Cyclization of diazoacetamides catalyzed by N-heterocyclic carbene dirhodium(II) complexes

Article abstract of DOI:10.1055/s-0029-1217005

The axial coordination of N-heterocyclic carbene ligands onto dirhodium(II) complexes was examined, together with its role in the intramolecular C-H insertion reactions of a-diazoacetamides. The formation of a decarbonylated product occurs by a free-carbene mechanism in which the structures of the catalyst and the acetamide play a decisive role.

Full text of DOI:10.1055/s-0029-1217005

SPECIAL TOPIC
3519
Cyclization of Diazoacetamides Catalyzed by N-Heterocyclic Carbene
Dirhodium(II) Complexes
R
hodium-Cataly
u
ze
d
Cycliza
i
tionof
s
Diazoacetamide
F
s
. R. Gomes,a Alexandre F. Trindade,a Nuno R. Candeias,b Luís F. Veiros,c Pedro M. P. Gois,b
Carlos A. M. Afonso*a
a
CQFM, Centro de Química–Física Molecular, Institute of Nanosciences and Nanotechnology, Instituto Superior Técnico,
1049-001 Lisboa, Portugal
b
iMed.UL, Faculdade de Farmácia da Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal
CQE, Centro de Química Estrutural, Instituto Superior Técnico, 1049-001 Lisboa, Portugal
c
Fax +351(21)8464455/7; E-mail: carlosafonso@ist.utl.pt
Received 23 July 2009
In line with this observation, we recently showed that
these new complexes also have an interesting effect on
conventional intramolecular C–H insertion reactions of
diazoacetamides.5 Here, we present our results of studies
Abstract: The axial coordination of N-heterocyclic carbene ligands
onto dirhodium(II) complexes was examined, together with its role
in the intramolecular C–H insertion reactions of a-diazoacetamides.
The formation of a decarbonylated product occurs by a free-carbene
mechanism in which the structures of the catalyst and the acetamide on the effects of the axial coordination of NHCs in dirhod-
play a decisive role.
ium(II) complexes and, consequently, on catalytic intra-
molecular C–H insertion reactions.
Key words: carbenoids, carbene complexes, catalysis, diazo com-
pounds, rhodium
N-Heterocyclic carbenes are neutral, two-electron donor
(s-donating) ligands with a small p-back-bonding tenden-
cy, and their coordination to dirhodium(II) complexes is
occurs essentially through s-donation from the carbene
lone pair to the lowest unoccupied molecular orbital of the
dirhodium(II) complex.6 This is a Rh–Rh antibonding or-
bital (s*) derived from the out-of-phase combination of
two z2 orbitals.4,7 Thus, the formation of a Rh–NHC bond
corresponds to an electron transfer from the carbene to the
metallic fragment, and to the population of the Rh–Rh
antibonding orbital.4
Density functional theory (DFT) calculations8 performed
on dirhodium(II) complexes showed that the length of the
Rh–Rh bond increases to 2.46 Å in complexes 4 and 5,
compared with a value of 2.39 Å in the dirhodium com-
plex 1, which has vacant axial positions. In addition, elec-
tron donation from the NHC affects the charge on the
metallic fragment, resulting in an increase in the electron
density on the terminal rhodium atom as a result of charge
transfer through the Rh–Rh bond (Figure 1 and Table 1).
The functionalization of saturated C–H bonds is a trans-
formation that is of considerable importance in modern
synthetic organic chemistry. The possibility of creating
new C–C bonds from nonfunctionalized C–H bonds
opens new and exciting possibilities for accessing mole-
cules with complex structures. Among the methods that
are available for this transformation, the use of a combi-
nation of a diazo compound and a dirhodium(II) complex
has emerged as one that gives simple and efficient activa-
tion of C–H bonds in both intramolecular and intermolec-
ular reactions.1–3
The success that can be achieved by the use of a combina-
tion of a diazo compound and a dirhodium(II) complex re-
lies on the reactivity of the resulting metallocarbenes,
which are the pivotal intermediates in the activation of
nonfunctionalized C–H bonds.1–3 Such complexes contain
a Rh–Rh bond and four bridging ligands that are respon-
sible for controlling the electrophilicity and asymmetry of
the catalyst.1,2 In comparison with the four bridging
ligands, the two axial ligands (which are normally solvent
molecules) form weaker bonds with the electrophilic cen-
ter and are thought to play a less important role in catalysis
because they are easily displaced.1,2 Despite this general
assumption, we have recently shown that some axial
ligands, namely N-heterocyclic carbenes (NHCs), can
have a profound impact on the overall reactivity of the
complex. The arylation of aldehydes by using boronic ac-
ids catalyzed by NHC-dirhodium(II) complexes is a clear
example of the ability of axial ligands to influence the re-
activity profile of dirhodium(II) complexes.4
The NHC-dirhodium(II) complexes 4 and 5 display some
interesting structural features. They show an almost per-
fect structural match between the NHC and the dirhodi-
um(II) lantern structure, as the isopropyl groups fit in
between the acetoxy bridges, and the carbene ring stays in
an eclipsed conformation, thereby providing a high degree
of stereoprotection to the rhodium centre, as shown in
Figure 2.4 This arrangement contributes decisively to the
stability of the complex under our reaction conditions.5
This contrasts with the stability of complex 6, prepared by
Snyder et al.,7 which fragmented in the presence of vari-
ous diazo substrates. For this reason, the results obtained
with complex 6 were identical to those observed when the
parent dirhodium(II) complex was used.7
SYNTHESIS 2009, No. 20, pp 3519–3526
Advanced online publication: 15.09.2009
DOI: 10.1055/s-0029-1217005; Art ID: C03509SS
x
x.
x
x
.
