Copper-catalyzed tandem oxidation-olefination process

Article abstract of DOI:10.1021/ol802299d

A novel catalytic sequence aerobic oxidation-olefination has been developed. A single and inexpensive copper catalyst provides a large range of olefins from alcohols in good to excellent yields. The reaction exhibits excellent functional group compatibili

Full text of DOI:10.1021/ol802299d

ORGANIC
LETTERS
2009
Vol. 11, No. 1
41-44
Copper-Catalyzed Tandem
Oxidation-Olefination Process
Michae¨l Davi and He´le`ne Lebel*
´
De´partement de Chimie, UniVersite´ de Montre´al, 2900 Boul. Edouard Montpetit,
Montre´al, Que´bec, Canada H3T 1J4
helene.lebel@umontreal.ca
Received October 3, 2008
ABSTRACT
A novel catalytic sequence aerobic oxidation-olefination has been developed. A single and inexpensive copper catalyst provides a large
range of olefins from alcohols in good to excellent yields. The reaction exhibits excellent functional group compatibility, and the nonbasic
reaction conditions allow the transformation of chiral substrates without racemization.
Multistep processes to perform oxidation followed by ole-
fination reactions are important transformations often em-
ployed in syntheses, including the synthesis of natural
products.1 Consequently, there has been much interest in the
development of one-pot oxidation-olefination processes.2,3
This approach is a more green alternative to classical
multistep oxidation-olefination through the minimization of
the amount of solvent and reagents needed for the reactions
and purifications. Furthermore, the isolation of potentially
sensitive aldehydes (to overoxidation and/or enolization) is
avoided. Nevertheless, available one-pot processes are
restricted to benzylic, allylic, and aliphatic primary alcohols
and involve the use of stoichiometric oxidants.
Recently, our group has disclosed several efficient catalytic
olefination reactions using Rh,4 Ir,5 and Cu6 catalysts.7
Moreover, these transition-metal-catalyzed transformations
have successfully been used in various one-pot procedures.8
In particular, we have reported the first multicatalytic one-
pot palladium-catalyzed oxidation9-rhodium-catalyzed me-
(1) For recent selected examples, see: (a) Donohoe, T. J.; Harris, R. M.;
Burrows, J.; Parker, J. J. Am. Chem. Soc. 2006, 128, 13704–13705. (b)
Wang, Y.-G.; Takeyama, R.; Kobayashi, Y. Angew. Chem., Int. Ed. 2006,
45, 3320–3323. (c) Young, I. S.; Kerr, M. A. J. Am. Chem. Soc. 2007, 129,
1465–1469. (d) Yang, H.; Carter, R. G.; Zakharov, L. N. J. Am. Chem.
Soc. 2008, 130, 9238–9239. (e) Selig, P.; Bach, T. Angew. Chem., Int. Ed.
2008, 47, 5082–5084.
(3) For recent and selected applications of these tandem processes in
total synthesis, see: (a) Shet, J.; Desai, V.; Tilve, S. Synthesis 2004, 1859–
1863. (b) Yadav, J. S.; Reddy, M. S.; Rao, P. P.; Prasad, A. R. Synthesis
2006, 4005–4012. (c) Goksel, H.; Stark, C. B. W. Org. Lett. 2006, 8, 3433–
3436. (d) Ichikawa, Y.; Yamaoka, T.; Nakano, K.; Kotsuki, H. Org. Lett.
2007, 9, 2989–2992. (e) Bull, J. A.; Balskus, E. P.; Horan, R. A. J.; Langner,
M.; Ley, S. V. Chem.sEur. J. 2007, 13, 5515–5538. (f) Yadav, J. S.; Reddy,
P. M. K.; Reddy, P. V. Tetrahedron Lett. 2007, 48, 1037–1039. (g) Majik,
M.; Shet, J.; Tilve, S.; Parameswaran, P. S. Synthesis 2007, 663–665. (h)
Reddy, J. S.; Rao, B. V. J. Org. Chem. 2007, 72, 2224–2227. (i) Yadav,
J. S.; Kumar, N. N.; Prasad, A. R. Synthesis 2007, 1175–1178. (j) Pandya,
B. A.; Snapper, M. L. J. Org. Chem. 2008, 73, 3754–3758.
(2) Swern: (a) Ireland, R. E.; Norbeck, D. W. J. Org. Chem. 1985, 50,
2198–2200. DMP: (b) Barrett, A. G. M.; Hamprecht, D.; Ohkubo, M. J.
