Cooperativity in bimetallic dihydroalkoxylation catalysts built on aromatic scaffolds: Significant rate enhancements with a rigid anthracene scaffold

Article abstract of DOI:10.1021/om2007826

This work describes investigations into metal-catalyzed sequential reactions using a series of single metal and bimetallic Rh(I) and/or Ir(I) pyrazolyl complexes. Monometallic complexes with bis(1-pyrazolyl)methane (bpm) ligands [M(CO)₂(bpm)]BAr^F ₄ (1), bimetallic complexes [M₂(CO)₂(L_scaffold)][BAr^F ₄]₂ (2-4) where M = Rh(I) or Ir(I) bearing bitopic ligands L_scaffold = bis(1-pyrazolyl)methane-derived ligands, p-C ₆H₄[CH(pz)₂]₂ (L_p), m-C₆H₄[CH(pz)₂]₂ (L_m), and anthracene-bridged 1,8-C₁₄H₈[CH(pz)₂] ₂ (L_Ant), [M₂(CO)₄(L _p)]-[BAr^F ₄]₂ (2), [M ₂(CO)₄(L_m)][BAr^F ₄] ₂ (3), and [M₂(CO)₄(L_Ant)][BAr ^F ₄]₂ (4) were used as catalysts. The efficiency of the complexes as catalysts was tested for the dihydroalkoxylation of a series of alkyne diol substrates, 2-(6-hydroxyhex-1-ynyl)benzyl alcohol (5), 1-methyl-3-heptyne-1,7-diol (6), 2-(5-hydroxypent-1-ynyl)benzyl alcohol (7), and 2-(4-hydroxybut-1-ynyl)benzyl alcohol (8), forming spiroketals. All complexes tested were highly effective catalysts for the intramolecular dihydroalkoxylation reaction. The homobimetallic complexes 2-4 showed significant enhancement in activity and selectivity relative to the single metal catalysts (1). The order of catalytic activity of the bimetallic complexes was found to be [M₂(CO)₄(L_Ant)][BAr^F ₄]₂ > [M₂(CO)₄(L _m)][BAr^F ₄]₂ > [M ₂(CO)₄(L_p)][BAr^F ₄] ₂ for all substrates, and the bimetallic cooperativity index was established for each reaction.

Full text of DOI:10.1021/om2007826

Article
pubs.acs.org/Organometallics
Cooperativity in Bimetallic Dihydroalkoxylation Catalysts Built on
Aromatic Scaffolds: Significant Rate Enhancements with a Rigid
Anthracene Scaffold
Joanne H. H. Ho,† Sandra W. S. Choy,† Stuart A. Macgregor,‡ and Barbara A. Messerle*,†
†School of Chemistry, University of New South Wales, Kensington, NSW, 2052 Australia
‡School of Engineering and Physical Sciences, Heriot-Watt University, Edinburgh, EH14 4AS, U.K.
ABSTRACT: This work describes investigations into metal-catalyzed sequential
reactions using a series of single metal and bimetallic Rh(I) and/or Ir(I) pyrazolyl
complexes. Monometallic complexes with bis(1-pyrazolyl)methane (bpm) ligands
[M(CO)2(bpm)]BArF (1), bimetallic complexes [M2(CO)2(Lscaffold)][BArF ]
4
4 2
(2−4) where M = Rh(I) or Ir(I) bearing bitopic ligands Lscaffold = bis(1-
pyrazolyl)methane-derived ligands, p-C6H4[CH(pz)2]2 (Lp), m-C6H4[CH(pz)2]2
(Lm), and anthracene-bridged 1,8-C14H8[CH(pz)2]2 (LAnt), [M2(CO)4(Lp)]-
[BArF ] (2), [M2(CO)4(Lm)][BArF ] (3), and [M2(CO)4(LAnt)][BArF ] (4)
4 2
4 2
4 2
were used as catalysts. The efficiency of the complexes as catalysts was tested for
the dihydroalkoxylation of a series of alkyne diol substrates, 2-(6-hydroxyhex-1-
ynyl)benzyl alcohol (5), 1-methyl-3-heptyne-1,7-diol (6), 2-(5-hydroxypent-1-
ynyl)benzyl alcohol (7), and 2-(4-hydroxybut-1-ynyl)benzyl alcohol (8), forming
spiroketals. All complexes tested were highly effective catalysts for the intramolecular dihydroalkoxylation reaction. The
homobimetallic complexes 2−4 showed significant enhancement in activity and selectivity relative to the single metal catalysts
(1). The order of catalytic activity of the bimetallic complexes was found to be [M2(CO)4(LAnt)][BArF ]2
>
4
[M2(CO)4(Lm)][BArF ] > [M2(CO)4(Lp)][BArF ] for all substrates, and the bimetallic cooperativity index was established
4 2
4 2
for each reaction.