2
0
0
9
On the basis of these results, we examined the cyclization
of substrates 7–9 with various dirhodium(II) complexes
© Georg Thieme Verlag Stuttgart · New York

3520
L. F. R. Gomes et al.
SPECIAL TOPIC
CF3
O
O
O
O
O
N
Rh
Rh
Rh
Rh
Rh
Rh
2
1
3
O
O
O
O
Rh
Figure 2 Optimized geometry for the Rh2(OAc)4(NHC) complex 4
(left; the NHC ligand is darkened); for clarity, only one of the four
bridging acetyl groups in the dirhodium complex is shown in the
structural diagram
Rh
N
N
Rh
Rh
N
N
3, but no decarbonylation products were formed with any
of the other catalysts, nor were they observed in our recent
studies on UV-promoted cyclization reactions of diazo-
acetamides (Table 2, entry 6).9 With regard to the other di-
azoacetamides shown in Scheme 1, liberation of carbon
monoxide was more pronounced in substrate 8, which has
a more electron-withdrawing a-substituent, whereas the
sulfonyl-diazoacetamide 9 gave a rather complex mixture
in which the decarbonylation product was not identified.
4
5
O
O
Rh
N
Rh
R
6 R = Me
6' R = H
N
R
Figure 1 Dirhodium(II) complexes used in the intramolecular C–H
insertion reaction of a-diazoacetamides; for clarity, only one of the
four bridging ligands in each dirhodium complex is shown
These results confirmed the influence of both the catalyst
and diazoacetamide structure on the occurrence of a de-
carbonylation mechanism. We therefore examined the cy-
clization reactions of various diazoacetamides catalyzed
by 4 and/or 5 (Scheme 1, Tables 3 and 4). In general these
substrates afforded the expected lactams without forming
the decarbonylation product. Interestingly, in the case of
the substrate 10, the cyclization was even more selective
than when dirhodium tetracetate was used.
(Table 2). Not surprisingly, the reaction proceeded much
more slowly when 4 or 5 were used. This reflects a less fa-
vorable nucleophilic attack by the diazo compound on the
dirhodium(II) complex as a result of the decreased atomic
charge on the terminal Rh centre in complexes 4 and 5.
More important than the impact on the reaction rate was
the effect on the cyclization selectivity for these sub-
strates, which are known to afford essentially the g-lactam
isomers 7a–9a. When cyclization of diazoacetamide 7
was performed using catalysts 4 and 5, the yield of the g-
lactam isomer decreased and some b-lactam 7b was
formed (Table 2, entries 1–5). More importantly, a new
decarbonylated product 7c was isolated (Table 2, entries 4
and 5). Traces (less than 2%) of this product could also be
found in the crude reaction mixture when using complex
O
O
X
O
X
R' catalyst (1 mol%)
X
R'
N
N
and/or
R''
solvent, reflux
R''
N
N2
R'
R'''
Scheme 1 Cyclization of various diazocetamides using complexes
1, 4, and 5
Table 1 DFT-Calculateda Data for Dirhodium Complexes 1–6¢ and 20
Atomic Chargeb Atomic Chargeb
d
Rh–Rh (Å)
WIRh–Rh
dC(NHC)–Rh (Å)
WIC(NHC)–Rh
c
c
Entry
Complex
(RhTerminal
)
(RhNHC
0.93
0.95
0.81
0.92
0.92
0.88
0.92
)
1
2
3
4
5
6d
7
1
0.93
2.39
2.39
2.39
2.46
2.46
2.44
2.45
0.79
0.80
0.76
0.54
0.54
0.49
0.56
–
–
2
0.95
–
–
3
0.81
–
–
4
0.75
2.17
2.18
2.08
2.20
0.38
0.38
0.44
0.35
5
0.76
6¢
20
0.71
0.77
a DFT calculations were performed at the B3LYP/631LAN level of theory.
b Natural population analysis charge.
c WI = Wiberg index.
d Calculations performed at the B3PW91/631LAN level using complex 6¢ as a model.
