Regio- and stereoselective dirhodium(II)-catalysed intramolecular C-H insertion reactions of α-diazo-α-(dialkoxyphosphoryl)acetamides and -acetates

Article abstract of DOI:10.1002/ejoc.200300330

α-Diazo-α-(dialkoxyphosphoryl)acetates and -acetamides afforded α-(dialkoxyphosphoryl)lactones and lactams, respectively, in moderate to high yields through dirhodium(II)-catalysed intramolecular carbon-hydrogen insertion reactions. In the case of α-diazo

Full text of DOI:10.1002/ejoc.200300330

FULL PAPER
Regio- and Stereoselective Dirhodium(II)-Catalysed Intramolecular C؊H
Insertion Reactions of α-Diazo-α-(dialkoxyphosphoryl)acetamides
and -acetates
Pedro M. P. Gois[a] and Carlos A. M. Afonso*[a]
Keywords: CϪH activation / Diazo compounds / Lactams / Phosphonates / Rhodium
α-Diazo-α-(dialkoxyphosphoryl)acetates and -acetamides af-
markable preference for the formation of γ-lactam was ob-
forded α-(dialkoxyphosphoryl)lactones and lactams, respect- served, with stereocontrol in favour of the trans diastereomer.
ively, in moderate to high yields through dirhodium(II)-cata-
lysed intramolecular carbon−hydrogen insertion reactions. In
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
the case of α-diazo-α-(dialkoxyphosphoryl)acetamides a re- Germany, 2003)
Introduction
This result prompted us to study the Rh(II)-catalysed
cyclization of α-diazo-α-(dialkoxyphosphoryl)acetates and
-acetamides in an attempt to understand and extend the
scope of the reaction.
The use of dirhodium() acetate and related carboxylates
as catalysts for the formation of metal carbenes from diazo-
carbonyl compounds affords a route to a broad spectrum
of chemical transformations,[1] one of the most useful of
which is the intramolecular carbonϪhydrogen (CϪH) inser-
tion reaction, and its use in the carboxylic and heterocyclic
ring synthesis.[2]
Results and Discussion
The utility of this approach is directly related to the level
of regio- and stereoselectivity of the CϪH insertion process.
This selectivity not only depends on the type of α-diazocar-
bonyl and rhodium catalyst utilised, but is also governed by
steric, conformational and electronic factors.[3]
The desired substrates 4bϪf were easily prepared in a
two-step procedure from commercially available ethyl (di-
ethoxyphosphoryl)acetate (1) by transesterification or ami-
nolysis. Substrates 4gϪm were prepared from 2-bromo-
acetamides 2gϪm by MichaelisϪArbusov reactions.[7] Sub-
sequent diazo transfer with p-toluenesulfonyl azide yielded
the corresponding α-diazo-α-(dialkoxyphosphoryl)acetates
and -acetamides 4aϪm (Scheme 1).
In contrast with the vast body of work on diazocarbonyl
compounds, rhodium()-catalysed cyclization of diazo-
phosphonates has been much less widely studied, but the
synthesis of new phosphorus-containing compounds has
nevertheless continued to increase in interest, due to their
significant chemical and biological profiles.[4] The reported
cyclizations of diazophosphonates are mostly associated
with intra- and intermolecular OϪH and NϪH insertion
reactions, and with construction of α-(dialkoxyphosphoryl)-
cyclopentanones through CϪH insertion into alkyl chains
of α-diazo-α-(dialkoxyphosphoryl)-n-alkyl ketones.[5] Min-
ami et al.[6] showed that construction of α-(dialkoxyphos-
phoryl)lactams was also possible, though low yields were
obtained.
Scheme 1. Preparation of α-diazo-α-(diethoxyphosphoryl)acetates
4aϪc and -acetamides 4dϪm; conditions: (Method A): 1, alcohol
or amine (12 equiv., d diisopropylamine, e diethylamine, f di-n-bu-
tylamine), molecular sieves, toluene (for alcohols) or xylene (for
amines), reflux; (Method B): 2, triethylphosphite (1.2 equiv.),
dichloroethane, reflux; (i) 2, NaH (1.2 equiv.) or DBU (1.1 equiv.),
TsN3 (1.2 equiv.), THF
[a]
´
REQUIMTE/CQFB, Departamento de Quımica, Faculdade de
ˆ
Ciencias e Tecnologia, Universidade Nova de Lisboa,
2829-516 Caparica, Portugal
Fax: (internat.) ϩ351-21-2948550
E-mail: cma@dq.fct.unl.pt
3798
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/ejoc.200300330
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Regio- and Stereoselective Dirhodium(II)-Catalysed Intramolecular CϪH Insertion Reactions
FULL PAPER
The [Rh2(OAc)4]-catalysed cyclization of α-diazo-α-di- formation of five-membered rings with stereocontrol in fav-
ethoxyphosphorylacetamides afforded α-phosphoryl- our of the trans diastereoisomer (Table 1, Entries 2 and 3).
lactams 5 and 6 in high yields (Table 1). The formation of These observations can be interpreted in terms of tran-
the lactams 5d and 6f in lower yields (42% and 67%, respec- sition-state structures in which the substituents are prefer-
tively, probably due to the occurrence of decomposition entially in the more stable pseudoequatorial positions[8]
during flash chromatography on silica gel) had previously (conformational effect), as shown in Scheme 2.
been reported.[6] We observed that the decomposition could
be minimised by use of basic alumina instead of silica gel,
allowing the isolation of the β-lactam 5d and the γ-lactam
6f in 88% and 87% yields, respectively (Table 1, Entries 1
and 3).
Table 1. [Rh2(OAc)4]-catalysed cyclization of α-diazo-α-(diethoxy-
phosphoryl)acetamides 4dϪj
Scheme 2
Doyle et al.[9] established that metal electron-withdrawing
ligands increase the electrophilicity of the carbene, causing
bond formation to take place at a greater distance from the
reacting CϪH bond (early transition state) with a resulting
decrease in selectivity. In the case of α-aceto-α-diazoaceta-
mide analogue of substrate 4g it was reported that the selec-
tivity was improved in favour of the γ-lactam when a Rh
catalyst with a electron-donating ligand was used (late tran-
sition state).[10] Likewise, since our α-(dialkoxyphosphoryl)
group is less electron-withdrawing than its carbonyl
counterpart, it stabilises the electrophilic carbenoid carbon,
thereby causing the insertion reaction to proceed through a
relatively late transition state, with a resulting increase in
selectivity in line with recently reported observations con-
cerning the phenylsulfonyl group (Scheme 3).[3c]
Scheme 3. Comparative results for the [Rh2(OAc)4]-catalysed cycli-
zation of α-diazoacetamides, between the α-(dialkoxyphosphoryl)
and the reported α-acetyl[3f] and α-sulfonyl[3c] groups
[a]
[b]
Rh2(OAc)4 (1 mol%), C2H4Cl2, reflux. Isolated yields of lac-
tames after purification by flash chromatography; in bracket is pre-
sented the observed conversion by 31P NMR of the crude reaction
Substituent effects close to the insertion centre are also
known to influence the reaction,[11] and a series of α-diazo-
α-(dialkoxyphosphoryl)acetamides 4iϪj was prepared in
order to explore the electronic effect on regioselectivity
(Table 1, Entries 5Ϫ6).
[c]
mixture. Isolated only the trans isomer (5 J3,4 ϭ 2.0Ϫ2.2 Hz; 6
J
3,4 ϭ 4.2Ϫ4.9 Hz, except for 6h J3,4 ϭ 2.0 Hz). [d] The crude reac-
[e]
tion mixture contains the trans and cis isomers (1.0:2.4).
The
crude reaction mixture contains the E and Z isomers (1.0:2.2).
[f]
Isolated as a 1.2:1 trans diastereoisomeric mixture.
Substrate 4h (Entry 5), as expected, afforded the trans γ-
With regard to these results, the bulky dialkoxyphospho- lactam in high yield, which is a result of the activation of
ryl group appears to induce a remarkable preference for the the electron-donating group and also of the conformational
Eur. J. Org. Chem. 2003, 3798Ϫ3810
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P. M. P. Gois, C. A. M. Afonso
FULL PAPER
effect. Substrate 4i (Entry 6) formed β-lactam as a cis/trans
mixture in nearly quantitative yield, even though CϪH in-
sertion into the position α to the carboxylate substituent
would have produced a favourable γ-lactam. This result is
due to the deactivating effect of the electron-withdrawing
carboxylate on CϪH insertion into the α-methylene
group.[3c]
Table 2. [Rh2(OAc)4]-catalysed cyclization of α-diazo-α-(diethoxy-
phosphoryl)acetamides 4kϪm
The unexpected observation that substrate 4i underwent
β-lactam formation as a cis/trans mixture and not exclus-
ively as trans prompted us to study the influence of the N-
substituent of the amide group. It should be mentioned that
the cis isomer epimerises to the more stable trans isomer in
the presence of basic alumina. A similar observation for α-
acetyl- and α-methoxycarbonyl-β-lactams has recently
been reported.[3f]
According to Doyle et al.,[11b][11c][12a] the overlap of the
nonbonded nitrogen electrons with the carbonyl π-system
fixes the amide conformation so that the larger N-substitu-
ent is positioned syn to the sterically less demanding amide
carbonyl group, while the smaller N-substituent is posi-
tioned close to the reactive rhodium carbenoid centre, facili-
tating the CϪH insertion (Scheme 4).
[a]
[b]
Rh2(OAc)4 (1 mol%), CH2Cl2 or C2H4Cl2, reflux.
Observed
cis/trans ratio by 31P NMR of crude reaction mixture. Isolated
only the corresponding trans-β-lactam (5 J3,4 ϭ 2.0Ϫ2.4 Hz) due
to the occurrence of epimerization during purification by flash
chromatography (basic alumina).
[c]
Scheme 4
When such conformational bias is absent, the selectivity
is lost and a mixture of products arising from insertion onto
both N-substituents is obtained. The importance of this
conformational effect can be seen in the results from the
cyclization of substrate 4j (Table 1, Entry 7). Cyclization of
4j in 1,2-dichloroethane furnished 81% of γ-lactam and
only 19% of β-lactam, despite β-lactam formation resulting
from insertion into a more activated CϪH bond.
The symmetric acetamides considered in this study
underwent γ-lactam formation with high regio- and stereo-
selectivity, a similar result being obtained when the tert-
butyl group was introduced into the molecule (substrate
4g).
Scheme 5
When a methyl group was introduced (substrate 4m,
Table 2, Entry 3), the difference in the sizes of the two
In terms of stereoselectivity, strikingly different results groups was not as high as in substrate 4l, thus yielding a
were observed when only β-lactam formation was con- 60:40 mixture of cis and trans isomers.
sidered, as shown in Table 2. The structure of the starting compound 4l was deter-
When the benzylic substituent was replaced by the bulky mined by X-ray analysis (Figure 2).
tert-butyl group, the conformation was altered. The aro-
In this conformation the larger N-substituent is posi-
matic group, which in the substrate 4k had been in a more tioned syn to the sterically less demanding amide carbonyl
stable equatorial position (Table 2, Entry 1), was now prob- group, while the smaller N-substituent is situated close to
ably forced into the axial position by the tert-butyl group the diazo centre (and supposedly the carbenoid), as sug-
(steric effect) in the substrate 4l (Entry 2), as shown in gested by Doyle et al.[10] (Scheme 5). Moreover, if the new
Scheme 5.
CϪC bond was formed with this conformation, between C1
Figure 1 presents the obtained X-ray structure of the β- and C4, a trans β-lactam would have been formed, so the
lactam 5l, showing the trans geometry of the phenyl and favourable conformation for the cis β-lactam formation was
dialkoxyphosphoryl groups as well as the anti relationship due to the conformationally constrained nature of the inter-
between the phenyl and tert-butyl groups, probably due to mediate metal carbenoid, and was not predefined in the
steric repulsion.
starting α-diazo-α-(dialkoxyphosphoryl)acetamide.
3800
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Regio- and Stereoselective Dirhodium(II)-Catalysed Intramolecular CϪH Insertion Reactions
FULL PAPER
Table 3. [Rh2(OAc)4]-catalysed cyclization of α-diazo-α-(diethoxy-
phosphoryl)acetates 4aϪc
Figure 1. Crystal structure of the β-lactam 5l (30% probability le-
˚
vel); selected bond lengths [A] and angles [°]: N(1)ϪC(2) 1.349(2),
N(1)ϪC(5) 1.475(2), N(1)ϪC(4) 1.480(2), C(2)ϪO(9) 1.208(2),
C(2)ϪC(3) 1.533(3), C(3)ϪC(4) 1.558(2), C(3)ϪP(10) 1.7899(19),
C(3)ϪH(3) 0.98, C(4)ϪC(41) 1.501(2), C(4)ϪH(4) 0.98;
C(2)ϪN(1)ϪC(5) 132.35(16), C(5)ϪN(1)ϪC(4) 130.20(15),
O(9)ϪC(2)ϪN(1) 133.20(19), O(9)ϪC(2)ϪC(3) 134.33(18),
C(2)ϪC(3)ϪP(10) 115.31(13), C(4)ϪC(3)ϪP(10) 114.18(12),
[a]
Rh2(OAc)4 (1 mol%), C2H4Cl2, reflux, reaction time: entry 1 (6
[b]
h), entry 2 (2.5 h) and entry 3 (2 h). Isolated yields of lactones
after purification by flash chromatography.
trans isomer, assigned by H NMR (J3,4 ϭ 4.4 Hz).
a mixture of trans (J3,4 ϭ 4.4 Hz) and cis (J3,4 ϭ 10.3 Hz) isomers,
ratio trans/cis ϭ 1.4:1. Isolated only the trans isomer (J3,4 ϭ 6.5
Hz). Isolated only the cis isomer (J3,4 ϭ 10.4 Hz).
[c]
Isolated only the
1
[d]
Isolated as
C(2)ϪC(3)ϪH(3)
113.1,
C(4)ϪC(3)ϪH(3)
113.1,
N(1)ϪC(4)ϪC(41) 117.47(14), C(41)ϪC(4)ϪC(3) 117.67(15),
[e]
N(1)ϪC(4)ϪH(4) 111, C(41)ϪC(4)ϪH(4) 111, C(3)ϪC(4)ϪH(4)
[f]
111
Reported CϪH insertion reactions of alkylmethyldi-
azomalonates resulted in the formation of β- and γ- lac-
tones, the selectivity depending both on the substitution
pattern of the insertion centres, with a preference for meth-
ine CϪH insertion, and on the conformational bias of the
metallocarbene, which directed the insertion towards β-lac-
tone formation.[13] Our results suggest that when a dial-
koxyphosphoryl group is used as an α-substituent, the in-
sertion process is more dependent on the conformational
effect than on the insertion centre.
Conclusion
In summary, the dirhodium()-catalysed cyclization of α-
diazo-α-(dialkoxyphosphoryl)acetamides proved to be a
highly regio- and stereocontrolled procedure for the con-
struction of α-(dialkoxyphosphoryl)lactams. Confor-
mational and electronic effects in the γ-lactam formation
were studied. The steric effect exerted by the N-substituent
of the amide was determinant in the stereoselectivity of the
β-lactam formation. Preparation of α-diazo-α-(dialkoxy-
phosphoryl)lactones was also achieved, but only moderate
yields and reduced regio- and stereoselectivities were ob-
served.
