Passerini three-component reaction of alcohols under catalytic aerobic oxidative conditions

Article abstract of DOI:10.1021/ol100012y

"Chemical eqation presented" Alcohols Instead of aldehydes were used In the Passerini three-component reaction under catalytic aerobic conditions. Mixing alcohols, isocyanides, and carboxylic acids In toluene In the presence of a catalytic amount of cupric chloride, NaNO₂, and TEMPO afforded, under an oxygen atmosphere, the P-3CR adducts In good yields.

Full text of DOI:10.1021/ol100012y

ORGANIC
LETTERS
2010
Vol. 12, No. 7
1432-1435
Passerini Three-Component Reaction of
Alcohols under Catalytic Aerobic
Oxidative Conditions
Julien Brioche, Ge´raldine Masson,* and Jieping Zhu*
Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles, CNRS,
91198 Gif-sur-YVette Cedex, France
zhu@icsn.cnrs-gif.fr; masson@icsn.cnrs-gif.fr
Received January 3, 2010
ABSTRACT
Alcohols instead of aldehydes were used in the Passerini three-component reaction under catalytic aerobic conditions. Mixing alcohols,
isocyanides, and carboxylic acids in toluene in the presence of a catalytic amount of cupric chloride, NaNO2, and TEMPO afforded, under an
oxygen atmosphere, the P-3CR adducts in good yields.
Tandem oxidative processes (TOP) in which oxidation of
alcohols are combined with the subsequent elaboration of
the carbonyl intermediates have been developed into power-
ful synthetic tools.1,2 Although great progress has been made
in developing bimolecular TOP processes, studies on com-
bining alcohol oxidation with a multicomponent reaction
(MCR)3 remain scarce. The difficulties associated with the
development of such one-pot oxidation/MCR processes are
self-evident due to the presence of mutli-functionalities/multi-
intermediates and the complexity of the reaction mechanism
intrinsic to MCRs. This is unfortunate since aldehydes are
ubiquitous substrates in many powerful MCRs. Therefore,
the ability to perform domino oxidation/MCR would widen
significantly the versatility and scope of these aldehyde-based
MCRs. In this context, we recently reported a Passerini three-
component reaction (P-3CR)4 of primary alcohols using
O-iodoxybenzoic acid (IBX) as an oxidant.5,6 In addition to
its wide application scope, this protocol proved to be
particularly valuable when the desired aldehydes were
inaccessible as demonstrated in Wessjohann’s elegant syn-
thesis of macrocycles.7 Although both IBX and its reduced
form (IBA) are easily removable by simple filtration, the
need to use an excess amount of IBX was nevertheless a
drawback of this methodology. As a continuation of this
(1) (a) Taylor, R. J. K.; Reid, M.; Foot, J.; Raw, S. A. Acc. Chem. Res.
2005, 38, 851–869. (b) Ekoue-Kovi, K.; Wolf, C. Chem.sEur. J. 2008,
14, 6302–6315. (c) Tietze, L. F.; Brasche, G.; Gericke, K. M. Domino
Reactions in Organic Synthesis; Wiley-VCH: Weinheim, 2006
.
(2) For recent examples, see: (a) Davi, M.; Lebel, H. Org. Lett. 2009,
11, 41–44. (b) Maki, B. E.; Scheidt, K. A. Org. Lett. 2009, 11, 1651–1654.
(c) Donald, J. R.; Edwards, M. G.; Taylor, R. J. K. Tetrahedron Lett. 2007,
48, 5201–5204. (d) McAllister, G. D.; Oswald, M. F.; Paxton, R. J.; Raw,
S. A.; Taylor, R. J. K. Tetrahedron 2006, 62, 6681–6694. (e) Bromley,
W. J.; Gibson, M.; Lang, S.; Raw, S. A.; Whitwood, A. C.; Taylor, R. J. K.
(4) (a) Passerini, M. Gazz. Chim. Ital. 1921, 51, 126–129. (b) Passerini,
M. Gazz. Chim. Ital. 1922, 52, 432–435. For a review, see: (c) Banfi, L.;
RivaR. In Organic Reactions; Charette, A. B., Ed.; Wiley : New York,
2005; Vol. 65, pp 1-140.
Tetrahedron 2007, 63, 6004–6014
.
(3) For reviews on isocyanide-based multicomponent reactions, see: (a)
Orru, R. V. A.; De Greef, M. Synthesis 2003, 1471–1499. (b) Nair, V.;
Rajesh, C.; Vinod, A. U.; Bindu, S.; Sreekanth, A. R.; Mathen, J. S.;
Balagopal, L. Acc. Chem. Res. 2003, 36, 899–907. (c) Zhu, J. Eur. J. Org.