approximately inversely proportional to the intermetallic
distance of the two metal centers.8
INTRODUCTION
■
In recent years there has been increasing focus on the
application of bimetallic complexes as homogeneous cata-
lysts,1−6 and the highly desired synergistic effect that can occur
upon using bimetallic catalysts has been shown in some cases to
lead to more effective catalysis. Having two metal centers in
close proximity (3.5−6.0 Å) may in some cases lead to
enhanced substrate activation or to a more stabilized reaction
center.7 Thus far, bimetallic catalyst systems have been
extensively studied for a number of single-step organic
transformations, such as Yuen and Marks’ binuclear organo-
lanthanide catalyst for hydroamination6 and Broussard and co-
workers' [Rh2(nbd)2(et,ph-P4)]2+ active catalyst for hydro-
formylation.5 In 2002, Jones and James investigated the use of
Pt/Pd bimetallic complexes as catalysts for a Heck coupling
reaction and reported the bimetallic catalyst systems to be more
active than the predicted sum of activities of the monometallic
“half-unit” analogues. As a result, they proposed a bimetallic
cooperativity index (α) as a measure of intermetallic
cooperativity between adjacent metal centers in a multimetallic
complex with n metal centers.3 Bimetallic “constrained
geometry” catalysts consisting of homobimetallic titanium
(Ti2) and zirconium (Zr2) complexes, as well as a
heterobimetallic TiZr complex for ethylene polymerization,
have shown that the degree of bimetallic cooperativity between
the metal centers in the olefin polymerization reactions is
One-pot tandem reactions allow highly efficient approaches
to the synthesis of complex compounds via the formation of
several bonds in a single synthetic operation without requiring
the isolation of intermediates, addition of reagents, or changing
of reaction conditions.9 This approach is particularly important
in the synthesis of natural products, such as berkelic acid10 and
aspidophytine.11 As a result, transition metal catalyzed one-pot
tandem organic transformations have received increasing
attention as more efficient and atom-economical approaches
to organic heterocycles over traditional multiple single-step
reactions.12 Single metal complexes of Ru(II), Rh(I), and Ir(I)
have been previously reported to successfully catalyze tandem
reactions of olefin metathesis,12 hydroformylation,12 dihydroal-
koxylation,13,14 and hydroamination/hydrosilylation15 in good
yields and under mild reaction conditions. Multimetallic
complexes can also be particularly useful for catalyzing tandem
reactions, as multiple metal centers can interact with each other
more efficiently for sequential step reactions than monometallic
complexes.7 Comparably less has been reported of bimetallic
catalysts for tandem sequential transformations.16 One such
example has been reported by Peris and co-workers in 2008,
where heterobimetallic complexes using triazolyl-diylidine
Received: August 23, 2011
Published: October 20, 2011
© 2011 American Chemical Society
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scaffolds were shown to be highly effective catalysts for a
tandem two-step reaction involving the oxidative cyclization of
2-aminophenyl ethyl alcohol, followed by alkylation of the
resulting imidazole with a primary alcohol. The IrI(COD)/
Cp*IrIII bimetallic catalyst system displayed cooperative effects
with catalytic activity far exceeding the sum of the individual
activities of the Cp*IrIIICl2 and IrICl(COD) complexes.17
The catalyzed one-pot tandem organic transformation
approach has been used for the efficient synthesis of spiroketals,
biologically active compounds found as components of HIV
protease inhibitors,18 cancer cell inhibitors,19 and insect sex
pheromones.20 Traditional approaches to the synthesis of
spiroketals often involve relatively harsh reaction conditions
and multiple steps that require further purification.21,22 A more
direct route to the synthesis of spiroketals is the transition
metal catalyzed dihydroalkoxylation of alkyne diols.13,14,23 This
sequential two-step transformation involves the initial intra-
molecular hydroalkoxylation of an alkyne to form the first O-
heterocycle (step A of Scheme 1), followed by a second
Scheme 1. Tandem Two-Step Dihydroalkoxylation Reaction
Figure 1. Bimetallic complexes employing binucleating ligands p-
C6H4[CH(pz)2]2 (Lp), m-C6H4[CH(pz)2]2 (Lm), and 1,8-C14H8[CH-
(pz)2]2 (LAnt).
cyclization to complete the spiroketal moiety (step B of Scheme
1).13 There have been several reports of the metal-catalyzed
dihydroalkoxylation reaction, using Rh(I),13,14,23 Ir(I),13,14,23
Pt(II),24 and Pd(II),25,26 complexes as well as Ir(III) hydrides,27
Hg salts,28 and Au(I) and Au(III) halides29,30 as catalysts.
However the use of bimetallic complexes as catalysts for this
two-step dihydroalkoxylation reaction has not yet been
reported.
1
progress was monitored by H NMR spectroscopy at regular
intervals, where conversion of substrate to product was
determined by integration of the product resonances relative
1
to the substrate resonances in the H NMR spectra. Catalytic
efficiency was measured by the TOF (h−1) taken at the point of
50% conversion of substrate to product, as the amount of
product formed by one mole of catalyst per hour. The alkyne
diol substrates screened included 2-(6-hydroxyhex-1-ynyl)-
benzyl alcohol (5), 1-methyl-3-heptyne-1,7-diol (6), 2-(5-
hydroxypent-1-ynyl)benzyl alcohol (7), and 2-(4-hydroxybut-
1-ynyl)benzyl alcohol (8).