˚
Figure 2. Crystal structure of the diazo 4l; selected bond lengths [A]
and angles [°]: PϪC(1) 1.778(2), O(1)ϪC(2) 1.225(3), N(1)ϪN(2)
1.125(3), N(1)ϪC(1) 1.311(3), C(1)ϪC(2) 1.488(3), C(2)ϪN(3)
1.359(3); O(2)ϪPϪC(1) 118.9(3), N(1)ϪC(1)ϪP 116.07(17),
C(2)ϪC(1)ϪP
121.29(15),
O(1)ϪC(2)ϪN(3)
123.6(2),
O(1)ϪC(2)ϪC(1) 115.92(19), N(3)ϪC(2)ϪC(1) 120.50(18),
C(2)ϪN(3)ϪC(4) 120.56(17), C(2)ϪN(3)ϪC(5) 118.93(17)
In clear contrast with those of the α-diazo-α-(dialkoxy-
phosphoryl)acetamides, the [Rh2(OAc)4]-catalysed cycliza-
tions of α-diazo-α-(diethoxyphosphoryl)acetates 4aϪc
(Table 3) afforded β- and γ- lactones in moderate yields and
with low regio- and stereoselectivities, although β-lactones
nevertheless seemed to be the preferred insertion products
even when more reactive methine CϪH bonds were avail-
able (Entry 3).
Experimental Section
General Remarks: Tetrahydrofuran (THF) and diethyl ether were
distilled from over calcium hydride/benzophenone immediately
prior to use, while triethylamine, dichloromethane and dichloro-
Eur. J. Org. Chem. 2003, 3798Ϫ3810
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P. M. P. Gois, C. A. M. Afonso
ethane were freshly distilled from over calcium hydride. Ethyl acetate 13.42, 13.58 (NCH2CH2CH2CH3), 16.51, 18.31 [NCH(CH3)Ar],
FULL PAPER
was distilled from over potassium carbonate. p-Toluenesulfonyl az-
ide was prepared from p-toluenesulfonyl chloride and sodium az-
ide.[14] Sodium hydride was used as a 55% dispersion in mineral oil.
All reactions were performed in oven-dried glassware under argon.
Flash chromatography was carried out on silica gel 60  from MN
(ref. 815381) or on aluminium oxide basic from MN (ref. 815010,
Brockmann activity 1). Reaction mixtures were analysed by TLC
on ALUGRAM SIL G/UV254 from MN (ref. 818133, silica gel
60) and aluminium oxide 60F254 neutral plates (type E) from Merck
(ref. 5550). Visualisation of TLC spots was effected by use of UV
and phosphomolybdic acid solution or I2. Infrared spectra (IR)
spectra were recorded with a Mattson Instruments Satellite FTIR
model as thinly dispersed films. High- and low-resolution mass
spectra (EI, FAB) were carried out by the mass spectrometry ser-
vice of the University of Santiago de Compostela (Spain). NMR
spectra were recorded with a Bruker AMX 400 with CDCl3 as sol-
vent and (CH3)4Si (1H) as internal standard. 31P chemical shifts are
reported in ppm relative to H3PO4 (external standard). All coupling
constants are expressed in Hz.
20.19, 20.32 (NCH2CH2CH2CH3), 26.88 (BrCH2CO), 30.36, 33.36
(NCH2CH2CH2CH3), 43.58, 44.36 (NCH2CH2CH2CH3), 51.92,
44.36 [NCH(CH3)Ar], 126.70, 127.46, 127.75, 128.39, 128.65,
139.80 (q), 140.21 (q), 166.48, 166.84 (CϭO) ppm.
α-Bromoacetyl-N-(tert-butyl)-N-(α-phenylethyl)amide (2m): (1-Bro-
moethyl)benzene (1.36 g, 7.33 mmol) in DMF (2.9 mL) was added
at room temperature during a 20 min period to a solution of tert-
butylamine (1.16 g, 11.00 mmol), sodium carbonate (0.77 g,
7.26 mmol), and sodium iodine (0.09 g) in freshly distilled dimeth-
ylformamide (DMF, 14.7 mL). The reaction mixture was heated to
65 °C, maintained at that temperature, with constant stirring, for
4 h, and then left overnight at room temperature. After addition of
water (15 mL), the reaction mixture was extracted three times with
CH2Cl2 (15 mL) and washed with brine. The combined organic
layers were then dried with anhydrous MgSO4, and the solvent was
removed under reduced pressure. The residue was distilled at 87 °C/
1 Torr, yielding the N-(tert-butyl)-N-(α-phenylethyl)amine (0.74 g,
57%) as a colourless liquid.
α-Bromoacetyl bromide (2.50 g, 12.40 mmol) was slowly added at
0 °C to a stirred solution of N-(tert-butyl)-N-(α-phenylethyl)amine
(2.00 g, 11.30 mmol) and anhydrous triethylamine (1.89 mL,
13.6 mmol) in anhydrous CH2Cl2 (25 mL). The mixture was briefly
stirred at 0 °C and then at room temperature for 1 h. The reaction
mixture was washed with HCl (5%, 20 mL) and the aqueous layer
was extracted with CH2Cl2. The combined organic layers were
washed with saturated NaHCO3 solution, followed by brine, and
then dried with Na2SO4. The solvent was removed under reduced
pressure and the residue was purified by flash chromatography
(SiO2, EtOAc/hexanes, 0.5:9.5), yielding the α-bromoacetamide
(2m, 2.62 g, 78%) as a viscous, yellow oil, Rf ϭ 0.35 (EtOAc/hex-
CCDC-208988 (4l) and CCDC-208987 (5l) contain the supplemen-
tary crystallographic data for this paper. These data can be ob-
tained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html
(or from the Cambridge Crystallographic Data Centre,12 Union
Road, Cambridge CB2 1EZ,UK; fax: (ϩ44)1223-336-033; or
E-mail: deposit@ccdc.cam.ac.uk).
Preparation of Starting Amines and α-Bromoacetamides 2
(R)-(؉)-α-Bromoacetyl-N-butyl-N-(α-phenylethyl)amide (2j): Butyr-
aldehyde (2.60 g, 36.00 mmol) was added to a solution of (R)-(ϩ)-
α-phenylethylamine (3.00 g, 25.00 mmol) in anhydrous CH2Cl2
anes, 1:4). IR (film): ν˜max ϭ 2975, 1649, 1192 cmϪ1 1H NMR
.
˚
(120 mL) with molecular sieves (4 A, 30.00 g). After 3 h 30 min
(400 MHz, CDCl3, 25 °C, TMS): δ ϭ 1.52 [s, 9 H, NC(CH3)3], 1.78
(d, J ϭ 8.0 Hz, 3 H, NCH(CH3)Ar], 3.56 (d, J ϭ 12.0 Hz, 2 H,
BrCH2CO), 5.10 (q, J ϭ 8.0 Hz, 1 H, NCH(CH3)Ar], 7.23Ϫ7.39
[m, 5 H, NCH(CH3)Ar] ppm. 13C NMR (100 MHz, CDCl3, 25 °C):
δ ϭ 20.72 [NCH(CH3)Ar], 29.09 [NC(CH3)3], 31.22 (BrCH2CO),
53.07 [NCH(CH3)Ar], 59.57 [NC(CH3)3], 125.68, 127.04, 129.00,
142.97 (q), 168.73 (CϭO) ppm.
stirring at room temperature, the mixture was filtered and concen-
trated under reduced pressure. Diethyl ether (90 mL) and LiAlH4
(1.90 g, 50.00 mmol) were added to the residue, and the mixture
was stirred overnight at room temperature. H2O (2 mL) was added
and the white solid formed was filtered and washed with diethyl
ether. The organic layers were concentrated under reduced pressure,
and the residue was distilled at 40 °C/0.02 Torr, yielding the (R)-
(ϩ)-N-butyl-N-(α-phenylethyl)amine (3.11 g, 70%) as a colourless
liquid.
α-Bromo-N-(tert-butyl)-N-(4-methoxy-3-oxobutyl)acetamide (2i): α-
Bromoacetyl bromide (2.82 g, 14.00 mmol) was slowly added at 0
°C to a stirred solution of methyl 3-(N-tert-butylamino)propano-
ate[14] (2.00 g, 12.60 mmol) and anhydrous triethylamine (2.1 mL,
15.0 mmol) in anhydrous CH2Cl2 (26 mL). The mixture was briefly
stirred at 0 °C and then at room temperature for 1 h. The reaction
mixture was washed with HCl (5%, 20 mL) and the aqueous layer
was extracted with CH2Cl2. The combined organic layers were
washed with saturated NaHCO3 solution, followed by brine, and
then dried with Na2SO4. The solvent was removed under reduced
pressure and the residue was purified by flash chromatography
(SiO2, EtOAc/hexanes, 3:7), yielding the α-bromoacetamide (2i,
0.82 g, 87%) as a viscous, yellow oil, Rf ϭ 0.50 (EtOAc/hexanes,
α-Bromoacetyl bromide (3.11 g, 15.40 mmol) was slowly added at 0
°C to a stirred solution of (R)-(ϩ)-N-butyl-N-(α-phenylethyl)amine
(2.50 g, 14.00 mmol) and anhydrous triethylamine (2.34 mL,
16.8 mmol) in anhydrous CH2Cl2 (28 mL). The mixture was briefly
stirred at 0 °C and then at room temperature for 1 h. The reaction
mixture was washed with 5% HCl (20 mL) and the aqueous layer
was extracted with CH2Cl2. The combined organic layers were
washed with saturated NaHCO3 solution, followed by brine, and
then dried with Na2SO4. The solvent was removed under reduced
pressure and the residue was purified by flash chromatography
(SiO2, EtOAc/hexanes, 0.5:9.5), yielding the α-bromoacetamide (2j,
2.42 g, 58%) as a viscous, yellow oil, Rf ϭ 0.20 (EtOAc/hexanes,
3:7). IR (film): ν˜max ϭ 2981, 1737, 1651, 1266 cmϪ1 1H NMR
.
(400 MHz, CDCl3, 25 °C, TMS): δ ϭ 1.37 [s, 9 H, NC(CH3)3],
2.56Ϫ2.60 (m, 2 H, NCH2CH2CO2CH3), 3.62Ϫ3.65 (m, 5 H,
0.5:9.5). IR (film): ν˜max ϭ 2961, 1639, 1447 cmϪ1 1H NMR
.
(400 MHz, CDCl3, 25 °C, TMS): δ ϭ 0.76Ϫ0.81 (m, 3 H,
NCH2CH2CH2CH3), 1.10Ϫ1.17 (overlapped signals, m,
NCH2CH2CH2CH3 and NCH2CH2CH2CH3), 1.36Ϫ1.49 (over-
lapped signals, m, NCH2CH2CH2CH3), 1.52, 1.67 [d, J ϭ 6.8 Hz,
NCH2CH2CO2CH3 and NCH2CH2CO2CH3), 3.84 (s,
3 H,
BrCH2CO) ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ ϭ 28.25
[NC(CH3)3], 29.57 (BrCH2CO), 36.17 (NCH2CH2CO2CH3), 41.41
(NCH2CH2CO2CH3),
51.75
(NCH2CH2CO2CH3),
57.71
1
H, rotamers 1:1.25, NCH(CH3)Ar], 2.87Ϫ3.25 (m,
2 H,
[NC(CH3)3], 167.15 (CONϪ), 170.94 (COOCH3) ppm.
NCH2CH2CH2CH3), 3.88Ϫ3.99 (m, 2 H, BrCH2CO), 5.12, 5.89
[q, J ϭ 6.8 Hz, 1 H, rotamers 1:1.25, NCH(CH3)Ar], 7.26Ϫ7.37 General Procedure for the Synthesis of α-(Diethoxyphosphoryl)acet-
[NCH(CH3)Ar] ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ ϭ ates 3bϪc:
mixture of ethyl (diethoxyphosphoryl)acetate
A
3802
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2003, 3798Ϫ3810

Regio- and Stereoselective Dirhodium(II)-Catalysed Intramolecular CϪH Insertion Reactions
FULL PAPER
(1.00 mmol), alcohol (12.00 mmol) and powdered molecular sieves
(4 A) in toluene (7 mL) was heated at reflux under argon. The
as a yellow oil, Rf ϭ 0.20 (EtOAc/hexanes, 7:3). IR (film): ν˜max
ϭ
1637, 1265, 1039 cmϪ1. 1H NMR (400 MHz, CDCl3, 25 °C, TMS):
δ ϭ 1.10 [d, J ϭ 7.0 Hz, 6 H, NCH(CH3)2], 1.25 (t, J ϭ 7.0 Hz, 6
˚
reaction mixture was stirred at this temperature until all transesteri-
fication was achieved (1Ϫ2 days, confirmed by 31P NMR). The H, OCH2CH3), 1.32 [d, J ϭ 6.6 Hz, 6 H, NCH(CH3)2], 2.97 (d,
mixture was filtered and concentrated under reduced pressure. The
residue was distilled, yielding the desired phosphonates.
JH-P ϭ 22.0 Hz, 2 H, POCH2CO), 3.39 [m, 2 H, NCH(CH3)2],
4.04Ϫ4.16 (m, J ϭ 7.0 Hz, 4 H, OCH2CH3) ppm. 13C NMR
(100 MHz, CDCl3, 25 °C): δ ϭ 16.20 (OCH2CH3), 20.25, 20.63
[NCH(CH3)2], 35.32 (d, JC,P ϭ 131.0, POCH2CO), 46.02, 50.25
[NCH(CH3)2], 62.26 (OCH2CH3), 163.17 (CϭO) ppm. 31P NMR
(160 MHz, CDCl3, 25 °C): δ ϭ 22.30 ppm. MS (EI): m/z ϭ 280,
179, 151, 100, 58. HMRS (EI): m/z calcd. [M]ϩ 279.159947, found
[M]ϩ 279.160152.
