
(Figure 2).[27,28] Preliminary studies have shown that efficiently catalyzed by 1 mol% Pd
these ligands form highly efficient catalysts for the isopropylamine to afford 1-(2,6-dimethylphenyl)-
1,3-dimethylbenzene and trimethylsilylacetylene was
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
Buchwald–Hartwig amination and Suzuki–Miyaura ethyne 10a, after protodesilylation, the corresponding
cross-coupling of a wide range of aryl chlorides, which coupling between trimethylsilylacetylene and 2-iodo-
for the vast majority of substrate combinations out- 1,3-dimethoxybenzene gave disappointingly low yields
perform their o-(dicyclohexylphosphino)biphenyl- even with 5 mol% loading of Pd
ACHTUNGTREN(NUNG PPh3)4. Gratifyingly,
based counterparts. Herein we describe an alternative 1 mol% Pd2A(dba)3/9a was an excellent catalyst for this
CTHUNGTRENNUNG
complementary route to KITPHOS monophosphines coupling and 10b was eventually isolated in 73%
and report that ortho,ortho’-substitution of the proxi- yield. 1-Alkynylphosphine oxides 12a and b were ob-
mal aryl ring enhances catalyst performance for both tained by quenching a THF solution of the derived 1-
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ortho,ortho’-Substituted KITPHOS Monophosphines
Scheme 1. Synthesis of ortho,ortho’-substituted alkynylphosphine oxides 12a and b.
Scheme 2. Synthesis of ortho,ortho’-substituted electron-rich KITPHOS monophosphines 14a and b.
lithio-1-alkyne with chlorodicyclohexylphosphine fol-
lowed by oxidation prior to work-up. With the aim of
developing a convergent route to KITPHOS mono-
phosphines we reasoned that 1-alkynylphosphine
oxide 11 could be prepared at an early stage of the
synthesis and subsequently coupled with a range of
aromatic iodides to generate a library of aryl-substi-
tuted alkynylphosphine oxides, as shown in Scheme
1b. To this end, initial efforts to couple 11 with either
2-iodo-1,3-dimethylbenzene or 2-iodo-1,3-dimethoxy-
benzene using PdACTHNUTRGENN(UG PPh3)4 or Pd2CAHTUNGTERN(NUGN dba)3/L (L=DAVE-
PHOS or 9a) in diisopropylamine were marred by
low yields due to a competing Michael addition of the
amine. However, the yields were improved quite dra-
matically when diisopropylamine was replaced with
triethylamine and under these conditions 1 mol% Pd-
ACHTUNGTRENNUNG(PPh3)4/CuI catalyst gave 12a and 12b in 69 and 52%
yield, respectively.
The Diels–Alder cycloadditions between 1-alkynyl-
phosphine oxides 12a and b and anthracene were
most conveniently conducted in an Asynt DrySynꢂ
multi-position heating block to give 13a and b in good
yield. Reduction of 13a and b was achieved by heat-
ing a toluene solution of the oxide, trichlorosilane and
triethylamine at 1108C for 48 h (Scheme 2).[27a] The
identity of 14a and b has been established using con-
Figure 3. Structure of one of the two crystallographically in-
dependent molecules of 14a, with 30% probability displace-
ment ellipsoids. H atoms and one disorder component of a
cyclohexyl ring have been omitted for clarity.
ventional spectroscopic and analytical techniques and (1)], we chose this transformation to investigate the
in the case of 14a confirmed by a single-crystal X-ray effect on catalyst performance of introducing or-
structure determination; a perspective view of the tho,ortho’-substituents onto the aryl ring. Our initial
molecular structure is shown in Figure 3.
evaluation focused on the amination of aryl and het-
Having already demonstrated that KITPHOS eroaryl chlorides with cyclic secondary alkylamines,
monophosphines 9a and b are effective ligands for the secondary anilines and primary alkylamines using
palladium-catalyzed amination of aryl chlorides [Eq. 0.5 mol% Pd2ACTHNUTRGNEN(UG dba)3 with 2.5 mol% KITPHOS in tolu-
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Simon Doherty et al.
Table 1. Comparison of the palladium-catalyzed amination of aryl chlorides using ligands 9a, 14a and 14b.[a]
UPDATES
Entry
L
Aryl chloride
Amine
Time [h]
Conversion [%][b]
Yield [%][c]
1
2
3
4
5
6
7
8
9a
1
98
100
76
88
>99
97
98
88
92
96
89
100
83
>99
>99
52
89
75
44
96
100
69
89
89
87
94
88
93
100
98
55
46
89
98
81
89
20
49
83
89
66
82
89
91
91
80
86
87
79
92
71
90
92
44
81
70
39
83
92
58
80
83
72
88
79
85
91
83
47
37
83
89
73
77
12
40
53
55
94
89
81
91
94
93
87
76
81
70
92
14a
14b
9a
14a
14b
9a
14a
14b
9a
14a
14b
9a
14a
14b
9a
14a
14b
9a
14a
14b
9a
14a
14b
9a
14a
14b
9a
14a
14b
9a
14a
14b
9a
14a
14b
9a
14a
14b
9a
14a
14b
9a
14a
14b
9a
14a
14b
9a
0.5
0.5
2
10.5
20.5
0.5
2
0.5
0.5
2
1
1
6
4
4
6
6
5
5
5
1
0.5
0.5
1
1
1
2
2
1
6
4
4
6
3
3
6
3
3
6
3
3
6
3
3
4
4
4
10
6
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
60
67
100
100
89
97
>99
100
92
83
88
14a
14b
77
100
6
[a]
Reactions conditions: 1.0 equiv. of ArCl, 1.1 equiv. of amine, 1.4 equiv. of NaO-t-Bu, 0.5 mol% Pd
14a or 14b, toluene, 1008C.
