Rh(i)-catalyzed formal [2+2+2] cycloadditions of 1,6-diynes with potassium (Z)-(2-bromovinyl)trifluoroborate: A new strategy and a facile entry to polysubstituented benzene derivatives

Article abstract of DOI:10.1039/c001830a

A new strategy for Rh(i)-catalyzed [2+2+2] cycloadditions of 1,6-diynes with potassium (Z)-(2-bromovinyl)trifluoroborate as the third two-atom unit has been realized, which provides a facile entry to polysubstituented benzene derivatives.

Full text of DOI:10.1039/c001830a

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Rh(I)-catalyzed formal [2+2+2] cycloadditions of 1,6-diynes with
potassium (Z)-(2-bromovinyl)trifluoroborate: a new strategy and
a facile entry to polysubstituented benzene derivativesw
Xianjie Fang, Junyao Sun and Xiaofeng Tong*
Received 27th January 2010, Accepted 22nd March 2010
First published as an Advance Article on the web 15th April 2010
DOI: 10.1039/c001830a
A new strategy for Rh(I)-catalyzed [2+2+2] cycloadditions of
1,6-diynes with potassium (Z)-(2-bromovinyl)trifluoroborate as
the third two-atom unit has been realized, which provides a facile
entry to polysubstituented benzene derivatives.
Several issues have to be addressed to make this new
strategy work. First, the large-scale synthesis of potassium
(2-bromovinyl)trifluoroborate 2 needs to be readily available7
and (Z)-configuration of alkene in 2 is mandatory for the
oxidative addition step. Second, necessary manipulations
should be conducted to avoid potential competition of cyclo-
metallation8 between Rh(I)-complex and 1,6-diyne.
Transition metal catalyzed trimerization of alkynes has been
recognized as one of the most powerful and straightforward
synthetic methods for polysubstituted benzene derivatives.1
Particularly, the cycloaddition between 1,6-diyne 1 and
monoalkynes has attracted increasing attention2 and has been
widely used3 in the field of materials science, fine chemical
synthesis and natural product synthesis. In this context,
rhodium catalysis has shown great potential, with the
considerable successes of high degrees of chemo-, regio- and
even enantioselectivity, as evident from recent reports, which
mainly result from, under mechanistic consideration, the
putative rhodacyclopentadiene Rh(III) intermediate A (part A,
Scheme 1).4 Although these great successes have already been
achieved, new mechanistic strategies for cycloaddition still
remain as an important goal to demonstrate the potentials
of rhodium chemistry. Herein, we report a novel Rh(I)-
catalyzed [2+2+2] cycloaddition of 1,6-diyne 1 with potassium
(Z)-(2-bromovinyl)trifluoroborate 2, in which substrate 2
could be viewed as a novel third two-atom unit (eqn (1) in
Scheme 1). This strategy might provide a complementary
protocol to classical Rh(I)-catalyzed synthesis of poly-
substituented benzene derivatives (part B, Scheme 1).
In the first attempt to test our new strategy, the reaction
between 1a and 2a (1.5 equiv.) was examined in the presence of
10 mol% Rh(OH)(cod) with the mixture of dioxane and water
(20 : 1) as solvent (Table 1, entry 1). To our delight, the desired
[2+2+2] cycloaddition product could be obtained although
the yield was only 7% (Table 1, entry 1). The ligand had a
positive effect on reaction yield (entries 2 and 3), PPh3 seemed
to be better than BINAP (entry 7). Addition of caesium
fluoride also played an important role, increasing the yield
to 57% (entry 4). Other Rh(I)-catalyst precursors, such as
Rh(CO)2(acac), [Rh(cod)2]BF4, RhCl(PPh3)3 and RhCl(cod),
were workable but with slightly less efficiency (Table 1, entries
9–12). Further screening has identified that the optimum
conditions were 10 mol% Rh(OH)(cod), 20 mol% PPh3, and
3.0 equivalents of substrate 2a and CsF (Table 1, entry 6).
