Intramolecular palladium-catalyzed aminocarboxylation of olefins as a direct route to bicyclic oxazolidinones

Article abstract of DOI:10.1002/adsc.201000889

An efficient, direct synthesis of oxazolidinones fused to six-membered heterocyclic rings starting from carbamate-protected aminoalkenes has been developed. This procedure is based on an oxidative palladium(II)-catalyzed reaction performed in the presence

Full text of DOI:10.1002/adsc.201000889

FULL PAPERS
DOI: 10.1002/adsc.201000889
Intramolecular Palladium-Catalyzed Aminocarboxylation of
Olefins as a Direct Route to Bicyclic Oxazolidinones
Elena Borsini,a Gianluigi Broggini,a,* Andrea Fasana,a Simona Galli,a
Maisaa Khansaa,a Umberto Piarulli,a and Micol Rigamontia
a
Dipartimento di Scienze Chimiche e Ambientali, Universitꢀ dell’Insubria, via Valleggio 11, 22100 Como, Italy
Fax : (+39)-(0)31-238-6449; phone: (+39)-(0)31-238-6444; e-mail: gianluigi.broggini@uninsubria.it
Received: November 25, 2010; Revised: January 24, 2011; Published online: April 13, 2011
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201000889.
Abstract: An efficient, direct synthesis of oxazolidi- pounds arise from a domino aminocarboxylation
nones fused to six-membered heterocyclic rings start- process through the direct intervention of the carba-
ing from carbamate-protected aminoalkenes has mate oxygen after the initial palladium-promoted
been developed. This procedure is based on an oxi- transfer of the nitrogen atom on the C=C double
dative palladium(II)-catalyzed reaction performed in bond.
the presence of stoichiometric copper chloride,
which is determinant to promote the formation of
the bicyclic product and prevent the isolation of the Keywords: amination; carboxylation; domino reac-
monocyclic amination product. Oxazolidinone com- tions; nitrogen heterocycles; palladium
Introduction
hetero
ACHTUNGTRENpNUNG olycyclic nitrogen-containing compounds by
means of intramolecular Pd-catalyzed procedures,[10]
Nitrogen-containing heterocycles are widely present involving also reactions in oxidative conditions onto
in natural and synthetic compounds endowed with multiple carbon-carbon bonds.[11] Herein, we report a
biological and pharmaceutical properties.[1] As a con- direct, one-step synthesis of oxazolidinones fused to
sequence, the development of synthetic procedures six-membered heterocyclic rings by a domino amino-
for the construction of mono- and polycyclic skeletons carboxylation reaction on allylamides of N-alkoxycar-
containing one or more nitrogen atoms represents a bonyl-protected a-amino acids under oxidative condi-
continuous goal in organic synthesis. Among the most tions.
investigated approaches that rely on amination reac-
Our work plan relies on the use of a carbamate
tions, palladium-catalyzed processes occupy a promi- group as oxygen source to build directly a carbon-
nent role.[2] For instance, the Pd-catalyzed coupling of oxygen bond in Pd-catalyzed reactions. This is pre-
aryl halides with various amines, pioneered by the dictably reasonable according to (i) the well known
groups of both Buchwald and Hartwig,[3] have been behaviour of the carbonyl oxygen as nucleophile in
broadly exploited to synthesize different kinds of such reactions[12] and (ii) the Au-catalyzed procedures
pharmaceutical compounds.[4] On the other hand, oxi- aimed at the synthesis of oxazolidinones involving
dative Pd-catalyzed reactions, which enable direct tert-butyl carbamates, already described in the litera-
amination of C=C double bonds, have been the main ture.[13] In our case, the carbonyl group would have to
focus in recent years.[5] In this latter field, notwith- intervene on a s-alkyl-palladium complex generated
standing their rarity in the literature, particularly ap- in situ subsequently to direct amination of an alkene
pealing are the domino processes such as carboamina- (Figure 1).
tions,[6] diaminations,[7] oxoaminations[8] and aminoha-
The oxazolidinone skeleton is found in several
logenations[9] of alkenes, that allow an easy access to drug-like molecules (Figure 2).[14] Moreover, it also
(poly)functionalized compounds or to bicyclic ring deserves interest from the synthetic point of view,
systems.
being able to act as a precursor of 1,2-amino alco-
Over the last decade, studies in our laboratory have hols,[15] which in turn are prevalent motifs in a diverse
been concentrated on the synthesis of complex range of important natural and pharmaceutical prod-
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Figure 1. Approach to a Pd-catalyzed synthesis of bicyclic oxazolidinones involving a carbamate group.
Figure 2. Examples of biologically active compounds con-
taining oxazolidinone skeleton.
Scheme 1. Aminocarboxylation vs. amination process.
ucts. Several procedures for the formation of oxazoli-
Conversely, treatment of the allylamide 1 with
dinones have been already reported,[16] some of which PdCl
2ACHTUNGTRENUNG(MeCN)2 (5 mol%) and CuCl2 (10 mol%)/O2 as
featuring an intramolecular Pd-catalyzed amination of the oxidant system in DMF at 1008C resulted in the
O-allyl or O-homoallyl carbamates.[8a,9a,b,15a,17] Con- dihydropyrazinone derivative 3, arising from a 6-exo-
versely, our approach allows the construction of the trig cyclization, followed by a b-hydride elimination
oxazolidinone ring from easily accessible carbamate- from the Pd(II) intermediate, and double bond iso-
protected aminoalkenes, with the simultaneous forma- merization of the exo-methylene product (Scheme 1,
tion of a fused-heterocycle ring.
path b). This result represents an alternative route to
the already reported Pd-catalyzed procedures to
access the piperazine ring.[18]
Results and Discussion
Gratified by the effective conversion of 1 into bicy-
clic oxazolidin-2-one 2, which represents a much
In order to evaluate the feasibility of the aminocar- more valuable result than the simple amination pro-
boxylation reaction, we selected Boc-glycine N-allyl- cess, we then focused our efforts to optimize the con-
N-cyclohexyl-amide (1) as a model substrate, on ditions for the aminocarboxylation process.
which a survey of the activity of different catalysts
As apparent from Table 1, an excess of CuCl2 yield-
and oxidants was undertaken. At the outset of our ed 2 in higher amounts (entry 2 vs. 1). Both palladium
screening, we tested two different catalytic systems and cupric chloride were required, since the conver-
based on the use of PdCl
(MeCN)2 as catalyst coupled sion of
1
was precluded by the removal of
with CuCl2, which revealed a remarkable role as oxi- PdCl
dant. Indeed, CuCl2 was able to promote the diver-
gent formation of two cyclization products, depending
solely on its amount, catalytic vs. stoichiometric. In
particular, compound 2 was obtained using PdCl2
2ACHTUNGTERN(NUNG MeCN)2 as well as by the use of other oxidants
ACHTUNGTRENNUNG(MeCN)2 (5 mol%) and a stoichiometric amount of
CuCl2 in DMF at 1008C (Scheme 1, path a); i.e., the
domino product was obtained through the planned
aminocarboxylative process based on an initial
carbon-nitrogen bond formation, followed by an in-
tramolecular carboxylation reaction, involving the
tert-butoxycarbonyl group.