Conversions determined by GC analysis of the reaction mixture and based on aryl chloride. Average of two runs.
2ACHTUNGTREN(NGNU dba)3, 2.5 mol% 9a,
[b]
[c]
Isolated yield after purification by column chromatography.
ene at 1008C with NaO-t-Bu as base, full details of show that catalysts derived from Pd
2ACHTUNGTREN(NUNG dba)3 and either
which are given in Table 1. Preliminary studies clearly 14a or 14b efficiently promote the amination of elec-
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ortho,ortho’-Substituted KITPHOS Monophosphines
tron-rich and electron-poor aryl chlorides as well as 96% and 69% conversion, respectively, in the same
heteroaryl chlorides and that ortho,ortho’-Me or time. Finally, the coupling of n-hexylamine with aryl
-OMe substitution results in a marked and in some and heteroaryl chlorides (entries 37–51) further high-
cases substantial enhancement in catalyst perfor- lights the efficacy of 14a and 14b as both combine
mance compared with the corresponding systems with Pd2ACHTUNGTERN(NUNG dba)3 to form catalysts that give good to ex-
based on their unsubstituted and monosubstituted cellent conversions with aryl and heteroaryl chlorides.
counterparts, 9a and 9b, respectively.
For each substrate tested monoaryl/diaryl product
ratios are typically greater than 20/1 and significantly
longer reactions times were also required to achieve
comparable conversions with Pd(0)/9a. High monoar-
yl/biaryl product ratios have previously been obtained
with catalysts based on either QPHOS[30] or an elec-
tron-rich biarylmonophosphine,[8b] although in the
The beneficial influence of ortho,ortho’-substitution latter case an excess of amine was required to achieve
is particularly evident in the amination of 4-chloro- these ratios.
benzonitrile with morpholine as 1 mol% Pd(0)/14a
Having established that ortho,ortho’-substitution of
and Pd(0)/14b gives conversions of 88 and 92%, re- KITPHOS monophosphines improves their perfor-
À
spectively, after only 30 min at 1008C, whereas Pd(0)/ mance in palladium-catalyzed C N bond formation,
9a requires 2 h to reach 98% conversion (entries 7–9). catalyst testing was extended to include the Suzuki–
Catalysts based on 14a and 14b also promote this ami- Miyaura coupling. Following a previously reported
nation at 808C and reach 78% and 81% conversion, protocol,[10a,14b] catalysts composed of Pd
ACTHNUTRGNEU(GN OAc)2 and
respectively, after 1 h, while that based on 9a was in- 14a or 14b (Pd:L, 1:2.5) efficiently promoted the cou-
effective at this temperature. Similarly, these systems pling of a range of aryl and heteroaryl chlorides with
both gave excellent conversions for the reaction be- phenylboronic acid and 2-methylphenyl boronic acid,
tween 4-chloroanisole and morpholine in only 30 min, in toluene at 40–808C, full details of which are pre-
while that based on 9a required 2 h to reach 96% con- sented in Table 2 [Eq. (2)]. Under these conditions
version (entries 10–12). Gratifyingly, 14a and 14b also
form highly efficient catalysts for the amination of
sterically hindered substrates such as 2-chloro-meta-
xylene and 2-chloro-para-xylene with morpholine and
pyrrolidine (entries 13–24); both give markedly
higher conversions than Pd(0)/9a in the same time.
Under our conditions, catalyst generated from 14a
and 14b either rival or outperform their electron-rich
biaryl counterparts; this is clearly evident from the good to excellent conversions were obtained for a
amination of 2- and 3-chloropyridine with morpho- range of electron-rich and electron-poor aryl chlor-
line. For instance, catalysts based on 14a and 14b both ides as well as heteroaryl partners. Table 2 reveals
gave excellent conversions for the reaction between that, although catalysts supported by 14a or 14b out-
2-chloropyridine and morpholine in short reaction perform that based on their unsubstituted counterpart
times (0.5–1 h), whereas that based on 2-(di-tert-butyl- 9a, for the vast majority of substrate combinations,
phosphino)biphenyl (JohnPhos) required heating at the improvement is less marked than that for the cor-
1108C for 4 h to reach 70% conversion.[8b] Good con- responding C N coupling. Activated aryl chlorides
À
versions were also obtained for the amination of 3- typically gave good conversions under mild conditions
chloropyridine after 4 h using 0.5 mol% Pd2ACTHNUTRGNE(UNG dba)3 in while electron-rich and sterically hindered coupling
combination with 2.5 mol% of 14a or 14b (entries 28– partners typically required high temperatures and/or
30); for comparison systems based on an electron-rich longer reaction times to reach comparable conver-
biarylmonophosphine[8b] or triaminophosphine[29] re- sions. In this regard, the sterically challenging sub-
quired 22 and 20 h, respectively, to reach comparable strate combination of 2-methylphenylboronic acid and
conversions. A comparison with catalyst generated 1-chloro-2,6-dimethylbenzene catalyzed by PdACTHUNTRGNE(UNG OAc)2/
from SPHOS was also undertaken since this ligand is 14a at 808C gave 75% conversion after 7 h, which was
architecturally similar to 14b in that the non-phos- a significant improvement on the conversion of 36%
phine-containing aryl ring is substituted with methoxy achieved with its unsubstituted counterpart, after the
groups at the 2- and 6-positions. We were encouraged same time (entries 46–48). Similarly, 14a and 14b also
that, in our hands and under the same conditions, formed highly efficient catalysts for the coupling of 2-
Pd(0)/14b competed favorably with or outperformed chloroacetophenone with 2-methylphenylboronic
its SPHOS counterpart which catalyzed the amination acid; the conversions of 86 and 91%, respectively, ob-
of 2- and 3-chloropyridine with morpholine to afford tained after 4 h at 708C, were markedly higher than
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Simon Doherty et al.