We have previously reported the use of Rh(I) and Ir(I) single
metal complexes bearing 1-[2-(diphenylphosphino)ethyl]-
pyrazole (PyP) and bis(N-methylimidazol-2-yl)methane
(bim) ligands as catalysts for the dihydroalkoxylation
reaction.13 More recently we have also shown that Rh(I) and
Ir(I) complexes bearing bis(1-pyrazolyl)methane (bpm)
ligands, including both monometallic catalysts and dual-metal
catalysts where two monometallic complexes are used
simultaneously, are highly efficient catalysts for the dihydroal-
koxylation of alkyne diols.23 Significant enhancement of
reaction rates was observed in some cases using the dual-
metal catalyst systems.23 We have also recently reported the
synthesis of a series of bimetallic Rh(I) and Ir(I) complexes
[M2(CO)4(Lp)][BArF ] (2), [M2(CO)4(Lm)][BArF ]2 (3),
According to Baldwin’s rules, there is a potential for
regioselectivity toward either 5-exo or 6-endo ring cyclization
in the dihydroalkoxylation of alkyne diols such as those used
here.32 The rate and regioselectivity of the cyclization can be
influenced by several factors including the open-chain structure
of the substrate or substituents on the substrate and the size of
the ring that is formed. We have previously reported that the
efficiency of the ring cyclization as catalyzed by Rh(I) and Ir(I)
complexes with bpm ligands was primarily dependent on the
ring sizes of the products that are formed. Additionally, the
monometallic Ir(I) catalysts with bpm ligands were found to
promote 5-exo ring cyclization with greater efficiency than their
Rh(I) counterparts, while the monometallic Rh(I) catalysts
were more effective for the 6-endo ring cyclization than the Ir(I)
catalysts.23 We were interested in establishing the effect of
bimetallic catalysts for these reactions.
4 2
4
and [M2(CO)4(LAnt)][BArF ] (4) (Figure 1).31 Here we
4 2
report the catalytic activities of bimetallic complexes 2−4 for
the intramolecular dihydroalkoxylation of alkyne diols and
investigate the bimetallic cooperativity the complexes display.
RESULTS AND DISCUSSION
■
Regioselectivity: Dependence on Metal Center. a.
Cyclization of 2-(6-Hydroxyhex-1-ynyl)benzyl Alcohol (5).
The catalyzed double cyclization reaction of the alkyne diol 2-
(6-hydroxyhex-1-ynyl)benzyl alcohol (5) using both the
monometallic and bimetallic Rh(I) and Ir(I) complexes 1−4
led to the formation of product 5a exclusively, which resulted
from two 6-endo cyclizations. Each of the catalyzed reactions
Catalyzed Dihydroalkoxylation of Alkyne Diols. The
aim of this study was to evaluate the catalytic efficiency of a
series of bimetallic complexes (2−4) as catalysts for the
dihydroalkoxylation of alkyne diols in the synthesis of
spiroketals and establish the degree of bimetallic cooperativity.
The Rh(I) and Ir(I) bimetallic catalyst systems, 2−4, as well as
their monometallic analogues [M(CO)2(bpm)]BArF (1.1 and
4
1.2), were assessed for their catalytic activity for the cyclization
of a series of alkyne diol substrates (5−8). The reaction
using the homobimetallic complexes [Rh2(CO)4(Lm)][BArF ]
4 2
(3.1), [Ir2(CO)4(Lm)][BArF ]2 (3.2), [Rh2(CO)4(LAnt)]-
4
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a
Table 1. Catalyzed Tandem Dihydroalkoxylation of Alkyne Diol 5 into the 6,6-Spiroketal Product 5a
b
b
catalyst [M] or [M2]
time [h]
conv [%]
TOF [h−1
]
catalyst [M] or [M2]
time [h]
conv [%]
TOF [h−1
]
[Rh(CO)2(bpm)]BArF (1.1)
1.59
0.59
1.20
0.47
0.50
0.37
98
98
98
98
98
98
98
102
152
218
644
480
1012
974
[Ir(CO)2(bpm)]BArF (1.2)
12.67
17.63
23.80
18.92
52
86
60
68
4
5
4
4
c
c
[Rh(CO)2(bpm)]BArF (1.1)
[Ir(CO)2(bpm)]BArF (1.2)
4
4
c
c
[Rh2(CO)4(Lp)][BArF ]2 (2.1)
[Ir2(CO)4(Lp)][BArF ]2 (2.2)
6
4
4
[Rh2(CO)4(Lm)][BArF ]2 (3.1)
[Ir2(CO)4(Lm)][BArF ]2 (3.2)
12
4
4
c
[Rh2(CO)4(Lm)][BArF ]2 (3.1)
4
[Rh2(CO)4(LAnt)][BArF ]2 (4.1)
[Ir2(CO)4(LAnt)][BArF ]2 (4.2)
7.28
70
28
4
4
c
[Rh2(CO)4(LAnt)][BArF ]2 (4.1)
0.30
4
a
b
c
1
Determined by H NMR spectroscopy. Time taken for product conversion. C2D2Cl4 was used as the solvent instead of CDCl3.
[BArF ]2 (4.1), and [Ir2(CO)4(LAnt)][BArF ]2 (4.2) was
Table 2. Catalyzed Tandem Dihydroalkoxylation of Alkyne
Diol 6 into the Nonaromatic 5,5-Spiroketal Product (6a)
4
4
a
performed at 60 °C in CDCl3 for the double cyclization
reaction of alkyne diol 5 (Table 1). The catalyzed reactions
using the para-substituted phenyl complexes [Rh2(CO)4(Lp)]-
[BArF ] (2.1) and [Ir2(CO)4(Lp)][BArF ] (2.2) were each
4 2
4 2
carried out with C2D2Cl4 as solvent due to their lack of
solubility in CDCl3 at 60 °C. The catalyzed reactions using
complexes 3.1 and 4.1 were also carried out using C2D2Cl4 as
solvent so that the efficiencies of the bimetallic complexes can
be compared in the different solvents (Table 1).