In the presence of a proper rhodium catalyst, potassium
(Z)-(2-bromovinyl)trifluoroborate 2 is thought to be transformed
to the corresponding vinyl-Rh(I) intermediate B,5 which will
undergo insertion of the alkyne of 1,6-diyne 1 to generate
intermediate C, followed by the formation of intermediate D
via a second insertion of an alkyne (path a, Scheme 1). Then,
intramolecular oxidative addition6 of Rh(I) to vinylbromine
occurs to produce intermediate F, which can also be generated
via path b, consisting of oxidative addition of Rh(I) to vinyl-
bromine in intermediate C and insertion of alkyne in E (path b,
Scheme 1). In the end, the reductive elimination of F would
release the Rh(I)-catalyst and deliver polysubstituented benzene
derivatives 3, furnishing a formal [2+2+2] cycloaddition.
Key Laboratory for Advanced Materials and Institute of Fine
Chemicals, East China University of Science and Technology,
Shanghai, 200237, China. E-mail: tongxf@ecust.edu.cn;
Tel: +86 21-64253881
w Electronic supplementary information (ESI) available: Experimental
details and spectroscopic and analytical data for all new compounds.
See DOI: 10.1039/c001830a
Scheme 1 New scenario for Rh(I)-catalyzed [2+2+2] cycloaddition
of 1,6-diyne.
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Table 1 Optimization for cycloaddition of 1a with 2aa
Scheme 2 Synthesis of phenylenedimethanol derivative 4.
Table 2 The scope of [2+2+2] cycloaddition between 1 and 2a
Entry Rh(I)
Ligand 2a (equiv.) CsF (equiv.) Yield (%)e
b
1
Rh(OH)(cod)
—
1.5
1.5
1.5
1.5
3.0
3.0
—
—
—
7
29
33
57
62
76
62
69
53
50
61
63
2c
3
Rh(OH)(cod) PPh3
Rh(OH)(cod) PPh3
Rh(OH)(cod) PPh3
Rh(OH)(cod) PPh3
Rh(OH)(cod) PPh3
4
5
6
CsF (1.5)
CsF (1.5)
CsF (3.0)
CsF (3.0)
CsF (3.0)
CsF (3.0)
CsF (3.0)
CsF (3.0)
CsF (3.0)
7c
8d
9
Rh(OH)(cod) BINAP 3.0
Rh(OH)(cod) PPh3
Rh(CO)2(acac) PPh3
[Rh(cod)2]BF4 PPh3
RhCl(PPh3)3
RhCl(cod)
3.0
3.0
3.0
3.0
3.0
10
11
12
1 (R1, X)
2 (R2)
t/h
Yield (%)b
b
Entry
—
PPh3
1
2
1a (Ph, NTs)
1b (H, NTs)
1c (Ph, O)
2a (Ph)
2a (Ph)
2a (Ph)
2a (Ph)
2a (Ph)
2a (Ph)
2a (Ph)
2b (Bu)
2b (Bu)
2b (Bu)
24
12
5
3
2
1
2
3
5
76 (3aa)
20 (3ba)
75 (3ca)
83 (3da)
88 (3ea)
60 (3fa)
40 (3ga)
85 (3db)
75 (3ab)
70 (3cb)
a
Reaction conditions: the mixture of dioxane and water (3 mL, 20 : 1)
was injected into 1a (0.3 mmol), 2a, ligand, Rh(I) and additive in
reaction vessel (10 mL). The resulting mixture was stirred at 100 1C for
3
4c
5
1d (Ph, Y)
b
c
d
1e (Bu, NTs)
1f (CH2OMe, NTs)
1g (CH2OAc, NTs)
1d (Ph, Y)
1a (Ph, NTs)
1c (Ph, O)
24 h. Without ligand. 10 mol% ligand was used. 5 mol% Rh(I)
e
and 10 mol% PPh3 were used. Isolated yield.