Synthesis 2009, No. 20, 3519–3526 © Thieme Stuttgart · New York

SPECIAL TOPIC
Rhodium-Catalyzed Cyclization of Diazoacetamides
3521
Table 2 Cyclization of Diazoacetamides 7–9 by Using Complexes 1–5
O
O
tBu
X
O
X
tBu
X
tBu
N
N
X
N
+
+
N
Ph
N2
Ph
tBu
Ph
Ph
7b X = PO(OEt)2
8b X = COMe
9b X = SO2Ph
7
8
9
X = PO(OEt)2
X = COMe
X = SO2Ph
7a X = PO(OEt)2
8a X = COMe
9a X = SO2Ph
7c X = PO(OEt)2
8c X = COMe
Entry
Substrate
(amount)
Catalyst
(amount)
Conditions
Yield (%)
cis/transb Yield (%) cis/transb Yield (%)
of 7a–9aa
of 7b–9b
of 7c–8ca
1
2
7 (0.3 mmol)
7 (0.157 mmol)
7 (0.157 mmol)
7 (0.3 mmol)
7 (0.3 mmol)
7 (0.103 mmol)
8 (0.3 mmol)
8 (0.3 mmol)
8 (0.3 mmol)
9 (1.0 mmol)
9 (0.3 mmol)
9 (0.3 mmol)
1 (1 mol%)
2 (1 mol%)
3 (1 mol%)
4 (1 mol%)
5 (1 mol%)
–
DCE (0.1 M), reflux, 4 h
DCE (0.1 M), reflux, 12 h
DCE (0.1 M), reflux, 7 h
DCE (0.1 M), reflux, 46 h
DCE (0.1 M), reflux, 24 h
hn,c hexanes (1 mL), 8.5 h
DCE (0.03 M), reflux, 6 h
DCE (0.03 M), reflux, 6 h
DCE (0.03 M), reflux, 6 h
CH2Cl2, reflux, 12 h
81 (91)
66 (82)
76 (80)
56 (60)
66 (79)
64 (66)
47 (65)
17 (18)
18 (32)
95
0.06:1
0.02:1
0.09:1
0.07:1
0.06:1
1:1
(5)
2.1:1
3.9:1
2.3:1
2.7:1
2.6:1
–
–
10 (11)
3 (3)
–
3
0 (<2)
4
7 (9)
23 (25)
5
7 (8)
9 (9)
6
–
–
7
1 (1 mol%)
4 (1 mol%)
5 (1 mol%)
1 (2.5 mmol)
4 (2.5 mol%)
5 (2.5 mol%)
0:1
25 (34)
35 (46)
14 (39)
–
0:1
–
8
0:1
0:1
– (36)
9
0:1
0:1
– (29)
1012
11
12
0:1
–
–
–
–
CH2Cl2 (0.1 M), reflux, 53 h
DCE (0.1 M), reflux, 4 h
67 (89)
54 (64)
0:1
5 (8)
0:1
0:1
21 (30)
0:1
a Isolated yields; the conversion determined by 31P NMR or 1H NMR spectroscopy of the crude mixture is given in parentheses.
b The cis/trans ratios were determined by 31P NMR or 1H NMR spectroscopy on the crude mixture.
c UV irradiation (Hg lamp, Hanau TQ150).
Table 3 Products from the Cyclization of Various Diazocetamides Using Complexes 1, 4, and 5 According to Scheme 1
Catalyst, amount
(mol%)
Solvent
(concn)
Diazo compd
(mmol)
Tempa
Time
(h)
Product, yield
(%)b
PO(OEt)2
O
(EtO)2OP
O
N
N
Ph
Ph
10b
10a
Ph
1 (1 mol%)10
4 (1 mol%)
5 (1 mol%)
DCE (0.1 M)
DCE (0.1 M)
DCE (0.1 M)
0.150 mmol
0.130 mmol
0.130 mmol
24
53
53
(12)
6 (7)
12 (12)
(83)
80 (90)
76 (85)
(EtO)2OP
O
11b
i-Pr
N
1 (1 mol%)
5 (1 mol%)
CH2Cl2 (0.09 M)
CH2Cl2 (0.09 M)
0.50 mmol
0.126 mmol
6.5
21
88 (99)
80 (88)
O
(EtO)2OP
nBu
N
12a
1 (1 mol%)
5 (1 mol%)
DCE (0.1 M)
DCE (0.1 M)
0.30 mmol
0.126 mmol
2
16
87 (92)
89 (93) cis/trans = 0.07:1
Synthesis 2009, No. 20, 3519–3526 © Thieme Stuttgart · New York

3522
L. F. R. Gomes et al.
SPECIAL TOPIC
Table 3 Products from the Cyclization of Various Diazocetamides Using Complexes 1, 4, and 5 According to Scheme 1 (continued)
Catalyst, amount
(mol%)
Solvent
(concn)
Diazo compd
(mmol)
Tempa
Time
(h)
Product, yield
(%)b
(EtO)2OP
Ph
O
13b
N
Ph
1 (1 mol%)
5 (1 mol%)
DCE (0.08 M)
DCE (0.08 M)
0.150 mmol
0.118 mmol
1.5
47
56 (77) cis/trans = 1:1.2
53 (73) cis/trans = 0.74:1
O
NO2
MeO2C
N
14a
Ph
1 (2 mol%)
5 (1 mol%)
CH2Cl2 (0.26 M)
DCE (0.08 M)
0.360 mmol
0.128 mmol
r.t.
reflux
17
24
98 cis/trans = 0:1
98 cis/trans = 0:1
O
TMS
MeO2C
N
TMS
15a
Ph
1 (2 mol%)
5 (2 mol%)
CH2Cl2 (0.2 M)
CH2Cl2 (0.2 M)
0.180 mmol
0.119 mmol
1.25
20
93 (>97%) cis/trans = 0:1
95 (>97%) cis/trans = 0:1
a Unless otherwise indicate, all reactions were carried out under reflux.
b Isolated yields; the conversion determined by 31P NMR or 1H NMR spectroscopy of the crude mixture is given in parentheses.