Scheme 2. Aminocarboxylation of different carbamates.
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Intramolecular Palladium-Catalyzed Aminocarboxylation of Olefins
Table 1. Optimization of the aminocarboxylation reaction conditions.
Entry
Catalyst
Oxidant (equiv.)
Solvent
T [8C]
Yield [%][a]
1
2
3
4
5
6
7
8
PdCl
PdCl
–
PdCl
PdCl
PdCl
PdCl
PdCl
PdCl
PdCl
G
CuCl2 (1)
CuCl2 (3)
CuCl2 (3)
DMF
DMF
DMF
DMF
DMF
DMF
DMF
THF
CH2Cl2
Toluene
DMF
DMF
100
100
100
100
100
100
r.t.
reflux
reflux
80
69
81
n.r.
n.r.
n.r.
traces
64
40
26
n.r.
n.r.
n.r.
Cu
1,4-BQ (2)
PhI(OAc)2 (3)
ACHTUNGRTEN(NUNG OAc)2 (3)
ACHTUNGTRENNUNG
CuCl2 (3)
CuCl2 (3)
CuCl2 (3)
CuCl2 (3)
9
10
11
12
Pd
Pd
U
Cu
N
100
100
1,4-BQ (2)
[a]
Isolated yield.
such as CuACHTUNGTRENNUNG(OAc)2, 1,4-benzoquinone, or PhIAHCUTGNTREN(NUGN OAc)2 took place (entries 11 and 12). It is worth mentioning
(entries 3–6). Similar yields were obtained by running that the formation of the intramolecular amination
the reaction in an open vessel or under a nitrogen at- product 3 was never observed using CuCl2 in stoichio-
mosphere. The reaction occurred also at room tem- metric or excess amounts.
perature, but the yield of 2 was somehow lower
Then, we investigated the feasibility of this domino
(entry 7). Further screening of different solvents reaction on allylamides of a-amino acids bearing dif-
proved to be unfruitful to improve the yields or to ferent N-alkoxycarbonyl groups. As depicted in
gain milder conditions (entries 8–10). When using Scheme 2, the oxazolidin-2-one 2 is accessible also
other typical catalyst systems based on a different from a variety of alkenyl carbamates. In fact, when
source of palladium, namely Pd
ACHTUNGRTEN(NUNG OAc)2 in the pres- Cbz-, Fmoc- and ethoxycarbonyl-glycine amides 4a–c
ence of Cu(OAc)2 or 1,4-benzoquinone, no conversion were subjected to the optimized reaction conditions
ACHTUNGTRENNUNG
Table 2. Scope of the aminocarboxylation reaction.
Entry
R
R’
dr (6/7)[a]
Isolated product (yield)
1
2
3
4
5
6
7
8
9
10
isopropyl
isopropyl
isopropyl
isobutyl
isobutyl
isobutyl
benzyl
benzyl
methyl
methyl
cyclohexyl
cyclopentyl
benzyl
cyclohexyl
cyclopentyl
benzyl
cyclohexyl
cyclopentyl
cyclohexyl
cyclopentyl
70:30
75:25
85:15
80:20
80:20
80:20
75:25
70:30
80:20
80:20
6a (56%)
6b (48%)
6c (67%)
6d (62%)
6e (62%)
6f (64%)
6g (41%)
6h (57%)
6i (55%)
6j (49%)
7a (23%)
7b (18%)
7c (10%)
7d (15%)
7e (9%)
7f (19%)
7g (13%)
7h (25%)
[a]
Determined by 1H NMR analysis of the crude reaction mixture.
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Figure 3. ORTEP representation, at 30% probability level, of the molecular structure in compound 6b (left) and 7b (right).
(entry 2, Table 1), the conversion to product 2 was ob-
tained, although in lower yields (48%, 23% and 40%,
respectively, vs. 81% of the corresponding Boc deriva-
tive).
The scope of this transformation was then explored,
examining the behaviour of the easily obtained allyla-
mides 5a–h, and the results are summarized in
Table 2. In the cases of amides arising from l-valine,
l-leucine and l-phenylalanine, the reactions provided
the desired oxazoloACTHNUGRTENUNG[3,4-a]pyrazine derivatives as a
separable mixture of two diastereoisomers, while in
the case of l-alanine allylamides we were unable to
isolate the two products. The relative configurations
of the major and minor products, namely trans and
Scheme 3. Aminocarboxylation processe on different Boc-
aminoalkenes.
cis, were identified by single-crystal X-ray analysis, the NMR spectra of the crude reaction mixtures
performed on compounds 6b and 7b (Figure 3).[19]
under these conditions.
It should be stressed that the amination products
On the other hand, the dihydropyrazinone deriva-
(Scheme 1, path b) were never isolated or detected in tives 8 resulted as the sole products when a number
of allylamides 5 were treated with CuCl2 (10 mol%)/
O2 as the oxidant. This confirms the selectivity of
these procedures which depends only on the amount
of CuCl2 (Table 3).
Table 3. Scope of the the amination reaction.
The domino process was then extended to other
carbamate-protected aminoalkenes, to further in-
crease the scope of this methodology: Boc-amino allyl
ethers 9a and 9b as well as N’-allyl-N’-tosyl-N-Boc-
ethylenediamine 9c, having a more flexible tether be-
tween the reacting centres, were submitted to the
aminocarboxylation conditions. To our delight, all the
substrates gave the bicyclic morpholino and piperazi-
no derivatives 10a–c in good yields (Scheme 3).
Two more reactions were studied to have a better
insight into this domino aminocarboxylative process.