6
7
8c
9
Notably, all of these experiments could be performed under air
without affecting the reaction results.
10
5
a
Reaction conditions: the solvent of dioxane and water (3 mL, 20 : 1)
was injected into the mixture of 1 (0.3 mmol), 2 (0.9 mmol), PPh3
(15.7 mg, 0.06 mmol), Rh(OH)(cod) (6.8 mg, 0.03 mmol) and CsF
(136.8 mg, 0.9 mmol) in reaction vessel. The resulting mixture was
b
c
stirred at 100 1C. Isolated yield. Y = C(CO2Et)2.
substrates exhibited almost the same reactivity under the
standard conditions, in which two corresponding ‘‘normal’’
products 3ja-1 and 3ja-2 could be isolated in a yield of 56%
and 50%, respectively; meanwhile a common ‘‘abnormal’’
product, compound 5, could be obtained in a yield of 11%
and 10%, respectively.
ð2Þ
Having established the optimized reaction conditions, we
setout to explore the scope of this transformation (Table 2).
In general, the Rh(I)-catalyzed [2+2+2] cycloadditions can
be smoothly achieved to provide benzene derivatives 3 in
moderate to good yields irrespective of whether the 1,6-diynes
are nitrogen, oxygen or carbon linked. When terminal diyne 1b
is used, the yield would dramatically drop, probably due to its
reactivity9 towards the Rh(I)-complex (entry 2, Table 2). The
oxo-substituented diynes can be employed to offer 1,4-phenyl-
enedimethanol derivatives 3fa and 3ga with lower yields
(entries 6 and 7). It is noted that some unidentified side
products are detected in all cases, which are thought to be
the reason for lower yields of 3. With respect to the third
2-atom unit, trifluoroborate 2b, with a butyl group at 2-position,
can be also employed and exhibits similar reactivity (entries
8–10, Table 2). However, asymmetric diyne 1h, with an
electron-deficient alkyne, presents worse results and generates
two isomers with low regeoselectivity (2 : 1) (eqn (2)). Similar
performance also happens to diyne 1i, providing a mixture of
3i-1 and 3i-2 (2.5 : 1) which could be readily reduced to offer
phenylenedimethanol derivative 410 (Scheme 2).
On the basis of these results, the detailed mechanism is
outlined in Scheme 4 and we conclude that the reaction
pathway should involve intermediate D-2 which corresponds
to the formation of compound 5. At present, we do not have
convincing evidence to distinguish these two different mechanisms
(Schemes 1 and 4), but the outcome in Scheme 3 tempts us to
conclude that our new strategy for Rh(I)-catalyzed [2+2+2]
cycloaddition is really operating via path a.
To shed the light on the mechanism, two control experiments
were designed and performed with compounds 1j-1 and 1j-2 as
the substrates (Scheme 3). Interestingly, these two different
Scheme 3 Two control experiments
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Scheme 4 Explanation for the formation of compounds 3ja and 5.
In summary, we have realized a novel Rh(I)-catalyzed
formal [2+2+2] cycloaddition between 1,6-diyne 1 and
potassium (Z)-(2-bromovinyl)trifluoroborate 2, which provides
a facile access to highly substituted benzene derivatives. In this
transformation, compound 211 is thought to be crucial to fulfil
this new strategy for Rh(I)-catalyzed [2+2+2] cycloaddition
due to its dual structural functions with nucleophilic vinyl
borate and electrophilic vinylbromine. Further studies on the
mechanism and synthetic utility are underway in our laboratory
and will be reported in due course.
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are
greatly
appreciated
for
funding
supporting
(09ZR1408500). Special gratitude also goes to Professors
Xingyi Wang and Dao Li and Ms Shuzhen Jiang for their
long-term support.
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This journal is The Royal Society of Chemistry 2010
3802 | Chem. Commun., 2010, 46, 3800–3802