Org. Chem. 1997, 62, 9376–9378. BaMnO4: (c) Shuto, S.; Niizuma, S.;
Matsuda, A. J. Org. Chem. 1998, 63, 4489–4493. MnO2: (d) Wei, X.;
Taylor, R. J. K. Tetrahedron Lett. 1998, 39, 3815–3818. (e) Blackburn, L.;
Wei, X.; Taylor, R. J. K. Chem. Commun. 1999, 1337–1338. (f) Blackburn,
L.; Pei, C.; Taylor, R. Synlett 2002, 215–218. (g) Taylor, R. J. K.; Reid,
M.; Foot, J.; Raw, S. A. Acc. Chem. Res. 2005, 38, 851–869. IBX: (h)
Crich, D.; Mo, X.-S. Synlett 1999, 67–68. (i) Maiti, A.; Yadav, J. S. Synth.
Commun. 2001, 31, 1499–1506. TPAP/NMO: (j) MacCoss, R. N.; Balskus,
E. P.; Ley, S. V. Tetrahedron Lett. 2003, 44, 7779–7781. PCC: (k) Bressette,
A. R.; Glover, L. C., IV. Synlett 2004, 738–740. SO3-pyridine: (l)
Crisostomo, F. R. P.; Carrillo, R.; Martin, T.; Garcia-Tellado, F.; Martin,
V. S. J. Org. Chem. 2005, 70, 10099–10101. TEMPO/BAIB: (m) Vate`le,
(4) (a) Lebel, H.; Paquet, V.; Proulx, C. Angew. Chem., Int. Ed. 2001,
40, 2887–2890. (b) Grasa, G. A.; Moore, Z.; Martin, K. L.; Stevens, E. D.;
Nolan, S. P.; Paquet, V.; Lebel, H. J. Organomet. Chem. 2002, 658, 126–
131. (c) Lebel, H.; Paquet, V. Org. Lett. 2002, 4, 1671–1674. (d) Lebel,
H.; Guay, D.; Paquet, V.; Huard, K. Org. Lett. 2004, 6, 3047–3050. (e)
Lebel, H.; Paquet, V. J. Am. Chem. Soc. 2004, 126, 320–328. (f) Paquet,
V.; Lebel, H. Synthesis 2005, 1901–1905.
J.-M. Tetrahedron Lett. 2006, 47, 715–718
.
(5) Lebel, H.; Ladjel, C. Organometallics 2008, 27, 2676–2678.
10.1021/ol802299d CCC: $40.75
Published on Web 12/05/2008
2009 American Chemical Society

thylenation4 process.10,11 Terminal alkenes were obtained in
high yields, but two rather expensive catalysts were required.
Our recent successes with copper-catalyzed olefination
reactions using diazo compounds6 prompted us to study a
novel catalytic oxidation-olefination tandem process. Herein,
we describe the use of copper chloride phenanthroline
complex in tandem catalysis to efficiently synthesize various
alkenes from alcohols.
Copper-catalyzed aerobic oxidation reactions have emerged
as a powerful methodology for the transformation of alcohols
into carbonyl compounds.12 Among these methods, Marko´
et al. have developed the most general and efficient catalytic
oxidation of aliphatic, allylic, benzylic, primary, as well as
secondary alcohols using CuCl/Phen/DBAB complex (phen
) 1,10-phenanthroline, DBAB ) di-tert-butyl azodicarboxy-
late) (eq 1).13-15 The use of such a system in combination
with a olefination reaction involving diazo reagents and
triphenylphosphine would provide a monocatalytic approach
for a one-pot oxidation-olefination process.
isolated in 74% yield (the same yield was obtained using 5
mol % of CuCl in THF).6a Furthermore, the presence of a
catalytic amount of either t-BuOK, DBAB, or NMI did not
inhibit the reaction. These encouraging results led us to
explore the one-pot oxidation-methylenation tandem process
(Table 1). Treatment of the 4-methoxybenzyl alcohol under
Table 1. Copper-Catalyzed Oxidation-Methylenation Tandem
Process of 4-Methoxybenzyl Alcohol (eq 2)
Preliminary studies demonstrated that there was no ligand
effect in the copper-catalyzed methylenation reaction, and
CuCl/Phen complex provided results similar to those with
CuCl. For instance, when the p-anisaldehyde was treated with
1.1 equiv of 2-propanol, 1.1 equiv of PPh3, and 1.4 equiv of
TMSCHN2 in the presence of 5 mol % of CuCl/Phen in
fluorobenzene at 60 °C, the corresponding styrene was
entry
i-PrOH (equiv)
TMSCHN2 (equiv)
yielda (%)
1
2
1.1
1.1
2.0
2.0
5.0
5.0
5.0
5.0
1.4
4.0
2.0
2.0
2.0
2.0
3.0
3.0
36
54
29
45
52
72
71
85
(6) (a) Lebel, H.; Davi, M.; Diez-Gonzalez, S.; Nolan, S. P. J. Org.