Overall, the rhodium complexes were found to be superior
catalysts compared to their iridium analogues in the formation
of the 6,6-spiroketal 5a, achieving turnover frequencies greater
than 100 h−1 and quantitative conversions in less than two
hours (Table 1). The same preference was found previously,
where Rh(I) complex 1.1 was observed to promote the
selective formation of the 6,6-spiroketal 5a at a greater rate than
the Ir(I) analogue 1.2.23
b
catalyst [M] or [M2]
time [h]
conv [%]
TOF [h−1
]
[Rh2(CO)4(LAnt)][BArF ]2 (4.1)
16.1
4.87
22.5
3.15
1.17
92
92
95
95
92
48
25
4
[Ir(CO)2(bpm)]BArF (1.2)
4
c
[Ir2(CO)4(LP)][BArF ]2 (2.2)
10
4
[Ir2(CO)4(LM)][BArF ]2 (3.2)
84
4
[Ir2(CO)4(LAnt)][BArF ]2 (4.2)
326
4
a
b
Determined by 1H NMR spectroscopy. Time taken for product
c
conversion. C2D2Cl4 used as solvent instead of CDCl3.
For cyclizing alkyne diol 6, the order of activity of the iridium
complexes in terms of TOF is Ir2(LAnt) > Ir2(Lm) > Ir(bpm) >
Ir2(Lp) (Table 2). Chart 1 compares the reaction profiles for
For both the rhodium and iridium complexes, the order of
activity for the double cyclization of 5 is M2(LAnt) > M2(Lm) >
M2(Lp) > M(bpm). All of the bimetallic complexes were more
reactive than their monometallic equivalents for the dihy-
droalkoxylation reaction of 5. The dirhodium and diiridium
complexes where the two metals are held on the anthracene
scaffold, M2(LAnt), were in all cases the best catalyst systems.
They are much more active than the corresponding meta-
phenylene-linked bimetallic complexes, M2(Lm), which are in
turn better than the para-phenylene-linked complexes, M2(Lp)
(Table 1).
Chart 1. Reaction Profiles of the Iridium-Catalyzed
Dihydroalkoxylation of 1-Methyl-3-heptyne-1,7-diol (6) to
Give Spiroketal 6a in CDCl3 at 60 °C with 0.5 mol %
[ I r 2 ( C O ) 4 ( L A n t ) ] [ B A r F
]
,
4 . 2 ( ▲ ) ,
4
2
[Ir2(CO)4(Lm)][BArF ] , 3.2 (×), [Ir(bpm)(CO)2]BArF ,
4 2
4
1.2 (◇), or [Ir2(CO)4(Lp)][BArF ] , 3.2 (■)
4 2
b. Cyclization of 1-Methyl-3-heptyne-1,7-diol (6). The
catalytic activity for the dihydroalkoxylation of the allylic
alkyne diol 1-methyl-3-heptyne-1,7-diol (6) of the diiridium
complexes, 2.2, 3.2, and 4.2, and the most active dirhodium
complex, 4.1, was investigated in CDCl3 or C2D2Cl4 at 60 °C
(Table 2). The reaction proceeded in all cases to exclusively
form the 5,5-spiroketal 6a without any other byproducts. We
have previously reported Ir(I) catalysts to be more active than
the Rh(I) complexes for promoting the formation of 5,5-
spiroketals from the alkyne diol substrates,23 and therefore only
the best Rh(I) catalyst system (4.1) was compared here against
a series of Ir(I) catalysts. The iridium complexes were
confirmed to be superior catalysts over [Rh2(CO)4(LAnt)]-
[BArF ] (4.1). [Ir2(CO)4(LAnt)][BArF ] (4.2) was the best
the iridium complexes, showing the distinct differences between
each of the diiridium complexes. [Ir2(CO)4(LAnt)][BArF ]2
4
(4.2) exhibits a remarkably enhanced reactivity, with the
most rapid initial reaction rate, giving the desired spiroketal in a
reaction time of 1.17 h even at a low catalyst loading of 0.5 mol
%. Once again, the high reactivity of the meta-phenylene and
anthracene-bimetallic complexes shows that a bimetallic
4 2
4 2
catalyst for the formation of the 5,5-spiroketal (6a), where a
turnover frequency of 326 h−1 and conversion of 92% in
approximately one hour was observed.
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Table 3. Catalyzed Tandem Dihydroalkoxylation of Alkyne Diol 7 into the 6,5-Spiroketal (7a) and 5,6-Spiroketal (7b)
a
Products
b
b
catalyst [M] or [M2]
time [h]
conv 7a:7b
TOF [h−1
]
catalyst [M] or [M2]
time [h]
conv 7a:7b
TOF [h−1
]
[Rh(CO)2(bpm)]BArF (1.1)
0.22
0.10
0.06
1.4:1
1.7:1
1.4:1
1.3:1
961
3174
5988
9523
[Ir(CO)2(bpm)]BArF (1.2)
0.58
0.70
0.55
0.27
1.1:1
1.4:1
1.4:1
1.7:1
374
826
4
4
[Rh2(CO)4(Lp)][BArF ]2 (2.1)
[Ir2(CO)4(Lp)][BArF ]2 (2.2)
4
4
[Rh2(CO)4(Lm)][BArF ]2 (3.1)
[Ir2(CO)4(Lm)][BArF ]2 (3.2)
1092
2468
4
4
[Rh2(CO)4(LAnt)][BArF ]2 (4.1)
0.08
[Ir2(CO)4(LAnt)][BArF ]2 (4.2)
4
4
a
b
1
Determined by H NMR spectroscopy. Time taken to reach >98% conversion of substrate to 7a and 7b.
cooperative pathway is likely to exist in the catalyzed
dihydroalkoxylation reaction.