Propyl α-(Diethoxyphosphoryl)acetate (3b): This compound was
prepared by the General Procedure, with the use of ethyl (diethoxy-
phosphoryl)acetate (3.00 g, 13.40 mmol). The reaction mixture was
heated at reflux for 1 day and after distillation at 93 °C/0.01 Torr
the desired phosphate (3b, 2.63 g, 82%) was obtained as a colour-
less oil, Rf ϭ 0.27 (EtOAc/hexanes, 1:1). IR (film): ν˜max ϭ 1732,
1
1265, 1054 cmϪ1. H NMR (400 MHz, CDCl3, 25 °C, TMS): δ ϭ
α-(Diethoxyphosphoryl)-N,N-diethylacetamide (3e):[15] This com-
pound was prepared by Method A with the use of ethyl (diethoxy-
phosphoryl)acetate (2.0 g, 8.9 mmol). The reaction mixture was
heated at reflux for 5 days and after distillation at 110Ϫ115 °C/
0.4 Torr the desired phosphonate (3e, 1.22 g, 56%) was obtained as
0.84Ϫ0.86 (m, J ϭ 7.2 Hz, 3 H, OCH2CH2CH3), 1.35 (t, J ϭ 6.4
Hz, 6 H, OCH2CH3), 1.66Ϫ1.71 (m, 2 H, OCH2CH2CH3), 2.97 (d,
JH-P ϭ 21.6 Hz, 2 H, POCH2CO), 4.10Ϫ4.20 (overlapped signals, 6
H, m, OCH2CH2CH3 and OCH2CH3) ppm. 13C NMR (100 MHz,
CDCl3, 25 °C): δ ϭ 10.04 (OCH2CH2CH3), 16.06 (OCH2CH3),
21.64 (OCH2CH2CH3), 33.09 (d, JC,P ϭ 134.0, POCH2CO), 62.39
(OCH2CH3), 66.88 (OCH2CH2CH3), 165.63 (CϭO) ppm. 31P
NMR (160 MHz, CDCl3, 25 °C): δ ϭ 20.31 ppm. MS (EI): m/z ϭ
239, 211, 19, 179, 123. HMRS (EI): m/z calcd. [M]ϩ 238.097012,
found [M]ϩ 238.097167.
a yellow oil, Rf ϭ 0.19 (EtOAc/hexanes, 3:2). IR (film): ν˜max
ϭ
1639, 1265, 1053 cmϪ1. 1H NMR (400 MHz, CDCl3, 25 °C, TMS):
δ ϭ 1.05 (t, J ϭ 7.0 Hz, 3 H, NCH2CH3), 1.12 (t, J ϭ 7.1 Hz, 3
H, NCH2CH3), 1.25 (t, J ϭ 6.9 Hz, 6 H, OCH2CH3), 2.94 (d, JH-
ϭ 20.0 Hz, 2 H, POCH2CO), 3.28Ϫ3.38 (m, 4 H, NCH2CH3),
P
4.02Ϫ4.12 (m, 4 H, OCH2CH3) ppm. 13C NMR (100 MHz, CDCl3,
25 °C):
(OCH2CH3), 33.16 (d, JC,P
δ
ϭ
12.69 (NCH2CH3), 13.98 (NCH2CH3), 16.17
134.0, POCH2CO), 40.30
Isobutyl α-(Diethoxyphosphoryl)acetate (3c): This compound was
prepared by the General Procedure with use of ethyl (diethoxypho-
sphoryl)acetate (5.00 g, 22.30 mmol). The reaction mixture was
heated at reflux for 2 days and after distillation at 85 °C/0.01 Torr,
the desired phosphonate (3c, 2.90 g, 52%) was obtained as a colour-
less oil, Rf ϭ 0.48 (EtOAc/hexanes, 4:1). IR (film): ν˜max ϭ 1731,
ϭ
(NCH2CH3), 42.83 (NCH2CH3), 62.34 (OCH2CH3), 163.77 (Cϭ
O) ppm. 31P NMR (160 MHz, CDCl3, 25 °C): δ ϭ 22.15 ppm.
N,N-Dibutyl-α-(diethoxyphosphoryl)acetamide (3f):[6] This com-
pound was prepared by Method A with the use of ethyl (diethoxy-
phosphoryl)acetate (2.0 g, 8.9 mmol). The reaction mixture was
heated at reflux for 1 day and after distillation at 160 °C/0.3 Torr
the desired phosphonate (3f, 1.78 g, 66%) was obtained as a yellow
oil, Rf ϭ 0.28 (EtOAc/hexanes, 3:2). IR (film): ν˜max ϭ 1642, 1255,
1
1272, 1025 cmϪ1. H NMR (400 MHz, CDCl3, 25 °C, TMS): δ ϭ
0.95 [d, J ϭ 6.4 Hz, 6 H, OCH2CH(CH3)2], 1.35 (t, J ϭ 7.2 Hz, 6
H, OCH2CH3), 1.91Ϫ2.00 [m,
J ϭ 6.8 Hz, 6.4 Hz, 1 H,
OCH2CH(CH3)2], 2.98 (d, JH-P ϭ 21.6 Hz, 2 H, POCH2CO), 3.93
[d, J ϭ 6.8 Hz, 2 H, OCH2CH(CH3)2], 4.14Ϫ4.21 (m, J ϭ 7.2 Hz,
4 H, OCH2CH3) ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ ϭ
1027 cmϪ1 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ ϭ
.
0.83Ϫ0.90 (m, J ϭ 7.1 Hz, 6 H, NCH2CH2CH2CH3), 1.20Ϫ1.29
(overlapped signals, 10 H, m, NCH2CH2CH2CH3 and OCH2CH3),
1.42Ϫ1.52 (m, 4 H, NCH2CH2CH2CH3), 2.95 (d, JH-P ϭ 22.1 Hz,
2 H, POCH2CO), 3.24Ϫ3.29 (m, 4 H, NCH2CH2CH2CH3),
4.07Ϫ4.16 (m, J ϭ 7.0 Hz, 4 H, OCH2CH3) ppm. 13C NMR
(100 MHz, CDCl3, 25 °C): δ ϭ 13.93 (NCH2CH2CH2CH3), 16.16
16.16
(OCH2CH3),
18.83
[OCH2CH(CH3)2],
27.53
[OCH2CH(CH3)2], 34.17 (d, JC,P ϭ 134.0, POCH2CO), 62.46
(OCH2CH3), 71.47 [OCH2CH(CH3)2], 165.74 (CϭO) ppm. 31P
NMR (160 MHz, CDCl3, 25 °C): δ ϭ 20.44 ppm. MS (EI): m/z ϭ
253, 197, 179, 151, 123, 57. HMRS (EI): m/z calcd. [M ϩ H]ϩ
253.120487, found [M ϩ H]ϩ 253.120246.
(OCH2CH3),
19.94
(NCH2CH2CH2CH3),
29.56,
30.95
(NCH2CH2CH2CH3), 33.21 (d, JC,P ϭ 133.0, POCH2CO), 45.83,
48.50 (NCH2CH2CH2CH3), 62.34 (OCH2CH3), 164.16 (CϭO)
ppm. 31P NMR (160 MHz, CDCl3, 25 °C): δ ϭ 22.21 ppm. MS
(EI): m/z ϭ 179, 151, 128, 86, 58. HMRS (EI): m/z calcd. [M]ϩ
307.1911247, found [M]ϩ 307.192572.
General Procedure for the Synthesis of α-(Diethoxyphosphoryl)acet-
amides 3d؊m. Method A: A mixture of ethyl (diethoxyphosphoryl)-
acetate (1.00 mmol), amine (12.00 mmol) and powdered molecular
˚
sieves (4 A) in xylene (7 mL) was heated at reflux under argon. The
reaction mixture was stirred at this temperature until total conden-
sation was achieved (confirmed by 31P NMR). The mixture was
filtered and concentrated under reduced pressure. The residue was
distilled or chromatographed, yielding the desired phosphonates.
N-(tert-Butyl)-α-(diethoxyphosphoryl)-N-(phenylethyl)acetamide
(3g): This compound was prepared by Method B with the use of
α-bromoacetyl-N-(tert-butyl)-N-(phenylethyl)amide[3c,10]
(2.50 g,
8.42 mmol). The reaction mixture was heated at reflux for 4 h, and
after flash chromatography (SiO2, EtOAc/hexanes, 7:3) the desired
phosphonate (3g, 2.41 g, 81%) was obtained as a brown oil, Rf ϭ
0.33 (EtOAc/hexanes, 7:3). IR (film): ν˜max ϭ 1642, 1249, 1029
Method B: Triethyl phosphite (6.00 mmol) was added under argon
atmosphere to a stirring solution of the appropriate α-bromoaceta-
mide (5.00 mmol) in anhydrous dichloroethane (2 mL). The mix-
ture was heated at reflux until all α-bromoacetamide had been con-
sumed. The volatile compounds were then evaporated. The residue
was purified by distillation under reduced pressure or by flash chro-
matography.
1
cmϪ1. H NMR (400 MHz, CDCl3, 25 °C, TMS): δ ϭ 1.24Ϫ1.27
(m, 6 H, OCH2CH3), 1.46 [s, 9 H, NC(CH3)3], 2.78Ϫ2.79 (m, 2 H,
NCH2CH2Ar), 2.91 (d, JH-P
ϭ
21.9 Hz,
2
H, POCH2CO),
H,
3.57Ϫ3.59 (m, H, NCH2CH2Ar), 4.06Ϫ4.13 (m,
2
4
α-(Diethoxyphosphoryl)-N,N-(diisopropyl)acetamide[6] (3d): This OCH2CH3), 7.12Ϫ7.26 (m, 5 H, NCH2CH2Ar) ppm. 13C NMR
compound was prepared by Method A with the use of ethyl (di-
ethoxyphosphoryl)acetate (2.0 g, 8.9 mmol). The reaction mixture [NC(CH3)3], 35.08 (d, JC,P
(100 MHz, CDCl3, 25 °C):
δ
ϭ
16.17 (OCH2CH3), 28.76
131.0, POCH2CO), 37.95
ϭ
was heated at reflux for 2 days and after distillation at 93 °C/
0.03 Torr the desired phosphonate (3d, 1.73 g, 70%) was obtained
(NCH2CH2Ar), 47.47 (NCH2CH2Ar), 57.73 [NC(CH3)3], 62.26
(OCH2CH3), 126.59, 128.28, 128.63, 137.91 (q), 165.30 (CϭO)
Eur. J. Org. Chem. 2003, 3798Ϫ3810
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3803

P. M. P. Gois, C. A. M. Afonso
FULL PAPER
ppm. 31P NMR (160 MHz, CDCl3, 25 °C): δ ϭ 22.23 ppm. MS 3 H, m, NCH2CH2CH2CH3 and NCH2CH2CH2CH3), 1.28Ϫ1.41
(EI): m/z ϭ 264, 208, 151, 179, 91. HMRS (EI): m/z calcd. [M]ϩ
(overlapped signals, 7 H, m, NCH2CH2CH2CH3 and OCH2CH3),
1.51, 1.64 (d, J ϭ 7.1 Hz, 3 H, rotamers 1:1.45, NCH(CH3)Ar],
2.84Ϫ3.32 (m, JH-P ϭ 22.1, overlapped signals, 4 H, POCH2CO
and NCH2CH2CH2CH3), 4.09Ϫ4.22 (m, J ϭ 7.2 Hz, 4 H,
OCH2CH3), 5.27, 5.94 [q, J ϭ 7.0 Hz, 1 H, rotamers 1:1.45,
NCH(CH3)Ar] ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ ϭ
13.47, 13.60 (NCH2CH2CH2CH3), 16.26 (OCH2CH3), 16.83,
18.57, [NCH(CH3)Ar], 20.17, 20.37 (NCH2CH2CH2CH3), 30.77
(NCH2CH2CH2CH3), 33.57, 34.03 (d, JC,P ϭ 139 and JC,P ϭ 132.0,
POCH2CO), 43.50, 44.31 (NCH2CH2CH2CH3), 51.50, 56.30
[NCH(CH3)Ar], 62.34 (OCH2CH3), 126.75, 127.30, 127.48, 128.28,
128.55, 141.67 (q), 165.04 (CϭO) ppm. 31P NMR (160 MHz,
CDCl3, 25 °C): δ ϭ 21.96, 22.22 ppm. MS (EI): m/z ϭ 355, 179,
176, 151, 120. HMRS (EI): m/z calcd. [M]ϩ 355.191247, found
[M]ϩ 355.191732.
355.191247, found [M]ϩ 355.190927.
α-(Diethoxyphosphoryl)-N,N-bis(2-methoxyethyl)acetamide (3h): α-
Bromoacetyl bromide (4.00 g, 19.80 mmol) was slowly added at 0
°C to a stirred solution of bis(2-methoxyethyl)amine (2.40 g,
18.00 mmol) and anhydrous triethylamine (3.0 mL, 21.6 mmol) in
anhydrous CH2Cl2 (40 mL). The mixture was briefly stirred at 0 °C
and then at room temperature for 1 h. The reaction mixture was
washed with 5% HCl (35 mL) and the aqueous layer was extracted
with CH2Cl2. The combined organic layers were washed with satu-
rated NaHCO3 solution, followed by brine, and then dried with
Na2SO4. The solvent was removed under reduced pressure and the
residue was distilled at 116 °C/0.3 Torr, yielding the α-bromoaceta-
mide (2h, 5.01 g, 98%) as a viscous oil. The α-(diethoxyphospho-
ryl)-N,N-bis(2-methoxyethyl)acetamide (3h) was prepared by
Method B, by use of α-bromoacetyl-N,N-bis(2-methoxyethyl)amide
(2h, 2.54 g, 10.00 mmol). The reaction mixture was heated at reflux
for 3 h, and after distillation at 165 °C/0.3 Torr the desired phos-
phonate (3h, 2.75 g, 88%) was obtained as a colourless oil, Rf ϭ
0.62 (EtOAc/hexanes, 9:1). IR (film): ν˜max ϭ 1639, 1246, 1029
cmϪ1. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ ϭ 1.28 (t, J ϭ
N,N-Dibenzyl-α-(diethoxyphosphoryl)acetamide (3k): α-Bromoace-
tyl bromide (2.24 g, 11.15 mmol) was slowly added at 0 °C to a
stirred solution of dibenzylamine (2.00 g, 10.14 mmol) and triethyl-
amine (1.69 mL, 12.17 mmol) in anhydrous CH2Cl2 (22 mL). The
mixture was briefly stirred at 0 °C and then at room temperature
for 1 h. The reaction mixture was washed with 5% HCl (16 mL)
and the aqueous layer was extracted with CH2Cl2. The combined
organic layers were washed with saturated NaHCO3 solution, fol-
lowed by brine, and then dried with Na2SO4. The solvent was re-
moved under reduced pressure and the residue was purified by flash
chromatography (SiO2, EtOAc/hexanes, 3:7), yielding the N,N-di-
benzyl-α-bromoacetylamide (2k, 2.80 g, 87%) as a viscous, yellow
oil. The N,N-dibenzyl-α-(diethoxyphosphoryl)acetamide (3k) was
prepared by Method B with the use of α-bromoacetamide (2k,
2.50 g, 7.88 mmol). The reaction mixture was heated at reflux for
6 h. After flash chromatography (SiO2, EtOAc/hexanes, 7:3) the de-
sired phosphonate (2.4 g, 81%) was obtained as a yellow oil, Rf ϭ
0.60 (EtOAc/hexanes, 7:3). IR (film): ν˜max ϭ 1737, 1265, 1027
cmϪ1. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ ϭ 1.32 (t, J ϭ
7.1 Hz, 6 H, OCH2CH3), 3.15 (d, JH-P
ϭ 21.8 Hz, 2 H,
POCH2CO), 3.26 (s, 6 H, NCH2CH2OCH3), 3.26Ϫ3.51 (over-
lapped signals, 6 H, m, NCH2CH2OCH3 and NCH2CH2OCH3),
3.65 (t, 2 H, NCH2CH2OCH3), 4.07Ϫ4.15 (m, J ϭ 7.2 Hz, 4 H,
OCH2CH3) ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ ϭ 16.17
(OCH2CH3), 33.40 (d, JC,P ϭ 133.0, POCH2CO), 46.57, 49.75
(NCH2CH2OCH3), 58.66, 58.93 (NCH2CH2OCH3), 62.29
(OCH2CH3), 70.57, 70.82 (NCH2CH2OCH3), 165.57 (CϭO) ppm.
31P NMR (160 MHz, CDCl3, 25 °C): δ ϭ 22.49 ppm. MS (EI):
m/z ϭ 266, 179, 120, 88. HMRS (EI): m/z calcd. [M ϩ H]ϩ
312.157601, found [M ϩ H]ϩ 312.158798.
