An unprecedented rhodium-catalysed self-conjugate reduction, cross-coupling tandem reaction of cinnamaldehydes with arylboronic acids

Article abstract of DOI:10.1039/b401511h

A novel rhodium-catalysed self-conjugate reduction, cross-coupling tandem reaction of cinnamaldehydes with arylboronic acids through a three-membered metallocyclopropanone intermediate is disclosed.

Full text of DOI:10.1039/b401511h

An unprecedented rhodium-catalysed self-conjugate reduction,
cross-coupling tandem reaction of cinnamaldehydes with arylboronic
acids
Zhiyong Wang, Gang Zou* and Jie Tang
Department of Chemistry, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062,
P. R. China. E-mail: gzou@chem.ecnu.edu.cn; Fax: 86-21-62232100; Tel: 86-21-62232764
Received (in Cambridge, UK) 2nd February 2004, Accepted 17th March 2004
First published as an Advance Article on the web 14th April 2004
A novel rhodium-catalysed self-conjugate reduction, cross-
coupling tandem reaction of cinnamaldehydes with arylboronic
acids through a three-membered metallocyclopropanone inter-
mediate is disclosed.
Arylboronic acids have recently attracted much attention as an air-
stable and non-toxic alternative to traditional organometallic
nucleophiles, such as organic magnesium (ArMgX), copper
(Ar2CuLi) and tin (ArSnBu3) compounds, in organic and inorganic
transformations, especially in transition-metal mediated C–C bond
forming processes.1–9 Rhodium has proven to be versatile for the
transformation of organoboronic acids. Both coupling-type and
addition-type reactions of arylboronic acids with multiple bonds in
Scheme 2 Rh-catalysed self-conjugate reduction, cross-coupling tandem
olefins, alkynes and carbonyls could be effected using rhodium-
reaction of cinnamaldehydes with arylboronic acids.
based catalysts with high selectivity. Based on knowledge from the
literature, there are three possible patterns for the reaction of
This novel reaction pattern has been unmistakeably confirmed
arylboronic acids with a,b-unsaturated aldehydes such as cinna-
for substituted cinnamaldehydes such as 4-nitro (electron deficient)
maldehyde: conjugate addition (1,4-addition), carbonyl addition
and 4-methoxy (electron-rich) cinnamaldehydes although acrolein
(1,2-addition) and Heck-type coupling (Scheme 1).
and crotonaldehyde decomposed under the basic conditions. Water
It is reported that the 1,2- and 1,4-reactions of arylboronic acids
seemed to play an important role in the tandem process. Only traces
with cinnamaldehyde could be switched by tuning rhodium
of the desired products were detected when the reaction was
catalysts.10 We have recently reported a sterically sensitive
conducted in pure THF or toluene. When the reaction was carried
rhodium–phosphine biphasic system that catalysed Heck-type
out in toluene–D2O, one deuterium ( > 98%) was incorporated into
reaction of arylboronic acids with a,b-unsaturated esters and
the product, b-phenylpropiophenone, at the a-position, supporting
nitriles under aqueous conditions.11 As a part of our continuing
exploration of catalysis with the biphasic system, we investigated
the possibility of switching the Heck-type coupling to 1,2-addition
of arylboronic acids to a,b-unsaturated aldehydes. Unexpectedly,
we uncovered a novel self-conjugate reduction, cross-coupling
tandem reaction of arylboronic acids with cinnamaldehyde and
analogues.
a hydrolysis of the Rh–C bond being involved in the process (eqn.
1).
(1)
Considering the steric hindrance of cinnamaldehyde, we had
originally expected a 1,2-carbonyl addition reaction with phenyl-
boronic acid to occur using our sterically dependent biphasic
catalysis system. However, reaction of 1.0 equivalent phenyl-
boronic acid with cinnamaldehyde catalysed by 3 mol% RhCl3–12
mol% PPh3 in an aqueous/toluene biphasic system at reflux in the
presence of excess K2CO3 gave only a trace of the expected alcohol
and Heck-type coupling products. Instead, a novel conjugate
reduction, cross-coupling tandem reaction occurred to produce b-
phenylpropiophenone as the major product (54% by GC-MS and
40% isolated yield). The isolated yield of b-phenylpropiophenone
could be increased to 59% (72% by GC-MS) using 2.0 equivalent
phenylboronic acid (Scheme 2).† To the best of our knowledge,
there is no literature reporting this kind of tandem reaction pattern
for a,b-unsaturated aldehydes.
To gain further insight into the mechanism of this novel tandem
process, 1-deuterated cinnamaldehyde was used to elucidate how
the CNC bond of the a,b-unsaturated aldehydes was saturated while
coupling with phenylboronic acid (eqn. 2). b-Deuterated (98%) b-
phenylpropiophenone was isolated in 41% isolated yield with a 1 :
1 mole ratio of 1-deuterated cinnamaldehyde and phenylboronic
acid, indicating that the CNC double bond of cinnamaldehyde was
self-reduced by the proton from the aldehyde group.
(2)
Control experiments for the H/D exchange of cinnamaldehyde
with toluene–D2O catalysed by Wilkinson catalyst (PPh3)3RhCl or
the RhCl3–PPh3 biphasic system in the absence of phenylboronic
acid showed no H/D exchange occurred in either case, implying
that neither RhI–Cl nor RhI–OH species initiated the tandem
process. Based on these experimental results, a plausible mecha-
nism for this rhodium-catalysed self-conjugate reduction, cross-
coupling tandem reaction of arylboronic acids 1 with cinnamalde-
hydes 2 is tentatively proposed (Scheme 3).12
Scheme 1 Possible reaction patterns for PhB(OH)2 with cinnamaldehyde
catalysed by rhodium-based catalysts.
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C h e m . C o m m u n . , 2 0 0 4 , 1 1 9 2 – 1 1 9 3
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 4