A surprisingly different result was obtained, however, The formation of phosphonate 16c appears to result from
when the cyclization of asymmetric diazoacetamide 16 a delicate balance between stereoelectronic effects of the
was promoted by NHC-dirhodium(II) catalysts 4 and 5. In diazoacetamide and phosphonate groups, since no decar-
this case, the decarbonylation product was obtained in up bonylation product was detected by 1H NMR spectrosco-
to 47% yield (Table 4).
py for the crude reaction product from the sulfonyl
diazoacetamide 17. This idea was reinforced by the cy-
Table 4 Cyclization of Asymmetric Diazoacetamide 16 and 17
tBu
N
O
X
O
X
tBu
Ph
Ph
X
+
catalyst
N
N
DCE or CH2Cl2,
reflux
tBu
N2
Ph
16c X = PO(OEt)2
17c X = SO2Ph
16b X = PO(OEt)2
17b X = SO2Ph
16 X = PO(OEt)2
17 X = SO2Ph
Entry
Diazo compound
(amount)a
Catalyst
(amount)
Time
(h)
Yield of b-lactam cis/trans
Yield of amine
(%)b
(%)b
111
2
16 (5.25 mmol)
16 (0.140 mmol)
16 (0.140 mmol)
16 (0.052 mmol)
17 (0.128 mmol)
17 (0.128 mmol)
17 (0.128 mmol)
1 (1 mol%)
4 (1 mol%)
5 (1 mol%)
4
25
25
77
1.5:1
–
15 (19)
17 (23)
56 (72)
33 (39)
51 (60)
52 (60)
0.44:1
0.63:1
1.38:1
47 (57)
3
44 (51)
4
1 (2 mol%) + 4 (2 mol%)
1 (2.5 mol%)
3
13 (18)
c
5
2.5
–
–
–
–
c
6
4 (2.5 mol%)
120
120
–
c
7
5 (2.5 mol%)
–
a All reactions were carried out in DCE (entries 1–4) or in CH2Cl2 (entries 5–7) (0.1 M).
b Isolated yields; the conversion determined by 31P NMR or 1H NMR spectroscopy of the crude mixture is given in parentheses.
c Only one isomer was observed.
Synthesis 2009, No. 20, 3519–3526 © Thieme Stuttgart · New York

SPECIAL TOPIC
Rhodium-Catalyzed Cyclization of Diazoacetamides
3523
clization of diazoacetamide 18, which again did not afford The atomic charge calculated for the terminal rhodium
the decarbonylated product, despite its structure similarity atom in complex 20 is similar to those of 4 and 5, but the
to substrate 16 (Scheme 2).
C(NHC)–Rh bond is slightly longer and weaker in com-
plex 20 (Table 1). This is confirmed by the corresponding
Wiberg index, which in complex 20 is 0.35, whereas it is
0.38 in complexes 4 and 5; this is probably due to the in-
ductive effect exerted by the two chlorine atoms in 20
(Scheme 3). Surprisingly complex 20 proved to be the
best complex to induce the formation of the decarbonylat-
ed product 16c, which was obtained with 61% conversion
(Scheme 4).
(EtO)2OP
O
O
(EtO)2OP
tBu
Ph
catalyst 5 (1 mol%)
N
N
Ph
tBu
DCE
47 h, reflux
N2
18b
18
84% (87%)
cis/trans = 1:0.22
Scheme 2 Cyclization of asymmetric diazoacetamide 18
To study the mechanism of the decarbonylation reaction,
we examined the decomposition of 16 with complex 4 in
1,2-dichloroethane saturated with deuterium oxide and in
deuterated 1,2-dichloroethane, as shown in Scheme 5.
The reaction in the presence of deuterium oxide resulted
in incorporation of deuterium in the decarbonylated prod-
uct, whereas no incorporation was detected when deuter-
ated 1,2-dichloroethane was used as the only solvent.
Additionally, no incorporation of deuterium was observed
on standing the amine 16c in a 2.3:1 mixture of tetrahy-
drofuran and deuterium oxide at 55 °C for 27 h. These ex-
periments showed that a Wolff mechanism may be
involved in the generation of 16c; this was corroborated
by the fact that when diazoacetamide 16 was thermally
decomposed in refluxing 1,2-dichloroethane it gave prod-
uct 16c in 33% yield together with 17% of the correspond-
ing b-lactam.
Despite a lower free-electron density at the coordination
site and, consequently, a lower reaction rate, catalyst 4 can
still compete with dirhodium tetraacetate for the decom-
position of substrate 16, affording 18% of the decarbony-
lated product 16c in a competitive reaction when both
catalysts 1 and 4 are present in the reaction medium (Ta-
ble 4, entry 4).