In a first instance, allylamide 1 was reacted using
CuCl2 (10 mol%)/O2 as oxidant in the presence of
excess LiCl (5 equiv.), leading only to 3 in low yield
(14%). Subsequently, the cyclization of the acetylgly-
cine amide 11, lacking the carbamate group, was in-
vestigated in the aminocarboxylative conditions. Also
Entry
R
R’
Product (Yield)[a]
1
2
3
4
5
6
7
8
isopropyl
isopropyl
isobutyl
isobutyl
benzyl
benzyl
methyl
methyl
cyclohexyl
methyl
cyclohexyl
methyl
cyclohexyl
methyl
cyclohexyl
methyl
8a (82%)
8b (55%)
8c (82%)
8d (72%)
8e (71%)
8f (65%)
8g (83%)
8h (70%)
[a]
Isolated yield.
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Adv. Synth. Catal. 2011, 353, 985 – 994

Intramolecular Palladium-Catalyzed Aminocarboxylation of Olefins
In summary, a general and highly efficient method-
ology for the synthesis of bicyclic oxazolidinones has
been developed starting from easily available allyl-
AHCTUNGTREGaNNUN mides of N-alkoxycarbonyl-protected a-amino acids.
The cyclization has been performed in oxidative
Pd(II)-catalyzed conditions, where the key role is
played by CuCl2 as oxidant agent. Depending on its
amount, more specifically catalytic vs. stoichiometric,
a divergent route to simple amination or domino ami-
nocarboxylation reaction can be selected.
Scheme 4. Cyclization under aminocarboxylative conditions
of acetylglycine allylamide.
Experimental Section
in this case, the substrate underwent the amination/b-
hydride elimination/isomerization sequence affording General Remarks
12 (Scheme 4). In both reactions, the putatively stable
Melting points were measured with a Bꢂchi B-540 apparatus
5-chloromethyl piperazinone,[9b] resulting from a nu-
cleophilic substitution of the Pd(II) moiety by a chlo-
ride anion, was never detected among the reaction
products.
and are uncorrected. Optical rotations (Na D line) were
measured on a Jasco P-1010 polarimeter. IR spectra were
recorded on a FT-IR spectrophotometer. Column chroma-
tography was performed on a Merck silica gel 60 (mesh size
63–200 mm). Nuclear magnetic resonance spectra were ac-
A possible rationalization of the aminocarboxyla-
tive reaction consists in an oxidative CuCl2-assisted
Pd-elimination from the s-alkylpalladium complex A,
in turn arising from the initial aminopalladation
(Figure 4). In this case, a PdCl+ species behaves as a
leaving group in the intramolecular nucleophilic
attack of the carbamate oxygen, generating the inter-
mediate B. CuCl2 would inhibit the more straightfor-
ward palladium b-hydride elimination through a tran-
sient palladium oxidation[7f,20] or by formation of a
heterobimetallic s-Pd/Cu complex.[21] An alternative
pathway may involve an initial alkene aminochlorina-
tion, followed by intramolecular displacement of the
chlorine, although the presence of chlorinated inter-
mediates was never observed.[9c] Finally, B can evolve
to the product 2 by loss of isobutene (in the case of
tert-butoxycarbonyl protecting group),[13b,c] or through
the intervention of a nucleophile such as the chloride
anion or water present in the reaction medium (on
different carbamates).
1
quired at 400 MHz for H and 100 MHz for 13C on a Bruker
AVANCE 400 spectrometer. Chemical shifts (d) for proton
nuclear magnetic resonance (1H NMR) spectra are reported
in parts per million downfield relative to the centre-line of
the CDCl3 singlet at 7.25 ppm. Chemical shifts for carbon
nuclear magnetic resonance (13C NMR) spectra are reported
in parts per million downfield relative to the centre-line of
the CDCl3 triplet at 77.23 ppm. 13C spectra are 1H decoupled
and multiplicities were determined by the APT pulse se-
quence. Mass spectra were determined on an HPLC-MS
LCQ-Advantage Thermo Finnigan instrument. Elemental
analyses were executed on a Perkin–Elmer CHN Analyzer
Series II 2400.
Detailed procedures for the preparation of allylamides
and allylethers as well as a general procedure for the amina-
tion of allylamides and details on the X-ray diffraction
measurements and analyses are available as Supporting In-
formation.
Figure 4. Proposed mechanistic key-steps for the Pd(II)/CuCl2-mediated aminocarboxylation reaction.
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AHCTUNGTREG(NNNU 5S,8aS)-7-Cyclopentyl-5-isopropyl-8,8a-dihydro-1H-
General Procedure for the Aminocarboxylation
Reactions
oxazoloACHTNUTRGENNUG[3,4-a]pyrazine-3,6HCATUNGTRENN(UGN 5H,7H)-dione (7b): Yield: 18%;
yellow solid; mp 118–1208C; [a]2D3: À13.8 (c 1.42, CHCl3);
IR: n=1749, 1634 cmÀ1 1H NMR (400 MHz, CDCl3): d=
;
A solution of alkene (1 mmol) in anhydrous DMF (10 mL)
was added to a solution of CuCl2 (3 mmol) and Pd-
ACHTUNGTRENNUNG(MeCN)2Cl2 (0.05 mmol) in anhydrous DMF (10 mL). The
reaction mixture was heated at 1008C for 24 h. Brine was
added and the mixture was extracted with CH2Cl2 (3ꢃ
10 mL). The organic phase was dried over Na2SO4 and the
solvent removed under reduced pressure. The crude was pu-
rified by silica gel column chromatography.
0.89 (d, J=7.0 Hz, 3H), 1.17 (d, J=7.0 Hz, 3H), 1.20–1.95
(m, 8H), 2.85 (dqq, J=3.0, 7.0, 7.0 Hz, 1H), 3.27 (dd, J=
12.0, 10.0 Hz, 1H), 3.36 (dd, J=12.0, 2.6 Hz, 1H), 3.95–3.98
(2H, m), 4.12 (d, J=3.0 Hz, 1H), 4.44–4.47 (m, 1H), 4.90–
4.99 (m, 1H); 13C NMR (100 MHz, CDCl3): d=16.1 (q),
19.8 (q), 24.0 (t), 24.1 (t), 28.2 (t), 28.3 (t), 29.3 (d), 43.8 (t),
53.1 (d), 54.6 (d), 62.4 (d), 64.7 (t), 155.6 (s), 165.8 (s); MS:
m/z=266 (M+); anal. calcd. for C14H22N2O3: C 63.13, H
8.33, N 10.52; found: C 62.87, H 8.45, N 10.31.