Chem. 2003, 113, 3–1144. (d) Do¨mling, A. Chem. ReV. 2006, 106, 17–89.
(e) Isambert, N.; Lavilla, R. Chem.sEur. J. 2008, 14, 8444–8454. (f) El
Kaim, L.; Grimaud, L. Tetrahedron 2009, 65, 2153–2171. (g) Wessjohann,
L. A.; Rivera, D. G.; Vercillo, O. E. Chem. ReV. 2009, 109, 796–814. (h)
Multicomponent Reactions; Zhu, J., Bienayme´, H., Eds.; Wiley-VCH:
Weinheim, 2005.
(5) Ngouansavanh, T.; Zhu, J. Angew. Chem., Int. Ed. 2006, 45, 3495–
3497
.
(6) MCRs involving oxidation of amines: (a) Ngouansavanh, T.; Zhu,
J. Angew. Chem., Int. Ed. 2007, 46, 5775–5778. (b) Fontaine, P.; Chiaroni,
A.; Masson, G.; Zhu, J. Org. Lett. 2008, 10, 1509–1512. (c) Jiang, G.; Chen,
J.; Huang, J.-S.; Che, C.-M. Org. Lett. 2009, 11, 4568–4571
.
(7) Leon, F.; Rivera, D. G.; Wessjohann, L. A. J. Org. Chem. 2008, 73,
1762–1767.
10.1021/ol100012y  2010 American Chemical Society
Published on Web 03/10/2010

research program, we report here the realization of Passerini
three-component reaction starting from alcohols under catalytic
conditions using oxygen as terminal oxidant (Scheme 1).
Table 1. Optimization of Reaction Parametersa
Scheme 1
.
Passerini Reaction of Alcohols under Catalytic
Oxidative Conditions
conversion
of (2a, %)
yield
of 1a,b
%
entry
conditions
1
2
3
4
5
6
7
8
9
A/toluene (0.25 M), O2, 80 °C
B/C6H5F (0.5 M), O2, 80 °C
C/C6H5F (0.5 M), O2, 80 °C
D/DCM (1 M), O2, rt
E/toluene (0.5 M), O2, rt
F/toluene (0.5 M), O2, rt
F/toluene (2.5 M), O2, rt
F/toluene (0.1 M), O2, rt
F/toluene (2.5 M), air, rt
F/toluene (0.5 M), O2, rt
NR
NR
NR
NR
100
100
100
75
0
0
0
0
30
The catalytic aerobic oxidation of alcohols using molecular
O2 as a terminal oxidant has attracted much attention in recent
years.8 Many efficient catalytic systems have been developed
using transition metals alone or in combination with TEMPO
as catalysts.7,9 While a wide range of benzylic alcohols have
been successfully oxidized to aldehydes and ketones, primary
nonactivated alcohols were known to be poor substrates due
to their low reactivities and side reactions such as overoxi-
dation, aldol, or Tishchenko reaction associated with the
resulting aldehydes.8,10-12 In spite of this discouraging
observation, we set out to examine the reaction of 2-phe-
nylethanol (2a), benzyl isocyanide (3a), and benzoic acid
(4a) under catalytic aerobic oxidation conditions, assuming
35
67c
ND
NDc
NDd
50
15
10
a General conditions: 2a/3a/4a )1:1:1, 24 h under conditions specified
as follows. Method A: TPAP (15 mol %), 4 Å molecular sieves. Method
B: CuCl (10 mol %), 1,10-phenantroline (10 mol %), DBAD (10 mol %),
tBuOK (10 mol %), NMI (15 mol %). Method C: CuBr·DMS (5 mol %),
4,4′-dinonyl-2,2′-bipyridine (5 mol %), TEMPO (10 mol %). Method D:
PyHBr3 (20 mol %), TEMPO (5 mol %), NaNO2 (20 mol %). Method E:
FeCl3·5H2O (15 mol %), TEMPO (15 mol %), NaNO2 (15 mol %). Method
F: CuCl2·2H2O (15 mol %), TEMPO (15 mol %), NaNO2 (15 mol %).
b Yield of isolated product. c 2.5 equiv of isonitrile. d In the absence of
NaNO2. Abbreviations: TEMPO ) 2,2,6,6-tetramethylpiperidine 1-oxyl;
TPAP, tetra-n-propylammonium perruthenate; DBAB ) dibenzyl azodi-
carboxylate, NMI ) N-methylimidazole; NR ) no reaction; ND ) not
determined.