N-(tert-Butyl)-α-(diethoxyphosphoryl)-N-[2-(methoxycarbonyl)-
ethyl]acetamide (3i): This compound was prepared by Method B
with the use of methyl 3-(bromoacetyl-tert-butylamino)propionate
(2i, 1.66 g, 5.93 mmol). The reaction mixture was heated at reflux
for 4 h, and after flash chromatography (SiO2, EtOAc/hexanes, 3:7)
the desired phosphonate (3i, 1.85 g, 92%) was obtained as a brown
oil, Rf ϭ 0.24 (EtOAc/hexanes, 3:7). IR (film): ν˜max ϭ 1736, 1648,
7.1 Hz, 6 H, OCH2CH3), 3.13 (d, JH-P
ϭ 22.1 Hz, 2 H,
POCH2CO), 4.14Ϫ4.22 (m, J ϭ 7.2 Hz, 4 H, OCH2CH3), 4.64 (s, 4
H, NCH2Ar), 7.16Ϫ7.39 (m, 10 H, Ar) ppm. 13C NMR (100 MHz,
CDCl3, 25 °C): δ ϭ 16.26 (OCH2CH3), 33.61 (d, JC,P ϭ 132.0,
POCH2CO), 48.58, 50.88 (NCH2Ar), 62.60 (OCH2CH3), 126.25;
127.31; 127.63; 127.83; 128.50; 128.93; 136.06 (q); 136.70 (q);
165.65 (CϭO) ppm. 31P NMR (160 MHz, CDCl3, 25 °C): δ ϭ
21.70 ppm. MS (FABϩ): m/z ϭ 376, 196, 179, 151, 106. HMRS
(FABϩ): m/z calcd. [M ϩ H]ϩ 376.167772, found 376.166961.
1
1285, 1030 cmϪ1. H NMR (400 MHz, CDCl3, 25 °C, TMS): δ ϭ
1.34 (t, J ϭ 7.1 Hz, 6 H, OCH2CH3), 1.45 [s, 9 H, NC(CH3)3],
2.60Ϫ2.64 (m, J ϭ 7.8 Hz, 2 H, NCH2CH2CO2CH3), 3.09 (d, JH-
ϭ 22.2 Hz, 2 H, POCH2CO), 3.70 (s, 3 H, NCH2CH2CO2CH3),
P
3.72Ϫ3.78 (m, 2 H, NCH2CH2CO2CH3), 4.13Ϫ4.22 (m, J ϭ 7.1
N-Benzyl-N-(tert-butyl)-α-(diethoxyphosphoryl)acetamide (3l): α-
Bromoacetyl bromide (4.06 g, 20.21 mmol) was slowly added at 0
°C to a stirred solution of N-benzyl-N-tert-butylamine (3.00 g,
18.37 mmol) and anhydrous triethylamine (3.07 mL, 22.04 mmol)
in anhydrous CH2Cl2 (40 mL). The mixture was briefly stirred at 0
°C and then at room temperature for 1 h. The reaction mixture was
washed with 5% HCl (35 mL), and the aqueous layer was extracted
with CH2Cl2. The combined organic layers were washed with satu-
rated NaHCO3 solution, followed by brine, and then dried with
Na2SO4. The solvent was removed under reduced pressure and the
residue was purified by flash chromatography (SiO2, EtOAc/hex-
anes, 3:7), yielding the N-benzyl-α-bromoacetyl-N-(tert-butyl)-
amide (2l, 5.01 g, 98%) as a viscous, yellow oil. The N-benzyl-N-
(tert-butyl)-α-(diethoxyphosphoryl)acetamide (3l) was prepared by
Method B, with use of α-bromoacetamide (2l, 3.94 g, 13.91 mmol).
The reaction mixture was heated at reflux for 4 h, and after distil-
Hz, 4 H, OCH2CH3) ppm. 13C NMR (100 MHz, CDCl3, 25 °C):
δ ϭ 16.23 (OCH2CH3), 28.77 [NC(CH3)3], 35.91 (d, JC,P
ϭ
133.0,
(NCH2CH2CO2CH3),
POCH2CO),
36.17
51.83
(NCH2CH2CO2CH3),
(NCH2CH2CO2CH3),
41.76
57.90
[NC(CH3)3], 62.45 (OCH2CH3), 165.50 [CON(CH3)3CH2), 171.13
(COOCH3) ppm. 31P NMR (160 MHz, CDCl3, 25 °C): δ ϭ 22.31
ppm. MS (EI): m/z ϭ 338, 306, 179, 158, 151. HMRS (EI): m/z
calcd. [M]ϩ 337. 165426, found [M]ϩ 337.164989.
(R)-(؉)-N-Butyl-α-(diethoxyphosphoryl)-N-(α-phenylethyl)acet-
amide (3j): This compound was prepared by Method B with the
use of (R)-(ϩ)-α-bromoacetyl-N-butyl-N-(α-phenylethyl)amide (2j,
2.42 g, 8.10 mmol). The reaction mixture was heated at reflux for
4 h, and after distillation at 180 °C /0.02 Torr the desired phos-
phonate (3j, 2.18 g, 77%) was obtained as a viscous, yellow oil,
Rf ϭ 0.15 (EtOAc/hexanes, 1:4). IR (film): ν˜max ϭ 1638, 1265, 1028
cmϪ1. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ ϭ 0.77 (t, J ϭ lation at 160 °C/0.03 Torr the desired phosphonate (3l, 3.44 g, 73%)
7.0 Hz, 3 H, NCH2CH2CH2CH3), 1.08Ϫ1.19 (overlapped signals, was obtained as a viscous, yellow oil, Rf ϭ 0.26 (EtOAc/hexanes,
3804
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2003, 3798Ϫ3810

Regio- and Stereoselective Dirhodium(II)-Catalysed Intramolecular CϪH Insertion Reactions
FULL PAPER
3:2). IR (film): ν˜max ϭ 1650, 1247, 1054 cmϪ1. 1H NMR (400 MHz, 10.62 ppm. MS (EI): m/z ϭ 264, 205, 151, 121, 109. HMRS (EI):
CDCl3, 25 °C, TMS): δ ϭ 1.31 (t, J ϭ 8.0 Hz, 6 H, OCH2CH3), m/z calcd. [M]ϩ 264.087510, found [M]ϩ 264.088161.
1.45 (9 H,s, NC(CH3)3], 2.96 (d, JH-P ϭ 20.0 Hz, 2 H, POCH2CO),
Isobutyl α-Diazo-α-(diethoxyphosphoryl)acetate (4c): A solution of
4.11Ϫ4.19 (m, J ϭ 8.0 Hz, 4 H, OCH2CH3), 4.79 (s, 2 H,
isobutyl α-(diethoxyphosphoryl)acetate (3c, 1.57 g, 5.53 mmol) in
THF was added at 0 °C to a mixture of sodium hydride and p-
toluenesulfonyl azide in THF. The mixture was stirred for 1 h at
this temperature and then allowed to reach room temperature over
3 h. Water and Et2O were added, and the aqueous layer was ex-
tracted with Et2O. After workup, the residue was chromatographed
(EtOAc/hexanes, 3:7), yielding the desired diazophosphonate (4c,
2.26 g, 77%) as a yellow oil, Rf ϭ 0.27 (EtOAc/hexanes, 3:7). IR
NCH2Ar), 7.21Ϫ7.38 (m,
5
H, NCH2Ar) ppm. 13C NMR
(100 MHz, CDCl3, 25 °C): δ ϭ 16.33, 16.39 (OCH2CH3), 28.57
[NC(CH3)3], 36.41 (d, JC,P ϭ 132.0, POCH2CO), 49.25 (NCH2Ar),
58.36 [NC(CH3)3], 62.46 (OCH2CH3), 125.30, 126.90, 128.66,
138.67 (q), 166.05 (CϭO) ppm. 31P NMR (160 MHz, CDCl3, 25
°C): δ ϭ 22.20 ppm. MS (EI): m/z ϭ 284, 179, 151, 148, 106.
HMRS (EI): m/z calcd. [M]ϩ 341.175597, found [M]ϩ 341.176400.
1
(film): ν˜max ϭ 2130, 1703, 1.280, 1021 cmϪ1. H NMR (400 MHz,
N-(tert-Butyl)-α-(diethoxyphosphoryl)-N-(α-phenylethyl)acetamide
(3m): This compound was prepared by Method B, with the use of
α-bromoacetyl-N-(tert-butyl)-N-(α-phenylethyl)amide (2m, 1.22 g,
4.11 mmol). The reaction mixture was heated at reflux for 8 h, and
after flash chromatography (SiO2, EtOAc/hexanes, 2:3), the desired
phosphonate 3m (1.09 g, 76%) was obtained as a viscous, yellow
oil, Rf ϭ 0.12 (EtOAc/hexanes, 2:3). IR (film): ν˜max ϭ 1640, 1247,
CDCl3, 25 °C, TMS):
δ ϭ 0.95 [d, J ϭ 6.4 Hz, 6 H,
OCH2CH(CH3)2], 1.36 (t, J ϭ 6.8 Hz, 6 H, OCH2CH3), 1.93Ϫ2.04
[m, J ϭ 6.8 Hz, 1 H 6.4, OCH2CH(CH3)2], 3.99 [d, J ϭ 6.8 Hz, 2
H, OCH2CH(CH3)2], 4.13Ϫ4.26 (m, J ϭ 6.8 Hz, 6 H, OCH2CH3)
ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ ϭ 16.01 (OCH2CH3),
18.81 [OCH2CH(CH3)2], 27.75 [OCH2CH(CH3)2], 63.56
(OCH2CH3), 71.56 [OCH2CH(CH3)2], 163.03 (CϭO) ppm. 31P
NMR (160 MHz, CDCl3, 25 °C): δ ϭ 10.89 ppm. MS (EI): m/z ϭ
279, 223, 205, 138, 57. HMRS (EI): m/z calcd. [M]ϩ 278.103160,
found [M]ϩ 278.104255.
1030 cmϪ1 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ ϭ 1.27
.
(q, J ϭ 7.1 Hz, 6 H, OCH2CH3), 1.54 [s, 9 H, NC(CH3)3], 1.81 (d,
J ϭ 7.1 Hz, 3 H, NCH(CH3)Ar], 4.03Ϫ4.12 (m, J ϭ 7.1 Hz, 4 H,
OCH2CH3), 5.13Ϫ5.15 [m, 1 H, NCH(CH3)Ar], 7.24Ϫ7.39 (m, 5
H, NCH2Ar) ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ ϭ 16.31
(OCH2CH3), 20.86 [NCH(CH3)Ar], 29.35 [NC(CH3)3], 53.05
[NCH(CH3)Ar], 59.45 [NC(CH3)3], 63.15 (OCH2CH3), 125.57,
126.75, 128.83, 143.23 (q), 167.31 (CϭO) ppm. 31P NMR
(160 MHz, CDCl3, 25 °C): δ ϭ 14.24 ppm. HMRS (EI): m/z ϭ
298, 236, 179, 151, 120; calcd. [M]ϩ 355.191247, found [M]ϩ
355.191898.
α-Diazo-α-(diethoxyphosphoryl)-N,N-(diisopropyl)acetamide (4d):[6]
A solution of α-(diethoxyphosphoryl)-N,N-(diisopropyl)acetamide
(3d, 1.57 g, 5.63 mmol) in THF was added at 0 °C to a mixture of
sodium hydride and p-toluenesulfonyl azide in THF. The mixture
was stirred for 1 h at this temperature and then allowed to reach
room temperature overnight. Water and Et2O were added, and the
aqueous layer was extracted with Et2O. After workup, the residue
was chromatographed (EtOAc/hexanes, 2:3), yielding the desired
diazophosphonate 4d (1.70 g, 97%) as a yellow oil, Rf ϭ 0.56
(EtOAc/hexanes, 7:3). IR (film): ν˜max ϭ 2095, 1625, 1265, 1022
cmϪ1. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ ϭ 1.27 [d, J ϭ
6.6 Hz, 6 H, NCH(CH3)2], 1.32 (t, J ϭ 7.0 Hz, 6 H, OCH2CH3),
3.73 [m, 2 H, NCH(CH3)2], 4.10Ϫ4.23 (m, 4 H, OCH2CH3) ppm.
13C NMR (100 MHz, CDCl3, 25 °C): δ ϭ 16.06 (OCH2CH3), 20.72
[NCH(CH3)2], 48.68 [NCH(CH3)2], 62.22 (OCH2CH3), 160.48 (Cϭ
O) ppm. 31P NMR (160 MHz, CDCl3, 25 °C): δ ϭ 14.70 ppm. MS
(EI): m/z ϭ 277, 179, 151, 100, 84. HMRS (EI): m/z calcd. [M Ϫ
N2]ϩ 277.144297, found [M Ϫ N2]ϩ 277.144614.
General Procedure for the Synthesis of Diazo Phosphates 4: A solu-
tion of the appropriate phosphonate 3 (1.00 mmol) in THF
(1.5 mL) was slowly added at 0 °C to a magnetically stirred mixture
of sodium hydride (1.2 equiv.) and p-toluenesulfonyl azide (1.2
equiv.) in THF (6.5 mL). The mixture was stirred at this tempera-
ture for 1 h and then allowed to reach room temperature. After
reaction of all phosphonate (confirmed by TLC), water (5.5 mL)
and Et2O (5.5 mL) were added to the reaction mixture. The aque-
ous layer was extracted with Et2O (4 ϫ 5.5 mL). The combined
ethereal extracts were dried with Na2SO4 and the solvent was eva-
porated. The residue was chromatographed (SiO2, EtOAc/hexanes)
to yield the diazo compound (4) as a yellow oil. The N-(tert-butyl)-
α-diazo-α-(diethoxyphosphoryl)-N-[3-(methylpropionate)]acet-
amide (4i) and the N-(tert-butyl)-α-diazo-α-(diethoxyphosphoryl)-
N-(phenylethyl)acetamide (4g) were prepared with the use of 1,8-
diazabicyclo[5.4.0]undec-7-ene (DBU) instead of sodium hydride.