7-Cyclohexyl-8,8a-dihydro-1H-oxazolo
(5H,7H)-dione (2): Yield: 81% (from 1), 48% (from 4a),
23% (from 4b), 40% (from 4c); yellow solid; mp 121–
1248C; IR: n=1751, 1630 cmÀ1 1H NMR (400 MHz,
ACHTUNGERTN[NUNG 3,4-a]pyrazine-3,6-
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
;
N
ACHTUNGTRENNUNG
CDCl3): d=1.00–1.95 (m, 10H), 3.26 (dd, J=12.1, 10.9 Hz,
1H), 3.39 (dd, J=12.1, 4.0 Hz, 1H), 3.89, 4.36 (AB system,
J=14.0 Hz, 2H), 3.98–4.05 (m, 1H), 4.11 (dd, J=9.1, 3.5 Hz,
1H), 4.48–4.52 (m, 2H); 13C NMR (100 MHz, CDCl3): d=
25.3 (t), 25.4 (t), 25.5 (t), 29.3 (t), 29.7 (t), 44.2 (t), 45.0 (t),
50.6 (d), 52.6 (d), 65.2 (t), 156.4 (s), 163.4 (s); MS: m/z=238
(M+); anal. calcd. for C12H18N2O3: C 60.49, H 7.61, N 11.76;
found: C 60.35, H 7.70, N 11.92.
;
1H NMR (400 MHz, CDCl3): d=0.95 (d, J=6.6 Hz, 3H),
1.06 (d, J=6.6 Hz, 3H), 2.71–2.73 (m, 1H), 3.21 (dd, J=4.3,
12.0 Hz, 1H), 3.36 (t, J=11.4 Hz, 1H), 3.97 (d, J=9.3 Hz,
1H), 4.03–4.07 (m, 1H), 4.29–4.33 (m, 2H), 4.37–4.42 (m,
1H), 4.95 (d, J=14.6 Hz, 1H), 7.22–7.35 (m, 5H); 13C NMR
(100 MHz, CDCl3): d=18.0 (q), 19.6 (q), 32.3 (d), 49.2 (t),
50.6 (t), 50.7 (d), 60.7 (d), 64.6 (t), 128.0 (d), 128.1 (d), 128.9
(d), 136.0 (s), 157.4 (s), 166.9 (s); MS: m/z=288 (M+); anal.
calcd. for C16H20N2O3: C 66.65, H 6.99, N 9.72; found: C
66.76, H 6.87, N 9.84.
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
;
AHCTUNGTREG(NNUN 5S,8aS)-7-Benzyl-5-isopropyl-8,8a-dihydro-1H-oxazolo-
(d, J=6.8 Hz, 3H), 0.99 (dd, J=6.8, 1.2 Hz, 3H), 1.15–1.80
(m, 10H), 2.57–2.70 (m, 1H), 3.19 (dd, J=11.9, 11.3 Hz,
1H), 3.30 (dd, J=11.9, 4.2 Hz, 1H), 3.97–4.06 (m, 2H),
4.13–4.17 (m, 1H), 4.40–4.53 (m, 2H); 13C NMR (100 MHz,
CDCl3): d=17.8 (q), 19.5 (q), 25.3 (t), 25.4 (t), 25.5 (t), 29.4
(t), 29.6 (t), 32.3 (d), 44.4 (t), 51.2 (d), 52.7 (d), 60.6 (d), 64.8
(t), 157.8 (s), 166.0 (s); MS: m/z=280 (M+); anal. calcd. for
C15H24N2O3: C 64.26, H 8.63, N 9.99; found: C 64.31, H 8.90,
N 9.76.
ACHUTNGREN[NUG 3,4-a]pyrazine-3,6ACHTUNGTERN(NUGN 5H,7H)-dione (7c): Yield: 10%; yellow
oil; [a]2D3: À50.3 (c 0.10, CHCl3); IR: n=1745, 1650 cmÀ1
;
1H NMR (400 MHz, CDCl3): d=0.91 (d, J=6.9 Hz, 3H),
1.22 (d, J=6.9 Hz, 3H), 2.91–2.97 (m, 1H), 3.29–3.35 (m,
2H), 3.85–3.96 (m, 2H), 4.20 (d, J=3.1 Hz, 1H), 4.36 (t, J=
6.7 Hz, 1H), 4.53 (d, J=14.4 Hz, 1H), 4.75 (d, J=14.4 Hz,
1H), 7.26–7.35 (m, 5H); 13C NMR (100 MHz, CDCl3): d=
16.2 (q), 19.8 (q), 29.5 (d), 48.2 (t), 50.7 (t), 52.8 (d), 62.3
(d), 65.2 (t), 128.1 (d), 128.5 (d), 128.9 (d), 135.9 (s), 155.7
(s), 166.1 (s); MS: m/z=288 (M+); anal. calcd. for
C16H20N2O3: C 66.65, H 6.99, N 9.72; found: C 66.51, H 7.09,
N 9.61.
ACHTUNGTRENNUNG(5S,8aS)-7-Cyclohexyl-5-isopropyl-8,8a-dihydro-1H-
oxazoloACHTUNGTRENNUNG[3,4-a]pyrazine-3,6CAHTUNGTRENN(UGN 5H,7H)-dione (7a): Yield: 23%;
orange solid; mp 137–1398C; [a]2D3: À57.8 (c 1.54, CHCl3);
IR: n=1755, 1635 cmÀ1 1H NMR (400 MHz, CDCl3): d=
;
AHCTUNGTRENNUNG
0.88 (d, J=7.4 Hz, 3H), 1.01–1.90 (m, 10H), 1.17 (d, J=
7.4 Hz, 3H), 2.86 (dqq, J=3.4, 7.4, 7.4 Hz, 1H,), 3.20 (dd,
J=12.0, 9.9 Hz, 1H), 3.45 (dd, J=12.0, 2.6 Hz, 1H), 3.88–
3.98 (m, 2H), 4.11 (d, J=3.4 Hz, 1H), 4.43–4.49 (m, 2H);
13C NMR (100 MHz, CDCl3): d=16.1 (q), 19.8 (q), 25.2 (t),
25.4 (t), 25.6 (t), 29.1 (t), 29.5 (d), 30.3 (t), 43.6 (t), 53.0 (d),
53.2 (d), 62.2 (d), 65.4 (t), 155.7 (s), 165.3 (s); MS: m/z=280
(M+); anal. calcd. for C15H24N2O3: C 64.26, H 8.63, N 9.99;
found: C 64.50, H 8.75, N 9.81.