Table 2. Comparison of the palladium-catalyzed Suzuki–Miyaura coupling of aryl chlorides using ligands 9a, 14a and 14b.[a]
UPDATES
Entry
L
Aryl chloride
Boronic acid
Time [h]
Temperature [8C]
Conversion [%][b]
Yield [%][c]
1
2
3
4
5
6
7
8
9a
6
3
3
3
3
3
2
2
2
4
4
4
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
4
4
4
4
4
4
2
2
2
2
2
2
2
2
2
6
6
6
7
7
7
80
80
80
80
80
80
30
30
30
50
50
50
40
40
40
50
50
50
60
60
60
60
60
60
80
80
80
50
50
50
70
70
70
40
40
40
50
50
50
60
60
60
40
40
40
80
80
80
84
100
92
84
96
>99
70
99
94
52
94
89
78
94
>99
61
56
66
70
82
91
56
80
82
16
56
63
62
80
89
43
86
91
76
94
69
79
88
71
92
97
60
91
89
47
89
82
63
90
89
59
45
61
62
75
83
40
65
77
11
52
60
55
73
81
36
66
69
70
90
96
12
61
73
53
59
53
89
83
91
29
55
67
14a
14b
9a
14a
14b
9a
14a
14b
9a
14a
14b
9a
14a
14b
9a
14a
14b
9a
14a
14b
9a
14a
14b
9a
14a
14b
9a
14a
14b
9a
14a
14b
9a
14a
14b
9a
14a
14b
9a
14a
14b
9a
14a
14b
9a
14a
14b
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
>99
16
71
77
71
64
58
>99
>99
96
36
75
78
[a]
Reactions conditions: 1.0 equiv. of ArCl, 1.5 equiv. of ArB(OH)2, 2.0 equiv. of K3PO4, 1.0 mol% Pd
14a or 14b, toluene (2 mL).
Conversions determined by GC analysis of the reaction mixture and based on aryl chloride. Average of three runs.
ACHTUNGRTEN(NGNU OAc)2, 2.5 mol% 9a,
[b]
[c]
Isolated yield after purification by column chromatography.
the 43% achieved with PdACHTNUGTRENUNG(OAc)2/9a (entries 31–33). pling of 2-methylphenylboronic acid with 1-chloro-
In a comparative study, parallel catalyst screening 2,6-dimethylbenzene and 2-chloroacetophenone, re-
with 1.0 mol% Pd(0)/SPHOS under the same condi- spectively, which further underpins the competitive
tions gave 66 and 73% conversion for the cross-cou- performance of these KITPHOS monophosphines
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ortho,ortho’-Substituted KITPHOS Monophosphines
against their well-established biaryl counterparts. Sys- mance associated with the aminations of aryl chlor-
tems supported by 14a and 14b also efficiently pro- ides is markedly more pronounced than that for the
moted the cross-coupling of 3-chloropyridine and 2- corresponding Suzuki–Miyaura cross-coupling across
chloroisoquinoline with arylboronic acids giving good the range of substrates examined. An alternative con-
conversions to the corresponding heterobiaryl in short vergent route to KITPHOS monophosphines has
reaction times (entries 19–21 and 37–42). However, been developed which involves a Sonogoshira cou-
for these substrates the differences in performance pling between ethynyl(dicyclohexyl)phosphine oxide
between 14a and b and 9a were less marked than for and an aryl halide as an integral step, a modular pro-
aryl chloride coupling and, moreover, in the case of 3- tocol that will enable substitution and functionality to
chloropyridine, the Pd
marginally more efficient than the corresponding sys- facilitating the construction of a structurally diverse li-
tems based on 14a and 14b (Table 2, entries 16–18). brary of ligands. Further studies are currently under-
ACHTUNGRTEN(NUNG OAc)2/9a combination was be introduced on to the neighbouring aryl ring, thus
As the high efficiency of catalysts based on elec- way to expand the substrate scope and applications of
tron-rich biarylmonophosphines has been shown to be this new class of phosphine, particularly with respect
associated with a stabilizing Pd(0)-h1-arene interac- to more challenging transformations, and to develop a
tion with the ipso carbon atom of the non-phosphine- chiral KITPHOS monophosphine for use in asymmet-
containing aryl ring,[10a,14] monophosphine 15 was pre- ric catalysis.
pared in order to further examine parallels between
these systems. KITPHOS monoxide 15 was prepared
by a Diels–Alder cycloaddition between alkynylphos- Experimental Section
phine oxide 11 and anthracene and subsequently re-
duced with SiHCl3/NEt3 in xylenes to afford 16. The Synthesis of DicyclohexylACTHUNRTGNEUNG(ethynyl)phosphine Oxide
(11)
A flame-dried Schlenk flask was charged with tetrahydrofur-
an (10 mL) and trimethylsilylacetylene (0.32 mL, 2.2 mmol),
cooled to À788C and n-BuLi (2.34M in hexanes, 0.95 mL,
2.2 mmol) was added dropwise over 4 min. The resulting
mixture was stirred and allowed to warm to 08C over
20 min, then cooled to À788C and chlorodicyclohexylphos-
phine (0.47 mL, 2.1 mmol) added dropwise over 2 min. The
resulting mixture was allowed to warm to room temperature
over 2 h then cooled to 08C and H2O2 (35% aqueous,
0.77 mL, 2.4 mmol) added. After warming to room tempera-
ture over 30 min water (20 mL) was added, the aqueous
phase extracted with diethyl ether (3ꢃ20 mL), the organic
phases combined, washed with sodium sulfite (2.0 g in
20 mL water), dried over MgSO4, and the solvent removed
under reduced pressure. The residue was purified by column
chromatography (ethyl acetate/CH2Cl2, 3:2) to afford 11 as
an off-white solid; yield: 0.48 g (92%); mp 142–1448C.