α-Diazo-α-(diethoxyphosphoryl)-N,N-diethylacetamide (4e): A solu-
tion of α-(diethoxyphosphoryl)-N,N-diethylacetamide (3e, 1.14 g,
4.53 mmol) in THF was added at 0 °C to a mixture of sodium
hydride and p-toluenesulfonyl azide in THF. The mixture was
stirred at this temperature for 1 h and then allowed to reach room
temperature overnight. Water and Et2O were added, and the aque-
ous layer was extracted with Et2O. After workup, the residue was
chromatographed (EtOAc/hexanes, 2:3), yielding the desired diazo-
phosphonate (4e, 0.96 g, 56%) as a yellow oil, Rf ϭ 0.41 (EtOAc/
Propyl α-Diazo-α-(diethoxyphosphoryl)acetate (4b): A solution of
propyl α-(diethoxyphosphoryl)acetate (3b, 2.44 g, 5.53 mmol) in
THF was added at 0 °C to a mixture of sodium hydride and p-
toluenesulfonyl azide in THF. The mixture was stirred at this tem-
perature for 10 min. Water and Et2O were added, and the aqueous
layer was extracted with Et2O. After workup, the residue was chro-
matographed (EtOAc/hexanes, 1:1), yielding the desired diazophos-
phonate (4b, 2.19 g, 81%) as a yellow oil, Rf ϭ 0.45 (EtOAc/hex-
anes, 1:1). IR (film): ν˜max ϭ 2131, 1707, 1282, 1022 cmϪ1. 1H NMR
(400 MHz, CDCl3, 25 °C, TMS): δ ϭ 0.88 (t, J ϭ 7.2 Hz, 3 H,
OCH2CH2CH3), 1.28 (t, J ϭ 7.2 Hz, 6 H, OCH2CH3), 1.57Ϫ1.66
(m, 2 H, OCH2CH2CH3), 4.03Ϫ4.19 (overlapped signals, 6 H, m,
OCH2CH2CH3 and OCH2CH3) ppm. 13C NMR (100 MHz,
CDCl3, 25 °C): δ ϭ 10.02 (OCH2CH2CH3), 15.93 (OCH2CH3),
1
hexanes, 2:3). IR (film): ν˜max ϭ 2098, 1615, 1277, 1023 cmϪ1. H
NMR (400 MHz, CDCl3, 25 °C, TMS): δ ϭ 1.14 (t, J ϭ 7.0 Hz, 6
H, NCH2CH3), 1.32 (t, J ϭ 7.0 Hz, 6 H, OCH2CH3), 3.36 (q, J ϭ
7.0 Hz, 4 H, NCH2CH3), 4.13Ϫ4.22 (m, J ϭ 7.1 Hz, 4 H,
OCH2CH3) ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ ϭ 13.12
(NCH2CH3), 16.02 (OCH2CH3), 41.72 (NCH2CH3), 63.42
(OCH2CH3), 161.65 (CϭO) ppm. 31P NMR (160 MHz, CDCl3, 25
°C): δ ϭ 13.94 ppm. MS (EI): m/z ϭ 249, 179, 151, 123, 72. HMRS
(EI): m/z calcd. [M Ϫ N2]ϩ 249.112997, found [M Ϫ N2]ϩ
249.112027.
21.88 (OCH2CH2CH3), 63.45 (OCH2CH3), 67.01 (OCH2CH2CH3), N,N-Dibutyl-α-diazo-α-(diethoxyphosphoryl)acetamide (4f):[6]
163.39 (CϭO) ppm. 31P NMR (160 MHz, CDCl3, 25 °C): δ ϭ solution of N,N-di(butyl)-α-diazo-α-(diethoxyphosphoryl)acetam-
A
Eur. J. Org. Chem. 2003, 3798Ϫ3810
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3805

P. M. P. Gois, C. A. M. Afonso
ide (3f, 1.70 g, 5.53 mmol) in THF was added at 0 °C to a mixture N-(tert-Butyl)-α-diazo-α-(diethoxyphosphoryl)-N-[2-(methoxy-
FULL PAPER
of sodium hydride and p-toluenesulfonyl azide in THF. The mix-
carbonyl)ethyl]acetamide (4i): 1,8-Diazabicyclo[5.4.0]undec-7-ene
ture was stirred for 1 h at this temperature and then allowed to
(DBU, 0.81 g, 5.33 mmol) was slowly added at room temperature
reach room temperature overnight. Water and Et2O were added, to a solution of N-(tert-butyl)-α-(diethoxyphosphoryl)-N-[2-(meth-
and the aqueous layer was extracted with Et2O. After workup, the
residue was chromatographed (EtOAc/hexanes, 1:1), yielding the
desired diazophosphonate (4f, 1.52 g, 83%) as a yellow oil, Rf ϭ
0.62 (EtOAc/hexanes, 3:2). IR (film): ν˜max ϭ 2097, 1620, 1255, 1022
oxycarbonyl)ethyl]acetamide (3i, 1.64 g, 4.85 mmol) and p-tolu-
enesulfonyl azide in THF (22 mL). The mixture was stirred at this
temperature for 24 h. The reaction mixture was concentrated, water
(20 mL) and Et2O (20 mL) were added, and the aqueous layer was
cmϪ1. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ ϭ 0.86 (t, J ϭ extracted with Et2O. The organic layers were washed with brine
7.3 Hz, 6 H, NCH2CH2CH2CH3), 1.20Ϫ1.31 (overlapped signals,
10 H, m, NCH2CH2CH2CH3 and OCH2CH3), 1.44Ϫ1.52 (m, ure. The residue was chromatographed on SiO2 (EtOAc/hexanes,
H, NCH2CH2CH2CH3), 3.25 (t, 7.6 Hz, H, 1:1), yielding the desired diazophosphonate (4i, 1.01 g, 58%) as a
NCH2CH2CH2CH3), 4.09Ϫ4.16 (m, J ϭ 7.2 Hz, 4 H, OCH2CH3) yellow oil, Rf ϭ 0.24 (EtOAc/hexanes, 3:7). IR (film): ν˜max ϭ 2119,
(50 mL), dried with Na2SO4 and concentrated under reduced press-
4
J
ϭ
4
1
ppm. 13C NMR (100 MHz, CDCl3, 25 °C):
δ
ϭ
13.70 1732, 1633, 1257, 1022 cmϪ1. H NMR (400 MHz, CDCl3, 25 °C,
20.00 TMS) 1.36 (t, J ϭ 7.0 Hz, 6 H, OCH2CH3), 1.42 [s, 9 H,
47.36 NC(CH3)3], 2.65 (t, J ϭ 7.5 Hz, 2 H, NCH2CH2CO2CH3), 3.69 (s,
H, NCH2CH2CO2CH3), 3.78 (t, 7.5 Hz, H,
(NCH2CH2CH2CH3),
(NCH2CH2CH2CH3),
16.07
30.00
(OCH2CH3),
(NCH2CH2CH2CH3),
(NCH2CH2CH2CH3), 63.46 (OCH2CH3), 161.81 (CϭO) ppm. 31P
3
J
ϭ
2
NMR (160 MHz, CDCl3, 25 °C): δ ϭ 14.23 ppm. MS (EI): m/z ϭ NCH2CH2CO2CH3), 4.13Ϫ4.24 (m, J ϭ 7.1 Hz, 4 H, OCH2CH3)
305, 276, 263, 179, 128. HMRS (EI): m/z calcd. [M Ϫ N2]ϩ
305.175597, found [M Ϫ N2]ϩ 305.174593.
ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ ϭ 16.06 (OCH2CH3),
28.74
[NC(CH3)3],
35.72
51.74
(NCH2CH2CO2CH3),
(NCH2CH2CO2CH3),
42.55
55.88
(NCH2CH2CO2CH3),
N-(tert-Butyl)-α-diazo-α-(diethoxyphosphoryl)-N-(phenylethyl)acet-
amide (4g): 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU, 0.65 g,
4.30 mmol) was slowly added at room temperature to a solution of
N-(tert-butyl)-N-(phenylethyl)-α-(diethoxyphosphoryl)acetamide
(3g, 1.39 g, 3.91 mmol) and p-toluenesulfonyl azide in THF
(20 mL). The mixture was stirredat this temperature for 24 h . The
reaction mixture was concentrated, water (15 mL) and Et2O
(15 mL) were added, and the aqueous layer was extracted with
Et2O. The organic layers were washed with brine, dried with
Na2SO4 and concentrated under reduced pressure. The residue was
chromatographed on SiO2 (EtOAc/hexanes, 2:3), yielding the de-
sired diazophosphonate 4g (1.02 g, 69%) as a yellow oil, Rf ϭ 0.45
(EtOAc/hexanes, 2:3). IR (film): ν˜max ϭ 2108, 1629, 1265, 1021
cmϪ1. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ ϭ 1.29 (t, J ϭ
7.1 Hz, 6 H, OCH2CH3), 1.48 [9 H,s, NC(CH3)3], 2.87 (t, J ϭ 7.9
Hz, 2 H, NCH2CH2Ar), 3.64 (t, J ϭ 8.0 Hz, 2 H, NCH2CH2Ar),
4.07Ϫ4.18 (m, 4 H, OCH2CH3), 7.18Ϫ7.31 (m, 5 H, NCH2CH2Ar)
ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ ϭ 16.00 (OCH2CH3),
29.01 [NC(CH3)3], 37.76 (NCH2CH2Ar), 48.61 (NCH2CH2Ar),
57.94 [NC(CH3)3], 63.36 (OCH2CH3), 126.64, 128.43, 129.52,
138.22 (q), 163.96 (CϭO) ppm. 31P NMR (160 MHz, CDCl3, 25
°C): δ ϭ 14.37 ppm. MS (EI): m/z ϭ 262, 206, 179, 151, 91, 57.
HMRS (EI): m/z calcd. [M Ϫ N2]ϩ 353.175597, found [M Ϫ
N2]ϩ 353.175128.
[NC(CH3)3], 63.34 (OCH2CH3), 164.68 [CON(CH3)3CH2], 171.25
(COOCH3) ppm. 31P NMR (160 MHz, CDCl3, 25 °C): δ ϭ 13.71
ppm. MS (EI): m/z ϭ 335, 308, 250, 252, 279, 206. HMRS (EI):
m/z calcd. [M Ϫ N2]ϩ 335.149776, found [M Ϫ N2]ϩ 335.149970.
(R)-(؉)-N-Butyl-α-diazo-α-(diethoxyphosphoryl)-N-(α-phenyl-
ethyl)acetamide (4j): A solution of (R)-(ϩ)-N-(butyl)-α-(diethoxy-
phosphoryl)-N-(α-phenylethyl)acetamide (3j, 1.90 g, 5.35 mmol) in
THF was added at 0 °C to a mixture of sodium hydride and p-
toluenesulfonyl azide in THF. The mixture was stirred at this tem-
perature for 2 h 30 min . Water and Et2O were added, and the aque-
ous layer was extracted with Et2O. After workup, the residue was
chromatographed (EtOAc/hexanes, 2:3), yielding the desired diazo-
phosphonate (4j, 1.87 g, 92%) as a yellow oil, Rf ϭ 0.45 (EtOAc/
hexanes, 2:3). IR (film): ν˜max ϭ 2982, 2097, 1621, 1265, 1020 cmϪ1
1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ ϭ 0.75 (t, J ϭ 7.0
Hz, H, NCH2CH2CH2CH3), 1.06Ϫ1.15 (m, H,
.
3
2
NCH2CH2CH2CH3), 1.28Ϫ1.31 (overlapped signals, 6 H, m,
NCH2CH2CH2CH3 and OCH2CH3), 1.56 [d, J ϭ 7.1 Hz, 3 H,
NCH(CH3)Ar], 2.72Ϫ2.80 (m,
1
H, NCH2CH2CH2CH3),
3.14Ϫ3.21 (m, 1 H, NCH2CH2CH2CH3), 4.12Ϫ4.18 (m, 4 H,
OCH2CH3), 5.38Ϫ5.43 [m, 1 H, NCH(CH3)Ar], 7.18Ϫ7.30 [m, 5
H, NCH(CH3)Ar] ppm. 13C NMR (100 MHz, CDCl3, 25 °C):
δ
ϭ 13.48 (NCH2CH2CH2CH3), 15.93 (OCH2CH3), 17.07
α-Diazo-α-(diethoxyphosphoryl)-N,N-bis(2-methoxyethyl)acetamide
(4h): A solution of α-(diethoxyphosphoryl)-N,N-bis(2-methoxy-
ethyl)acetamide (3h, 0.46 g, 1.47 mmol) in THF was added at 0 °C
to a mixture of sodium hydride and p-toluenesulfonyl azide in THF.
The mixture was stirred at this temperature for 45 min. Water and
Et2O were added, and the aqueous layer was extracted with Et2O.
After workup, the residue was chromatographed (EtOAc/hexanes,
gradient), yielding the desired diazophosphonate (4h, 0.46 g, 93%)
[NCH2(CH3)Ar],
(NCH2CH2CH2CH3),
20.15
44.11
(NCH2CH2CH2CH3),
(NCH2CH2CH2CH3),
31.34
53.80
[NCH2(CH3)Ar], 63.43 (OCH2CH3), 126.91, 129.27, 140.19,
140.19(q), 162.40 (CϭO) ppm. 31P NMR (160 MHz, CDCl3, 25
°C): δ ϭ 13.98 ppm. MS (EI): m/z ϭ 353, 216, 179, 176, 151.
HMRS (EI): m/z calcd. [M Ϫ N2]ϩ 353.175597, found [M Ϫ
N2]ϩ 353.175588.
as a yellow oil, Rf ϭ 0.47 (EtOAc). IR (film): ν˜max ϭ 2101, 1620,
N,N-Dibenzyl-α-diazo-α-(diethoxyphosphoryl)acetamide (4k):
A
1
1255, 1020 cmϪ1. H NMR (400 MHz, CDCl3, 25 °C, TMS) 1.36 solution of N,N-dibenzyl-α-(diethoxyphosphoryl)acetamide (3k,
(t, J ϭ 7.0 Hz, 6 H, OCH2CH3), 3.33 (s, 6 H, NCH2CH2OCH3), 0.88 g, 2.34 mmol) in THF was added at 0 °C to a mixture of so-
3.54 (t, J ϭ 5.4 Hz, 4 H, NCH2CH2OCH3), 3.64 (t, J ϭ 5.4 Hz, 4
H, NCH2CH2OCH3), 4.16Ϫ4.28 (m, 4 H, OCH2CH3) ppm. 13C stirred at this temperature for 1 h and then allowed to reach room
NMR (100 MHz, CDCl3, 25 °C): δ ϭ 15.84 (OCH2CH3), 47.85 temperature overnight. Water and Et2O were added, and the aque-
dium hydride and p-toluenesulfonyl azide in THF. The mixture was
(NCH2CH2OCH3), 58.55 (NCH2CH2OCH3), 63.25 (OCH2CH3), ous layer was extracted with Et2O. After workup, the residue was
70.36 (NCH2CH2OCH3), 162.30 (CϭO) ppm. 31P NMR chromatographed (EtOAc/hexanes, 3:2), yielding the desired diazo-
(160 MHz, CDCl3, 25 °C): δ ϭ 14.10 ppm. MS (FABϩ): m/z ϭ phosphonate 4k (0.85 g, 91%) as a yellow oil, Rf ϭ 0.33 (EtOAc/
1
338, 179, 132. HMRS (EI): m/z calcd. [M ϩ H]ϩ 338.148099, found
[M ϩ H]ϩ 338.147084.
hexanes, 1:1). IR (film): ν˜max ϭ 2100, 1621, 1255, 1020 cmϪ1. H
NMR (400 MHz, CDCl3, 25 °C, TMS): δ ϭ 1.29 (t, J ϭ 7.0 Hz, 6
3806
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2003, 3798Ϫ3810

Regio- and Stereoselective Dirhodium(II)-Catalysed Intramolecular CϪH Insertion Reactions
FULL PAPER
H, OCH2CH3), 4.08Ϫ4.23 (m, 4 H, OCH2CH3), 4.53 (s, 4 H,
NCH2Ar), 7.16Ϫ7.35 (m, 10 H, Ar) ppm. 13C NMR (100 MHz, of rhodium() tetraacetate in anhydrous C2H4Cl2. After having
CDCl3, 25 °C): δ ϭ 16.07 (OCH2CH3), 49.96 (NCH2Ar), 63.58 been heated at reflux for 6 h, the mixture was concentrated and the
2.00 mmol) in C2H4Cl2 was slowly added to a refluxing suspension
(OCH2CH3), 127.57, 127.65, 128.70, 136.03 (q), 163.35 (CϭO) residue was purified by flash chromatography (SiO2 EtOAc/hex-
ppm. 31P NMR (160 MHz, CDCl3, 25 °C): δ ϭ 13.61 ppm. MS anes, 3:2), yielding the trans-3-(diethoxyphosphoryl)-4-methyl-β-lac-
(FABϩ): m/z ϭ 402, 374, 236, 196, 179, 106. HMRS (FABϩ):
m/z calcd. [M ϩ H]ϩ 402.158270, found [M ϩ H]ϩ 402.159882.
tone (7a, 0.13 g, 30%) as a viscous, yellow oil, Rf ϭ 0.47 (EtOAc/
1
hexanes, 7:3). IR (film): ν˜max ϭ 1824, 1746, 1257, 1024 cmϪ1. H
NMR (400 MHz, CDCl3, 25 °C, TMS): δ ϭ 1.36Ϫ138 (m, 6 H,
OCH2CH3), 1.65 (d, J ϭ 6.0 Hz, 3 H, CHCH3), 3.78 (dd, JH-P
N-Benzyl-N-(tert-butyl)-α-diazo-α-(diethoxyphosphoryl)acetamide
(4l): A solution of N-benzyl-N-(tert-butyl)-α-(diethoxyphosphoryl)-
acetamide (3l, 2.00 g, 5.86 mmol) in THF was added at 0 °C to a
mixture of sodium hydride and p-toluenesulfonyl azide in THF.