N
ACHTUNGTRENNUNG
;
0.91 (d, J=6.4 Hz, 3H), 0.99 (d, J=6.4 Hz, 3H), 1.25–1.85
(m, 13H), 3.23 (dd, J=11.9, 10.9 Hz, 1H), 3.31 (dd, J=11.9,
4.5 Hz, 1H), 3.99–4.02 (m, 1H), 4.07 (dd, J=9.2, 6.0 Hz,
1H), 4.32 (dd, J=10.4, 3.6 Hz, 1H), 4.40–4.46 (m, 2H);
13C NMR (100 MHz, CDCl3): d=21.2 (q), 23.3 (q), 24.7 (d),
25.4 (t), 25.5 (t), 25.6 (t), 29.4 (t), 29.5 (t), 41.6 (t), 44.4 (t),
48.2 (d), 52.7 (d), 53.9 (d), 65.2 (t), 156.6 (s), 167.0 (s); MS:
m/z=294 (M+); anal. calcd. for C16H26N2O3: C 65.28, H
8.90, N 9.52; found: C 65.32, H 9.11, N 9.38.
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
;
AHCTUNGTREG(NNNU 5S,8aS)-7-Cyclohexyl-5-isobutyl-8,8a-dihydro-1H-
(d, J=7.0 Hz, 3H), 1.04 (d, J=7.0 Hz, 3H), 1.30–1.88 (m,
8H), 2.66 (dqq, J=3.2, 7.0, 7.0 Hz, 1H), 3.21–3.31 (m, 2H),
3.99–4.05 (m, 1H), 4.08 (dd, J=9.2, 1.6 Hz, 1H), 4.17 (d, J=
3.2 Hz, 1H), 4.44–4.49 (m, 1H), 4.95–5.01 (m, 1H);
13C NMR (100 MHz, CDCl3): d=17.8 (q), 19.5 (q), 23.9 (t),
24.2 (t), 27.4 (t), 28.7 (t), 32.3 (d), 44.6 (t), 51.2 (d), 54.6 (d),
60.7 (d), 64.8 (t), 157.8 (s), 166.5 (s); MS: m/z=266 (M+);
anal. calcd. for C14H22N2O3: C 63.13, H 8.33, N 10.52; found:
C 63.22, H 8.55, N 10.41.
oxazoloACHTNUTRGENNUG[3,4-a]pyrazine-3,6HCATUNGTRENN(UGN 5H,7H)-dione (7d): Yield: 15%;
red solid; mp 135–1368C; [a]2D3: À36.5 (c 2.23, CHCl3); IR:
1
n=1754, 1632 cmÀ1; H NMR (400 MHz, CDCl3): d=0.80–
1.02 (m, 6H), 1.05–2.16 (m, 13H), 3.22 (dd, J=12.0,
10.0 Hz, 1H), 3.48 (dd, J=12.0, 2.3 Hz, 1H), 3.92–3.97 (m,
2H), 4.17–4.21 (m, 1H), 4.40–4.48 (m, 2H); 13C NMR
(100 MHz, CDCl3): d=22.2 (q), 23.7 (q), 24.5 (d), 25.3 (t),
25.4 (t), 25.5 (t), 29.2 (t), 29.7 (t), 39.3 (t), 43.8 (t), 53.0 (d),
53.1 (d), 56.3 (d), 65.4 (t), 155.6 (s), 167.3 (s); MS: m/z=294
990
asc.wiley-vch.de
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2011, 353, 985 – 994

Intramolecular Palladium-Catalyzed Aminocarboxylation of Olefins
(M+); anal. calcd. for C16H26N2O3: C 65.28, H 8.90, N 9.52;
found: C 65.43, H 9.12, N, 9.41.
165.4 (s); MS: m/z=328 (M+); anal. calcd. for C19H24N2O3:
C 69.49, H 7.37, N 8.53; found: C 69.41, H 7.53, N 8.72.
(5S,8aS)-5-Benzyl-7-cyclohexyl-8,8a-dihydro-1H-oxazolo-
A
ACHTUNGTRENNUNG
A
E
ACHUTGTNREN[NUG 3,4-a]pyrazine-3,6ACHTUNTGREN(NUGN 5H,7H)-dione (7g): Yield: 13%; yellow
solid; mp 141–1428C; [a]2D3: À88.3 (c 2.05, CHCl3); IR: n=
1
;
1755, 1629 cmÀ1; H NMR (400 MHz, CDCl3): d=0.80–1.80
0.92 (d, J=6.5 Hz, 3H), 0.99 (d, J=6.5 Hz, 3H), 1.31–1.87
(m, 11H), 3.22–3.32 (m, 2H), 3.99–4.05 (m, 1H), 4.09 (dd,
J=9.2, 1.5 Hz, 1H), 4.31 (dd, J=10.7, 3.0 Hz, 1H), 4.42 (dd,
J=9.2, 8.2 Hz, 1H), 4.90–4.96 (m, 1H); 13C NMR (100 MHz,
CDCl3): d=21.2 (q), 23.4 (q), 23.9 (t), 24.2 (t), 24.7 (d), 27.4
(t), 28.4 (t), 41.7 (t), 44.4 (t), 48.2 (d), 53.9 (d), 54.6 (d), 65.2
(t), 156.6 (s), 167.5 (s); MS: m/z=280 (M+); anal. calcd. for
C15H24N2O3: C 64.26, H 8.63, N 9.99; found: C 64.33, H 8.82,
N 9.91.
(m, 11H), 2.95 (dd, J=8.5, 3.5 Hz, 1H), 3.24 (dd, J=13.6,
2.3 Hz, 1H), 3.64 (dd, J=10.5, 8.5 Hz, 1H), 3.80–3.90 (m,
2H), 4.32–4.52 (m, 3H), 7.16–7.27 (m, 5H); 13C NMR
(100 MHz, CDCl3): d=25.2 (t), 25.3 (t), 25.5 (t), 29.3 (t),
29.4 (t), 35.2 (t), 42.4 (t), 52.1 (d), 52.8 (d), 57.5 (d), 65.5 (t),
127.2 (d), 128.2 (d), 130.4 (d), 135.8 (s), 155.6 (s), 166.2 (s);
MS: m/z=328 (M+); anal. calcd. for C19H24N2O3: C 69.49, H
7.37, N 8.53; found: C 69.32, H 7.61, N 8.38.
