Rhodium-catalyzed selective anti -markovnikov addition of carboxylic acids to alkynes

Article abstract of DOI:10.1021/ol102365e

The selective intermolecular anti-Markovnikov addition of carboxylic acids to terminal alkynes yielding valuable Z-enol esters has been achieved for the first time under rhodium-catalyzed conditions. The catalyst system is applicable to a broad substrate

Full text of DOI:10.1021/ol102365e

ORGANIC
LETTERS
2010
Vol. 12, No. 23
5498-5501
Rhodium-Catalyzed Selective
anti-Markovnikov Addition of Carboxylic
Acids to Alkynes
Alexandre Lumbroso, Nicolas R. Vautravers, and Bernhard Breit*
Institut fu¨r Organische Chemie und Biochemie, Freiburg Institute for AdVanced
Studies (FRIAS), Albert-Ludwigs-UniVersita¨t Freiburg,
Albertstrasse 21, 79104, Freiburg, Germany
bernhard.breit@chemie.uni-freiburg.de
Received October 1, 2010
ABSTRACT
The selective intermolecular anti-Markovnikov addition of carboxylic acids to terminal alkynes yielding valuable Z-enol esters has been achieved
for the first time under rhodium-catalyzed conditions. The catalyst system is applicable to a broad substrate scope and displays a wide
functional group tolerance.
Transition metal-catalyzed addition of carboxylic acids to
terminal alkynes is an efficient and atom-economic method
Scheme 1. Addition of Carboxylic Acids to Terminal Alkynes
for the preparation of 1-alkenyl esters, which are widely used
as monomers for polymerization1 and mild acylating agents.2
Since Shvo and co-workers reported the first example of such
a reaction in 1983 using Ru3(CO)12 as catalyst,3 most
significant improvements have been attained employing
ligand modified ruthenium to furnish selectively either the
Markovnikov (M) and/or anti-Markovnikov (AM-Z, AM-
E) enol esters with high levels of regio- and stereocontrol
(Scheme 1).4 Other metals like iridium5 and rhenium6 have
also been used as catalysts for the intermolecular reaction
whereas rhodium7 or palladium8 have mainly been applied
for the intramolecular process yielding alkylidene lactones.
A single report on a polyphosphine modified rhodium catalyst
is known which allows for intermolecular Markovnikov-
selective addition of carboxylic acids to terminal alkynes.9
Herein, we disclose the first selective rhodium-catalyzed
intermolecular anti-Markovnikov addition of carboxylic acids
(1) Montheard, J. P.; Camps, M.; Seytre, G.; Guillet, J.; Dubois, J. C.
Angew. Makromol. Chem. 1978, 72, 45–55.
(2) (a) Bruneau, C.; Neveux, M.; Kabouche, Z.; Ruppin, C.; Dixneuf,
P. H. Synlett 1991, 755–763. (b) Tu, W.; Floreancig, P. E. Angew. Chem.,
Int. Ed. 2009, 48, 4567–4571. (c) Quirin, C.; Kazmaier, U. Eur. J. Org.
Chem. 2009, 48, 371–377.
(3) Rotem, M.; Shvo, Y. Organometallics 1983, 2, 1689–1691.
10.1021/ol102365e  2010 American Chemical Society
Published on Web 11/04/2010