Formation of Spiroketals with Mixed Ring Sizes. The
catalyzed dihydroalkoxylation reactions of alkyne diols 7 and 8
were carried out in C2D2Cl4 at 100 °C, each leading to two
products of different ring sizes (Tables 3 and 5). These
reactions proceeded notably faster than the dihydroalkoxylation
reactions of alkyne diols 5 and 6, which exclusively form single
products of a single ring size.
Cyclization of 2-(5-Hydroxypent-1-ynyl)benzyl Alcohol (7)
Yielding Both 5,6- and 6,5-Spiroketals. The efficiency of the
homobimetallic complexes as catalysts for the cyclization of 2-
(5-hydroxypent-1-ynyl)benzyl alcohol (7) to produce the
mixed 5,6- and 6,5-spiroketals (7a and 7b) was also investigated
using 0.50 mol % of the respective homobimetallic complexes
in C2D2Cl4 at 100 °C (Table 3). All of the homobimetallic
complexes were found to be much more active than their
respective monometallic analogues in promoting the cyclization
of 7. Of note is the change in regioselectivity from the
monometallic to the bimetallic catalyzed reaction, where
increased formation of 7a over 7b was observed in the
presence of the bimetallic complexes. In terms of bimetallic
reactivity, the anthracene-linked bimetallic complexes (4.1 and
4.2) were again more effective than the meta-phenylene
complexes (3.1 and 3.2), while the para-phenylene analogues
(2.1 and 2.2) were the least efficient bimetallic catalysts. This
order of bimetallic reactivity corresponds to the order of
reactivity for the catalyzed cyclization of alkyne diols (5 and 6)
described above. The Rh(I) complexes were consistently
superior catalysts to their Ir(I) analogues for this cyclization.
To establish the dependence of the catalyst efficiency on
catalyst loading, the catalyst loading of the dirhodium complex
Table 4. Conversion of Alkyne Diol 7 to Form 7a and 7b
with Variation in Both Temperature and Catalyst Loading
U s i n g [ R h 2 ( C O ) 4 ( L m ) ] [ B A r F
]
( 3 . 1 ) a n d
4
2
a
[Rh2(CO)4(LAnt)][BArF ] (4.1)
4 2
temp
[°C]
[M2]
mol %
time
b
conv
7a:7b
TOF
[h−1
catalyst [M2]
[h]
]
[Rh2(CO)4(L )]
25
0.50
0.50
0.50
0.50
0.25
0.10
2.42
0.16
0.08
0.06
0.09
0.24
0.5:1
0.8:1
0.8:1
1.4:1
1.3:1
1.3:1
72
Ant c
[BArF ]2 (4.1)
4
[Rh2(CO)4(LAnt)]
60
3424
[BArF ]2 (4.1)
4
[Rh2(CO)4(L )]
100
100
100
100
9522
Ant d
[BArF ]2 (4.1)
4
Rh2(CO)4(Lm)]
5988
[BArF ]2 (3.1)
4
Rh2(CO)4(Lm)]
8334
[BArF ]2 (3.1)
4
Rh2(CO)4(Lm)]
13 812
[BArF ]2 (3.1)
4
a
Determined by 1H NMR spectroscopy. C2D2Cl4 used as solvent
b
unless stated otherwise. Time taken to reach >98% conversion of
substrate to 7a and 7b. CD2Cl2 used as solvent. 97% conversion.
c
d
[Rh2(CO)4(Lm)][BArF ] (3.1) was varied from 0.50 mol % to
4 2
Table 5. Catalyzed Tandem Dihydroalkoxylation of Alkyne
Diol 8 into the 5,5-Spiroketal Product (8a) and
Monocyclized Product (8b)
0.25 mol % and 0.10 mol % (Table 4). No significant decrease
in reaction time was observed on decreasing the catalyst
loading. Indeed, the use of 0.10 mol % [Rh2(CO)4(Lm)]-
a
[BArF ] (3.1) for the catalyzed cyclization of 7 leads to
4 2
quantitative (>98%) conversion of the spiroketal products 7a
and 7b in 0.24 h, with a turnover frequency at 50% conversion
of 13 812 h−1 (Table 4). Although the initial reaction rate was
consistently higher with lower catalyst loading, the reaction
time for complete conversion increased slightly at the lowest
loading used. This suggests that this is the lower limit for
improving the effective catalyst loading. The temperature
dependence of the catalysis was established for
b
catalyst [M] or [M2]
time [h]
conv 8a:8b TOF [h−1
]
[Rh(CO)2(bpm)]BArF (1.1)
0.09
0.18
1.8:1
1.5:1
2.3:1
3.6:1
6.2:1
6.4:1
14.7:1
1121
2008
>3030
535
4
[Rh2(CO)4(Lm)][BArF ]2(3.1)
4
c
[Rh2(CO)4(LAnt)][BArF ]2 (4.1)
<0.03
4
[Ir(CO)2(bpm)]BArF (1.2)
0.42
0.33
0.23
0.14
[Rh2(CO)4(LAnt)][BArF ] (4.1) for the dihydroalkoxylation
4
4 2
[Ir2(CO)4(Lp)][BArF ]2 (2.2)
2066
2408
2754
4
of 7 (Table 4). As expected, changing the temperature from
100 °C to 60 °C and 25 °C led to an increase in substrate
conversion times (0.08 h to 0.16 h to 2.42 h) and a decrease in
turnover frequencies (9522 h−1 to 3424 h−1 to 72 h−1).