(8) For reviews on catalytic aerobic alcohol oxidations, see: (a) Mallat,
T.; Baiker, A. Chem. ReV. 2004, 104, 3037–3058. (b) Marko´, I. E.; Gilles,
P. R.; Tsukazaki, M.; Gautier, A.; Dumeunier, R.; Doda, K.; Philippart, F.;
Chelle´-Regnaut, I.; Mutonkole, J.-L.; Brown, S. M.; Urch, C. J. Aerobic,
Metal-catalyzed Oxidation of Alcohols. In Transition Metals for Organic
Synthesis, 2nd ed.; Beller, M., Bolm, C., Eds.; Wiley-VCH: Weinheim,
2004; Vol. 2, pp 437-478. (c) Zhan, B.-Z.; Thompson, A. Tetrahedron
2004, 60, 2917–2935. (d) Sheldon, R. A.; Arends, I. W. C. E. AdV. Synth.
Catal. 2004, 346, 1051–1071. (e) Punniyamurthy, T.; Velusamy, S.; Iqbal,
J. Chem. ReV. 2005, 105, 2329–2364. (f) Schultz, M. J.; Sigman, M. S.
Tetrahedron 2006, 62, 8227–8241. (g) Recupero, F.; Punta, C. Chem. ReV.
2007, 107, 3800–3842. (h) Sheldon, R. A.; Arends, I. W. C. E. J. Mol.
Catal. A: Chem. 2006, 251, 200–214. (i) Seki, T.; Baiker, A. Chem. ReV.
2009, 109, 2409–2454.
that in situ trapping of the aldehyde intermediate by
isocyanide could potentially avoid these aforementioned
undesired pathways. Initial experiments using ruthenium13
and copper14 as metal catalysts (entries 1-3, Table 1) and
under metal-free conditions15 (entry 4) were found to be
ineffective, leading only to the complete decomposition of
isocyanide 3a. Gratefully, the Passerini adduct 1a was
isolated in 30% yield using FeCl3-TEMPO-NaNO2 (0.15
equiv each) catalytic system developed by Liang and Hu
(entry 5, Table 1).16 Replacing FeCl3 by CuCl2 gave a cleaner
reaction, although the yield remained moderate (enrty 6).
By using 2.5 equiv of isocyanide 3a, the yield of 1a increased
to 65% (c ) 2.5 M) under otherwise identical conditions
(entry 7, Table 1). On the other hand, replacing oxygen gas
by air atmosphere (entry 9, Table 1) diminished significantly
the reaction efficiency. Another key factor is the concentra-
tion. The reaction had to be performed at high concentration
to guarantee the success of the overall domino process
(9) For transition metal/TEMPO-catalyzed aerobic alcohol oxidations,
see: (a) Gassama, A.; Hoffmann, N. AdV. Synth. Catal. 2008, 350, 35–39.
(b) Jiang, N.; Ragauskas, A. J. ChemSusChem 2008, 1, 823–825. (c)
Mannam, S.; Alamsetti, S. K.; Sekar, G. AdV. Synth. Cata. 2007, 349, 2253–
2258. (d) Shibuya, M.; Tomizawa, M.; Suzuki, I.; Iwabuchi, Y. J. Am. Chem.
Soc. 2006, 128, 8412–8413. (e) Jiang, N.; Ragauskas, A. J. J. Org. Chem.
2006, 71, 7087–7090. (f) Valusamy, S.; Srinivasan, A.; Punniyamurthy, T.
Tetrahedron Lett. 2006, 47, 923–926. (g) Jiang, N.; Ragauskas, A. J. Org.
Lett. 2005, 7, 3689–3692. (h) Minisci, F.; Recupero, F.; Cecchetto, A.;
Gambarotti, C.; Punta, C.; Faletti, R.; Paganelli, R.; Pedulli, G. F. Eur. J.
Org. Chem. 2004, 10, 9–119. (i) Minisci, F.; Recupero, F.; Pedulli, G. F.;
Lucarini, M. J. Mol. Catal. A: Chem. 2003, 204, 63–90. (j) Gamez, P.;
Arends, I. W. C. E.; Reedijk, J.; Sheldon, R. A. Chem. Commun. 2003,
2414–2415. (k) Ansari, I. A.; Gree, R. Org. Lett. 2002, 4, 1507–1509. (l)
Ben-Daniel, R.; Alsters, P.; Neumann, R. J. Org. Chem. 2001, 66, 8650–
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I. W. C. E.; Sheldon, R. A. J. Am. Chem. Soc. 2001, 123, 6826–6833. (n)
Cecchetto, A.; Fontana, F.; Minisci, F.; Recupero, F. Tetrahedron Lett. 2001,
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C. J.; Brown, S. M. J. Am. Chem. Soc. 1997, 119, 12661–12662.