until cinnamaldehyde was consumed (24–30 h). After cooling to room
temperature, the organic phase was concentrated and purified by flash
column chromatography to afford b-phenylpropiophenone (124 mg, 59%
based on cinnamaldehyde). Selected spectroscopic data: NMR (500 MHz,
CDCl3, 25 °C), d (ppm), 1H: 7.90–8.00 (dd, J1 = 8 Hz, J2 = 1 Hz, 2H, Ph),
7.50–7.55 (m, 1H, Ph), 7.40–7.50 (m, 2H, Ph), 7.10–7.30 (m, 5H, Ph), 3.30
(t, J = 7 Hz, 2H, CH2), 3.00 (t, J = 7 Hz, 2H, CH2); 13C: 199.0 (CNO),
141.0, 136.6, 132.8, 128.4, 128.3, 128.1, 127.8, 125.9, 40.1 (CH2), 29.9
(CH2), EI-MS, m/z: 210 (M+, 35%), 105 (100), 77 (24).
Analytical data for a- and b-deuterated b-phenylpropiophenone: For a-
deuterated b-phenylpropiophenone: NMR (300 MHz, CDCl3, 25 °C), d
(ppm), 1H: 7.90–8.00 (m, 2H, Ph), 7.50–7.60 (m, 1H, Ph), 7.40–7.50 (t, J =
8 Hz, 2H, Ph), 7.10–7.30 (m, 5H, Ph), 3.30 (d, J = 8 Hz, 2H, CH2), 3.10 (m,
1H, CHD); 13C: 199.1 (CNO), 141.2, 136.8, 132.9, 128.5, 128.4, 128.3,
127.9, 126.0, 39.9 (t, 75 Hz, CHD), 30.0 (CH2), EI-MS, m/z: 211(M+, 98%),
182 (100), 105 (100), 77 (99); HRMS (TOF-MS ES): Found: 234.1007,
Calc. for C15H13ODNa: 234.1005. For b-deuterated b-phenylpropiophe-
none: NMR (500 MHz, CDCl3, 25 °C), d (ppm), 1H: 7.90–7.95 (dd, J1 = 8
Hz, J2 = 1 Hz, 2H, Ph), 7.55–7.60 (m, 1H, Ph), 7.40–7.45 (t, J = 8 Hz, 2H,
Ph), 7.10–7.30 (m, 5H, Ph), 3.30 (d, J = 8 Hz, 2H, CH2), 3.05 (m, 1H,
CHD); 13C: 199.5 (CNO), 141.6, 137.2, 133.4, 128.9, 128.8, 128.7, 128.3,
126.4, 40.7 (CH2), 30.1 (t, JC–D = 80 Hz, CDH), EI-MS, m/z: 211 (M+,
70%), 105 (100), 77 (50); HRMS (TOF-MS ES): Found: 234.1007, Calc.
for C15H13ODNa: 234.1005.
Scheme 3 A plausible mechanism for the novel self-conjugate reduction,
cross-coupling of cinnamaldehyde with arylboronic acids.
1 For a review of Pd-catalysed Suzuki coupling: N. Miyaura and A.
Suzuki, Chem. Rev., 1995, 95, 2457. For a recent example see: R. B.
Bedford, S. L. Hazelwood, P. N. Horton and M. B. Hursthouse, J. Chem.
Soc., Dalton Trans., 2003, 4164.
2 For Rh-catalysed C–C bond forming reactions: K. Fagnou and M.
Lautens, Chem. Rev., 2003, 103, 169.
3 For Heck-type reaction of arylboronic acids, Ru-catalysed see: E. J.
Farrington, J. M. Brown, C. F. J. Barnard and E. Rowsell, Angew.
Chem., Int. Ed., 2002, 41, 169. For Ir-catalysed see: T. Koike, X. Du, T.
Sanada, Y. Danda and A. Mori, Angew. Chem., Int. Ed., 2003, 42, 89.
For Pd-catalysed see: C. S. Cho and S. Uemura, J. Organomet. Chem.,
1994, 465, 85.
4 For Rh-catalysed addition to alkynes: M. Lautens and M. Yoshida, J.
Org. Chem., 2003, 68, 762 and to alkenes: M. Murakami and H. Igawa,
Chem. Commun., 2002, 390. For Pd-catalysed coupling with alkynes: G.
Zou, J. Zhu and J. Tang, Tetrahedron Lett., 2003, 44, 8709; addition to
alkynes: C. H. Oh, H. H. Jung, K. S. Kim and N. Kim, Angew. Chem.,
Int. Ed., 2003, 42, 805; and to allene: C. H. Oh, T. W. Ahn and R. Reddy
V., Chem. Commun., 2003, 2622.
5 For Rh-catalysed 1,2-addition to aldehydes: A. Fürstner and H. Krause,
Adv. Synth. Catal., 2001, 343, 343 and to aldimines: M. Ueda and N.
Miyaura, J. Organomet. Chem., 2002, 595, 31.
6 For Rh-catalysed 1,4-addition: M. Sakai, H. Hayashi and N. Miyaura,
Organometallics, 1997, 16, 4229; R. Itooka, Y. Iguchi and N. Miyaura,
J. Org. Chem., 2003, 68, 6000. For Pd-catalysed 1,4-addition: T.
Nishikata, Y. Yamamoto and N. Miyaura, Angew. Chem., Int. Ed., 2003,
42, 2768.
7 For coupling with anhydrides and acid chlorides: Rh-catalysed, C. G.