Remarkably, the double cyclization reaction of 7 proceeds well
[Ir2(CO)4(Lm)][BArF ]2 (3.2)
4
[Ir2(CO)4(LAnt)][BArF ]2 (4.2)
4
a
b
1
Determined by H NMR spectroscopy. Time taken to reach >98%
c
conversion of substrate to 8a and 8b. Reaction completed in less than
1.8 min.
using 0.50 mol % of [Rh2(CO)4(LAnt)][BArF ] (4.1) at room
4 2
temperature, with quantitative conversion in 2.42 h.
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b. Cyclization of 2-(4-Hydroxybut-1-ynyl)benzyl Alcohol
(8). The catalyzed reaction of alkyne diol 2-(4-hydroxybut-1-
ynyl)benzyl alcohol 8 was carried out in C2D2Cl4 at 100 °C to
give a mixture of the double-cyclized 5,5-spiroketal (8a) and
monocyclized pyran (8b) products. Both rhodium and iridium
complexes were found to be highly efficient catalysts for this
reaction, with all catalysts achieving quantitative conversion in
less than half an hour (Table 5). Rhodium catalysts were faster
than iridium catalysts in carrying out the overall reaction, with
dirhodium catalyst 4.1 being the most efficient, achieving a
turnover frequency greater than 3030 h−1. However, signifi-
cantly higher selectivity for 5-exo cyclization is observed for the
iridium-catalyzed systems, in particular for complex 4.2, where
a product conversion ratio of 8a:8b = 14.7:1 was obtained. This
provides another example where Ir(I) catalysts are more
efficient at promoting 5-exo cyclization than Rh(I) catalysts.
The efficiency of the Ir(I) catalysts for the double cyclization to
form 8a notably decreases in the order Ir2(LAnt) > Ir2(LM) >
Ir2(LP) > Ir(bpm).
diol 7 in less than five minutes with a TOF of 9523 h−1 (Table
6). This suggests that for bimetallic catalyst systems the
catalytic efficiency for the dihydroalkoxylation of 7 is enhanced
to a greater degree by the cooperativity within the bimetallic
complex than is achieved by the cooperativity between the two
different metal complexes of the dual catalyst system.
Bimetallic Cooperativity: Dependence of Catalytic
Efficiency on Scaffold Structure. The bimetallic catalyst
systems used here are highly efficient and more importantly
demonstrate enhanced catalytic activity compared to their
monometallic analogues. This indicates that the presence of a
second metal in the bimetallic catalyst system produces a
synergistic or cooperative effect between adjacent metal
centers, which is absent in a monometallic catalyst system of
equivalent metal catalyst loading.
The cooperativity index (α), previously proposed by Jones
and James, was used in this work to gauge the degree of
intermetallic cooperativity of the bimetallic catalyst systems
(Table 7).3 The cooperativity index α was calculated using eq 1,
Single- versus Dual- Catalyst Systems. We have
previously reported a dual Rh(I)/Ir(I) monometallic catalyst
system that is highly efficient for the dihydroalkoxylation of 2-
(5-hydroxypent-1-ynyl)benzyl alcohol (7).23 The dual catalyst
system combining monometallic Rh(I) (1.1) and Ir(I) (1.2)
complexes was found to proceed at a rate approximately 17
times greater than the single Rh(I) (1.1) catalyst system at
equivalent metal catalyst loading (Table 6). The dual Rh(I)/
Table 7. Bimetallic Cooperativity Indices for the Catalyzed
Dihydroalkoxylation of Alkyne Diols 5, 6, and 7 at 60 °C in
a
C2D2Cl4 unless Otherwise Noted
Table 6. Catalyzed Tandem Dihydroalkoxylation of Alkyne
Diol 7 Using a Series of Monometallic and Bimetallic
a
Complexes
time
b
conv
7a:7b
TOF
[h−1
catalyst [M]
[M] mol %
[h]
]
[Rh(CO)2(bpm)]BArF (1.1)
1.0
0.22
0.13
1.4:1
0.8:1
961
4
[Rh(CO)2(bpm)]BArF (1.1) +
0.50 + 0.50
1694
4
c
[Ir(CO)2(bpm)]BArF4 (1.2)
[Rh2(CO)4(LAnt)][BArF ]2
0.25 + 0.25
0.50
0.23
0.08
0.6:1
1.3:1
5208
9523
(4.1) + [Ir2(CO)4(LAn4t)]
[BArF ]2 (4.2)
4
[Rh2(CO)4(LAnt)][BArF ]2
4
(4.1)
a
1
Determined by H NMR spectroscopy using 1 mol % catalyst in
b
C2D2Cl4 at 100 °C. Time taken to reach >98% conversion of
substrate to 7a and 7b. As previously reported.23
c
Ir(I) catalyst was found to work cooperatively to promote a
highly efficient dual activation pathway for both the 5-exo and
6-endo ring cyclization in the dihydroalkoxylation of alkyne
diols.23 Here a series of dual bimetallic catalyst systems were
screened against single-metal catalyst systems to test the effect
of varying metal centers and investigate the use of “dual”
bimetallic complexes. These reactions were carried out using a
total metal catalyst loading of 1 mol % in C2D2Cl4 at 100 °C
(Table 6).