AHCTUNGTREG(NNNU 5S,8aR)-5-Benzyl-7-cyclopentyl-8,8a-dihydro-1H-
A
oxazoloACHTNGUTRENNU[G 3,4-a]pyrazine-3,6CAHTUNGTRNE(NUNG 5H,7H)-dione (6h): Yield: 57%;
oxazolo
yellow solid; mp 83–868C; [a]2D3: +10.1 (c 2.22, CHCl3); IR:
brown solid; mp 101–1028C; [a]2D3: À8.3 (c 1.72, CHCl3); IR:
n=1751, 1634 cmÀ1; H NMR (400 MHz, CDCl3): d=1.07–
1
n=1760, 1630 cmÀ1; H NMR (400 MHz, CDCl3): d=0.85–
1.90 (m, 8H), 2.78–2.82 (m, 1H), 2.92–3.14 (m, 3H), 3.50 (d,
J=13.1 Hz, 1H), 3.84 (d, J=6.4 Hz, 1H), 4.11–4.15 (m,
1H), 4.51 (br s, 1H), 4.93–4.99 (m, 1H), 7.10–7.25 (m, 5H);
13C NMR (100 MHz, CDCl3): d=23.9 (t), 24.2 (t), 27.3 (t),
28.5 (t), 38.0 (t), 44.8 (t), 49.5 (d), 54.7 (d), 55.9 (d), 65.0 (t),
127.1 (d), 128.4 (d), 129.9 (d), 136.8 (s), 156.4 (s), 166.0 (s);
MS: m/z=314 (M+); anal. calcd. for C18H22N2O3: C 68.77, H
7.05, N 8.91; found: C 68.50, H 7.20, N 8.88.
1.00 (m, 6H), 1.20–2.17 (m, 11H), 3.28 (dd, J=12.0, 9.4 Hz,
1H), 3.40 (dd, J=12.0, 1.2 Hz, 1H), 3.94–4.09 (m, 2H), 4.20
(dd, J=7.1, 3.5 Hz, 1H), 4.46–4.50 (m, 1H), 4.91–4.99 (m,
1H); 13C NMR (100 MHz, CDCl3): d=22.0 (q),23.7 (q), 24.0
(t), 24.2 (t), 24.4 (d), 27.8 (t), 28.3 (t), 39.3 (t), 44.0 (t), 53.0
(d), 54.7 (d), 56.4 (d), 65.4 (t), 155.5 (s), 167.8 (s); MS:
m/z=280 (M+); anal. calcd. for C15H24N2O3: C 64.26, H
8.63, N 9.99; found: C 64.09, H, 8.50, N 10.24.
AHCTUNGERTG(NNUN 5S,8aS)-5-Benzyl-7-cyclopentyl-8,8a-dihydro-1H-oxazolo-
A
ACHUTGTNREN[NUG 3,4-a]pyrazine-3,6ACHTUNTGREN(NUGN 5H,7H)-dione (7h): Yield: 25%; orange
R
E
solid; mp 159–1618C; [a]2D3: À8.9 (c 2.57, CHCl3); IR: n=
1
;
1750, 1634 cmÀ1; H NMR (400 MHz, CDCl3): d=0.95–1.95
1H NMR (400 MHz, CDCl3): d=0.90 (d, J=6.4 Hz, 3H),
0.96 (d, J=6.4 Hz, 3H), 1.64–1.67 (m, 2H), 1.80–1.83 (m,
1H), 3.19–3.27 (m, 2H), 3.90–4.00 (m, 2H), 4.27–4.35 (m,
3H), 4.67 (d, J=14.6 Hz, 1H), 7.13–7.27 (m, 5H); 13C NMR
(100 MHz, CDCl3): d=21.1 (q), 23.4 (q), 24.6 (d), 41.4 (t),
47.4 (d), 49.3 (t), 50.4 (t), 53.7 (d), 65.1 (t), 127.9 (d), 128.0
(d), 128.8 (d), 135.9 (s), 156.6 (s), 167.8 (s); MS: m/z=302
(M+); anal. calcd. for C17H22N2O3: C 67.53, H 7.33, N 9.26;
found: C 67.66, H 7.25, N 9.12.
(m, 9H), 2.83 (dd, J=12.0, 3.2 Hz, 1H), 3.22 (dd, J=9.6,
2.7 Hz, 1H), 3.64 (dd, J=10.6, 8.4 Hz, 1H), 3.82–3.88 (m,
2H), 4.35 (dd, J=8.4, 7.8 Hz, 1H), 4.51 (dd, J=4.9, 2.7 Hz,
1H), 4.94–4.99 (m, 1H), 7.12–7.30 (m, 5H); 13C NMR
(100 MHz, CDCl3): d=24.0 (t), 24.2 (t), 27.4 (t), 28.3 (t),
35.3 (t), 42.4 (t), 51.9 (d), 54.2 (d), 57.6 (d), 65.6 (t), 127.2
(d), 128.2 (d), 130.3 (d), 135.9 (s), 155.5 (s), 166.7 (s); MS:
m/z=314 (M+); anal. calcd. for C18H22N2O3: C 68.77, H
7.05, N 8.91; found: C 68.60, H 7.20, N 8.68.
A
E
ACHTUNGTREN(NUNG 5S,8aR)-7-Cyclohexyl-5-methyl-8,8a-dihydro-1H-oxazolo-
a]pyrazine-3,6
G
ACHUTGTNREN[NUG 3,4-a]pyrazine-3,6ACHTUNTGREN(NUGN 5H,7H)-dione (6i): Yield: 55%; yellow
[a]D23: À29.3 (c 0.42, CHCl3); IR: n=1758, 1636 cmÀ1
solid; mp 121–1228C; [a]2D3: +27.2 (c 3.11, CHCl3); IR: n=
1H NMR (400 MHz, CDCl3): d=0.93–0.98 (m, 6H), 1.83–
1.98 (m, 1H), 2.10–2.15 (m, 2H), 3.33 (d, J=7.1 Hz, 2H),
3.82–3.87 (m, 1H), 3.93–3.99 (m, 1H), 4.24 (t, J=5.3 Hz,
1H), 4.36 (t, J=7.5 Hz, 1H), 4.49 (d, J=14.6 Hz, 1H), 4.74
(d, J=14.6 Hz, 1H), 7.22–7.35 (m, 5H); 13C NMR
(100 MHz, CDCl3): d=22.1 (q), 23.5 (q), 24.5 (d), 39.2 (t),
48.4 (t), 50.8 (t), 52.7 (d), 56.3 (d), 65.3 (t), 128.1 (d), 128.3
(d), 128.9 (d), 135.8 (s), 155.7 (s), 167.9 (s); MS: m/z=302
(M+); anal. calcd. for C17H22N2O3: C 67.53, H 7.33, N 9.26;
found: C 67.28, H 7.51, N 9.38.