The mixture was stirred at this temperature for 1 h and then at
room temperature for 1 h 30 min. Water and Et2O were added, and
the aqueous layer was extracted with Et2O. After workup, the resi-
due was chromatographed (EtOAc/hexanes, 2:3), yielding the de-
sired diazophosphonate (4l, 1.88 g, 87%) as a yellow oil, which
crystallized in the fridge after a long time (two weeks) as yellow
crystals (mp, 49Ϫ50 °C), Rf ϭ 0.33 (EtOAc/hexanes, 2:3). IR (film):
ν˜max ϭ 2097, 1638, 1265, 1023 cmϪ1. 1H NMR (400 MHz, CDCl3,
25 °C, TMS): δ ϭ 1.33 (t, J ϭ 8.0 Hz, 6 H, OCH2CH3), 1.38 [s, 9
H, NC(CH3)3], 4.11Ϫ4.24 (m, 4 H, OCH2CH3), 4.68 (s, 2 H,
ϭ
18.0, J ϭ 4.4 Hz, 1 H, POCHCO), 4.20Ϫ4.35 (m, 4 H, OCH2CH3),
4.82Ϫ4.89 (m, 1 H, CHCH3) ppm. 13C NMR (100 MHz, CDCl3,
25 °C): δ ϭ 16.16 (OCH2CH3), 20.20 (CHCH3), 55.35 (d, JC,P
ϭ
144.0 Hz, POCHCO), 63.15, 63.24 (OCH2CH3), 69.32 (CHCH3),
162.47 (CϭO) ppm. 31P NMR (160 MHz, CDCl3, 25 °C): δ ϭ
15.06 ppm. MS (EI): m/z ϭ 223, 179, 151, 163, 123. HMRS (EI):
m/z calcd. [M ϩ H]ϩ 223.07537, found [M ϩ H]ϩ 223.072219.
Cyclization of Propyl α-Diazo-α-(diethoxyphosphoryl)acetate (4b):
Propyl
α-diazo-α-(diethoxyphosphoryl)acetate
(4b,
0.50 g,
1.90 mmol) in C2H4Cl2 was slowly added to a refluxing suspension
of rhodium() tetraacetate in anhydrous C2H4Cl2. After having
been heated at reflux for 2 h 15 min, the mixture was concentrated
and the residue was purified by flash chromatography (SiO2,
EtOAc/hexanes, 3:2), yielding the 3-(diethoxyphosphoryl)-4-ethyl-
β-lactone (7b, 0.13 g, 28%) as a mixture of trans and cis isomers
(trans/cis 1.4:1) and the trans-3-(diethoxyphosphoryl)-4-methyl-γ-
lactone (8b, 0.14 g, 32%).
NCH2Ar), 7.24Ϫ7.36 (m,
5
H, NCH2Ar) ppm. 13C NMR
16.08 (OCH2CH3), 28.42
(100 MHz, CDCl3, 25 °C):
δ
ϭ
[NC(CH3)3], 50.64 (NCH2Ar), 58.81 [NC(CH3)3], 63.36
(OCH2CH3), 126.24, 127.22, 128.50, 139.07 (q), 164.57 (CϭO)
ppm. 31P NMR (160 MHz, CDCl3, 25 °C): δ ϭ 14.24 ppm. MS
(EI): m/z ϭ 339, 326, 179, 162, 91. HMRS (EI): m/z calcd. [M Ϫ
N2]ϩ 339.159947, found [M Ϫ N2]ϩ 339.160272.
3-(Diethoxyphosphoryl)-4-ethyl-β-lactone (7b): 7b was obtained a as
viscous, yellow oil, Rf ϭ 0.40 (EtOAc/hexanes, 3:2). IR (film):
ν˜max ϭ 1828, 1741, 1259, 1027 cmϪ1. 1H NMR (400 MHz, CDCl3,
25 °C, TMS): δ ϭ 0.85 (t, J ϭ 7.3 Hz, 3 H, CHCH2CH3, trans or
cis isomer), 1.05 (t, J ϭ 7.3 Hz, 3 H, CHCH2CH3, trans or cis),
1.31Ϫ138 (m, overlapped signals, 12 H, OCH2CH3, trans and cis
isomer), 1.49Ϫ1.51 (m, 2 H, CHCH2CH3, trans or cis isomer),
1.86Ϫ1.96 (m, 2 H, CHCH2CH3, trans or cis isomer), 3.78 (dd, JH-
N-(tert-Butyl)-α-diazo-α-(diethoxyphosphoryl)-N-(α-phenylethyl)-
acetamide (4m): A solution of N-(tert-butyl)-α-(diethoxyphospho-
ryl)-N-(α-phenylethyl)acetamide (3m, 0.85 g, 2.40 mmol) in THF
was added at 0 °C to a mixture of sodium hydride and p-toluenesul-
fonyl azide in THF. The mixture was stirred at this temperature for
1 h and then at room temperature for 1 h 30 min. Water and Et2O
were added, and the aqueous layer was extracted with Et2O. After
workup, the residue was chromatographed (EtOAc/hexanes, 3:7),
yielding the desired diazophosphonate (4m, 0.90 g, 98%) as a yel-
low oil, Rf ϭ 0.44 (EtOAc/hexanes, 3:7). IR (film): ν˜max ϭ 2097,
1632, 1270, 1021 cmϪ1. 1H NMR (400 MHz, CDCl3, 25 °C, TMS):
δ ϭ 1.25Ϫ1.39 [m, overlapped signals, 15 H, NC(CH3)3 and
OCH2CH3], 1.80 [d, J ϭ 7.2 Hz, 3 H, NCH(CH3)Ar], 4.09Ϫ4.21
ϭ 18.2 J ϭ 4.4 Hz, 1 H, POCHCO, 1.4 of trans isomer),
P
3.83Ϫ3.87 (m, 1 H, CHCH2CH3, trans or cis isomer), 4.12Ϫ4.28
(m, overlapped signals, J ϭ 7.2 Hz, 8 H, OCH2CH3, trans and cis
isomer), 4.36 (dd, JH-P ϭ 24.1, J ϭ 10.3 Hz, 1 H, POCHCO, 1 of
cis isomer), 4.62Ϫ4.63 (m, 1 H, CHCH2CH3, trans or cis) ppm.
13C NMR (100 MHz, CDCl3, 25 °C):
δ ϭ 8.60, 10.17
(CHCH2CH3, trans or cis isomer), 16.26 (OCH2CH3, trans and cis
isomer), 21.55, 27.47 (CHCH2CH3, trans or cis isomer), 54.01 (d,
(m,
4 H, OCH2CH3), 5.14Ϫ5.15 [m, 1 H, NCH(CH3)Ar],
7.23Ϫ7.38 [m, 5 H, NCH(CH3)Ar] ppm. 13C NMR (100 MHz,
CDCl3, 25 °C): δ ϭ 16.06 (OCH2CH3), 20.16 [NCH(CH3)Ar],
29.43 [NC(CH3)3], 56.15 [NCH(CH3)Ar], 59.58 [NC(CH3)3], 63.47
(OCH2CH3), 126.89, 127.12, 128.61, 141.93 (q), 166.58 (CϭO)
ppm. 31P NMR (160 MHz, CDCl3, 25 °C): δ ϭ 14.24 ppm. MS
(FABϩ): m/z ϭ 326, 278, 222, 179, 120. HMRS (EI): m/z calcd.
[M ϩ H]ϩ 382.189570, found [M ϩ H]ϩ 382.189155.
JC,P ϭ 147.0, POCHCO, trans or cis isomer), 53.70 (d, JC,P
ϭ
145.0, POCHCO, trans or cis isomer), 63.19, 63.34 (OCH2CH3,
trans or cis isomer), 63.91, 64.55 (OCH2CH3, trans or cis isomer),
67.97, 73.61 (CHCH2CH3, trans or cis isomer), 162.79, 166.17 (Cϭ
O, trans or cis isomer) ppm. 31P NMR (160 MHz, CDCl3, 25 °C):
δ ϭ 14.44 (1.4 of trans isomer), 15.25 (1.0 of cis isomer) ppm. MS
(FABϩ): m/z ϭ 237, 193, 179, 137. HMRS (FABϩ): m/z calcd. [M
ϩ H]ϩ 237.089187, found [M ϩ H]ϩ 237.089495.
General Procedure for the Rhodium(II)-Catalysed Cyclization of α-
(Diethoxyphosphoryl)acetates and -Acetamides: The appropriate di-
azo compound (4, 1 mmol) in C2H4Cl2 or CH2Cl2 (1.2 mL) was
slowly added under argon atmosphere to a magnetically stirred,
refluxing suspension of rhodium() tetraacetate (1 mol %) in anhy-
drous C2H4Cl2 or CH2Cl2 (10 mL). The reaction mixture was
heated at reflux until disappearance of the substrate (determined
by TLC). The mixture was concentrated under reduced pressure
and the residue was purified by flash chromatography (silica or
basic alumina with EtOAc/hexanes), yielding the desired com-
pounds.
trans-3-(Diethoxyphosphoryl)-4-methyl-γ-lactone (8b): 8b was ob-
tained as a viscous, yellow oil, Rf ϭ 0.20 (EtOAc/hexanes, 3:2). IR
(film): ν˜max ϭ 1769, 1252, 1027 cmϪ1. 1H NMR (400 MHz, CDCl3,
25 °C, TMS): δ ϭ 1.27 [d, J ϭ 6.8 Hz, 3 H, CH(CH3)CH2O],
1.34Ϫ1.39 (m, 6 H, OCH2CH3), 2.68 (dd, JH-P ϭ 23.4 J ϭ 6.5 Hz,
1 H, POCHCO), 2.92Ϫ3.04 [1 H, CH(CH3)CH2O], 3.88 [t, J ϭ 6.0
Hz, 1 H, CH(CH3)CH2O], 4.17Ϫ4.27 (m, J ϭ 7.2 Hz, 4 H,
OCH2CH3), 4.53 [t, J ϭ 8.3 Hz, 1 H, CH(CH3)CH2O] ppm. 13C
NMR (100 MHz, CDCl3, 25 °C): δ ϭ 16.27 (OCH2CH3), 18.74
[CH(CH3)CH2O], 32.95 [CH(CH3)CH2O], 46.55 (d, JC,P ϭ 142.0,
POCHCO), 62.81, 63.52 (OCH2CH3), 73.72 [C(CH3)CH2O],
Cyclization of Ethyl α-Diazo-α-(diethoxyphosphoryl)acetate (4a):[16]
Ethyl
α-diazo-α-(diethoxyphosphoryl)acetate
(4a,
0.50 g, 171.83 (CϭO) ppm. 31P NMR (160 MHz, CDCl3, 25 °C): δ ϭ
Eur. J. Org. Chem. 2003, 3798Ϫ3810
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3807

P. M. P. Gois, C. A. M. Afonso
FULL PAPER
20.62 ppm. MS (EI): m/z ϭ 237, 221, 193, 179, 138. HMRS (EI): (4e, 0.30 g, 1.10 mmol) in C2H4Cl2 was slowly added to a refluxing
m/z calcd. [M]ϩ 236.081362, found [M]ϩ 236.081521.
suspension of rhodium() tetraacetate in anhydrous C2H4Cl2. After
having been heated at reflux for 3 h, the mixture was concentrated
and the residue was purified by flash chromatography (basic alum-
ina, EtOAc/hexanes, 7:3), yielding trans-3-(diethoxyphosphoryl)-1-
ethyl-4-methyl-β-lactam (5e, 0.05 g, 18%) and 3-(diethoxyphospho-
ryl)-1-ethyl-γ-lactam (6e, 0.13 g, 50%).
Cyclization of Isobutyl α-Diazo-α-(diethoxyphosphoryl)acetate (4c):
Isobutyl α-diazo-α-(diethoxyphosphoryl)acetate (4c, 0.50 g,
1.80 mmol) in C2H4Cl2 was slowly added to a refluxing suspension
of rhodium() tetraacetate in anhydrous C2H4Cl2. After having
been heated at reflux for 2 h, the mixture was concentrated and
the residue was purified by flash chromatography (SiO2, EtOAc/
hexanes, 3:2), yielding the cis-3-(diethoxyphosphoryl)-4-isopropyl-
β-lactone (7c, 0.14 g, 30%) and the 3-(diethoxyphosphoryl)-4,4-di-
methyl-γ-lactone (8c, 0.11 g, 24%).
trans-3-(Diethoxyphosphoryl)-1-ethyl-4-methyl-β-lactam (5e): 5e
was obtained as a colourless oil, Rf ϭ 0.26 (neutral alumina,
1
EtOAc/hexanes, 7:3). IR (film): ν˜max ϭ 1749, 1239, 1023 cmϪ1. H
NMR (400 MHz, CDCl3, 25 °C, TMS): δ ϭ 1.12 (t, J ϭ 7.2 Hz, 3
H, NCH2CH3), 1.31 (t, J ϭ 7.0 Hz, 6 H, OCH2CH3), 1.36 [d, J ϭ
6.0 Hz, 3 H, CH(CH3)N], 3.03Ϫ3.07 (m, J ϭ 7.1 Hz, 1 H,
NCH2CH3), 3.23 (dd, JH-P ϭ 14.8 J ϭ 2.2 Hz, 1 H, POCHCO),
3.37Ϫ3.46 (m, J ϭ 7.1 Hz, 1 H, NCH2CH3), 3.85Ϫ3.91 [m, J ϭ
2.2 Hz, 1 H, CH(CH3)N], 4.16Ϫ4.23 (m, 4 H, OCH2CH3) ppm.
13C NMR (100 MHz, CDCl3, 25 °C): δ ϭ 13.03 (NCH2CH3), 16.32
(OCH2CH3), 18.50 [CH(CH3)N], 35.33 (NCH2CH3), 48.65
[CH(CH3)N], 53.94 (d, JC,P ϭ 145.4, POCHCO), 62.37, 62.55
(OCH2CH3), 160.83 (CϭO) ppm. 31P NMR (160 MHz, CDCl3, 25
°C): δ ϭ 20.64 ppm. MS (EI): m/z ϭ 250, 233, 221, 179, 163, 123.