a
b
1
Determined by H NMR spectroscopy. The index of cooperativity
c
was determined using eq 1. CDCl3 used as solvent.
The dual bimetallic catalyst system {[Rh2(LAnt)] (4.1) +
[Ir2(LAnt)] (4.2)} was more efficient in terms of initial TOF
than either dual monometallic or single monometallic catalysts
(Table 6). More surprisingly, however, is that the single
where Ao is taken as the TOF values at 50% conversion of
substrate to products of the bimetallic catalyst system, and AP as
the predicted total TOF value at 50% conversion of substrate to
products of the multimetallic catalyst with n metal centers (eq
2). For the bimetallic cooperativity index α to be applicable, it is
assumed that the reaction being considered is first order.
Although the kinetics of the catalyzed dihydroalkoxylation
bimetallic catalyst system of [Rh2(CO)4(LAnt)][BArF ] was
4 2
found to be the most efficient catalyst, more efficient than the
dual bimetallic catalyst system of {[Rh2(LAnt)] (4.1) +
[Ir2(LAnt)] (4.2)}. The single [Rh2(CO)4(LAnt)][BArF ]2-
4
catalyzed system achieved quantitative conversion of alkyne
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Organometallics
Article
reaction discussed here is not known, pseudo-first-order
kinetics has been assumed in the first instance (Chart 2).
diol, the presence of an adjacent metal center in a bimetallic
catalyst system may play a similar role to that of methanol for
the intermolecular cyclization. Thus the close proximity of a
second metal center may influence the reactivity of both the
initial and second cyclization steps. In this model, the unbound
metal center orientates and stabilizes the key reaction
intermediates through interactions with the second hydroxyl
group (e.g., Scheme 2, for the second cyclization step). Such an
(1)
(2)
Scheme 2. Proposed Key Intermediate for the Bimetallic
Catalyzed Intramolecular Dihydroalkoxylation of an Alkyne
Diol
Chart 2. Reaction Profile for Rhodium-Catalyzed Tandem
Dihydroalkoxylation of Alkyne Diol 5 into the 6,6-Spiroketal
Product 5a, in CDCl3 at 60 °C with 0.5 mol %
[ R h 2 ( C O ) 4 ( L A n t ) ] [ B A r F 4 ] 2 , 4 . 1 ( ▲ ) ,
F
[ R h ( C O ) ( L ) ] [ B A r
] ,
2
3 . 1 ( × ) ,
2
4
m
4
[ R h 2 ( C O ) 4 ( L p ) ] [ B A r F 4 ] 2 , 2 . 1 ( ■ ) , o r
[Rh(bpm)(CO)2]BArF , 1.1 (◇)
4
intermediate could then facilitate rapid intramolecular addition
to the metal-bound alkene. Similarly in the initial step of the
reaction cycle one of the two metal centers could associate with
the alkyne triple bond, with the second metal weakly interacting
with the first hydroxyl group. As a result, the cooperative effects
of having two metal centers in close proximity can help
accelerate the cyclization steps and achieve greater efficiencies
for the dihydroalkoxylation reaction. A further possibility is that
the alkyne could coordinate initially to both metal centers,
making it more susceptible to nucleophilic attack by the OH
group than would be the case with coordination to a single
metal center.
A consistent increase in the bimetallic cooperativity based on
scaffold structure, M2(Lp) < M2(Lm) < M2(LAnt), was observed
for all of the catalyzed dihydroalkoxylation reactions studied
(Table 7). This phenomenon may be attributed to differences
in structure of the bimetallic catalyst systems. The bimetallic
SUMMARY AND CONCLUSIONS
■
Homobimetallic dirhodium(I) and diiridium(I) complexes
[M2(CO)4(LAnt)][BArF ] (4.1, 4.2) [M2(CO)4(Lm)][BArF ]
4 2
4 2
(3.1, 3.2), and [M2(CO)4(Lp)][BArF ]2 (2.1, 2.2) were
4
investigated as catalysts for the intramolecular dihydroalkox-
ylation of a series of alkyne diol substrates, 2-(6-hydroxyhex-1-
ynyl)benzyl alcohol (5), 1-methyl-3-heptyne-1,7-diol (6), 2-(5-
hydroxypent-1-ynyl)benzyl alcohol (7), and 2-(4-hydroxybut-1-
ynyl)benzyl alcohol (8), forming a series of 5,5- 6,6-, 5,6-, and
6,5-spiroketal units.
In the formation of the 6,6-spiroketals, the dirhodium
complexes were more effective as catalysts for the cyclization of
2-(6-hydroxyhex-1-ynyl)benzyl alcohol (5) than their diiridium
analogues. On the other hand, the diiridium complexes were
found to be more active in cyclizing 1-methyl-3-heptyne-1,7-
diol (6) and 2-(4-hydroxybut-1-ynyl)benzyl alcohol (8) to
produce 5,5-spiroketals.