to terminal alkynes yielding valuable Z-enol esters employing
a new rhodium catalyst.
As a model system, we studied the reaction of benzoic
acid with 1-octyne employing [(COD)RhCl]2 [COD ) 1,5-
cyclooctadiene] as the catalyst precursor in the presence of
donor ligands (Table 1).
(bis(diphenylphosphino)alkane)Ru(η3-methallyl)2 as the
catalyst.4b While the reaction did not proceed without ligand
(yield <5%, entry 5), the use of Wilkinson’s catalyst
significantly enhanced both the regioselectivity in favor of
the Z-anti-Markovnikov product (72/16/12, AM-Z/AM-E/
M) and the rate of the reaction (79% yield, entry 6). Goossen
et al. found that the addition of catalytic amounts of pyridine
or DMAP to a ruthenium catalyst generated in situ from ((p-
cumene)RuCl2)2 and P(p-Cl-C6H4)3 favored the formation of
AM-Z.10 Unfortunately, addition of pyridine in the presence
of [(COD)RhCl]2 and PPh3 did not furnish a more selective
catalyst (entry 7). However, when employing a ligand that
combines a pyridine moiety and a diphenylphosphine donor
function, 2-(diphenylphosphinomethyl)pyridine (L), high
yield (90%) and regioselectivity (94/3/3, AM-Z/AM-E/M)
were reached (entry 8). The reaction has been run on a 5
mmol scale giving slightly better yield (93%) and the same
selectivity as the standard conditions (entry 8). Ligand L
can be easily prepared on a gram-scale starting from
2-picoline and chlorodiphenylphosphine in two steps.11
Interestingly, using diphenyl(2-pyridyl)phosphine (DPP) as
the ligand did not furnish an efficient catalyst (entry 9). This
suggests that ligand L acts as a chelating ligand via P/N-
coordination. A quick screen of suitable solvents revealed
THF to be the optimal in terms of catalyst activity and
selectivity (entries 8 and 10-12). Similar strong solvent
effects have previously been observed for the ruthenium
hydride (PCy3)2(CO)RuHCl catalyst system.12 Changing the
metal precursor from rhodium to iridium or ruthenium was
deleterious (entries 13 and 14, respectively).
Table 1. Optimization of Hydro-oxycarbonylation Conditionsa
entry
ligand
solvent
AM-Z/AM-E/Mb
% yieldc
1
2
3
4
PPh3
DPPE
DPPP
DPPB
-
-
Ph3P/Py
L
DPP
L
L
L
L
L
THF
THF
THF
THF
THF
THF
THF
THF
THF
Et2O
CH2Cl2
toluene
THF
THF
46/22/32
14/8/78
22/5/73
64/4/32
n.d.
72/16/12
45/25/30
94/3/3
33/31/36
44/12/44
37/22/41
51/13/36
21/37/42
40/27/33
28
24
<10
21
<5
79
36
90
<10
<10
<10
18
5
6d
7e
8f
9g
10
11
12
13h
14i
40
60
a Reaction conditions: 0.0044 mmol of [(COD)RhCl]2, 0.0088 mmol
of ligand, 0.44 mmol of benzoic acid, and 0.66 mmol of 1-octyne in 400
µL of solvent were heated in a closed Schlenk vessel at 110 °C for 16 h.
b Determined by integration of the ethylenic protons in the crude 1H NMR
(see the Supporting Information). c Isolated yields. d [RhCl(PPh3)3] was used
as rhodium precursor. e [(COD)RhCl]2/PPh3/Py ) 1/1/1 [Py ) pyridine].
f Determined by integration of the ethylenic protons in the crude 1H NMR
and GC analyses. g [DPP ) diphenyl(2-pyridyl)phosphine]. h [(COD)IrCl]2
was used as catalyst. i [(COD)RuCl2] was used as catalyst. [COD )
cyclooctadiene].
With a highly active catalyst system in hand (Table 1,
entry 8), we explored the substrate scope of the reaction
(Table 2). Reasonable yields and regioselectivities ranging
from 90% to 65% and 94/3/3 to 77/-/23, respectively,
were obtained for the addition of various terminal alkynes
to benzoic acid, with better yields for less hindered
substrates (entries 1-4). No reaction was observed with
phenylacetylene, which is usually converted in good yields
with other metals (entry 5).4-6,10 Both electron-donating
as well as electron-withdrawing substituents at the aryl
carboxylic acid system were well tolerated (entries 6-12).
Even an unprotected phenol function was compatible with
the reaction conditions (entry 10). Furthermore, heterocycle-
based carboxylic acids (entries 13 and 14), aliphatic acids
(entries 15 and 16), unsaturated acids (entries 17 and 18),
and N-carbamoyl-protected R-amino acids (entries 19 and
20) were efficient reaction partners, thus highlighting the
wide functional group tolerance of this catalyst system.
Taking into account that internal alkynes do not show
reactivity with our rhodium-catalyst system together with
the anti-Markovnikov selectivity observed in this reaction,
a reaction mechanism involving a rhodium vinylidene
species is most likely (Scheme 2). The first step is the
Poor yields were obtained in THF at 110 °C upon moving
from the monodentate PPh3 (28%, entry 1) to the bidentates
dppe, dppp, and dppb (24%, <10%, and 21%, respectively,
entries 2-4), with a notable change in the regioselectivity
within the latter family: anti-Markovnikov product being
favored with dppb as opposed to the gem-enol ester type
product observed with dppe. Similar observations have
already been made by Dixneuf and co-workers using
(4) (a) Mitsudo, T.; Hori, Y.; Yamakawa, Y.; Watanabe, Y. J. Org.
Chem. 1987, 52, 2230–2239. (b) Doucet, H.; Martin-Vaca, B.; Bruneau,
C.; Dixneuf, P. H. J. Org. Chem. 1995, 60, 7247–7255. (c) Le Paih, J.;
Monnier, F.; De´rien, S.; Dixneuf, P. H.; Clot, E.; Eisenstein, O. J. Am.
Chem. Soc. 2003, 125, 11964–11975. (d) Melis, K.; Samulkiewicz, P.;
Rynkowski, J.; Verpoort, F. Tetrahedron Lett. 2002, 43, 2713–2716. (e)
Alonso, F.; Beletskaya, I. P.; Yus, M. Chem. ReV. 2004, 104, 3079–3159.
(f) Drozdzak, R.; Allaert, B.; Ledoux, N.; Dragutan, I.; Dragutan, V.;
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B. A. J. Organomet. Chem. 2000, 607, 97–104. (c) Mas-Marza´, E.; Sanau`,
M.; Peris, E. Inorg. Chem. 2005, 44, 9961–9967.
(9) Bianchini, C.; Meli, A.; Peruzzini, M.; Zanobini, F.; Bruneau, C.;
Dixneuf, P. H. Organometallics 1990, 9, 1155–1160.
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(8) (a) Lambert, C.; Utimoto, K.; Nozaki, H. Tetrahedron Lett. 1984,
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Org. Lett., Vol. 12, No. 23, 2010
5499