1747, 1632 cmÀ1; H NMR (400 MHz, CDCl3): d=0.98–1.08
1
(m, 1H), 1.20–1.45 (m, 4H), 1.46 (d, J=7.1, 3H), 1.55–1.80
(m, 5H), 3.22 (dd, J=11.9, 10.6 Hz, 1H), 3.36 (dd, J=11.9,
3.9 Hz, 1H), 3.99–4.08 (m, 2H), 4.33 (q, J=7.1 Hz, 1H),
4.40–4.96 (m, 2H); 13C NMR (100 MHz, CDCl3): d=18.3
(q), 25.4 (t), 25.5 (t), 29.2 (t), 29.4 (t), 29.6 (t), 45.0 (t), 48.3
(d), 51.0 (d), 52.8 (d), 65.2 (t), 156.1 (s), 167.1 (s); MS:
m/z=252 (M+); anal. calcd. for C13H20N2O3: C 61.88, H
7.99, N 11.10; found: C 61.70, H 8.26, N 11.01.
AHCTUNGTREG(NNNU 5S,8aR)-7-Cyclopentyl-5-methyl-8,8a-dihydro-1H-
A
oxazoloACHTNGUTRENNU[G 3,4-a]pyrazine-3,6CAHTUNGTRNE(NUNG 5H,7H)-dione (6j): Yield: 49%;
[3,4-a]pyrazine-3,6
red solid; mp 137–1388C; [a]2D3: +37.2 (c 1.64, CHCl3); IR:
1
solid; mp 170–1718C; [a]2D3: À6.6 (c 1.76, CHCl3); IR: n=
n=1749, 1633 cmÀ1; H NMR (400 MHz, CDCl3): d=1.20–
1758, 1627 cmÀ1; H NMR (400 MHz, CDCl3): d=0.82–1.79
1.87 (m, 8H), 1.46 (d, J=7.1 Hz, 3H), 3.28–3.30 (m, 2H),
4.00–4.09 (m, 2H), 4.35 (q, J=7.1 Hz, 1H), 4.43–4.48 (dd,
J=8.6, 8.1 Hz, 1H), 4.90–4.99 (m, 1H); 13C NMR (100 MHz,
CDCl3): d=18.2 (q), 23.9 (t), 24.2 (t), 27.5 (t), 28.4 (t), 45.0
(t), 48.3 (d), 51.0 (d), 54.6 (d), 65.3 (t), 156.1 (s), 167.4 (s);
MS: m/z=238 (M+); anal. calcd. for C12H18N2O3: C 60.49, H
7.61, N 11.76; found: C 60.55, H 8.51, N 11.58.
(m, 10H), 2.75–2.83 (m, 1H), 3.01–3.08 (m, 3H), 3.57 (dd,
J=13.4, 3.5 Hz, 1H), 3.85 (dd, J=8.9, 3.6 Hz, 1H), 4.17 (dd,
J=8.9, 8.4 Hz, 1H), 4.47–4.58 (m, 2H), 7.16–7.27 (m, 5H);
13C NMR (100 MHz, CDCl3): d=25.3 (t), 25.4 (t), 25.5 (t),
29.3 (t), 29.5 (t), 37.9 (t), 44.7 (t), 49.5 (d), 52.9 (d), 55.8 (d),
65.0 (t), 127.1 (d), 128.4 (d), 129.9 (d), 136.7 (s), 156.4 (s),
Adv. Synth. Catal. 2011, 353, 985 – 994
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
991

Elena Borsini et al.
FULL PAPERS
5,6,8,8a-Tetrahydrooxazolo
[4,3-c]
E
818; f) J. F. Hartwig, Angew. Chem. Int. Ed. 1998, 37,
2046–2067; g) L. Jiang, S. L. Buchwald, in: Metal Cata-
lyzed Cross-Coupling Reactions, (Eds.: A. de Meijere,
F. Diederich), 2nd edn., Wiley-VCH, Weinheim, 2004,
pp 699–760; h) J. F. Hartwig, Synlett 2006, 1283–1294;
i) J. F. Hartwig, in: Modern Arene Chemistry, (Ed.: D.
Astruc), Wiley-VCH, Weinheim, 2002, p 107; j) S. L.
Buchwald, A. R. Muci, Top. Curr. Chem. 2002, 219,
131–209.
(10a): Yield: 75%; colourless oil; IR: n=1745 cmÀ1
;
1H NMR (400 MHz, CDCl3): d=3.17–3.33 (m, 2H), 3.45
(ddd, J=11.8, 11.7, 3.0 Hz, 1H), 3.72 (dd, J=13.3, 3.0 Hz,
1H), 3.87–3.97 (m, 4H), 4.40 (dd, J=8.0, 7.9 Hz, 1H);
13C NMR (100 MHz, CDCl3): d=41.3 (t), 52.3 (d), 64.2 (t),
66.1 (t), 69.8 (t), 156.6 (s); MS: m/z=143 (M+); anal. calcd.
for C6H9NO3: C 50.35, H 6.34, N 9.79; found: C 50.54, H
6.49, N 9.58.
5,5-Dimethyl-5,6,8,8a-tetrahydrooxazoloACTHNUTRGNEUG[N 4,3-c]-
[4] For some examples of application of Buchwald–Hart-
wig reaction in the synthesis of pharmaceuticals see:
a) M.-J. R. P. Queiroz, R. C. Calhelha, L. A. Vale-Silva,
E. Pinto, M. S¼o-Josꢄ Nascimento, Eur. J. Med. Chem.
2010, 45, 5732–5738; b) A. Bouhlel, C. Curti, A.
Dumtre, M. Laget, M. D. Crozet, N. Azas, P. Vanelle,
Bioorg. Med. Chem. 2010, 18, 7310–7320; c) R. R. R.
Taylor, H. C. Twin, W. W. Wen, R. J. Mallot, A. J.