31P{1H} NMR (161.8 MHz, CDCl3): d=36.5; 1H NMR
coupling of 4-chlorotoluene and of 4-chloroanisole
with phenylboronic acid were selected as benchmark
reactions for comparison and under the same condi-
tions PdACHTUNGTRENNUNG(OAc)2/16 was an extremely poor catalyst for
both substrate combinations, giving conversions of 3
and 11%, respectively, after 3 h at 808C, compared
with conversions of 98 and 91%, respectively, ob-
tained with 14a. The disparate performance between
KITPHOS monophosphines 14a and 16 is entirely
consistent with experimental and computational stud-
ies undertaken which demonstrated that an interac-
tion between a neighbouring arene ring and the metal
was necessary to achieve high catalyst efficiency.[14]
In conclusion, electron-rich KITPHOS monophos-
phines with ortho,ortho’-Me and -OMe substituents
on the neighbouring aryl ring form highly efficient
ꢀ
(400.0 MHz, CDCl3): d=3.06 (d, J=9.2 Hz, 1H, PC CH),
1.80–0.95 (m, 22H, 2ꢃC6H11); 13C{1H} NMR (100.5 MHz,
ꢀ
ꢀ
CDCl3): d=93.2 (d, J=19.2 Hz, PC CH), 76.2 (s, PC CH),
37.5 (d, J=78.1 Hz, Cy), 26.9 (d, J=7.6 Hz, Cy), 26.6 (d, J=
6.7 Hz, Cy), 26.4 (Cy), 26.1 (d, J=2.9 Hz, Cy), 25.1 (d, J=
2.9 Hz, Cy); TOF-MS (ES+): m/z=261.1384, exact mass
calcd. for C14H23NaOP [M+Na]+: 261.1367; anal. calcd for
C14H23OP: C 70.56, H 9.73; found: C 70.77, H 10.01; IR:
nmax =3090, 2927, 2852, 2038, 1166 cmÀ1 (P=O).
À
À
catalysts for C C and C N cross-coupling of a range
of aryl and heteroaryl chlorides, at relatively low cata-
lyst loadings and with good functional group toler-
ance. Moreover, comparative catalyst testing has
shown that for the vast majority of substrate combina-
tions ortho,ortho’-substitution enhances the perfor-
mance of this class of ligand for both palladium-cata-
Synthesis of 2-(Dicyclohexylphosphinoylethynyl)-1,3-
dimethylbenzene (12a): Method A
To a solution of compound 10a (1.158 g, 8.90 mmol) in THF
(60 mL) cooled to À788C was added n-BuLi (3.63 mL,
2.45M, 8.65 mmol) dropwise. The reaction was allowed to
warm to 08C, stirred for 20 min and then cooled to À788C.
À
À
lyzed C C and C N bond formation, compared with
their unsubstituted and monosubstituted counterparts.
Interestingly, the enhancement in catalyst perfor- Chlorodicyclohexylphosphine (1.90 mL, 8.65 mmol) was
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207

Simon Doherty et al.
UPDATES
added dropwise and the solution allowed to warm to room
temperature and stirred for a further 2.5 h. The reaction
mixture was then cooled to 08C, hydrogen peroxide (35%
aqueous solution, 3.25 mL, 11.6 mmol) added dropwise, and
the solution allowed to warm to room temperature and
stirred for 30 min. Water (20 mL) was added and the prod-
uct extracted with diethyl ether (3ꢃ20 mL). The combined
organic extracts were dried over MgSO4 and the solvent re-
moved under vacuum to leave a brown liquid which was pu-
rified by column chromatography, eluting with CH2Cl2/ethyl
acetate (2:3), to give the desired product as a yellow solid;
yield: 1.99 g (67%); mp 92–958C. 31P{1H} NMR (202.5 MHz,
CDCl3): d=36.4; 1H NMR (500 MHz, CDCl3): d=7.18 (t,
J=7.83 Hz, 1H, Ar-H), 7.04 (d, J=8.29 Hz, 2H, Ar-H), 2.45
(s, 6H, CH3), 2.14–1.89 (m, 10H, Cy-H), 1.74 (br, 2H, Cy-
H), 1.56 (m, 4H, Cy-H), 1.29–1.24 (m, 6H, Cy-H); 13C{1H}
NMR (75.5 MHz, CDCl3): d=142.0 (C-OCH3), 129.9 (C6H3
p-C), 127.3 (C6H3 m-C), 120.9 (d, J=12.0 Hz, C6H3Q), 101.0
(ESI+); m/z=375.2089, exact mass calcd. for C22H32O3P
[M+H]+: 375.2090; anal. calcd. for C22H31O3P: C 70.57, H
8.34; found: C 70.89, H 8.58.