Chem. 2007, 72, 144–149. (b) Lebel, H.; Davi, M.; Stoklosa, G. T. J. Org.
Chem. 2008, 73, 6828–6830. (c) Lebel, H.; Davi, M. AdV. Synth. Catal.
2008, 350, 2352–2358.
3
4b
5
(7) For recent examples of application in total synthesis, see: (a)
Nagashima, H.; Gondo, M.; Masuda, S.; Kondo, H.; Yamaguchi, Y.;
Matsubara, K. Chem. Commun. 2003, 442–443. (b) Kwon, M. S.; Woo,
S. K.; Na, S. W.; Lee, E. Angew. Chem., Int. Ed. 2008, 47, 1733–1735. (c)
Zhang, H.; Reddy, M. S.; Phoenix, S.; Deslongchamps, P. Angew. Chem.,
Int. Ed. 2008, 47, 1272–1275. (d) Lebel, H.; Parmentier, M. Org. Lett. 2007,
9, 3563–3566.
6b
7
8b
a Isolated yield. b TMSCHN2 was added in two portions.
(8) (a) Lebel, H.; Ladjel, C. J. Organomet. Chem. 2005, 690, 5198–
5205. (b) Lebel, H.; Ladjel, C. J. Org. Chem. 2005, 70, 10159–10161. (c)
Lebel, H.; Ladjel, C.; Brethous, L. J. Am. Chem. Soc. 2007, 129, 13321–
13326. (d) Davi, M.; Lebel, H. Chem. Commun. 2008, 4974–4976.
(9) (a) Jensen, D. R.; Schultz, M. J.; Mueller, J. A.; Sigman, M. S.
Angew. Chem., Int. Ed. 2003, 42, 3810–3813. (b) Schultz, M. J.; Hamilton,
S. S.; Jensen, D. R.; Sigman, M. S. J. Org. Chem. 2005, 70, 3343–3352.
(c) Sigman, M. S.; Jensen, D. R. Acc. Chem. Res. 2006, 39, 221–229.
(10) Lebel, H.; Paquet, V. J. Am. Chem. Soc. 2004, 126, 11152–11153.
(11) Kim and co-workers have reported a tandem oxidation-olefination
process using a ruthenium-catalyzed aerobic oxidation and stoichiometric
stabilized phosphorus ylides; see: Kim, G.; Lee, D. G.; Chang, S. Bull.
Korean Chem. Soc. 2001, 22, 943–944.
standard copper-catalyzed aerobic oxidation, followed by the
addition of TMSCHN2, 2-propanol, and triphenylphosphine,
led to the formation of the desired styrene 1, albeit in
moderate yields when not using an excess of 2-propanol
(entries 1-4). However, in the presence of 5 equiv of
2-propanol and 3 equiv of TMSCHN2 added in two portions,
85% of styrene 1 was obtained (entry 8).16,17
These reaction conditions were general and could be applied
to a wide variety of alcohol substrates (Table 2). Terminal
alkenes from linear primary alcohols as well as sterically
(12) For reviews, see: (a) Punniyamurthy, T.; Rout, L. Coord. Chem.
ReV. 2008, 252, 134–154. (b) Marko´, I. E.; Giles, P. R.; Tsukazaki, M.;
Gautier, A.; Dumeunier, R.; Dodo, K.; Philippart, F.; Chelle-Regnault, I.;
Mutonkole, J.-L.; Brown, S. M.; Urch, C. J. Aerobic, metal-catalyzed
oxidation of alcohols, Transition Metals for Organic Synthesis; Wiley-VCH:
Wemheim, 2004; Vol. 2, pp 437-478. (c) Schultz, M. J.; Sigman, M. S.
Tetrahedron 2006, 62, 8227–8241.