Table 2. Intermolecular Hydro-oxycarbonylation of Terminal Alkynes under Rhodium-Catalyzed Conditionsa
a Reaction conditions: 0.0044 mmol of [(COD)RhCl]2, 0.0088 mmol of L, 0.44 mmol of acid, and 0.66 mmol of alkyne in 400 µL of THF were heated
in a closed Schlenk vessel at 110 °C. b Determined by GC analyses and integration of the ethylenic protons in the crude 1H NMR (see the Supporting
Information). c Isolated yields. d 0.022 mmol of catalyst was used. [COD ) cyclooctadiene].
oxidative addition of the carboxylic acid to the Rh(I)
center as the prevalence of O-H oxidative addition over
the C-H one of terminal alkynes has already been
demonstrated.9 η2-Coordination of the alkyne to the metal
was followed by rearrangement to an η1-vinylidene-
rhodium species, which was then attacked by the car-
boxylic acid at the more electrophilic carbon atom.13
Reductive elimination liberates the Z-anti-Markovnikov
product and regenerates the catalyst.13a The Z stereochem-
istry would be preferred in order to minimize the steric
repulsion between the R2 group and the bulky rhodium
catalyst, in agreement with observations from Mistudo14
and Dixneuf15 employing ruthenium catalysts.
(13) (a) Bruneau, C.; Dixneuf, P. H. Acc. Chem. Res. 1999, 32, 311–
323. (b) Park, Y. J.; Kwon, B.-I.; Ahn, J.-A.; Lee, H.; Jun, C.-H. J. Am.
Chem. Soc. 2004, 126, 13892–13893.
5500
Org. Lett., Vol. 12, No. 23, 2010

alkynes to furnish the corresponding Z-anti-Markovnikov
enol esters in good to high yields and excellent stereoselec-
tivities. The catalyst system is applicable to a broad substrate
scope and displays a wide functional group tolerance.
Scheme 2. Proposed Mechanism for the
Hydro-oxycarbonylation of Terminal Alkynes under
Rhodium-Catalyzed Conditions in the Presence of L
Acknowledgment. This work was supported by the DFG,
the International Research Training Group “Catalysts and
Catalytic Reactions for Organic Synthesis” (IRTG 1038), the
Fonds der Chemischen Industrie, the Krupp Foundation
(Alfried Krupp Award for young university teachers to B.B.),
and the Humboldt Foundation (postdoctoral fellowship to
N.R.V.). We thank Umicore, BASF, and Wacker for gener-
ous gifts of chemicals.
Supporting Information Available: Detailed experimen-
tal procedures, characterizations, and copies of NMR spectra
of the products. This material is available free of charge via
the Internet at http://pubs.acs.org.
OL102365E
(14) Mitsudo, T.; Hori, Y.; Yamakawa, Y.; Watanabe, Y. Tetrahedron
Lett. 1987, 38, 4417–4418.
In summary, we have developed the first rhodium catalyst
for the intermolecular hydro-oxycarbonylation of terminal
(15) Mahe, R.; Sasaki, Y.; Bruneau, D.; Dixneuf, P. H. J. Org. Chem.
1989, 54, 1518–1523.
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