HMRS (EI): m/z calcd. [M]ϩ 249.112997, found [M]ϩ 249.111823.
cis-3-(Diethoxyphosphoryl)-4-isopropyl-β-lactone (7c): 7c was ob-
tained as a viscous, yellow oil, Rf ϭ 0.40 (EtOAc/hexanes, 3:2). IR
(film): ν˜max ϭ 1741, 1265, 1024 cmϪ1. 1H NMR (400 MHz, CDCl3,
25 °C, TMS): δ ϭ 0.84 [d, J ϭ 6.7 Hz, 6 H, CHCH(CH3)2],
1.31Ϫ139 (m, J ϭ 7.0 Hz, 6 H, OCH2CH3), 1.74Ϫ1.81 [m, J ϭ
6.6 Hz, 1 H, CHCH(CH3)2], 3.62Ϫ3.70 [m, 1 H, CHCH(CH3)2],
4.12Ϫ4.28 (m, 4 H, OCH2CH3), 4.40 (dd, JH-P ϭ 24.1, J ϭ 10.4
Hz, 1 H, POCHCO) ppm. 13C NMR (100 MHz, CDCl3, 25 °C):
δ
ϭ
16.16 (OCH2CH3), 18.70 [CHCH(CH3)2], 27.36
[CHCH(CH3)2] 53.94 (d, JC,P ϭ 148.0, POCHCO), 63.75, 64.46
(OCH2CH3), 72.33 [CHCH(CH3)2], 166.10 (CϭO) ppm. 31P NMR
(160 MHz, CDCl3, 25 °C): δ ϭ 14.45 ppm. MS (EI): m/z ϭ 210,
166, 138, 91. HMRS (EI): m/z calcd. [M ϩ H]ϩ 251.104837, found
[M ϩ H]ϩ 251.104256.
3-(Diethoxyphosphoryl)-1-ethyl-γ-lactam (6e): 6e was obtained as a
colourless oil, Rf ϭ 0.12 (neutral alumina, EtOAc/hexanes, 7:3). IR
(film): ν˜max ϭ 1687, 1249, 1024 cmϪ1. 1H NMR (400 MHz, CDCl3,
25 °C, TMS): δ ϭ 1.10 (t, J ϭ 7.2 Hz, 3 H, NCH2CH3), 1.32 (q,
J ϭ 7.0 Hz, 6 H, OCH2CH3), 2.26Ϫ2.39 (m, 2 H, CH2CH2N),
2.91 (dq, JH-P ϭ 22.0 J ϭ 5.0 Hz, 1 H, POCHCO), 3.26Ϫ3.38 (m,
overlapped signals, 3 H, CH2CH2N and NCH2CH3), 3.46Ϫ3.50
(m, 1 H, CH2CH2N), 4.11Ϫ4.26 (m, 4 H, OCH2CH3) ppm. 13C
NMR (100 MHz, CDCl3, 25 °C): δ ϭ 12.22 (NCH2CH3), 16.35
(OCH2CH3), 20.33 (CH2CH2N), 37.55 (NCH2CH3), 41.16 (d,
3-(Diethoxyphosphoryl)-4,4-dimethyl-γ-lactone (8c): 8c was ob-
tained as a viscous, yellow oil, Rf ϭ 0.20 (EtOAc/hexanes, 3:2). IR
(film): ν˜max ϭ 1778, 1258, 1022 cmϪ1. 1H NMR (400 MHz, CDCl3,
25 °C, TMS): δ ϭ 1.30 [s, 6 H, C(CH3)2CH2O], 1.34Ϫ1.39 (m, J ϭ
7.2 Hz, 6 H, OCH2CH3), 2.80 (d, JH-P ϭ 24.4 Hz, 1 H, POCHCO),
3.92 [d, J ϭ 8.4 Hz, 1 H, C(CH3)2CH2O], 4.14 [d, J ϭ 8.4 Hz, 1
H, C(CH3)2CH2O], 4.17Ϫ4.28 (m, J ϭ 7.2 Hz, 6 H, OCH2CH3)
ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ ϭ 14.31 (OCH2CH3),
20.42 [C(CH3)2CH2O], 25.02 [C(CH3)2CH2], 38.21 [C(CH3)2CH2],
48.68 (d, JC,P ϭ 143.4, POCHCO), 60.38, 61.20 (OCH2CH3), 70.01
[C(CH3)2CH2O], 170.02 (CϭO) ppm. 31P NMR (160 MHz, CDCl3,
25 °C): δ ϭ 16.74 ppm. MS (EI): m/z ϭ 251, 235, 179, 151, 123.
HMRS (EI): m/z calcd. [M]ϩ 250.097012, found [M]ϩ 250.096068.
JC,P
ϭ 141.0, POCHCO), 45.17 (CH2CH2N), 62.15, 62.87
(OCH2CH3), 168.77 (CϭO) ppm. 31P NMR (160 MHz, CDCl3, 25
°C): δ ϭ 24.94 ppm. MS (EI): m/z ϭ 249, 192, 179, 111, 71. HMRS
(EI): m/z calcd. [M]ϩ 249.112997, found [M]ϩ 249.113069.
Cyclization
of
N,N-Dibutyl-α-diazo-α-(diethoxyphosphoryl)-
acetamide (4f): N,N-Dibutyl-α-diazo-α-(diethoxyphosphoryl)aceta-
mide (4f, 0.10 g, 0.30 mmol) in C2H4Cl2 was slowly added to a
refluxing suspension of rhodium() tetraacetate in anhydrous
C2H4Cl2. After having been heated at reflux for 2 h, the mixture
was concentrated and the residue was purified by flash chromatog-
raphy (basic alumina, EtOAc/hexanes, 7:3), yielding the trans-1-
butyl-3-(diethoxyphosphoryl)-4-ethyl-γ-lactam[6] (6f, 0.08 g, 87%) as
a brownish oil, Rf ϭ 0.24 (neutral alumina, EtOAc/hexanes, 3:2).
Cyclization
of
α-Diazo-α-(diethoxyphosphoryl)-N,N-(diisopro-
pyl)acetamide (4d): α-Diazo-α-(diethoxyphosphoryl)-N,N-(diiso-
propyl)acetamide (4d, 0.15 g, 0.50 mmol) in CH2Cl2 was slowly ad-
ded to a refluxing suspension of rhodium() tetraacetate in anhy-
drous CH2Cl2. After having been heated at reflux for 6 h 30 min,
the mixture was concentrated and the residue was purified by flash
chromatography (basic alumina, EtOAc/hexanes, 2:3), yielding the
3-(diethoxyphosphoryl)-1-isopropyl-4,4-dimethyl-β-lactam[6]
(5d,
IR (film): ν˜max ϭ 1686, 1265, 1053 cmϪ1 1H NMR (400 MHz,
.
0.12 g, 88%) as a colourless oil, Rf ϭ 0.30 (neutral alumina, EtOAc/
CDCl3, 25 °C, TMS): δ ϭ 0.93 [q, overlapped signals, J ϭ 7.2 Hz,
6 H, CH(CH2CH3)CH2N and NCH2CH2CH2CH3], 1.32Ϫ1.37 (m,
overlapped signals, J ϭ 7.1 Hz, 8 H, NCH2CH2CH2CH3 and
OCH2CH3), 1.43Ϫ1.54 [m, overlapped signals, J ϭ 7.2, 7.4 Hz, 3
H, CH(CH2CH3)CH2N and NCH2CH2CH2CH3], 1.60Ϫ1.65 (m, 1
H, NCH2CH2CH2CH3), 2.55Ϫ2.68 (overlapped signals, 1 H, m,
CH(CH2CH3)CH2N and 1 H, dd, JH-P ϭ 21.8, J ϭ 4.4 Hz), 2.98
[dd, J ϭ 3.1 Hz, 9.7 Hz, 1 H, CH(CH2CH3)CH2N], 3.22Ϫ3.35 (m,
hexanes, 2:3). IR (film): ν˜max ϭ 1746, 1249, 1047 cmϪ1. H NMR
1
(400 MHz, CDCl3, 25 °C, TMS): δ ϭ 1.26Ϫ1.30 [m, overlapped
signals, J ϭ 7.1 Hz, 12 H, OCH2CH3 and NCH(CH3)2], 1.42 [s, 3
H, CHC(CH3)2N], 1.56 [s, 3 H, CHC(CH3)2N], 3.19 (d, JH-P
ϭ
17.2 Hz, 1 H, POCHCO), 3.44Ϫ3.51 [m, 1 H, NCH(CH3)2],
4.10Ϫ4.15 (m, J ϭ 7.0 Hz, 4 H, OCH2CH3) ppm. 13C NMR
(100 MHz, CDCl3, 25 °C): δ ϭ 16.26 (OCH2CH3), 21.50, 21.60
[NCH(CH3)2], 22.30, 27.92 [CHC(CH3)2N], 44.56 [NCH(CH3)2],
57.56 (d, JC,P ϭ 145.1, POCHCO) 58.02 [CHC(CH3)2N], 62.02,
62.18 (OCH2CH3), 160.13 (CϭO) ppm. 31P NMR (160 MHz,
CDCl3, 25 °C): δ ϭ 19.34 ppm. MS (EI): m/z ϭ 277, 262, 192, 136,
83. HMRS (EI): m/z calcd. [M]ϩ 277.144297, found [M]ϩ
277.143893.
2
H, NCH2CH2CH2CH3), 2.98 [t,
CH(CH2CH3)CH2N], 4.13Ϫ4.28 (m, 4 H, OCH2CH3) ppm. 13C
NMR (100 MHz, CDCl3, 25 °C): 10.85, 13.60
[NCH2CH2CH2CH3, and CH(CH2CH3)CH2N],
(OCH2CH3), 19.76 (NCH2CH2CH2CH3), 28.09,
(NCH2CH2CH2CH3), 29.04 [CH(CH2CH3)CH2N],
J ϭ 9.0 Hz, 1 H,
δ
ϭ
16.28
28.19
34.75
Cyclization of α-Diazo-α-(diethoxyphosphoryl)-N,N-diethylacet-
[CH(CH2CH3)CH2], 42.46 (NCH2CH2CH2CH3), 47.35 (d, JC,P ϭ
amide (4e): α-Diazo-α-(diethoxyphosphoryl)-N,N-diethylacetamide 139.9 Hz, POCHCO), 51.26 [CH(CH2CH3)CH2N], 61.98, 62.86
3808  2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim www.eurjoc.org
Eur. J. Org. Chem. 2003, 3798Ϫ3810

Regio- and Stereoselective Dirhodium(II)-Catalysed Intramolecular CϪH Insertion Reactions
(OCH2CH3), 168.49 (CϭO) ppm. 31P NMR (160 MHz, CDCl3, 25 CHCH2CO2CH3), 2.90 (dd,
FULL PAPER
ϭ 3.5 Hz, 14.5 Hz, 1 H,
J
°C): δ ϭ 24.60 ppm. MS (EI): m/z ϭ 305, 290, 276, 263, 179, 127. CHCH2CO2CH3), 3.40 (dd, JH-P ϭ 15.0 J ϭ 2.0 Hz, 1 H,
HMRS (EI): m/z calcd. [M]ϩ 305.175597, found [M]ϩ 305.176528. POCHCO), 3.73 (s, 3 H, CHCH2CO2CH3), 4.08Ϫ4.35 (m, over-
lapped signals, 5 H, CHCH2CO2CH3 and OCH2CH3) ppm. 13C
Cyclization of N-(tert-Butyl)-α-diazo-α-(diethoxyphosphoryl)-N-
NMR (100 MHz, CDCl3, 25 °C): δ ϭ 16.32 (OCH2CH3), 28.14
(phenylethyl)acetamide (4g): N-(tert-Butyl)-α-diazo-α-(diethoxy-
[NC(CH3)3], 39.48 (CHCH2CO2CH3), 48.62 (CHCH2CO2CH3),
phosphoryl)-N-(phenylethyl)acetamide (4g, 0.11 g, 0.30 mmol) in
51.11 (d, JC,P ϭ 144.0 Hz, POCHCO), 51.93 (CHCH2CO2CH3),
C2H4Cl2 was slowly added to a refluxing suspension of rhodium()
62.56 (OCH2CH3), 162.10 (CONCHCH2), 169.63 (COOCH3) ppm.
tetraacetate in anhydrous C2H4Cl2. After having been heated at
reflux for 4 h, the mixture was concentrated and the residue was
31P NMR (160 MHz, CDCl3, 25 °C): δ ϭ 20.22 ppm. MS (EI):
m/z ϭ 336, 277, 263, 206, 179. HMRS (EI): m/z calcd. [M]ϩ
purified by flash chromatography (basic alumina, EtOAc/hexanes,
335.149776, found [M]ϩ 335.149767.
1:1), yielding trans-1-(tert-butyl)-3-(diethoxyphosphoryl)-4-phenyl-γ-
lactam (6g, 0.08 g, 81%) as a viscous, yellow oil, Rf ϭ 0.49 (neutral
alumina, EtOAc/hexanes, 1:1). IR (film): ν˜max ϭ 1682, 1265, 1051
cmϪ1. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ ϭ 1.19 (t, J ϭ
7.1 Hz, 3 H, OCH2CH3), 1.24 (t, J ϭ 7.0 Hz, 3 H, OCH2CH3),
1.37 [s, 9 H, NC(CH3)3], 2.95 (dd, JP-H ϭ 22.2, J ϭ 4.9 Hz, 1
H, POCHCO), 3.37 (dd, J ϭ 3.4 Hz, 9.7 Hz, 1 H, CHArCH2N),
3.62Ϫ3.69 (m, 1 H, CHArCH2N), 3.93 (t, J ϭ 9.3 Hz, 1 H,
CHArCH2N), 3.98Ϫ4.17 (m, 4 H, OCH2CH3), 7.16Ϫ7.28 (m, 5 H,
Ar) ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ ϭ 16.35
(OCH2CH3), 27.54 [NC(CH3)3], 38.24 (CHArCH2N), 51.01 (d,
JC,P ϭ 139.0, POCHCO), 52.49 (CHArCH2N), 54.74 [NC(CH3)3],
62.25, 62.95 (OCH2CH3), 126.50, 127.28, 128.95, 143.54 (q), 168.75
(CϭO) ppm. 31P NMR (160 MHz, CDCl3, 25 °C): δ ϭ 23.59 ppm.
MS (EI): m/z ϭ 353, 296, 176, 119, 57. HMRS (EI): m/z calcd.
[M]ϩ 353.174851, found [M]ϩ 353.175597.
Cyclization
of
(R)-(؉)-N-Butyl-α-(diethoxyphosphoryl)-N-(α-
phenylethyl)acetamide (4j): (R)-(ϩ)-N-butyl-α-(diethoxyphospho-
ryl)-N-(α-phenylethyl)acetamide (4j, 0.10 g, 0.26 mmol) in C2H4Cl2
was slowly added to a refluxing suspension of rhodium() tetra-
acetate in anhydrous C2H4Cl2. After having been heated at reflux
for 2 h, the mixture was concentrated and the residue was purified
by flash chromatography (basic alumina, EtOAc/hexanes, 3:7),
yielding 0.087 g of a 1.2:1.0 mixture of trans-1-(R)-(ϩ)-3-(diethoxy-
phosphoryl)-4-ethyl-N-(α-phenylethyl)-γ-lactam (6j, 76%) and (E/
Z)-1-butyl-α-(diethoxyphosphoryl)-4-methyl-4-phenyl-β-lactam
(5j, 18%).