Synthesis of 2-(Dicyclohexylphosphinoylethynyl)-1,3-
dimethoxybenzene (12b): Method B
Compound 12b was prepared according to method B de-
scribed above for 12a, on the same scale, and isolated as an
off-white crystalline solid after purification by column chro-
matography, eluting with CH2Cl2/ethyl acetate (2:3); yield:
2.14 g (52%). The spectroscopic properties were the same a
those described above.
Synthesis of 2-(Dicyclohexylphosphinoyl)-12-(2,6-
dimethylphenyl)-9,10-dihydro-9,10-ethenoanthracene
(13a)
ꢀ
ꢀ
(d, J=84.0 Hz, PC C), 89.5 (PC C), 37.2 (d, J=78.0 Hz,
Cy), 26.7 (d, J=6.3 Hz, Cy), 26.6 (d, J=6.1 Hz, Cy), 26.4 (d,
J=2.8 Hz, Cy), 26.3 (Cy), 25.4 (d, J=3.0 Hz, Cy), 21.4
(CH3); HR-MS (ESI+): m/z=343.2191, exact mass calcd. for
C22H32OP [M+H]+: 343.2191; anal. calcd. for C22H31OP: C
77.16, H 9.12; found: C 77.31, H 9.49.
1-Alkynylphosphine oxide 12a (1.992 g, 5.82 mmol) and an-
thracene (3.11 g, 17.45 mmol) were mixed in a flask which
was gradually heated to 2208C using a DrySynꢂ multi-posi-
tion heating block. The temperature was then lowered to
2008C and the mixture heated for a further 7 days. The re-
sulting dark solid residue was purified by column chroma-
tography by eluting with CH2Cl2/ethyl acetate (1:0 then 3:2)
to afford 13a as a pale yellow solid; yield: 1.61 g (53%); mp
246–2498C. 31P{1H} NMR (202.5 MHz, CDCl3) d=45.3;
1H NMR (500 MHz, CDCl3): d=7.34 (d, J=6.9 Hz, 2H, Ar-
H), 7.30 (d, J=6.9H, 2H, Ar-H), 7.07–7.00 (m, 5H, Ar-H),
6.94 (d, J=7.8 Hz, 2H, Ar-H), 5.41 (d, J=6.4 Hz, 1H,
bridgehead), 5.09 (d, J=2.3 Hz, 1H, bridgehead), 1.90–1.82
(m, 2H, Cy-H), 1.78 (br s, 6H, CH3), 1.77–1.72 (br m, 6H,
Cy-H), 1.65–1.59 (br m, 4H, Cy-H), 1.45–1.40 (m, 2H, Cy-
H), 1.26–1.09 (m, 8H, Cy-H); 13C{1H} NMR (125.5 MHz,
CDCl3): d=166.0 (d, J=4.7 Hz, C=CP), 145.2 (C6H4Q),
144.5 (C6H4Q), 138.7 (d, J=2.9 Hz, C6H3Q), 136.9 (d, J=
79.1 Hz, C=CP), 134.9 (C6H3 o-C), 127.2 (C6H3 m-C+p-C),
125.2 (C6H4), 125.0 (C6H4), 123.7 (C6H4), 123.3 (C6H4), 60.8
(d, J=8.6 Hz, bridgehead), 53.2 (d, J=9.5 Hz, bridgehead),
37.2 (d, J=66.7 Hz, Cy), 26.8 (d, J=12.4 Hz, Cy), 26.7 (d,
J=12.4 Hz, Cy), 26.6 (d, J=2.0 Hz, Cy), 26.0 (Cy), 25.7 (d,
J=1.9 Hz, Cy), 21.3 (CH3); HR-MS (ESI+): m/z=521.2973,
exact mass calcd. for C36H42OP [M+H]+: 521.2972; anal.
calcd. for C36H41OP: C 83.04, H 7.94; found: C 83.11, H
8.17.
Synthesis of 2-(Dicyclohexylphosphinoylethynyl)-1,3-
dimethylbenzene (12a): Method B
A flame-dried Schlenk flask was charged with 1-iodo-2,6-di-
methylbenzene (2.78 g, 12.0 mmol), 11 (2.69 g, 11.0 mmol),
PdACHTUNGTRENNUNG(PPh3)4 (0.130 g, 0.11 mmol 1.00 mol%) and CuI (0.021 g,
0.11 mmol, 1.00 mol%) and then evacuated and re-filled
with argon. Triethylamine (100 mL) was added and the reac-
tion mixture heated to 808C for 16 h after which time
NH4Cl (100 mL, saturated aqueous solution) was added and
the aqueous phase extracted with dichloromethane (3ꢃ
100 mL). The organic phases were combined, washed with
citric acid (100 mL, saturated aqueous solution) and water
(60 mL), dried over MgSO4, and the solvent removed under
reduced pressure to afford a brown oily residue. Purification
by column chromatography eluting with CH2Cl2/ethyl ace-
tate (2:3), gave 12a; yield: 2.59 g (69%). The spectroscopic
properties were the same as those described above.