Lough, S. D. Gray-Owen, R. A. Batey, Tetrahedron
2010, 66, 3370–3377; d) A. R. Das, A. Medda, R.
Singha, Tetrahedron Lett. 2010, 51, 1099–1102; e) S.
Lemaire, B. Willemsens, I. E. Markꢅ, Synlett 2007, 709–
712; f) M. L. Gelmi, D. Pocar, G. Pontremoli, S. Pelle-
grino, E. Bombardelli, G. Fontana, A. Riva, W. Baldui-
ni, S. Carloni, M. Cimino, F. Johnson, J. Med. Chem.
2006, 49, 5571–5577; g) E. M. Beccalli, G. Broggini, G.
Paladino, C. Zoni, Tetrahedron 2005, 61, 61–68; h) S.
Grasl, C. Meier, Nucleos. Nucleot. Nucl. 2003, 22,
1119–1121; i) D. Chakraborti, L. Colis, R. Schneider,
A. K. Basu, Org. Lett. 2003, 5, 2861–2864.
[1,4]oxazin-3(1H)-one (10b): Yield: 82%; colourless oil; IR:
1
n=1740 cmÀ1; H NMR (400 MHz, CDCl3): d=1.32 (s, 3H),
1.51 (s, 3H), 3.16–3.26 (m, 2H), 3.47 (d, J=12.6 Hz, 1H),
3.68–3.72 (m, 1H), 3.92–4.00 (m, 1H), 4.04 (dd, J=10.4,
3.6 Hz, 1H), 4.29 (dd, J=8.1, 7.7 Hz, 1H); 13C NMR
(100 MHz, CDCl3): d=20.5 (q), 22.5 (q), 50.8 (d), 53.1 (s),
63.9 (t), 70.1 (t), 76.5 (t), 155.9 (s); MS: m/z=171 (M+);
anal. calcd. for C8H13NO3: C 56.13, H 7.65, N 8.18; found: C
56.31, H 7.56, N 8.04.
7-Tosyl-1,5,6,7,8,8a-hexahydrooxazolo
[3,4-a]pyrazine
3-
;
one (10c): Yield: 72%; colourless oil; IR: n=1738 cmÀ1
1H NMR (400 MHz, CDCl3): d=2.45 (s, 3H), 3.16–3.25 (m,
2H), 3.73 (d, J=3.7, 1H), 3.76 (d, J=3.7 Hz, 1H), 3.84 (d,
J=3.7 Hz, 1H), 3.88 (dd, J=2.4, 3.7 Hz, 1H), 3.90–3.92 (m,
1H), 3.94–4.02 (m, 1H), 4.42 (dd, J=8.4, 8.5 Hz, 1H), 7.36
(d, J=8.2 Hz, 2H), 7.62 (d, J=8.2 Hz, 2H); 13C NMR
(100 MHz, CDCl3): d=21.5 (q), 40.5 (t), 45.1 (t), 49.2 (t),
52.7 (d), 64.9 (t), 127.6 (d), 130.3 (d), 132.3 (s), 144.5 (s),
156.4 (s); MS: m/z=296 (M+); anal. calcd. for C13H16N2O4S:
C 52.69, H 5.44, N 9.45; found: C 52.78, H 5.22, N 9.28.
[5] For reviews see: a) E. M. Beccalli, G. Broggini, M.
Martinelli, S. Sottocornola, Chem. Rev. 2007, 107,
5318–5365; b) V. Kotov, C. C. Scarborough, S. S. Stahl,
Inorg. Chem. 2007, 46, 1910–1923; c) M. S. Sigman,
M. J. Schultz, Org. Biomol. Chem. 2004, 2, 2551–2554.
For some examples of Pd(II)-catalyzed intermolecular
aminations, see: d) Y. Shimizu, Y. Obora, Y. Lshii, Org.
Lett. 2010, 12, 1372–1374; e) G. Liu, G. Yin, L. Wu,
Angew. Chem. Int. Ed. 2008, 47, 4733–4736; f) M. M.
Rogers, V. Kotov, J. Chatwichien, S. S. Stahl, Org. Lett.
2007, 9, 4331–4334; g) N. Sakai, A. Ridder, J. F. Hart-
wig, J. Am. Chem. Soc. 2006, 128, 8134–8135; h) V. I.
Timokhin, N. R. Anastasi, S. S. Stahl, J. Am. Chem.
Soc. 2003, 125, 12996–12997. For some examples of
Pd(II)-catalyzed intramolecular aminations, see:
i) K. C. Majumdar, S. Samanta, R. K. Nandi, B. Chatto-
padhyay, Tetrahedron Lett. 2010, 51, 3807–3810; j) Y.-J.
Bian, X.-Y. Liu, K.-G. Ji, X.-Z. Shu, L.-N. Guo, Y.-M.
Liang, Tetrahedron 2009, 65, 1424–1429; k) L. Wu, S.
Qiu, G. Liu, Org. Lett. 2009, 11, 2707–2710; l) G. Liu,
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[6] For some examples of cyclization/functionalization re-
actions, see: a) C. F. Rosewall, P. A. Sibbald, D. V.
Liskin, F. E. Michael, J. Am. Chem. Soc. 2009, 131,
9488–9489; b) C. E. Houlden, C. D. Bailey, J. Gair
Ford, M. R. Gagnꢄ, G. C. Lloyd-Jones, K. I. Booker-
Milburn, J. Am. Chem. Soc. 2008, 130, 10066–10067;
c) C. C. Scarborough, S. S. Stahl, Org. Lett. 2006, 8,
3251–3254. For some examples leading to bicyclic com-
pounds, see: d) K.-T. Yip, N.-Y. Zhu, D. Yang, Org.
Lett. 2009, 11, 1911–1914; e) W. He, K.-T. Yip, N.-Y.
Zhu, D. Yang, Org. Lett. 2009, 11, 5626–5628; f) B.
Zhu, G.-W. Wang, Org. Lett. 2009, 11, 4334–4337;
Acknowledgements
MIUR is acknowledged for financial support (PRIN
2008KRBX3B) and PhD fellowship to M.R. (Progetto Gio-
vani 2006). We are heartily grateful to Dr. Francesca D’Anna
and Prof. Renato Noto for helpful discussions. We are also
grateful to the Centro Interuniversitario di Ricerca sulle Rea-
zioni Pericicliche e Sintesi di Sistemi Etero e Carbociclici.
References
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