(E)-1-Butyl-α-(diethoxyphosphoryl)-4-methyl-4-phenyl-β-lactam
(5j): 5j was obtained as a 1.2:1.0 mixture of 6j and 5j. Rf ϭ 0.29
(neutral alumina, EtOAc/hexanes, 3:7); Relevant signals in the mix-
1
ture for the β-lactam: H NMR (400 MHz, CDCl3, 25 °C, TMS):
Cyclization of α-Diazo-α-(diethoxyphosphoryl)-N,N-bis(2-methoxy-
ethyl)acetamide (4h): α-Diazo-α-(diethoxyphosphoryl)-N,N-bis(2-
methoxyethyl)acetamide (4h, 0.05 g, 0.15 mmol) in C2H4Cl2 was
slowly added to a refluxing suspension of rhodium() tetraacetate
in anhydrous C2H4Cl2. After having been heated at reflux for 1 h,
the mixture was concentrated and the residue was purified by flash
chromatography (basic alumina, EtOAc/hexanes, 7:3), yielding
trans-3-(diethoxyphosphoryl)-4-methoxy-1-(2-methoxyethyl)-γ-
lactam (6h, 0.04 g, 89%) as a viscous, yellow oil, Rf ϭ 0.50 (neutral
alumina, EtOAc/hexanes, 2:3). IR (film): ν˜max ϭ 1692, 1245, 1026
δ ϭ 2.03 [s, 3 H, C(CH3)Ar], 3.48 (d, JH-P ϭ 17.5 Hz, 1 H,
POCHCO) ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ ϭ 60.96
(d, JC,P ϭ 143.0 Hz, POCHCO) ppm. 31P NMR (160 MHz, CDCl3,
25 °C): δ ϭ 18.06 ppm.
trans-1-(R)-(؉)-3-(Diethoxyphosphoryl)-4-ethyl-N-(α-phenylethyl)-
γ-lactam (6j): 6j was obtained as a viscous, yellow oil, diastereoiso-
meric mixture (1.2:1.0), Rf ϭ 0.29 (neutral alumina, EtOAc/hex-
anes, 3:7). IR (film): ν˜max ϭ 1678, 1243, 1053 cmϪ1 1H NMR
.
(400 MHz, CDCl3, 25 °C, TMS): δ ϭ 0.77, 0.92 [1:1.2, t, J ϭ 7.2
Hz, CH(CH2CH3)CH2N], 1.25Ϫ1.36 (m, overlapped signals,
OCH2CH3), 1.42Ϫ1.49 [m, CH(CH2CH3)CH2N], 1.53 [d, J ϭ 6.8
Hz, 6 H, NCH(CH3)Ar], 1.61Ϫ1.68 [m, CH(CH2CH3)CH2N], 2.52
[m, CH(CH2CH3)CH2N], 2.60 [J ϭ 9.6 Hz, CH(CH2CH3)CH2N],
2.67 (dd, JH-P ϭ 22.5, POCHCO), 2.71 (dd, JH-P ϭ 22.4, J ϭ 4.2
Hz, POCHCO), 2.91 [d, J ϭ 8.2 Hz, CH(CH2CH3)CH2N], 3.21 [t,
cmϪ1 1H NMR (400 MHz, CDCl3, 25 °C, TMS) 1.27Ϫ1.32 (m,
.
J ϭ 7.0 Hz, 6 H, OCH2CH3), 3.00 (dd, JH-P ϭ 23.6 J ϭ 2.0 Hz,
1 H, POCHCO), 3.26 (s, 6 H, NCH2CH2OCH3), 3.34Ϫ3.50 [m,
overlapped signals, 5 H, NCH2CH2OCH3, NCH2CH2OCH3 and
CH(OCH3)CH2N], 3.76Ϫ3.80 [m,
1 H, CH(OCH3)CH2N],
4.11Ϫ4.18 (m, 4 H, OCH2CH3) ppm. 13C NMR (100 MHz, CDCl3,
25 °C): δ ϭ 16.20 (OCH2CH3), 42.70 (NCH2CH2OCH3), 48.29 (d,
JC,P ϭ 135.0 Hz, POCHCO), 54.05 [CH(OCH3)CH2N], 56.13,
58.55 (NCH2CH2OCH3), 62.29, 63.05 (OCH2CH3), 70.66
(NCH2CH2OCH3), 75.13 [CH(OCH3)CH2N], 167.41 (CϭO) ppm.
31P NMR (160 MHz, CDCl3, 25 °C): δ ϭ 20.83 ppm. MS (EI):
m/z ϭ 294, 278, 221, 179, 173. HMRS (EI): m/z calcd. [M]ϩ
295.114006, found [M]ϩ 295.113815.
J
ϭ 8.6 Hz, CH(CH2CH3)CH2N], 3.57 [t, J ϭ 8.4 Hz,
CH(CH2CH3)CH2N], 4.14Ϫ4.30 (m, OCH2CH3), 5.50 [q, J ϭ 6.8
Hz, 6 H, NCH(CH3)Ar], 7.29Ϫ7.33 [m, 10 H, NCH(CH3)Ar] ppm.
13C NMR (100 MHz, CDCl3, 25 °C):
δ ϭ 10.68, 10.82
[CH(CH2CH3)CH2N], 15.71 [NCH(CH3)Ar], 16.00, 16.34
(OCH2CH3), 27.81, 28.16 [CH(CH2CH3)CH2N), 34.57, 34.71
[CH(CH2CH3)CH2N), 46.30, 46.55 [CH(CH2CH3)CH2N], 47.56
(d, JC,P ϭ 140.0 Hz, POCHCO), 47.73 (d, JC,P ϭ 138.0 Hz,
POCHCO), 49.13, 49.31 [NCH(CH3)Ar], 62.70, 62.82 (OCH2CH3),
126.98, 127.38, 127.50, 128.41, 139.48 (q), 139.74 (q), 168.38 (Cϭ
O) ppm. 31P NMR (160 MHz, CDCl3, 25 °C): δ ϭ 24.45, 24.55
ppm. MS (EI): m/z ϭ 353, 248, 220, 192, 105. HMRS (EI): m/z
calcd. [M]ϩ 353.175597, found [M]ϩ 353.174327.
Cyclization of N-(tert-Butyl)-α-diazo-α-(diethoxyphosphoryl)-N-[2-
(methoxycarbonyl)ethyl]acetamide (4i): N-(tert-Butyl)-α-diazo-α-
(diethoxyphosphoryl)-N-[2-(methoxycarbonyl)ethyl]acetamide (4i,
0.20 g, 0.51 mmol) in C2H4Cl2 was slowly added to a refluxing sus-
pension of rhodium() tetraacetate in anhydrous C2H4Cl2. After
having been heated at reflux for 2 h, the mixture was concentrated
and the residue was purified by flash chromatography (basic alum-
ina, EtOAc/hexanes, 1:1), yielding trans-1-(tert-butyl)-3-(diethoxy-
Cyclization
of
N,N-Dibenzyl-α-diazo-α-(diethoxyphosphoryl)-
acetamide (4k): N,N-Dibenzyl-α-diazo-α-(diethoxyphosphoryl)ace-
phosphoryl)-4-(methoxycarbonyl)-β-lactam (5i, 0.17 g, 94%) as a tamide (4k, 0.10 g, 0.25 mmol) in CH2Cl2 was slowly added to a
brown oil, Rf ϭ 0.29 (neutral alumina, EtOAc/hexanes, 1:1). IR
refluxing suspension of rhodium() tetraacetate in anhydrous
CH2Cl2. After having been heated at reflux for 9 h, the mixture was
(film): ν˜max ϭ 1745, 1247, 1028 cmϪ1. 1H NMR (400 MHz, CDCl3,
25 °C, TMS): δ ϭ 1.30Ϫ1.37 [m, overlapped signals, 15 H, concentrated and the residue was purified by flash chromatography
OCH2CH3 and NC(CH3)3], 2.60 (dd, J ϭ 7.9 Hz, 14.7 Hz, 1 H, (basic alumina, EtOAc/hexanes, 2:3), yielding the trans-1-benzyl-3-
Eur. J. Org. Chem. 2003, 3798Ϫ3810
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3809

P. M. P. Gois, C. A. M. Afonso
FULL PAPER
(diethoxyphosphoryl)-4-phenyl-β-lactam (5k, 0.08, 81%) as a vis-
cous, yellow oil, Rf ϭ 0.50 (neutral alumina, EtOAc/hexanes, 2:3).
Acknowledgments
ˆ
We thank the Fundac¸a˜o para a Ciencia e Tecnologia (ref. SFRH/
IR (film): ν˜max ϭ 1759, 1265, 1026 cmϪ1 1H NMR (400 MHz,
.
BD/3097/2000) for financial support.
CDCl3, 25 °C, TMS): δ ϭ 1.29 (t, J ϭ 7.0 Hz, 6 H, OCH2CH3),
3.49 (dd, JH-P ϭ 14.7, J ϭ 2.0 Hz, 1 H, POCHCO), 3.82 (d, J ϭ
15.2 Hz, 1 H, NCH2Ar), 4.13Ϫ4.21 (m, J ϭ 7.1 Hz, 4 H,
OCH2CH3), 4.63 (dd, JP-H ϭ 8.4, J ϭ 2.0 Hz, 1 H, CHArN), 4.89
(d, J ϭ 15.2 Hz, 1 H, NCH2Ar), 7.19Ϫ7.38 (m, 10 H, Ar) ppm.
13C NMR (100 MHz, CDCl3, 25 °C): δ ϭ 16.18 (OCH2CH3), 44.79
(NCH2Ar), 55.05 (CHArN), 56.85 (d, JC,P ϭ 144.0 Hz, POCHCO),
62.51 (OCH2CH3), 126.25, 127.64, 128.16, 128.57, 128.79, 128.99,
129.25, 134.61 (q), 136.07 (q), 161.79 (CϭO) ppm. 31P NMR
(160 MHz, CDCl3, 25 °C): δ ϭ 18.91 ppm. MS (EI): m/z ϭ 373,
236, 208, 131, 91. HMRS (EI): m/z calcd. [M]ϩ 373.144297, found
[M]ϩ 373.143275.
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phosphoryl)acetamide (4l): N-Benzyl-N-(tert-butyl)-α-diazo-α-(di-
ethoxyphosphoryl)acetamide (4l, 0.20 g, 5.45 mmol) in CH2Cl2 was
slowly added to a refluxing suspension of rhodium() tetraacetate
in anhydrous CH2Cl2. After having been heated at reflux for 7 h,
the mixture was concentrated and the residue was purified by flash
chromatography (basic alumina, EtOAc/hexanes, 2:8), yielding
trans-1-(tert-butyl)-3-(diethoxyphosphoryl)-4-phenyl-β-lactam (5l,
0.17 g, 89%) as a viscous, yellow oil, which crystallized in the fridge
after a long time period (one month) as white crystals (mp, 85Ϫ86
°C), Rf ϭ 0.34 (neutral alumina, EtOAc/hexanes, 2:8). IR (film):
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R. T.
ν˜max ϭ 1750, 1252, 1027 cmϪ1 1H NMR (400 MHz, CDCl3, 25
.
°C, TMS): δ ϭ ): 1.27Ϫ1.37 [m, overlapped signals, 15 H,
OCH2CH3 and NC(CH3)3], 3.27 (dt, JP-H ϭ 14.6, J ϭ 2.4 Hz, 1
[5f]
M. Miko-
H, POCHCO), 4.12Ϫ4.27 (m, 4 H, OCH2CH3), 4.77 (dt, JP-H
9.3, J ϭ 2.4 Hz, 1 H, NCHAr), 7.32Ϫ7.42 (m, 5 H, NCHAr) ppm.
13C NMR (100 MHz, CDCl3, 25 °C):
16.29, 16.34
(OCH2CH3), 27.93 [NC(CH3)3], 54.64 (NCHAr), 55.88 (d, JC,P
ϭ
[5g]
M. Mikolajczyk, M. Mikina, R. Zurawinski, J.
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W. Dayoub, Y. Diab, A.
δ
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ϭ
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141.0 Hz, POCHCO), 62.48, 62.60 (OCH2CH3), 126.17, 128.59,
128.92, 139.32 (q), 161.84 (CϭO) ppm. 31P NMR (160 MHz,
CDCl3, 25 °C): δ ϭ 19.92 ppm. MS (EI): m/z ϭ 339, 282, 241, 131,
83. HMRS (EI): m/z calcd. [M]ϩ 339.159947, found [M]ϩ
339.159033.
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Cyclization of N-(tert-Butyl)-α-diazo-α-(diethoxyphosphoryl)-N-(α-
phenylethyl)acetamide (4m): N-(tert-Butyl)-α-diazo-α-(diethoxy-
phosphoryl)-N-(α-phenylethyl)acetamide (4m, 0.20 g, 5.25 mmol)
in C2H4Cl2 was slowly added to a refluxing suspension of rho-
dium() tetraacetate in anhydrous C2H4Cl2. After having been
heated at reflux for 4 h, the mixture was concentrated and the resi-
due was purified by flash chromatography (basic alumina, EtOAc/
hexanes, 2:8), yielding the trans-1-(tert-butyl)-3-(diethoxyphospho-
ryl)-4-methyl-4-phenyl-β-lactam (5m, 0.14 g, 75%) as a viscous, yel-
low oil, Rf ϭ 0.18 (neutral alumina, EtOAc/hexanes, 1:4). IR (film):
M. P. Doyle, L. J. Westrum, W. N. E. Wolthuis, M. M. See,
W. P. Boone, V. Bagheri, M. M. Pearson, J. Am. Chem. Soc.
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ν˜max ϭ 1741, 1248, 1028 cmϪ1 1H NMR (400 MHz, CDCl3, 25
.
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°C, TMS): δ ϭ 1.26Ϫ1.38 [m, overlapped signals, 15 H, OCH2CH3
and NC(CH3)3], 2.23 [s, 3 H, C(CH3)Ar], 3.44 (d, JP-H ϭ 17.5 Hz,
1 H, POCHCO), 4.09Ϫ4.34 (m, 4 H, OCH2CH3), 7.28Ϫ7.63 [m, 5
H, C(CH3)Ar] ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ ϭ
16.30 (OCH2CH3), 21.01 [NC(CH3)Ar], 28.35 [NC(CH3)3], 55.96
[NC(CH3)Ar], 61.17 (d, JC,P ϭ 141.0 Hz, POCHCO), 62.10, 62.42
(OCH2CH3), 125.13, 127.84, 128.68, 143.97 (q), 162.19 (CϭO)
ppm. 31P NMR (160 MHz, CDCl3, 25 °C): δ ϭ 17.79 ppm. MS
(EI): m/z ϭ 353, 338, 296, 254, 198. HMRS (EI): m/z calcd. [M]ϩ
353.175597, found [M]ϩ 353.176020.
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Received May 29, 2003
3810
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2003, 3798Ϫ3810