Intramolecular metal-catalyzed amination of pseudo-anomeric C-H bonds

Article abstract of DOI:10.1016/j.tetlet.2005.05.043

Intramolecular metal-catalyzed amination of a pseudo-anomeric C-H bond in a C-glycoside is reported. Treatment of α,β-C-carbamoyloxymethyl- or β-C-sulfamoyloxymethyl glycosides with Rh₂(OAc)₄, PhI(OAc)₂, and MgO provided o

Full text of DOI:10.1016/j.tetlet.2005.05.043

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 4731–4735
Intramolecular metal-catalyzed amination of
pseudo-anomeric C–H bonds
Sylvestre Toumieux, Philippe Compain* and Olivier R. Martin
´ ´ ´
Institut de Chimie Organique et Analytique, UMR CNRS 6005, Universite, d’Orleans, BP 6759, 45067 Orleans Cedex 2, France
Received 12 April 2005; revised 11 May 2005; accepted 11 May 2005
Available online 31 May 2005
Abstract—Intramolecular metal-catalyzed amination of a pseudo-anomeric C–H bond in a C-glycoside is reported. Treatment of
a,b-C-carbamoyloxymethyl- or b-C-sulfamoyloxymethyl glycosides with Rh2(OAc)4, PhI(OAc)2, and MgO provided original spiro-
oxazolidines or spirooxathiazolidines in reasonable yields. No correlation between ÔanomericÕ stereochemistry and insertion effi-
ciency was found for the conversion of carbamate derivatives whereas amination reactions of the corresponding sulfamate esters
were found to be strongly dependent on the anomeric configuration.
Ó 2005 Elsevier Ltd. All rights reserved.
The catalytic selective functionalization of unactivated
C–H bonds represents a major challenge in organic
chemistry and provides chemists with fertile ground
for the synthesis of complex molecules.1 In this context,
the latest work of Du Bois and co-workers2 and Che
and co-workers3 on the intramolecular Rh-catalyzed
amination reactions of sulfamates or carbamates is of
particular interest for the efficient preparation of nitro-
gen-containing structures.4 The elegant synthesis of
(ꢀ)-tetrodotoxin has recently underscored the synthetic
power of this methodology.5 In connection with our
studies on iminosugars and C-glycosides,6 we were par-
ticularly interested in applying Rh-catalyzed amination
reactions to carbohydrate frameworks. It has long been
acknowledged that Ôhalf of sugar chemistry resides at the
anomeric carbon atomÕ.7 We therefore designed C-gly-
cosides I as test substrates to develop efficient access
to original glycomimetics of biological interest and to
study the regioselectivity and the mechanism of the
intramolecular nitrogen atom transfer (Scheme 1).
Amination of the C-2 position would open a general
route to hexosamine C-glycosides8 from III whereas
nitrogen atom insertion into the C–H anomeric bond
would yield glycomimetics II containing a N,O-acetal
structure that could serve as surrogate iminium ions
(Scheme 1).9 To the best of our knowledge, there has
OR
O
H
N
O
O
RO
RO
S
OR
II
O
O
H2N
O
Rh2(OAc)4
RO
RO
O
and/or
OR
1
S
2
PhI(OAc)2
MgO
I
O
O
RO
RO
α- or β-configuration
NH
O
O
S
III
O
Scheme 1.
been no reports of an intramolecular metal-catalyzed
amination of ÔanomericÕ C–H bond of a carbohydrate.10
The increased reactivity of axial anomeric C–H bonds,
compared to equatorial C–H bonds, in a number of
reactions such as radical H-abstraction, represents an
attractive opportunity to get further insights into the
mechanism of the intramolecular nitrogen atom trans-
fer.11 Sulfamate esters were firstly evaluated since they
generally lead to the formation of the corresponding
six-membered ring insertion products whereas carba-
mates afforded five-membered rings.
The synthesis of the test substrates 6 and 8 was
performed from commercially available tri-O-benzyl-D-
glucal 1 (Scheme 2). Heptenitol 2 was obtained in two
steps by the conversion of 1 into the corresponding
Keywords: C-Glycosides; Amination; C–H insertion; Rhodium; N,O-
Acetals.