The results of our calculations show that catalysts 4 and 5
are very similar in terms of their electronic and physical
structures (Table 1); however, their catalytic activities
show some differences. For example, complex 4 appears
to be more prone to give product 16c. We therefore decid-
ed to prepare a new complex with chloride groups at-
tached to the NHC backbone to examine the effect of
electronic effects of the NHC on the selectivity of the re-
action (Scheme 3). Complex 20 was obtained in 85%
yield by treating the NHC 1913 with dirhodium tetraace-
tate.
By considering these results, we hypothesized that the
presence of a s-donating NHC ligand could weaken the
bond between the carbene and the terminal rhodium cen-
tre. In fact, DFT analysis of these two structures con-
2.20 Å
(WI = 0.35)
Atomic charge
0.77
O
O
N
O
O
Cl
Rh
Rh
N
+
N
Rh
Rh
Cl
Cl
N
Cl
2.45 Å
(WI = 0.56)
19
1
20
Scheme 3 Synthesis of complex 20 and some relevant structural and electronic calculated data; for clarity, only one of the four bridging acetyl
ligands in each of the dirhodium complexes is shown.
tBu
N
O
(EtO)2OP
O
(EtO)2OP
tBu
Ph
Ph
(EtO)2OP
catalyst 20 (1 mol%)
+
N
N
DCE, reflux, 20 h
tBu
N2
Ph
16b
16
16c
40% (61%)
11% (12%)
cis/trans = 0.49:1
Scheme 4 Effect of catalyst 20 on the formation of product 16c. Reagents and conditions: diazo compound (0.121 mmol), DCE (0.1 M), and
catalyst (1 mol%).
Synthesis 2009, No. 20, 3519–3526 © Thieme Stuttgart · New York

3524
L. F. R. Gomes et al.
SPECIAL TOPIC
tBu
O
tBu
N
(EtO)2OP
O
(EtO)2OP
(EtO)2OP
N
Ph
(EtO)2OP
tBu
Ph
catalyst 4 (1 mol%)
+
+
N
N
R
R
tBu
N2
Ph
Ph
R = H, D
16
16b
16c
21
–
DCE–D2O, reflux, 24 h
C2D4Cl2, reflux, 24 h
15% (16%)
50% (59%)
–
cis/trans = 0.45:1
28% (60%)
5% (27%)
cis/trans = 0.67:1
Scheme 5 Decomposition of diazoacetamide 16 with catalyst 4 in deuterated solvents
Figure 3 Relevant structural and electronic parameters calculated for the metallo-carbene and NHC-metallo-carbene derived from diazo com-
pound 16
firmed this effect, as the rhodium–carbene bond became In conclusion, we have shown that axial coordination of
0.08 Å longer as a result of the presence of the axial NHC ligands in dirhodium(II) complexes can have an im-
ligand, as shown in Figure 3.
portant effect on the rates and selectivities of intramolec-
ular reactions. Most importantly, the possibility of the
NHC engaging in a push–pull mechanism favors the gen-
eration of a free carbene-type intermediate that affords a
decarbonylated product. In addition to this effect, the di-
azoacetamide structure also contributes decisively to this
reaction pathway.
Taking the experimental and theoretical results together,
we hypothesized that the effect of the NHC relies on the
possibility that this ligand can participate in a push–pull
mechanism. As shown in Scheme 6, the reaction of the
NHC-dirhodium(II) with the diazo species forms the met-
allo-carbene. In this species, the presence of the Rh=Cdiazo
bond weakens the Rh–CNHC bond (pull), although the in-
tegrity of the bond is, to some extent, secured by the ste-
reochemical protection conferred by the structure of the
NHC. On the other hand, the NHC also weakens the met-
allo-carbene (push), which, in combination with the ste-
reochemical effects exerted by the acetamide structure,
may lead to the generation of a free carbene-type interme-
diate that undergoes a typical Wolff rearrangement to
form the decarbonylated product.
DCE, toluene, DME, PhCl, Et3N, and CH2Cl2 were distilled over
CaH under argon. THF was distilled over Na/benzophenone. TsN3
was prepared from TsCl and NaN3.14 NaH was used as a 55% dis-
persion in mineral oil. DCE-d4 and D2O were acquired from Cam-
bridge Isotope Laboratories. Rh2(OAc)4 and Rh2(TFA)4 were
obtained from Aldrich. Catalysts 3,15 4,4b and 54b were prepared as
previously described. All reactions were carried out under argon.
Flash chromatography was carried out on silica gel [Merck (Ref.