Synthesis of 2-(Dicyclohexylphosphinoylethynyl)-1,3-
dimethoxybenzene (12b): Method A
Synthesis of 2-(Dicyclohexylphosphinoyl)-12-(2,6-
dimethoxyphenyl)-9,10-dihydro-9,10-
ethenoanthracene (13b)
Compound 12b was prepared according to method A de-
scribed above for 12a on the same scale and isolated as an
off-white crystalline solid after purification by column chro-
matography eluting with CH2Cl2/ethyl acetate (2:3); yield:
1.19 g (37%), mp 103–1078C. 31P{1H} NMR (202.5 MHz,
CDCl3): d=36.1; 1H NMR (500 MHz, CDCl3): d=7.21 (t,
J=8.2 Hz, 1H, Ar-H), 6.42 (d, J=8.2 Hz, 2H, Ar-H), 3.77
(s, 6H, OCH3), 2.14–2.02 (m, 4H, Cy-H), 1.83 (m, 6H, Cy-
H), 1.70 (br, 2H, Cy-H), 1.60–1.58 (m, 4H, Cy-H), 1.28–1.24
(m, 6H, Cy-H); 13C{1H} NMR (125.5 MHz, CDCl3): d=
162.8 (C-OCH3), 131.8 (C6H3 p-C), 103.4 (C6H3 m-C), 99.5
Compound 13b was prepared according to the procedure
described above for 13a on the same scale, at 2008C for 3
days, and isolated as an analytically pure off-white solid
after purification by column chromatography by eluting
with CH2Cl2/ethyl acetate (1:1); yield: 1.96 g (61%); mp
272–2768C. 31P{1H} NMR (202.5 MHz, CDCl3): d=47.12;
1H NMR (300 MHz, CDCl3) d=7.30–7.26 (m, 2H, Ar-H),
7.19–7.11 (m, 3H, Ar-H), 6.98–6.86 (m, 4H, Ar-H), 6.41 (d,
J=9.1 Hz, 2H, Ar-H), 5.55 (d, J=6.1 Hz, 1H, bridgehead),
4.93 (d, J=2.4 Hz, 1H, bridgehead), 3.38 (s, 6H, OMe),
1.67–1.62 (m, 4H, Cy-H), 1.48–1.30 (m, 6H, Cy-H), 1.28–
1.09 (m, 6H, Cy-H), 1.05–0.94 (m, 4H, Cy-H), 0.90–0.82 (m,
ꢀ
(d, J=3.8 Hz, C6H3Q), 96.3 (d, J=16.3 Hz, PC C), 89.1 (d,
J=141.1 Hz, PC C), 56.0 (OCH3), 37.3 (d, J=78.1 Hz, Cy),
ꢀ
26.6 (d, J=14.3 Hz, Cy), 26.5 (d, J=14.3 Hz, Cy), 26.1 (Cy),
25.8 (d, J=2.2 Hz, Cy), 24.8 (d, J=2.9 Hz, Cy); HR-MS
208
asc.wiley-vch.de
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 201 – 211

ortho,ortho’-Substituted KITPHOS Monophosphines
2H, Cy-H); 13C{1H} NMR (75.5 MHz, CDCl3): d=157.9 (C-
OCH3), 157.6 (d, J=3.5 Hz, C=CP), 146.1 (d , J=1.7 Hz,
C6H4Q), 145.3 (d, J=2.3 Hz, C6H4Q), 138.1 (d, J=81.9 Hz,
C=CP), 129.5 (C6H3 o-C), 124.6 (2ꢃC6H4), 123.5 (2ꢃC6H4),
118.1 (C6H3 QC), 104.4 (C6H3 m-C), 61.2 (d, J=9.8 Hz,
bridgehead), 55.6 (OCH3), 53.23 (d, J=8.2 Hz, bridgehead),
37.3 (d, J=67.5 Hz, Cy), 27.0 (d, J=13.9 Hz, Cy), 26.9 (d,
J=12.3 Hz, Cy), 26.3 (Cy), 26.1 (d, J=2.9 Hz, Cy), 25.9 (d,
J=2.9 Hz, Cy); HR-MS (ESI+): m/z=553.2872, exact mass
calcd. for C36H42O3P [M+H]+: 553.2878; anal. calcd. for
C36H41O3P: C 78.23, H 7.48; found: C 78.44, H 7.71.
(9:1); yield: 0.66 g (39%). An analytically and spectroscopi-
cally pure sample of 14b was obtained by slow diffusion of a
chloroform solution layered with methanol at room temper-
ature; mp 187–1908C. 31P{1H} NMR (202.5 MHz, CDCl3)
d=À10.71; 1H NMR (500 MHz, CDCl3) d=7.18 (t, J=
8.2 Hz, 1H, Ar-H), 7.29 (m, 2H, Ar-H), 7.23 (m, 2H, Ar-H),
6.97–6.94 (m, 4H, Ar-H), 6.48 (d, J=8.2 Hz, 2H, Ar-H),
5.42 (s, 1H, bridgehead), 5.00 (s, 1H, bridgehead), 3.49 (s,
3H, OCH3), 1.89 (t, J=11.9 Hz, 2H, Cy-H), 1.72–1.57 (m,
7H, Cy-H), 1.45–1.24 (m, 5H, Cy-H), 1.14 (t, J=12.8 Hz,
2H, Cy-H), 1.09 (t, J=11.9 Hz, 2H, Cy-H), 0.98–0.89 (m,
4H, Cy-H); 13C{1H} NMR (125.5 MHz, CDCl3) d=157.4 (C-
OCH3), 157.1 (d, J=30.5 Hz, C=CP), 146.3 (C6H4Q), 146.1
(C6H4Q), 141.9 (d, J=25.7 Hz, C=CP), 131.0 (C6H3 o-C),
128.8 (C6H3 m-C), 124.1 (C6H3 p-C), 124.0 (C6H4), 123.1
(C6H4), 122.6 (C6H4), 103.8 (C6H4), 59.1 (d, J=6.7 Hz,
bridgehead), 55.2 (OCH3), 54.1 (d, J=6.7 Hz, bridgehead),
34.0 (d, J=11.4 Hz, Cy), 30.4 (d, J=16.2 Hz, Cy), 30.0 (d,
J=9.5 Hz, Cy), 27.5 (d, J=11.4 Hz, Cy), 27.4 (d, J=7.6 Hz,
Cy), 26.6 (Cy); HR-MS (ESI+): m/z=537.2922, exact mass
calcd for C36H42O2P [M+H]+: 537.2921; anal. calcd. for
C36H41O2P: C 80.57, H 7.70; found: C 80.88, H 7.93.