(14) (a) Marko´, I. E.; Giles, P. R.; Tsukazaki, M.; Brown, S. M.; Urch,
C. J. Science 1996, 274, 2044–2046. (b) 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. (c) Betzemeier, B.; Cavazzini, M.;
Quici, S.; Kno¨chel, P. Tetrahedron Lett. 2000, 41, 4343–4346.
(15) (a) Wang, N.; Liu, R.; Chen, J.; Liang, X. Chem. Commun. 2005,
5322–5324. (b) Wang, X.; Liu, R.; Jin, Y.; Liang, X. Chem.sEur. J. 2008,
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AdV. Synth. Catal. 2009, 351, 89–92.
42, 6651–6653
.
(10) (a) Seki, T.; Nakajo, T.; Onaka, M. Chem. Lett. 2006, 35, 824–
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1173–1179
.
(11) Aldehydes have been used as sacrificial co-oxidants in aerobic
oxidation of olefins; see: Loeker, F.; Leitner, W. Chem.sEur. J. 2000, 6,
2011–2015
.
(12) Marko´’s procedure is an exception; see: Marko´, I. E.; Gautier, A.;
Dumeunier, R.; Doda, K.; Philippart, F.; Brown, S. M.; Urch, C. J. Angew.
(16) Liu, R.; Liang, X.; Dong, C.; Hu, X. J. Am. Chem. Soc. 2004, 126,
4112–4113.
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Org. Lett., Vol. 12, No. 7, 2010
.
1433

(entries 7 vs 8, Table 1). Other copper sources [Cu(SO4)2,
CuBr2, Cu(NO3)2, CuF2, CuI, CuBr], solvents (MeCN,
dichloroethane, and trifluorobenzene), and co-oxidants
Table 2. Scope and Limitation of the Reaction Conditionsa
t
(KNO2, Bu4NNO2, AgNO2, BuONO) were also examined
(data not shown). However, none of them afforded results
superior to those using the conditions shown in entry 7 (Table
1). Control experiments indicated that the use of a ternary
system (CuCl2-TEMPO-NaNO2, as well as their ratio (1/
1/1, 0.15 equiv each)) was important for the production of
3a. In the absence of one of them, the domino process
became less efficient. For example, in the absence of NaNO2
only a conversion equal to the catalysts loading was observed
(entry 10, Table 1). Its role seems to be important in the
turnover of the catalytic oxidation. It is worth noting that
the Passerini product resulting from over oxidation of alcohol
to the corresponding carboxylic acid and its subsequent
reaction with aldehyde and isocyanide was formed only in
a trace amount (<5%).17
Using optimized conditions [CuCl2 (0.15 equiv), TEMPO
(0.15 equiv), NaNO2 (0.15 equiv), O2, 2/3/4 ) 1/2.5/1, in
toluene (C 2.5 M), room temperature], the scope of the
oxidative Passerini reaction was examined with representative
primary alcohols, isonitriles, and carboxylic acids (Table 2).
Functional groups such as ester (entry 12), benzyl ether (entry
13), silyl ether (entry 17), acetal (entry 16), and double bond
(entry 14) were tolerated. The alcohol 2j afforded the low
yield of the P-3CR adduct presumably due to the coordina-
tion of alkyne unit to the copper species, consequently
blocking the catalytic cycle. Cyclopropylmethanol (2d) also
participated in the reaction to afford the corresponding adduct
in moderate yield (entry 7, Table 2). Finally, ꢀ-substituted
enantioenriched alcohols such as (R)-1,2-O-isopropylidene-
glycerol (2k, entry 16) and (S)-3-(tert-butyldiphenylsilyloxy)-
2-methylpropan-1-ol (2l, entry 17, Table 2), whose corre-
sponding aldehydes are known to be sensitive toward
racemization,18 were successfully engaged in this oxidative
P-3CR reaction. In both cases, the Passerini adducts were
obtained as a mixture (1:1) of two diastereomers in 75%
and 60% yields, respectively. The lack of diastereoselectivity
in P-3CR is not unexpected.3,19 To our delight, the chiral
HPLC analysis of 1q and 1r indicated that no racemization
of the transient aldehydes occurred under these conditions.