109385) or Scharlau (230–400 mesh ASTM)], neutral alumina
[Macherey-Nagel (Ref. 815020)] or basic alumina [Macherey-
Synthesis 2009, No. 20, 3519–3526 © Thieme Stuttgart · New York

SPECIAL TOPIC
Rhodium-Catalyzed Cyclization of Diazoacetamides
3525
O
(EtO)2OP
tBu
Ph
N
N2
16
2.50 Å
(WI = 0.48)
2.10 Å
(WI = 0.47)
O
O
O
N
(EtO)2OP
tBu
Ph
N
O
O
OEt
OEt
N
pull
+
Rh
Rh
N
P
N
Rh
O
push
Rh
O
N
tBu
Ph
2.39 Å
(WI = 0.20)
2.46 Å
(WI = 0.54)
2.18 Å
(WI = 0.38)
atomic charge
0.76
(EtO)2OP
C
O
tBu
N
(EtO)2OP
O
Ph
N
tBu
Ph
H2O
16b
tBu
N
(EtO)2OP
Ph
16c
Scheme 6 Proposed mechanism for the decomposition of diazoacetamide 16
Nagel (Ref. 815010, activity 1)]. Preparative TLC was carried out
on silica [Merck 60 G F254 (Ref. 105788)] or alumina [Merck 60 F254
(Ref. 107730)]. Reaction mixtures were analyzed by TLC on silica
60 F254 [Merck (ref. 105554)] or neutral alumina [60 F254, Merck
(ref. 105550)]; spots were visualized by UV irradiation and phos-
phomolybdic acid soln or I2. IR spectra were recorded with a Jasco
FT/IR-430 model as thinly dispersed films on NaCl. High- and low-
resolution mass spectra (EI, FAB+) were recorded by the mass spec-
trometry service of the University of Santiago de Compostela
(Spain). NMR spectra were recorded with a Bruker Ultrashield
Avance II 400 or 300 in toluene-d8 or CDCl3 as solvents and TMS
MS (FAB+): m/z = 897.9 [M+], 457.1.
HRMS (FAB+): m/z calcd for C35H46Cl2N2O8Rh2, 898.0741; found,
898.0745.
Dirhodium(II)-Catalyzed Decomposition of a-Diazoacet-
amides; General Procedure
A soln of the a-diazoacetamide in the anhyd chlorinated solvent was
added to the catalyst under argon. The soln was magnetically stirred
under reflux until the substrate was consumed (TLC). The solvent
was evaporated under reduced pressure, and a NMR spectrum was
recorded to determine the relative product ratio. The crude mixture
was purified by chromatography (silica or alumina).
1
as an external standard for H and 13C, and H3PO4 as an external
standard for 31P NMR. All coupling constants are expressed in Hz.
a-Diazoacetamides and products were obtained as previously de-
scribed,5 except for 17, which was obtained following a general pro-
cedure used previously.12 Substrates 11,11 13,9 14,16 and 15,17 and
products 11b,11 13b,9 14a,16and 15a,17 have already been reported
elsewhere.
Reactions with Deuterated Solvents; General Procedures
Diazo decomposition in wet DCE: DCE (3 mL) and D2O (300 mL)
were equilibrated for 11 days before the organic phase (1.4 mL) was
used in the reaction with the diazo compound (0.117 mmol) and cat-
alyst (1 mol%).
Diazo decomposition in 1,2-dichloroethane-d4: A sealed glass am-
poule containing the a mixture of the diazo compound (0.143
mmol), DCE-d4 (0.266 g), and catalyst (1 mol%) under argon was
introduced into a glass reactor containing DCE and heated at 85 °C
for 24 h. The ampoule was then opened, the solvent was evaporated
under reduced pressure, and a NMR spectrum was recorded to de-
termine the relative product ratio. The crude mixture was purified
by chromatography (alumina).
Dirhodium Complex 20
A flame-dried Schlenk tube was charged with a suspension of
Rh2(OAc)4 (50 mg, 0.11 mmol) in freshly distilled and dried toluene
(4 mL). Carbene 1913 (103 mg, 0.23 mmol) was added, and the mix-
ture was heated at 80 °C until the soln turned the color of red wine
(about 2 h). The soln was concentrated, and the residue was purified
by chromatography (30% EtOAc–hexane) to give a purple-bluish
powder; yield: 85%.
1H NMR (toluene-d8): d = 7.13–6.99 (m, toluene), 3.29–3.24 (m, 4
H), 2.15–2.12 (toluene), 1.34 (br s, 12 H), 1.25 (d, J = 6.6 Hz, 12
H), 1.08 (d, J = 6.6 Hz, 12 H).
13C NMR (toluene-d8): d = 188.57, 146.27, 137.40, 134.51, 129.68,
123.25, 119.23, 28.33, 23.91, 23.41, 22.70.
N-tert-Butyl-N-(1-phenylethyl)-2-(phenylsulfonyl)acetamide
This precursor of substrate 17 was prepared by following general
reported procedure,12 starting from 2-methyl-N-(1-phenylethyl)pro-
pan-2-amine11 (0.694 g, 3.92 mmol) as a white solid; yield: 0.739 g
(53%, two steps); mp 85–87 °C; Rf = 0.36 (EtOAc–hexanes, 3:7).
Synthesis 2009, No. 20, 3519–3526 © Thieme Stuttgart · New York

3526
L. F. R. Gomes et al.
SPECIAL TOPIC
IR (film): 2976, 1651, 1321, 1157, 725 cm–1.
(2) (a) Davies, H. M. L.; Beckwith, R. E. Chem. Rev. 2003, 103,
2861. (b) Doyle, M. P. J. Org. Chem. 2006, 71, 9253.