Reduction of 11-(Dicyclohexylphosphinoyl)-12-(2,6-
dimethylphenyl)-9,10-dihydro-9,10-ethenoanthracene
(13a)
A flame-dried Schlenk flask was charged with 13a (1.633 g,
3.14 mmol), toluene (60 mL) and triethylamine (21.7 mL,
157 mmol). Trichlorosilane (4.56 mL, 45.2 mmol) was added
slowly and the mixture heated at 1108C for 3 days. The reac-
tion mixture was diluted with diethyl ether (20 mL) and
added slowly to a mixture of ice (10 g) and 20% aqueous
NaOH (20 mL). After stirring vigorously at room tempera-
ture for 30 min, the organic layer was removed and the
aqueous phase extracted with diethyl ether (3ꢃ30 mL). The
organic fractions were combined, washed with saturated
aqueous NaHCO3 (2ꢃ20 mL), water (2ꢃ20 mL) and brine
(2ꢃ20 mL), dried over MgSO4, filtered and the solvent re-
moved under vacuum. The product was purified by column
chromatography eluting with hexane/ethyl acetate (93:7), to
afford 14a as a spectroscopically pure pale yellow solid;
yield: 1.09 g (69%); mp 169–1728C. An analytically pure
sample that was also suitable for a single-crystal X-ray study
was obtained by slow diffusion of a chloroform solution lay-
ered with methanol at room temperature; mp 181–1838C.
31P{1H} NMR (202.5 MHz, CDCl3): d=À12.36; 1H NMR
(300 MHz, CDCl3): d=7.32 (d, J=11.7 Hz, 2H, Ar-H), 7.25
(d, J=7.8 Hz, 2H, Ar-H), 7.09 (t, J=6.9 Hz, 1H, Ar-H),
7.02–6.97 (m, 6H, Ar-H), 5.52 (br s, 1H, bridgehead), 5.05
(s, 1H, bridgehead), 1.91 (br d, J=7.8 Hz, 2H, Cy-H), 1.79
(s, 6H, CH3), 1.71–1.62 (m, 8H, Cy-H), 1.57 (br d, J=
11.0 Hz, 2H, Cy-H), 1.31–1.19 (m, 4H, Cy-H), 1.11–0.97 (m,
6H, Cy-H); 13C{1H} NMR (125.5 MHz, CDCl3): d=163.0 (d,
J=36.1 Hz, C=CP), 145.9 (C6H4Q), 145.6 (C6H4Q), 142.5 (d,
J=32.3 Hz, C=CP), 139.7 (C6H3Q), 135.5 (C6H3 o-C), 127.3
(C6H3 m-C), 127.3 (C6H5 p-C), 124.7 (C6H4), 124.6 (C6H4),
123.3 (C6H4), 123.1 (C6H4), 59.3 (d, J=6.7 Hz, bridgehead
CH), 54.1 (d, J=5.7 Hz, bridgehead CH), 34.2 (d, J=
11.4 Hz, Cy), 31.1 (d, J=8.6 Hz, Cy), 30.4 (d, J=14.3 Hz,
Cy), 27.5 (Cy), 27.4 (Cy), 26.5 (Cy), 21.3 (CH3); HR-MS
(ESI+): m/z=505.3024, exact mass calcd. for C36H42P [M+
H]+: 505.3043; anal. calcd. for C36H41P: C 85.67, H 8.19;
found: C 85.92, H 8.43.
Synthesis of 11-(Dicyclohexylphosphinoyl)-9,10-
dihydro-9,10-etheneoanthracene (15)
A
100-mL stainless steel autoclave was charged with
dicyclohexyl(ethynyl)phosphine oxide 11 (0.504 g,
AHCTUNGTRENNUNG
1.90 mmol), toluene (10 mL) and anthracene (1.160 g,
6.5 mmol), flushed with nitrogen, and heated to 2008C.
After 36 h, the autoclave was turned off, allowed to cool,
and the reaction mixture extracted into dichloromethane
(20 mL). The solvent was removed under reduced pressure
and the resulting peach-coloured residue purified by column
chromatography, eluting with CH2Cl2/ethyl acetate (1:1), to
afford 15 as an off-white solid; yield: 0.46 g (54%); mp 203–
2078C; mp 230–2338C. 31P{1H} NMR (161.8 MHz, CDCl3):
1
d= 46.0; H NMR (300.0 MHz, CDCl3): d=7.72 (ddd, J=
16.8, 6.0, 1.8 Hz, 1H, Ar-H), 7.31 (m, 4H, Ar-H), 7.00 (m,
4H, Ar-H), 5.32 (dd, J=6.0, 2.1 Hz, 1H, bridgehead), 5.25
(dd, J=5.4, 1.5 Hz, 1H, bridgehead) 1.91–0.88 (m, 22H. Cy-
H); 13C{1H} NMR (75.5 MHz, CDCl3): d=154.0 (d, J=
3.3 Hz, C=CP), 154.1 (d, J=3.3 Hz, C=CP), 145.3 (d , J=
2.6 Hz, C6H4Q), 145.1 (d , J=2.9 Hz, C6H4Q) , 125.3 (C6H4),
125.0 (C6H4), 123.8 (C6H4), 123.6 (C6H4), 53.0 (d, J=7.6 Hz,
bridgehead), 52.9 (d, J=7.6 Hz, bridgehead), 35.7 (d, J=
68.7 Hz, Cy), 26.9 (d, J=6.7 Hz, Cy), 26.8 (d, J=6.2 Hz,
Cy), 26.7 (Cy), 26.2 (d, J=2.4 Hz, Cy), 25.2 (d, J=2.4 Hz,
Cy); TOF-MS (ES+): m/z=439.2167, exact mass calcd. for
C28H33NaOP [M+Na]+: 439.2164; IR: nmax =2927, 2851,
1620 (C=C), 1159 cmÀ1 (P=O); anal. calcd. for C28H33OP: C
80.74, H 7.99; found: C 80.93, H 8.12.