*
Corresponding author. Tel.: +33 (0) 2 38 49 48 55; fax: +33 (0) 2 38
41 72 81; e-mail: philippe.compain@univ-orleans.fr
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.05.043

4732
S. Toumieux et al. / Tetrahedron Letters 46 (2005) 4731–4735
OBn
O
OBn
OH
OBn
a,b
O
d
c
f
BnO
BnO
BnO
BnO
BnO
BnO
I
3
1
2
OBn
OBn
OBn
O
O
e
O
H2N
BnO
BnO
BnO
BnO
BnO
O
BnO
S
OH
5
4
OAc
6
O
O
g,h
OTBDMS
O
OTBDMS
e,i
O
H2N
TBDMSO
TBDMSO
TBDMSO
TBDMSO
O
S
OAc
O
O
7
8
Scheme 2. Reagents and conditions: (a) (i) NIS (1.1 equiv), CH3CN/H2O (95:5), 0 to 20 °C, 15 min. (ii) Na2S2O4 (4 equiv), NaHCO3 (10 equiv),
DMF/H2O (1:1), 5 h, 98%. (b) Ph3P+CH3Brꢀ (3.5 equiv), n-BuLi (3.3 equiv), 0–20 °C, 16 h, 80%. (c) I2 (1.7 equiv), NaHCO3 (1.8 equiv), Et2O/H2O
(5:2), 16 h, 72%. (d) n-Bu4NOAc (1.5 equiv), toluene, 50 °C, 15 h, 55%. (e) NaOMe/MeOH, 3 h, 95% (Bn groups); 20% (TBDMS groups). (f)
ClSO2NH2 (2 equiv), pyridine (2 equiv), CH2Cl2, 16 h, 90%. (g) H2, Pd/C, MeOH, 16 h, quant. (h) TBDMSCl (5 equiv), imidazole (10 equiv), DMF,
0–60 °C, 16 h (97%). (i) ClSO2NH2 (2 equiv+2 equiv after 16 h), pyridine (2 equiv), CH2Cl2, 16 h at room temperature +1 h at 40 °C, 27%.
2-deoxysugar by a mild one-pot procedure,12 followed
1. MgO, PhI(OAc)2
Rh2(OAc)4 cat.
CH2Cl2, ∆, 16h
by Wittig methylenation.13 The I2-promoted iodocycli-
OBn
OBn
Boc
N
O
zation of the d-hydroxy alkene 2 in the presence of NaH-
CO3 afforded the C-iodomethyl glycosides 3 with a
modest diastereoselectivity in favor of the a-anomer
(a/b 2:1). In our hands, the two diastereoisomers could
not been separated by flash chromatography. The rest
of the synthetic sequence was thus performed using the
mixture of the two diastereoisomers. After various at-
tempts, introduction of a protected hydroxyl group in
place of the iodine atom was efficiently achieved by
way of a nucleophilic substitution using n-Bu4NOAc
in toluene to yield the key intermediates 4.14 After
saponification of acetates 4, the corresponding alcohols
5 were reacted with sulfamoyl chloride and pyridine to
afford the benzylated test substrates 6 in high yield. To
study the influence of protecting groups on the insertion
reaction, we synthesized the corresponding TBDMS-
protected analogs 7 from the common intermediate 4.
Quantitative hydrogenolysis of 4 afforded the corre-
sponding triols, which were protected as silyl ethers to
yield compounds 7. Treatment with sodium methano-
late, followed by condensation with sulfamoyl chloride
afforded the desired substrates 8.
H2N
O
O
O
O
BnO
BnO
BnO
BnO
S
S
2. Boc2O, Py, 4h
O
O
O
18%
α/β 2/1
9 de > 98%
6
1.
MgO, PhI(OAc)2
Rh2(OAc)4 cat.
CH2Cl2, ∆, 16h
OTBDMS
O
O
S
OTBDMS
TBDMSO
O
O
N
O
O
H2N
O
TBDMSO
TBDMSO
2. Boc2O, Py, 4h
S
Boc
OTBDMS
10
O
17%
8 α/β 2/1
de 75%
Scheme 3.
isolated from this reaction. The structure of 9 was deter-
mined on the basis of mass and NMR spectral data (1H,
13
COSY, NOESY, and C).17
The configuration of the newly created stereogenic cen-
ter was unambiguously determined by the definite NOE
interactions between H0a and H-2eq and between H0a
and H-3 (Fig. 1). The regioselectivity of the reaction
may be rationalized by the fact that electron-donating
groups generally activate the a-C–H bond toward inser-
tion.16b In addition, insertion into tertiary C–H bonds is
generally preferred to secondary C–H bonds.