(c) Gois, P. M. P.; Afonso, C. A. M. Eur. J. Org. Chem.
2004, 3773.
1H NMR (400 MHz, CDCl3): d = 1.55 [s, 9 H, NC(CH3)3], 1.85 (d,
J = 6.8 Hz, 3 H, CH3CHN), 3.59 (d, J = 14.4 Hz, 1 H, SO2HHCO),
3.90 (d, J = 14.8 Hz, 1 H, SO2HHCO), 5.12 (q, J = 6.8 Hz, 1 H,
CH3CHN), 7.29–7.32 (m, 3 H, Ar), 7.38–7.41 (m, 2 H, Ar), 7.50–
7.54 (m, 2 H, Ar), 7.61–7.65 (m, 1 H, Ar), 7.81–7.83 (m, 2 H, Ar).
13C NMR (100 MHz, CDCl3): d = 21.32 (CH3CHPh), 29.04
[NC(CH3)3], 52.66 (CH3CHPh), 59.87 [NC(CH3)3], 63.38
(SO2CH2CO), 125,57, 127.20, 128.72, 128.81, 129.26, 133.57,
139.92 (q), 142.87 (q) (Ar), 164.01 (CO).
(3) For selected examples, see: (a) Catino, A. J.; Forslund,
R. E.; Doyle, M. P. J. Am. Chem. Soc. 2005, 126, 13622.
(b) Catino, A. J.; Nichols, J. M.; Choi, H.; Gottipamula, S.;
Doyle, M. P. Org. Lett. 2005, 7, 5167. (c) Liang, C.;
Peillard, F. R.; Fruit, C.; Müller, P.; Dodd, R. H.; Dauban, P.
Angew. Chem. Int. Ed. 2006, 45, 4641. (d) Reddy, R. R.;
Davies, H. M. L. Org. Lett. 2006, 8, 5013. (e) Fiori, K. W.;
Du Bois, J. J. Am. Chem. Soc. 2007, 129, 562. (f) Anada,
M.; Tanaka, M.; Washio, T.; Yamawaki, M.; Abe, T.;
Hashimoto, S. Org. Lett. 2007, 9, 4559. (g) Doyle, M. P.;
Valenzuela, M.; Huang, P. Proc. Natl. Acad. Sci. U.S.A.
2004, 101, 5391. (h) Anada, M.; Washio, T.; Shimada, N.;
Kitagaki, S.; Nakajima, M.; Shiro, M.; Hashimoto, S.
Angew. Chem. Int. Ed. 2004, 43, 2665. (i) Forslund, R. E.;
Cain, J.; Colyer, J.; Doyle, M. P. Adv. Synth. Catal. 2005,
347, 87. (j) Washio, T.; Nakamura, S.; Anada, M.;
Hashimoto, S. Heterocycles 2005, 66, 567. (k) Wang, Y.;
Wolf, J.; Zavalij, P.; Doyle, M. P. Angew. Chem. Int. Ed.
2008, 47, 1439. (l) Catino, A. J.; Nichols, J. M.; Gorslund,
R. E.; Doyle, M. P. Org. Lett. 2005, 7, 2787. (m) Gois,
P. M. P.; Candeias, N. R.; Afonso, C. A. M. J. Mol. Catal. A:
Chem. 2005, 227, 17.
N-tert-Butyl-2-diazo-N-(1-phenylethyl)-2-(phenylsulfonyl)acet-
amide (17)
The a-diazoacetamide 17 was prepared by following the reported
general procedure,12 starting from the acetamide precursor (0.516 g,
1.44 mmol), and obtained as a yellow solid; yield: 0.331 g (60 %);
Rf = 0.79 (EtOAc–hexanes, 3:7).
IR (film): 2976, 2091, 1643, 1333, 729 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.40 [s, 9 H, NC(CH3)3], 1.86 (d,
J = 7.2 Hz, 3 H, CH3CHN), 5.11 (q, J = 7.2 Hz, 1 H, CH3CHN),
7.30–7.33 (m, 1 H, Ar), 7.37–7.40 (m, 4 H, Ar), 7.54–7.58 (m, 2 H,
Ar), 7.62–7.66 (m, 1 H, Ar), 7.99–8.01 (m, 2 H, Ar).
13C NMR (100 MHz, CDCl3): d = 20.13 (CH3CHPh), 29.22
[NC(CH3)3], 55.56 (CH3CHPh), 59.80 [NC(CH3)3], 126.90, 127.44,
127.90, 128.64, 128.97, 133.48, 141.60 (q), 142.36 (q) (Ar), 162.37
(CO).
(4) (a) Gois, P. M. P.; Trindade, A. F.; Veiros, L. F.; Andre, V.;
Duarte, M. T.; Afonso, C. A. M.; Caddick, S.; Cloke,
F. G. N. Angew. Chem. Int. Ed. 2007, 46, 5750. (b) Gois,
P. M. P.; Trindade, A. F.; Veiros, L. F.; Andre, V.; Duarte,
M. T.; Afonso, C. A. M.; Caddick, S.; Cloke, F. G. N. J. Org.
Chem. 2008, 73, 1076.