Reduction of 11-(Dicyclohexylphosphinoyl)-9,10-
dihydro-9,10-etheneoanthracene (15)
Reduction of 11-(Dicyclohexylphosphinoyl)-12-(2,6-
dimethoxyphenyl)-9,10-dihydro-9,10-
ethenoanthracene (13b)
Compound 15 (0.47 g, 1.1 mmol) was reduced according to
the procedure described above for 13a to afford 16 as an
off-white solid after purification by column chromatography,
eluting with hexane/ethyl acetate (9:1); yield: 0.09 g (19%);
mp 147–1518C; mp: 137–1408C. 31P{1H} NMR (161.8 MHz,
CDCl3): d=À0.3; 1H NMR (400.0 MHz, CDCl3): d=7.18
Compound 13b was reduced according to the procedure de-
scribed above for 13a on the same scale to afford the de-
sired product as an off-white solid after purification by
column chromatography, eluting with hexane/ethyl acetate
Adv. Synth. Catal. 2010, 352, 201 – 211
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
209

Simon Doherty et al.
UPDATES
(m, 4H, Ar-H), 7.16 (m, 1H, Ar-H), 6.86 (m, 4H, Ar-H),
5.20 (s, 1H, bridgehead), 5.15 (d, J=5.5 Hz, 1H, bridge-
head), 1.85–0.75 (m, 22H, Cy-H); 13C{1H} NMR
(100.5 MHz, CDCl3): d=151.0 (d, J=33.5 Hz, C=CP), 145.8
(C6H4Q), 145.5 (C6H4Q), 15.0 (d, J=27.1 Hz, C=CP), 124.4
(C6H4), 124.2 (C6H4), 123.6 (C6H4), 123.1 (C6H4), 54.6 (d, J=
6.7 Hz, bridgehead), 52.4 (d, J=6.7 Hz, bridgehead), 33.0 (d,
J=7.9 Hz, Cy), 30.1 (d, J=4.3 Hz, Cy) 30.0 (Cy), 27.3 (d,
J=8.6 Hz, Cy), 27.1 (d, J=6.4 Hz, Cy), 26.4 (Cy); TOF-MS
(ES+): m/z=401.2403, exact mass calcd. for C28H34P [M+
H]+: 401.2398; IR: nmax =2925, 2820, 1620 cmÀ1 (C=C).
Acknowledgements
We gratefully acknowledge Johnson Matthey for generous
loans of palladium salt and the EPSRC for an equipment
grant.
References
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General Procedure for the Amination of Aryl
Halides
A flame-dried Schlenk flask was charged with tris(dibenzyli-
deneacetone)dipalladium (4.6 mg, 0.005 mmol), KITPHOS
(0.025 mmol), sodium tert-butoxide (0.134 g, 1.40 mmol),
decane (0.194 mL, 1 mmol) and toluene (2.0 mL) under ni-
trogen. Aryl halide (1.00 mmol) and amine (1.10 mmol)
were added and the resulting red solution heated at the ap-
propriate temperature with rapid stirring until reaction was
complete, as judged by GC analysis. The reaction mixture
was allowed to cool to room temperature, diluted with di-
ethyl ether (2–3 mL), passed through a short plug of silica
and the solvent removed to leave a yellow solid. Known
products were characterized by NMR spectroscopy and
mass spectrometry, and unknown products by NMR spec-
troscopy, mass spectrometry and high-resolution mass spec-
trometry (HR-MS).
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General Procedure for the Suzuki–Miyaura Coupling
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(2.2 mg, 0.01 mmol), KITPHOS (0.025 mmol), potassium
phosphate (0.424 g, 2.00 mmol), boronic acid (1.50 mmol),
decane (0.194 mL, 1 mmol) and toluene (2.0 mL) under ni-
trogen. Aryl chloride (1.00 mmol) was added and the result-
ing mixture heated at the required temperature and moni-
tored by GC analysis. After allowing the reaction mixture to
cool to room temperature, diethyl ether (2 mL) and water
(2 mL) were added, the organic layer passed through a short
silica plug, and the solvent removed to leave a yellow solid.
Known products were characterized by NMR spectroscopy
and mass spectrometry, and unknown products by NMR
spectroscopy, mass spectrometry and high-resolution mass
spectrometry (HR-MS).
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Supporting Information
General comments, synthesis and characterization data for
alkynylphosphine oxides 10a and b and details of catalyst
testing are available as Supporting Information. For 14a
(CCDC 740817), details of crystal data, structure solution
and refinement, atomic coordinates, bond distances, bond
lengths and anisotropic displacement parameters in CIF
format can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_
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Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax:
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210
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À
À
C C and C N bond formation, a host of other mono-
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heterocyclic carbenes, secondary dialkylphosphine
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