In the case of 2l, R-hydroxyamide derived from a nucleo-
philic addition of water to nitrilium intermediate20 was
isolated in about 10% yield together with 1r. Aromatic and
aliphatic isocyanides with different steric properties such as
a General conditions: 2/3/4 ) 1/2.5/1, O2 balloon, in toluene (c ) 2.5
M), 24 h. The oxidation of alcohol was performed in the presence of other
reactants (cf. Supporting Information). b Yield of isolated product. c dr )
1: 1. d dr determined by 1H NMR spectroscopy of the crude reaction mixture.
e 0.3 equiv each of CuCl2·2H2O, NaNO2, TEMPO was used instead.
(17) Shapiro, N.; Vigalok, A. Angew. Chem., Int. Ed. 2008, 47, 2849–
2852.
benzyl isocyanide (3a), cyclohexyl isocyanide (3b), 2,6-
dimethylphenyl isocyanide (3c), and tert-butyl isocyanide
(3d) participated in the reaction. The domino oxidation/P-
3CR process has also been applied to representative car-
boxylic acids including (R)-O-methyl mandelic acid (4c),
cyclopropyl carboxylic acid (4d), and R,ꢀ-unsaturated car-
boxylic acid (4g), etc. However, N-protected amino acids
failed to participate in this reaction (data not shown).
(18) (a) Bisseret, P.; Rohmer, M. J. Org. Chem. 1989, 54, 2958–2964.
(b) Roush, W. R.; Palkowitz, A. D.; Ando, K. J. Am. Chem. Soc. 1990,
112, 6348–6359.
(19) For recent development on enantioselective P-3CRs, see: (a)
Denmark, S.; Fan, Y. J. Am. Chem. Soc. 2003, 125, 7824–7825. (b)
Denmark, S.; Fan, Y. J. Org. Chem. 2005, 70, 9667–9676. (c) Kusebauch,
U.; Beck, B.; Messer, K.; Herdtweck, E.; Do¨mling, A. Org. Lett. 2003, 5,
4021–4024. (d) Andreana, P. R.; Liu, C. C.; Schreiber, S. L. Org. Lett.
2004, 6, 4231–4234. (e) Wang, S.-X.; Wang, M.-X.; Wang, D.-X.; Zhu, J.
Eur. J. Org. Chem. 2007, 407, 6–4080. (f) Wang, S.-X.; Wang, M.-X.;
Wang, D.-X.; Zhu, J. Org. Lett. 2007, 9, 3615–3618. (g) Wang, S.-X.; Wang,
M.-X.; Wang, D.-X.; Zhu, J. Angew. Chem., Int. Ed. 2008, 47, 388–391.
(h) Yue, T.; Wang, M.-X.; Wang, D.-X.; Zhu, J. Angew. Chem. Int. Ed
(20) See, for example: Grassot, J.-M.; Masson, G.; Zhu, J. Angew. Chem.,
Int. Ed. 2008, 47, 947–950.
2008, 47, 9454–9457
.
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Org. Lett., Vol. 12, No. 7, 2010

TEMPOH species 7 by NO2, produced from NaNO2 and
carboxylic acid,23 would regenerate the copper(II)-TEMPO
complex 5. Finally, NO2 is regenerated by oxidation of NO
with molecular oxygen, thus completing the dual catalytic
cycle. The observation that both CuCl2 and NaNO2 were
important for the reaction was in accord with the proposed
catalytic cycle. Nevertheless, at the present stage of the
development, we cannot exclude the pathway involving
oxoammonium intermediate.14b,24 The fact that cyclopropy-
lmethanol (2d) and hex-5-en-1-ol (2i) can be converted into
their corresponding P-3CR adducts, inferring that the ionic
mechanism may also be operating.25 However, it has to be
noted that substrates prone to radical cyclization have been
successfully oxidized to aldehydes under metal-catalyzed
aerobic conditions that are known to involve a radical
mechanism.26
Scheme 2. Mechanistic Proposal
In conclusion, we documented the first examples of an
efficient Passerini reaction of alcohols under aerobic condi-
tions in the presence of a catalytic amount of a ternary
system, CuCl2-NaNO2-TEMPO, using molecular oxygen as
a terminal oxidant. We believe that such a process could
find useful applications in view of the power of the Passerini
reaction and that the concept could be extended to other
MCRs involving aldehyde substrates.27
A possible reaction sequence for this aerobic oxidative
P-3CR reaction is shown in Scheme 2. Formation of
CuCl2-TEMPO complex 521 followed by ligand exchange
with alcohol would lead to a ternary complex 6. An
intramolecular hydrogen abstraction followed by fragmenta-
tion would then give the copper(I)-TEMPOH complex and
aldehyde 8. Subsequent reaction of 8 with isocyanide 3 and
carboxylic acid 4 afforded the Passerini three-component
adduct.22 On the other hand, oxidation of the copper(I)-
Acknowledgment. Financial support from CNRS and
ANR is gratefully acknowledged. J.B. thanks ICSN for a
postdoctoral fellowship.