Frost and K. J. Wadsworth, Chem. Commun., 2001, 2316; Pd-catalysed,
L. J. Gooben and K. Ghosh, Chem. Commun., 2001, 2084; L. J. Gooben
and K. Ghosh, Angew. Chem., Int. Ed., 2001, 40, 3458; Y. Urawa and K.
Ogura, Tetrahedron Lett., 2003, 44, 271.
8 For recent examples using arylboronic acids as nucleophile without
metal catalyst: S. C. Cole, M. P. Coles and P. B. Hitchcock, J. Chem.
Soc., Dalton Trans., 2003, 3663.
Oxidative addition of the C–H of the aldehyde group from
cinnamaldehyde 2 to the RhI–CAr species that is generated in situ by
reduction of RhCl3 with arylboronic acids initiates the tandem
process, followed by an intramolecular insertion of the CNC bond to
Rh–H of species 4, affording a ketene complex/three-membered
metallocyclopropanone intermediate 5. One path to complete the
self-conjugate reduction, cross-coupling tandem process involves a
reductive elimination from the RhIII 5 to release the strain of the
metallocyclopropanone and generate a RhI–Csp3 species 6, which
hydrolyses through oxidative addition of water to the RhI species 6
and reductive elimination from the resulting RhIII 7,13 affording 3
and rhodium hydroxide RhI–OH that produces the initiating species
Rh–Ar through a subsequent B to Rh transmetalation. The other one
includes a direct hydrolysis of the metallocyclopropanone 5,
generating rhodium hydroxide 8 and reductive elimination from the
hydroxide, completing the catalytic cycle after a B to Rh
transmetalation. Although the latter could not be excluded, from an
organometallic chemistry point of view the former path is preferred
considering that RhIII–Csp3 is quite inert towards direct hydroly-
sis.
In conclusion, we have observed an unprecedented self-
conjugate reduction, cross-coupling tandem reaction pattern be-
tween a,b-unsaturated arylaldehydes and arylboronic acids cata-
lysed by the RhCl3/PPh3 system through a novel three-membered
metallocyclopropanone intermediate. Optimisation of the proce-
dure, investigation of the scope of the rhodium-catalysed tandem
reaction and control of enantioselectivity with chiral phosphine
ligands, such as BINAP, are in progress in our laboratory.
We thank Shanghai Science
&
Technology Council
(02QA14016, 02JG05040) and NNSF, P. R. China (20242008) for
financial support.
9 For asymmetric 1,4-conjugate addition: T. Hayashi and K. Yamasaki,
Chem. Rev., 2003, 103, 2829; M. Kuriyama, K. Nagai, K. Yamada, Y.
Miwa, T. Taga and K. Tomioka, J. Am. Chem. Soc., 2002, 124, 8932.
10 M. Ueda and N. Miyaura, J. Org. Chem., 2000, 65, 4450.
11 G. Zou, Z. Wang, J. Zhu and J. Tang, Chem. Commun., 2003, 2438.
12 An alternative mechanism involving an addition of arylboronic acid to
the aldehyde group, followed by Rh-catalysed 1,3-allylic hydride
transfer cannot be completely excluded at present.
Notes and references
†
General procedure for the rhodium-catalysed self-conjugate reduction,
cross-coupling tandem reaction: To a suspension of phenylboronic acid
(0.25 g, 2.0 mmol), RhCl3(H2O)x (40% Rh, 15 mg, 0.06 mmol) and PPh3
(65 mg, 0.25 mmol) in toluene/water (15 mL/5 mL) was added
cinnamaldehyde (130 ml, 1.0 mmol). The mixture was stirred at 100 °C (bath
temperature) under nitrogen. The reaction progress was monitored by TLC
13 T. Yoshida, T. Okano, Y. Ueda and S. Otsuka, J. Am. Chem. Soc., 1981,
103, 3411.
C h e m . C o m m u n . , 2 0 0 4 , 1 1 9 2 – 1 1 9 3
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