The Du Bois reaction was first investigated with the epi-
meric mixture of the benzyl-protected derivatives 6. Fol-
lowing a standard protocol using PhI(OAc)2 (1.1 equiv),
MgO (2.3 equiv) and 5 mol % of Rh(OAc)4, a sluggish
conversion of the sulfamate esters was observed (Scheme
3). 1H and 13C NMR spectra of the crude product
proved quite complex and appeared to indicate the pres-
ence of a spirooxathiazolidine15 in equilibrium with the
corresponding open-chain imine form (ratio 2:1 in favor
of the oxathiazolidine). In particular, the carbon reso-
nance observed at d 183.6 in 13C NMR is consistent with
a sulfonimine ester structure.16 Since purification proved
difficult, the crude product was treated directly with
Boc2O in pyridine to afford, after a simple filtration on
silica gel, compound 9 in 18% yield from 6 and as a sin-
gle diastereoisomer. No other identifiable products were
H2ax
O
Boc
N
BnO
BnO
O
O
BnO
H
S
H'b2eq
H'a
O
H3
NOE effects
Figure 1.

S. Toumieux et al. / Tetrahedron Letters 46 (2005) 4731–4735
4733
As the low yield observed may be due to undesirable
side reactions generated by the presence of benzylic
methylenes in 6, we performed the intramolecular C–H
insertion from TBDMS-protected sulfamate esters 8.
After treatment of the crude product with Boc2O in pyr-
idine,18 we isolated spirooxathiazolidines 10 as a mix-
ture of two diatereoisomers (de 75%) in a yield similar
to the one obtained from 6 (17% from 8). Extensive
NMR analysis indicated that the major epimer exists
predominantly in a 1C4 chair conformation in which
all the O-silyloxy groups are in an axial position, the
C–N bond being equatorial.19 In this case, the normal
steric preference for the equatorial position due to the
bulky Boc group outweighs the small anomeric effect
of nitrogen substituents.20
find that oxathiazolidine 9 was obtained in 63% yield
from 6b after treatment with Boc2O in pyridine (Scheme
4). In sharp contrast, exposure of the a-epimer to
PhI(OAc)2, MgO and catalytic Rh(OAc)4 led to a mix-
ture of unidentifiable products. The starting material
6a was the only compound that could be isolated by
chromatography on silica gel after 16 h (ꢁ12% yield).
Longer reaction times led to the complete degradation
of compound 6a. These results are consistent with those
obtained for the diastereoisomeric mixture of 6 (Scheme
3).
The results observed for the sulfamate esters 6 and 8
prompted us to explore the reactivity of the correspond-
ing carbamates. The test substrates 11 were obtained in
79% yield from the epimeric mixture of alcohols 5 by
treatment with CCl3C(O)NCO followed by NH3/
H2O.21 Difficult separation of the mixture of diastereo-
isomers on silica gel afforded pure samples of the a-
and b-epimers of carbamates 11. In sharp contrast with
findings for sulfamates 6, both epimers of carbamates 11
provided the expected insertion products in similar
yields (60–63%) (Scheme 5). In addition, no trace of
the corresponding open-chain imine form of 12 was de-
tected by NMR analysis of the crude product. Conver-
sion of 11b afforded the spirooxazolidine 12a having
an anomeric a-configuration whereas the corresponding
epimer 11a led to a mixture of the two diastereoisomers
12a and 12b (a/b 1:2.2 after work-up; a/b 1:1.5 after
flash chromatography). In this latter reaction, due to a
small anomeric effect expected for nitrogen substituents,
the carbamate 12a was probably generated via
From results obtained with sulfamate esters 6 and 8, we
postulated that only the minor b-epimer was a substrate
for the cyclization reaction. This working hypothesis
was mainly based on two observations. According to
TLC, the conversion of 6 or 8 proceeded smoothly be-
fore slowing down significantly after a few hours. After
difficult purification of the reaction mixture, the starting
material recovered was isolated as a single diastereoiso-
mer having the a-anomeric configuration. No trace of
the b-epimer was detected. Our hypothesis prompted
us to find practical means to obtained diastereomerically
pure samples of the a- and b-epimers of sulfamate esters
6. Eventually, the mixture of diastereoisomers 6 could be
separated after careful purification on silica gel. The
intramolecular C–H insertion reaction was first investi-
gated with the sulfamate ester 6b. We were pleased to
1. MgO,PhI(OAc)2
Rh2(OAc)4 cat.