(15) Another catalytic system using copper in combination with TEMPO
derivatives has been developed. Nevertheless, due to the sterically hindered
environnement at the copper center, the secondary alcohols are slowly
oxidated. See: (a) Gamez, P.; Arends, I. W. C. E.; Reedijk, J.; Sheldon,
R. A. Chem. Commun. 2003, 2414–2415. (b) Gamez, P.; Arends, I. W. C. E.;
Sheldon, R. A.; Reedijk, J. AdV. Synth. Catal. 2004, 346, 805–811. (c)
Ansari, I. A.; Gree, R. Org. Lett. 2002, 4, 1507–1509. (d) Gamez, P.; Arends,
I. W. C. E.; Sheldon, R. A.; Reedijk, J. AdV. Synth. Catal. 2004, 346, 805–
811. (e) Jiang, N.; Ragauskas, A. J. Org. Lett. 2005, 7, 3689–3692. (f)
Jiang, N.; Ragauskas, A. J. J. Org. Chem. 2006, 71, 7087–7090. (g)
Velusamy, S.; Srinivasan, A.; Punniyamurthy, T. Tetrahedron Lett. 2006,
47, 923–926. (h) Striegler, S. Tetrahedron 2006, 62, 9109–9114. (i)
Mannam, S.; Alamsetti, S. K.; Sekar, G. AdV. Synth. Catal. 2007, 349, 2253–
2258. (j) Shen, H.-Y.; Ying, L.-Y.; Jiang, H,-L.; Judeh, Z. M. A. Int. J.
Mol. Sci. 2007, 8, 505–512.
(13) Marko´, I. E.; Gautier, A.; Dumeunier, R.; Doda, K.; Philippart, F.;
Brown, S. M.; Urch, C. J. Angew. Chem., Int. Ed. 2004, 43, 1588–1591
.
(14) For earlier work by Marko´, see: (a) Marko´, I. E.; Giles, P. R.;
Tsukazaki, M.; Brown, S. M.; Urch, C. J. Science 1996, 274, 2044–2046.
(b) Marko´, I. E.; Gautier, A.; Chelle-Regnaut, I.; Giles, P. R.; Tsukazaki,
M.; Urch, C. J.; Brown, S. M. J. Org. Chem. 1998, 63, 7576–7577. (c)
Marko´, I. E.; Giles, P. R.; Tsukazaki, M.; Chelle-Regnaut, I.; Gautier, A.;
Brown, S. M.; Urch, C. J. J. Org. Chem. 1999, 64, 2433–2439. (d) Marko´,
I. E.; Gautier, A.; Mutonkole, J. L.; Dumeunier, R.; Ates, A.; Urch, C. J.;
Brown, S. M. J. Organomet. Chem. 2001, 624, 344–347. (e) Marko´, I. E.;
Giles, P. R.; Tsukazaki, M.; Chelle-Regnaut, I.; Gautier, A.; Dumeunier,
R.; Philippart, F.; Doda, K.; Mutonkole, J.-L.; Brown, S. M.; Urch, C. J.
AdV. Inorg. Chem. 2004, 56, 211–240
.
42
Org. Lett., Vol. 11, No. 1, 2009

was also confirmed with N-Boc-valinol substrate (>99% ee).
Copper-catalyzed oxidation-methylenation provided the
corresponding alkene 15 in 81% yields and 99% ee (eq 4).
Table 2. Copper-Catalyzed Oxidation-Methylenation Tandem
Process of Primary Alcohols (eq 3)
To date, no monocatalytic oxidation-olefination one-pot
processes starting with secondary alcohols have been re-
ported. We were pleased to find that the copper-catalyzed
aerobic oxidation-methylenation process was also compat-
ible with aliphatic, allylic, or benzylic secondary alcohols
(Table 3). The corresponding 2,2-disubstituted alkenes were
isolated in good yields.
Table 3. Copper-Catalyzed Oxidation-Methylenation Tandem
Process of Secondary Alcohols (eq 5)
a Isolated yields. b 10 mol % of CuCl/Phen/DBAB. c c ) 0.05 M.
a Isolated yields.
hindered alcohols were isolated in good yields (entries 1-6).
Even substrates containing strong coordinating groups such as
pyridine were efficiently converted, although the use 10 mol
% of catalyst was required (Table 2, entry 3). Geraniol and
nerol afforded the expected terminal alkenes without isomer-
ization of the carbon-carbon double bond (Table 2, entries 7
and 8).18 Other activated alcohols, such as propargylic and
benzylic alcohols, were also suitable substrates (Table 2, entries
9-13). Overall, the reaction showed an excellent functional
group compatibility and alcohols were reacted in the presence
of nitro groups, amides, esters, and halides. Additionally, a wide
variety of protecting groups are tolerated (silyl and benzyl ether,
acetal, and carbamate).