In comparison to the single metal catalysts, the homo-
bimetallic catalyst systems showed significantly enhanced
activity and selectivity. The order of bimetallic reactivity was
M2(LAnt) > M2(Lm) > M2(Lp), where the anthracene-linked
complexes were observed to be the best catalysts in all of the
dihydroalkoxylation reactions. The enhancement observed was
attributed to cooperativity between the metal pairs, and a
bimetallic intermediate for the reaction pathway is proposed.
The dual bimetallic catalysts did not provide any greater
reactivity enhancement than the most effective single bimetallic
system.
complex [Ir2(CO)4(Lp)][BArF ] (2.2) consistently shows the
4 2
lowest bimetallic cooperativity with the iridium centers on
opposite ends of the phenyl scaffold. The negative α value
obtained for this diiridium catalyst (2.2) suggests that its para-
structure instigates a negative cooperative effect, which slows
the catalyzed tandem dihydroalkoxylation reaction (Table 7).
On the other hand, the more catalytically active
[Rh2(CO)4(LAnt)][BArF ] (4.1) complex with consistently
4 2
the highest cooperativity index has the two rhodium centers on
the same side of the anthracene scaffold and close together in
space. As this species obtained the highest α value of 32.6, this
suggests that having the adjacent metal centers in close
proximity to each other enhances intermetallic cooperativity.
Mechanism. We have previously proposed a mechanism
for the catalyzed intermolecular dihydroalkoxylation of 4-
pentyn-1-ol with methanol.13,33 NMR studies indicated the
cycle is initiated by π-coordination of the metal complex to the
alkyne, followed by nucleophilic attack of the hydroxy group at
the alkyne carbon with the greater carbocation character.13
Recent DFT studies on the mechanism for the Ir(I)
intermolecular catalyzed dihydroalkoxylation of 4-pentyn-1-ol
with methanol indicated that hydrogen bonding between the
alkynol and methanol serves to stabilize the positive charge that
develops at the hydroxyl proton upon ring closure.33 In the case
of the intramolecular catalyzed dihydroalkoxylation of an alkyne
The degree of intermetallic cooperativity was established
using an intermetallic cooperativity index. This indicated that
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the degree of bimetallic cooperativity followed the same trend
as the relative catalytic efficiency, with M2(LAnt) > M2(Lm) >
M2(Lp) in all cases. Where the complexes with the anthracene
scaffolds displayed significant levels of cooperativity between
metals, the complexes with the two complexes located para on
the phenylene backbone typically showed negative coopera-
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activity through bimetallic interactions was observed for the
complexes with the ligand pairs bound to the anthracene
scaffold, this was not the case for the complexes with the
ligands disposed para on the phenylene scaffold. Studies of the
relative stabilities of the three-dimensional structures of the
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EXPERIMENTAL SECTION
■
2-(6-Hydroxyhex-1-ynyl)benzyl alcohol (5),13 1-methyl-3-heptyne-1,7-
diol (6),13 2-(5-hydroxypent-1-ynyl)benzyl alcohol (7),13 2-(4-
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hydroxybut-1-ynyl)benzyl alcohol (8),13 [Rh(CO)2(bpm)]BArF
4
(1.1),34 [Rh2(CO)4(Lp)][BArF ]2 (2.1),31 [Rh2(CO)4(Lm)][BArF ]2
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4
4
(3.1),31 [Rh2(CO)4(LAnt)][BArF ]2 (4.1),31 [Ir(CO)2(bpm)]BArF
4
4
(1.2),34 [Ir2(CO)4(Lp)][BArF ]2 (2.2),31 [Ir2(CO)4(Lm)][BArF ]2
4
4
(3.2),31 and [Ir2(CO)4(LAnt)][BArF ]2 (4.2)31 were prepared
4
according to literature procedures. On cyclization of each of the
alkyne diol substrates, 2-(6-hydroxyhex-1-ynyl)benzyl alcohol (5), 1-
methyl-3-heptyne-1,7-diol (6), 2-(5-hydroxypent-1-ynyl)benzyl alco-
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5,6-, and 6,5-spiroketal units 5a,23 6a,23,35 7a and 7b,13,36 8a,13,36,37
and 8b13,36a were formed, respectively.
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Thermal-catalyzed dihydroalkoxylation reactions were conducted in
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The temperature in the NMR magnet was calibrated using an Omega
microprocessor thermometer (model HH23) or neat ethylene glycol.
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1
The reaction progress was monitored by H NMR spectroscopy at
regular intervals. Characterization of products was confirmed by
literature data. The conversion of substrate to product was determined
by integration of the product resonances relative to the substrate
resonances in the 1H NMR spectra. The TOF (h−1) taken at the point
of 50% conversion of substrate to product was calculated as the
amount of product formed by one mole of catalyst per hour.
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AUTHOR INFORMATION
■
Corresponding Author
*E-mail: b.messerle@unsw.edu.au.
ACKNOWLEDGMENTS
■
Financial support from the Australian Research Council and the
University of New South Wales is gratefully acknowledged.
J.H.H.H. thanks the University of New South Wales for a
University International Postgraduate Award (UIPA).
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