OBn
OBn
Boc
N
O
O
O
O
CH2Cl2, ∆,16h
BnO
BnO
BnO
BnO
O
O
S
S
2. Boc2O, Py
O
O
H2N
6β
9
63%
de > 98%
OBn
MgO, PhI(OAc)2
Rh2(OAc)4 cat.
O
H2N
O
O
O
BnO
BnO
degradation products
S
+ 6α (~12%)
CH2Cl2, ∆,16h
6α
Scheme 4.
MgO, PhI(OAc)2
Rh2(OAc)4 cat.
OBn
OBn
O
O
O
BnO
BnO
BnO
O
CH2Cl2, ∆, 16h
BnO
O
63%
N
H
H2N
12α
11β
de > 98%
O
MgO, PhI(OAc)2
Rh2(OAc)4 cat.
OBn
OBn
O
H
N
O
H2N
O
BnO
BnO
BnO
BnO
CH2Cl2, ∆, 20h
O
O
60%
O
11α
12α,β
(α/β 1/1.5)
Scheme 5.

4734
S. Toumieux et al. / Tetrahedron Letters 46 (2005) 4731–4735
OBn
O
References and notes
Boc2O (2 eq.)
Et3N (3.5 eq.)
DMAP cat.
OBn
Bn
O
O
O
BnO
BnO
O
1. (a) Shilov, A. E.; ShulÕpin, G. B. Chem. Rev. 1997, 97,
2879; (b) Labinger, J. A.; Bercaw, J. E. Nature 2002, 417,
507; (c) Kakiuchi, F.; Chatani, N. Adv. Synth. Catal. 2003,
345, 1077; (d) Schreiner, P. R.; Fokin, A. A. Chem. Record
2004, 3, 247; (e) Gois, P. M. P.; Afonso, C. A. M. Eur. J.
Org. Chem. 2004, 3773.
2. (a) Espino, C. G.; Wehn, P. M.; Chow, J.; Du Bois, J. J.
Am. Chem. Soc. 2001, 123, 6935; (b) Espino, C. G.; Du
Bois, J. Angew. Chem., Int. Ed. 2001, 40, 598.
3. Liang, J.-L.; Yuan, S.-X.; Huang, J.-S.; Yu, W.-Y.; Che,
C.-M. Angew. Chem., Int. Ed. 2002, 41, 3465.
4. For pioneering work on intramolecular nitrene C–H
insertion see: (a) Breslow, R.; Gellman, S. H. J. Am.
Chem. Soc. 1983, 105, 6728; For a recent study using chiral
O
O
BnO
H
2eq N
THF, 2h
N
H
Boc
H2ax
ed > 98%
65%
12α
13
Boc2O (2 eq.)
Et3N (3.5 eq.)
DMAP cat.
OBn
OBn
Boc
N
H
N
O
O
BnO
BnO
BnO
BnO
O
O
THF, 3h
O
14
ed > 98%
O
12β
90%
Scheme 6.
dirhodium(II) complexes see: (b) Fruit, C.; Muller, P.
¨
Helv. Chim. Acta 2004, 87, 1607.
equilibration of the initially formed epimer 12b.22 This
claim is supported by an equilibration experiment per-
formed from a pure sample of 12b. Under typical amina-
5. Hinman, A.; Du Bois, J. J. Am. Chem. Soc. 2003, 125,
11510.
6. See for example: (a) Godin, G.; Compain, P.; Masson,
G.; Martin, O. R. J. Org. Chem. 2002, 67, 6960; (b) Godin,
G.; Compain, P.; Martin, O. R. Org Lett. 2003, 5, 3269;
(c) Rousseau, C.; Martin, O. R. Org. Lett. 2003, 5,
3763.
7. Hanessian, S.; Lou, B. Chem. Rev. 2000, 100,
4443.
8. For a review on amino C-glycoside synthesis see: Xie, J.
Recent Res. Devel. Org. Chem. 1999, 3, 505.
9. Feming, J. J.; Fiori, K. W.; Du Bois, J. J. Am. Chem. Soc.
2003, 125, 2028.