Supporting Information Available: Experimental pro-
(21) X-ray structure of CuBr2-Tempo complex: (a) Caneschin, A.;
Grand, A.; Laugier, J.; Rey, P.; Subra, R. J. Am. Chem. Soc. 1988, 110,
2307–2309. X-ray structure of CuCl2-Tempo complex: (b) Laugier, J.;
Latour, J.-M.; Caneschi, A.; Rey, P. Inorg. Chem. 1991, 30, 4474–4477.
In ref b, the authors proposed that complexation of TEMPO by the copper
salt did not involve an electron transfer between the two fragments and
that the complex is better formulated as Cu2+(TEMPO•) rather than as
Cu3+(TEMPO-) or Cu+(TEMPO+).
1
cedures, product characterization, and copies of the H and
13C NMR spectra. This material is available free of charge
via the Internet at http://pubs.acs.org.
OL100012Y
(22) Note that isocyanides can undergo a number of competitive
reactions in the presence of cupric chloride under aerobic conditions. (a)
Oxidation to isocyanate: Saegusa, T.; Kobayashi, S.; Ito, Y. Bull. Chem.
Soc. Jpn. 1970, 43, 275–276. (b) Conversion to imidocarbonyl chloride:
Saegusa, T.; Ito, Y.; Kobayashi, S.; Hirota, K.; Takeda, N. Can. J. Chem.
1969, 47, 1217–1222. (c) Insertion to alcohol leading to formamidate:
Saegusa, T.; Ito, Y.; Kobayashi, S.; Takeda, N.; Hirota, K. Tetrahedron
Lett. 1967, 521–524. (d) Polymerization: Saegusa, T.; Ito, Y.; Kobayashi,
S. Tetrahedron Lett. 1967, 127, 3–1275. Control experiments have shown
that mixing the benzyl isocyanide and CuCl2 in toluene under oxygen
atmosphere led to the complete decomposition of the former after 20 h.
Therefore, to guarantee the success of the present domino oxidation/P-3CR,
the oxidation of alcohol to aldehyde and its subsequent P-3CR had to be
faster than these competitive reactions. We found that polymerization of
isocyanide was the main side reaction. However, in initial condition surveys,
oxidation of isocyanide to isocyanate was also observed.
(23) Miao, C.-X.; He, L.-N.; Wang, J.-Q.; Wang, J.-L. AdV. Synth Catal.
2009, 351, 2209–2216.
(24) For mechanistic discussion on the Cu-Tempo-catalyzed aerobic
oxidation, see: (a) Semmelhack, M. F.; Schmidt, C. R.; Corte´s, D. A.; Chou,
C. S. J. Am. Chem. Soc. 1984, 106, 3374–3376. (b) Semmelhack, M. F.;
Schmidt, C. R.; Cortes, D. A. Tetrahedron Lett. 1986, 27, 1119–1122. (c)
Dijiksman, A.; Arends, I. W. C. E.; Sheldon, R. A. Org. Biomol. Chem.
2003, 1, 3232–3237. (d) For a review, see: Galli, C.; Gentili, P.; Lanzalunga,
O. Angew. Chem., Int. Ed. 2008, 47, 4790–4796. See also ref 20.
(25) The reaction of 2a, 3a, and 4a in the absence of CuCl2 [TEMPO
(0.15 equiv), NaNO2 (0.15 equiv), O2, in toluene (C 2.5 M), rt] led to 50%
conversion of alcohol.
(26) Astolfi, P.; Brandi, P.; Galli, C.; Gentili, P.; Gerini, M. F.; Greci,
L.; Lanzalunga, O. New J. Chem. 2005, 29, 1308–1317.
(27) MCRs of in situ generated isocyanides : El Kaim, L.; Grimaud,
L.; Schiltz, A. Org. Biomol. Chem. 2009, 7, 3024–3026.
Org. Lett., Vol. 12, No. 7, 2010
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