We have previously observed that copper salts are general
catalysts that can be used with a number of diazo reagents,6c
a significant advantage over other catalyzed olefination
reactions. Similarly, the described one-pot process is compat-
ible with various diazocarbonyl reagents (Table 4). It was
indeed possible to produce the corresponding R,ꢀ-unsaturated
ester, ketone, or amides from 4-methoxybenzyl alcohol. In
all cases, the reaction proceeded in good yields and high
E-selectivities. Interestingly, in contrast to results in the
literature, the addition of a Brønsted acid does not enhance
the yield and/or selectivity.20
R-Chiral alcohols are converted into olefins without any
In conclusion, we have disclosed the use of a simple and
efficient copper catalyst for a tandem process aerobic
detectable racemization (Table 2, entries 5 and 6).19 This
Org. Lett., Vol. 11, No. 1, 2009
43

Professors Istva´n E. Marko´ and Freddi Philippart (Catholic
University of Louvain) for fruitful discussions.
Table 4. Oxidation-Olefination Tandem Process with Various
Diazo Reagents of 4-Methoxybenzyl Alcohol (eq 6)
Supporting Information Available: Experimental pro-
cedures and spectroscopic data for new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL802299D
(16) Typical procedure: CuCl (5 mg, 0.05 mmol) and 1,10-phenan-
throline (9 mg, 0.05 mmol) were placed in a vessel, and anhydrous
fluorobenzene was added (10 mL, c ) 0.1 M). The resulting solution was
stirred at room temperature until the solution became green and clear (5 to
entry
R3
CO2Et
COPh
CONMe2
product
yielda (%)
E/Zb
t
10 min). The alcohol (1.00 mmol) was added, followed by solid BuOK
(5.6 mg, 0.05 mmol). The solution was stirred at room temperature for 10
min, and NMI (120 mg, 1.4 mmol) and DBAD (230 mg, 1 mmol) were
added. The reaction mixture was heated at reflux under a gentle stream of
O2 until the reaction was completed as monitored by TLC. The resulting
mixture was cooled to 60 °C, and the vessel was backfilled with argon.
Triphenylphosphine (315 mg, 1.20 mmol) and 2-propanol (383 µL, 5.00
mmol) were added. Then, 1.50 of trimethylsilyldiazomethane (solution in
ether) was added, and the mixture was stirred for 2 h before a second portion
of 1.50 equiv of TMSCHN2 was added. The reaction was stirred until the
reaction was completed as gauged by GC, 1H NMR, or TLC analysis. The
solvent was removed under reduced pressure, and the crude alkene was
purified by flash chromatography on silica gel.
(17) An excess of 2-propanol accelerated the rate of the reaction, whereas
the excess of TMSCHN2 is required, as this reagent is destroyed over time
in the reaction mixture.
(18) In the palladium-catalyzed aerobic oxidation, only moderate conver-
sions were observed for the allylic alcohols (see ref 11). For modified
conditions for the palladium-catalyzed aerobic oxidation of allylic alcohols,
see: Batt, F.; Bourcet, E.; Kassab, Y.; Fache, F. Synlett 2007, 1869–1872.
(19) In some cases, racemization was observed during the palladium-
catalyzed aerobic oxidation, see ref 11.
1
2
3
4
21
22
23
24
1
87
70
74
81
94:6
91:9
95:5
97:3
CON(OMe)Me
a Isolated yields. Determined by H NMR of the crude product.
b
oxidation-olefination using primary and also secondary
alcohols. Some noteworthy attributes of the system include
its simple and inexpensive catalytic system, nonbasic reaction
conditions, compatibility with sensitive and enolizable
substrates, and functional group tolerance for the synthesis
of a large variety of alkenes from alcohols.
Acknowledgment. This research was supported by NSERC
(Canada), the Canada Foundation for Innovation, and the
Universite´ de Montre´al. Acknowledgement is also made to
the Donors of the American Chemical Society Petroleum
Research Fund for partial support of this research. We thank
(20) For examples of Bro¨nsted acid-catalyzed Wittig reaction, see: (a)
Ru¨chardt, C.; Eichler, S.; Panse, P. Angew. Chem., Int. Ed. 1963, 2, 619.
(b) Bose, A. K.; Manhas, M. S.; Ramer, R. M. J. Chem. Soc. C 1969, 2728–
2730. (c) Patil, V. J.; Ma¨vers, U. Tetrahedron Lett. 1996, 67, 1281–1284.
(d) Barrett, A. G. M.; Hamprecht, D.; White, A. J. P.; Williams, D. J. J. Am.
Chem. Soc. 1997, 119, 8608–8615.
44
Org. Lett., Vol. 11, No. 1, 2009