1
tion conditions, epimerization occurred and H NMR
analysis of the crude product indicated the following ra-
tio: 12a/12b 1:2.2 after 16 h. These results confirm that
the amination reaction proceed either via a direct inser-
tion mechanism or by H-abstraction/radical recombina-
tion where the second step is extremely fast,11 thus
preventing the formation of a planar p-type anomeric
radical intermediate.23
The cyclic carbamates 12 were protected with a Boc
group (Scheme 6). Interestingly, extensive NMR analy-
sis indicated that compound 1324 exists predominantly
in a B2,5 conformation in which the N-Boc and benzyl-
oxymethyl substituents adopted a pseudo-equatorial
position that minimizes steric interactions. Coupling
constants24 are in good agreement with the proposed
structure as well as NOE effects observed between H-5
and H-2ax, and between H0a and H-2eq. As a general
rule, C–N bond of the N-Boc spiranic derivatives 9,
10, 13, or 14 always adopt an equatorial position via epi-
merization or conformational interconversion.
10. (a) For an example of an intramolecular insertion of
alkylidene carbenes into anomeric C–H bond see: War-
drop, D. J.; Zhang, W.; Fritz, J. Org. Lett. 2002, 4, 489; (b)
For an example of an intramolecular N-glycosidation via
1,5-hydrogen abstraction and an oxocarbenium ion inter-
´
mediate see: Francisco, C. G.; Herrera, A. J.; Suarez, E.
J. Org. Chem. 2003, 68, 1012; (c) For an example of a
chemoselective insertion of a rhodium nitrene in an allylic
C–H bond of a carbohydrate see: Parker, K. A.; Chang,
W. Org. Lett. 2005, 7, 1785.
11. (a) Liang, J.-L.; Yuan, S.-X.; Huang, J.-S.; Che, C.-M. J.
Org. Chem. 2004, 69, 3610; (b) Au, S.-M.; Huang, J.-S.;
Yu, W.-Y.; Fung, W.-H.; Che, C.-M. J. Am. Chem. Soc.
1999, 121, 9120; (c) Wehn, P.; Lee, J.; Du Bois, J. Org.
Lett. 2003, 5, 4823; (d) Na¨gelli, I.; Baud, C.; Bernardinelli,
In conclusion, we have reported the first examples of
intramolecular metal-catalyzed amination of a pseudo-
anomeric C–H bonds in a C-glycoside. The oxidative
conversion of sulfamate esters 6b and carbamates 11
provides bicyclic glycomimetics25 containing a function-
alizable N,O-acetal structure. No correlation between
anomeric stereochemistry and insertion efficiency was
found for the conversion of carbamates 11. In contrast,
amination reactions of the corresponding sulfamate
esters 6 were found to be strongly dependent on the
ÔanomericÕ configuration. Exploration of the chemical
reactivity of the oxathiazolidines or oxazolidines synthe-
sized as well as further applications of Rh-catalyzed
amination reactions to carbohydrates are currently
under investigations in our laboratory.
G.; Jacquier, Y.; Moran, M.; Muller, P. Helv. Chim. Acta
1997, 80, 1087.
¨
12. Costantino, V.; Imperatore, C.; Fattorusso, E.; Mangoni,
A. Tetrahedron Lett. 2000, 41, 9177.
13. (a) Goujon, J.-Y.; Gueyrard, D.; Compain, P.; Martin, O.
R.; Asano, N. Tetrahedron: Asymmetry 2003, 14, 1969; (b)
Goujon, J.-Y.; Gueyrard, D.; Compain, P.; Martin, O. R.;
Ikeda, K.; Kato, A.; Asano, N. Bioorg. Med. Chem. 2005,
13, 2313.
14. Cho, I. H.; Paquette, L. A. Heterocycles 2002, 58,
43.
15. The presence of a quaternary carbon at d 90.7 in 13C
NMR is a characteristic of a N,O-acetal structure.
16. (a) Du Bois, personal communication, see Ref. 16b; (b)
Fiori, K. W.; Fleming, J. J.; Du Bois, J. Angew. Chem.,
Int. Ed. 2004, 43, 4349.