1-tert-Butyl-4-methyl-4-phenyl-3-(phenylsulfonyl)azetidin-2-
one (17b)
White solid; mp 134–138 °C; Rf = 0.18 (EtOAc–hexanes, 1:4).
(5) Gomes, L. F. R.; Trindade, A. F.; Candeias, N. R.; Gois,
P. M. P.; Afonso, C. A. M. Tetrahedron Lett. 2009, 49, 7372.
(6) (a) Hahn, F. E. Angew. Chem. Int. Ed. 2006, 45, 1348.
(b) Herrmann, W. A. Angew. Chem. Int. Ed. 2002, 41, 1290.
(c) N-Heterocyclic Carbenes in Transition Metal Catalysis;
Glorius, F., Ed.; Springer: Berlin, 2007. (d) N-Heterocyclic
Carbenes in Synthesis; Nolan, S. P., Ed.; Wiley-VCH:
Weinheim, 2006.
IR (film): 2980, 1751, 1319, 1150, 1084 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.37 [s, 9 H, NC(CH3)3], 2.52 [s,
3 H, CH3C(Ph)N], 4.24 (s, 1 H, SO2CHCO), 7.34–7.47 (m, 3 H, Ar),
7.49–7.51 (m, 2 H, Ar), 7.55–7.59 (m, 2 H, Ar), 7.64–7.71 (m, 1 H,
Ar), 8.04–8.07(m, 2 H, Ar).
13C NMR (100 MHz, CDCl3): d = 20.12 [CH3C(Ph)N], 28.41
[NC(CH3)3], 56.76 [NC(CH3)3], 65.24 [CH3C(Ph)N], 79.60
[SO2CHCO], 125.35, 128.28, 128.90, 129.00, 129.08, 134.19,
139.88 (q), 142.92 (q) (Ar), 159.39 (CO) ppm.
(7) Snyder, J. P.; Padwa, A.; Stengel, T.; Arduengo, A. J. III.;
Jockisch, A.; Kim, H.-L. J. Am. Chem. Soc. 2001, 123,
11318.
An ORTEP plot of the X-ray crystal structure is available in the
supporting information.
(8) (a) Parr, R. G.; Yang, W. Density Functional Theory of
Atoms and Molecules; Oxford University Press: New York,
1989. (b) The calculations were performed by using the
GAUSSIAN 98 package at the B3LYP/VDZP level for all
molecules except 6¢, where the B3PW91 functional was
used. A full account of the computational details and a
complete list of references are provided as Supporting
Information.
(9) Candeias, N. R.; Gois, P. M. P.; Veiros, L. F.; Afonso,
C. A. M. J. Org. Chem. 2008, 73, 3539.
(10) Candeias, N. R.; Gois, P. M. P.; Afonso, C. A. M. J. Org.
Chem. 2006, 71, 5489.
(11) Gois, P. M. P.; Afonso, C. A. M. Eur. J. Org. Chem. 2003,
3798.
Supporting Information for this article is available online at
http://www.thieme-connect.de/ejournals/toc/synthesis.
Acknowledgment
We thank to Fundação para a Ciência e Tecnologia (POCI 2010)
and FEDER (PTDC/QUI/66695/2006, PTDC/QUI/66015/2006,
SFH/BPD/46589/2008 and SFRH/BD/30619/2006) for their finan-
cial support, and the Portuguese NMR Network (IST-UTL Center)
for providing access to the NMR facility.
(12) Yoon, C. H.; Zaworotko, M. J.; Moulton, B.; Jung, K. W.
Org. Lett. 2001, 3 , 3539.
(13) Arduengo, A. J. III.; Krafczyk, R.; Schmutzler, R.; Craig,
H. A.; Goerlich, J. R.; Marshall, W. J.; Unverzagt, M.
Tetrahedron 1999, 55, 14523.
(14) Deyrup, J. A.; Moyer, C. L. J. Org. Chem. 1969, 34, 175.
(15) Doyle, M. P.; Westrum, L. J.; Wolthuis, W. N. E.; See,
M. M.; Boone, W. P.; Bagheri, V.; Pearson, M. M. J. Am.
Chem. Soc. 1993, 115, 958.
(16) Anada, M.; Hashimoto, S. Tetrahedron Lett. 1998, 39, 79.
(17) Wee, A. G. H.; Duncan, S. C. J. Org. Chem. 2005, 70, 8372.
References
(1) (a) Doyle, M. P.; McKervey, M. A.; Ye, T. Modern Catalytic
Methods for Organic Synthesis with Diazo Compounds:
From Cyclopropanes to Ylides; Wiley: New York, 1998.
(b) Lou, Y.; Remarchuk, T. P.; Corey, E. J. J. Am. Chem.
Soc. 2005, 127, 14223. (c) Cotton, F. A.; Hillard, E.;
Murillo, C. A. J. Am. Chem. Soc. 2002, 124, 5658.
(d) Zhang, Z.; Wang, J. Tetrahedron 2008, 64, 6577.
Synthesis 2009, No. 20, 3519–3526 © Thieme Stuttgart · New York