1
17. Selected data for 9: H (500 MHz, CDCl3): d (ppm) 7.32
(m, 15H, 3C6H5); 4.91 (d, 1H, CH2Bn, J = 10.7 Hz); 4.71–
Acknowledgements
4.64 (m, 4H, CH2Bn); 4.61 (d, 1H, H0 J = 9.8 Hz); 4.57
b
(d, 1H, CH2Bn, J = 12.1 Hz); 4.21 (d, 1H, H0 ,
a
Financial support of this study by grants from CNRS
is gratefully acknowledged. S.T. thanks the French
Department of Research for a fellowship (MENRT).
J = 9.8 Hz); 3.84 (dd, 1H, H6b, J = 7.8, 11.6 Hz); 3.76–
3.70 (m, 2H, H4, H6a), 3.59–3.50 (m, 2H, H3, H5); 3.02 (t,
1H, H2ax, J = 12.8 Hz); 2.23 (dd, H2eq, J = 4.7, 13.1 Hz);

S. Toumieux et al. / Tetrahedron Letters 46 (2005) 4731–4735
4735
1.54 (s, 9H, Boc). 13C NMR (62.9 MHz, CDCl3) d 147.3,
138.4, 138.1, 137.8, 128.7–127.7, 89.8, 86.3, 77.1, 76.8,
75.9, 75.4, 73.6, 72.1, 70.9, 68.3, 35.2, 28.0; HRMS (ES)
m/z 648.2241 [M+Na]+ (C33H39NO9NaS requires
648.2243).
23. (a) Togo, H.; He, W.; Waki, Y.; Yokoyama, M. Synlett
1998, 700; (b) Praly, J.-P. Adv. Carbohydr. Chem. Biochem.
2001, 56, 65.
24. Selected data for 13: 1H (500 MHz, CDCl3): d (ppm) 7.40–
7.19 (m, 15H, 3C6H5); 4.60–4.51 (m, 4H, CH2Bn); 4.49 (d,
1H, CH2Bn, J = 12 Hz); 4.42 (d, 1H, CH2Bn,
J = 11.5 Hz); 4.36 (ddd, 1H, H5, J ꢁ 3.0, 3.5, 9.5 Hz);
4.25 (d, 1H, H0 J = 10.0 Hz); 4.20 (d, 1H, H0
1
18. As it was observed for the reaction performed with 6, H
NMR analysis of the crude product seemed to indicate the
presence of the expected spirooxathiazolidine in equili-
brium with the corresponding open-chain imine form
(ratio 1:1).
b
a
J = 10.0 Hz); 4.07 (m, 1H, H3); 3.65 (d, 2H, H6,
J = 3.0 Hz); 3.62 (dd, 1H, H4, J ꢁ 2.5, 9.5); 3.04 (dd,
1H, H2ax, J = 4.0, 14.5 Hz); 2.07 (dd, 1H, Heq, J = 4.0,
14.5 Hz); 1.55 (s, 9H, Boc). 13C NMR (62.9 MHz, CDCl3)
d 151.9, 150.2, 138.4, 137.9, 137.8, 128.7–127.7, 89.8, 84.6,
76.7, 76.4, 74.6, 73.3, 72.4, 71.3, 69.5, 32.4, 28.1; HRMS
(ES) m/z 612.2570 [M+Na]+ (C34H39NO8Na requires
612.2573).
19. Bulky silyl groups on the 3,4-trans-hydroxy groups of
pyranoses are known to cause a conformation flip leading
to a 1C4 D-hexopyranose form. See for example: (a)
Tamura, S.; Abe, H.; Matsuda, A.; Shuto, S. Angew.
Chem., Int. Ed. 2003, 42, 1021; (b) Ichikawa, S.; Shuto, S.;
Matsuda, J. J. Am. Chem. Soc. 1999, 121, 10270.
ˇ
20. Tvaroska, I.; Bleha, T. Adv. Carbohydr. Chem. Biochem.
1989, 47, 45.
25. Spiro-C-glycosides of five-membered heterocycles are
known to display biological activities such as glycogen
phosphorylase inhibition or D-fructose transport inhibi-
tion. See for example: Schweizer, F. Angew. Chem., Int.
Ed. 2002, 41, 230; Tatiboue¨t, A.; Lawrence, S.; Rollin, P.;
Holman, G. D. Synlett 2004, 1945.
21. Gais, H.-J.; Loo, R.; Roder, D.; Das, P.; Raabe, G. Eur.
J. Org. Chem. 2003, 1500.
22. The mixture of epimers 12a/12b was separated on silica
gel.