Ytterbium triflate-catalyzed reactions of imines with a chiral non- racemic silyloxypyrrole

Article abstract of DOI:10.1016/S0040-4039(00)00625-0

In the presence of a catalytic amount of ytterbium triflate the reactions of various aromatic imines with a chiral non-racemic silyloxypyrrole proceeded smoothly to afford the corresponding aldol-type adducts in good yields and diastereoselectivities. (C)

Full text of DOI:10.1016/S0040-4039(00)00625-0

Tetrahedron Letters 41 (2000) 4367±4371
Ytterbium tri¯ate-catalyzed reactions of imines with a chiral
non-racemic silyloxypyrrole
Bruno Dudot,a Jacques Royer,a,*,y Mireille Sevrinb and Pascal Georgeb
aInstitut de Chimie des Substances Naturelles, CNRS, 91198 Gif-sur-Yvette Cedex, France
 Â
Sano®-Synthelabo, Departement de Recherche SNC, 31 avenue Paul Vaillant Couturier, 92220 Bagneux, France
b
Received 6 March 2000; accepted 14 April 2000
Abstract
In the presence of a catalytic amount of ytterbium tri¯ate the reactions of various aromatic imines with a
chiral non-racemic silyloxypyrrole proceeded smoothly to a€ord the corresponding aldol-type adducts in
good yields and diastereoselectivities. # 2000 Elsevier Science Ltd. All rights reserved.
In the search of new methods of access to variously substituted g-lactams, we recently reported
a simple one-step preparation of the chiral lactam 1,1 which was proved to be easily substituted at
several positions of the ®ve-membered ring.1 3 It has been shown that the silyloxypyrrole 2, easily
accessible from 1, reacted with achiral aldehydes at the C-5 position of the pyrrolidine ring to give
3 in good yield and with high diastereoselectivity.3
In this paper, we report the reaction of several imines 4 with silyloxypyrrole 2. As far as we
know, there is no example in the literature of such a reaction. Indeed, the reaction of silyloxy-
furan with potential N-acyl iminiums has been extensively reported4 and some examples exist
with imines or imine equivalents.5 In the silyloxypyrrole series only a few examples of condensation
with potential N-acyl-iminium were reported.6
Following the report on the silyloxyfuran condensation with imines5 and our previous work on
aldehydes, we ®rst examined the reaction of the chiral non-racemic silyloxypyrrole 2 with imines
.
in the presence of boron tri¯uoride etherate (BF3 Et2O) in methylene chloride. Unfortunately,
under these conditions, no reaction occurred and lactam 1b was the only product recovered from
the reaction mixture for attempts made at di€erent temperatures ranging from ^78ꢀC to rt.
We turned to the use of lanthanide tri¯ate reported by Kobayashi et al.7 as catalyst for the
condensation of aldimines with silyl enol ethers, ketene silylacetals, allyltributylstannane. Indeed,
* Corresponding author. E-mail: jacques.royer@pharmacie.univ-paris5.fr
y
Present address: Laboratoire de Chimie Therapeutique, Faculte de Pharmacie, 4 avenue de l'Observatoire, 75270
Paris Cedex 06, France.
0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00625-0

4368
the reaction of silyloxypyrrole 2 with imines, in the presence of a catalytic amount of ytterbium
tri¯ate, proceeded smoothly and underwent the formation of adduct 5 (Scheme 1). The reaction
was studied with various imines (1 equiv.) using a 10% mol. amount of Yb(OTf)3, in di€erent
experimental conditions, and the results are reported in Tables 1 and 2. The imines were prepared
by the condensation of amine and aldehyde without solvent.
Scheme 1.
Table 1
Yb(OTf)3-catalyzed condensation of imines derived from aniline with silyloxypyrrole 2
We ®rst examined the reaction of imines derived from aniline and various aldehydes by varying
the solvent and the temperature. From Table 1 it can be seen that imines formed from aromatic
aldehydes led to the corresponding adduct 5 in high yields irrespective of the solvent. Never-
theless, the reaction was not ecient with aliphatic aldimines, probably due to their high potency
to isomerize to enamines. The reaction was fairly diastereoselective, giving rise to mixtures of
diastereomers. Nevertheless, in most cases the major isomer was formed in more than 50% yield
and could be isolated.8 Furthermore, the erythro/threo selectivity (vide infra for determination of
the relative con®guration) was good in every case. Experimental conditions induced small variations
in the diastereoselectivity, showing better results at ^70ꢀC in CH2Cl2. All the assays described
below were undertaken using these conditions.

4369
Table 2
Yb(OTf)3-catalyzed condensation of imines derived from benzaldehyde with 2 (CH2Cl2, ^70ꢀC)
Silyloxypyrroles 6, 7 and 8 were prepared and checked on the reaction with imine 4b derived
from 2-furfural and aniline. Good yields but lower diastereoselectivity ratios were observed (an
average ratio of 45:25:25:5 was found in each case), con®rming that silyloxypyrrole 2 gave the
best results.
We also examined the in¯uence of the N-substituent R2 of imines 4 derived from benzaldehyde
upon the diastereoselectivity. It can be seen from the results reported in Table 2, that ortho-
substitution on the aromatic ring underwent signi®cative improvement of the diastereoselectivity.
The relative con®guration of the di€erent diastereomers was dicult to determine. Careful
1
examination of H NMR data indicated that the two major diastereomers possessed the same
relative con®guration at the two new created chiral centers: the diagnostic protons exhibited a
small coupling constant which was indicative for an erythro con®guration. This has been proved
by chemical transformations of one isomer of 5e (R1=Ph, R2=CH2Ph) to a bicyclic derivative.
The crude reaction mixture of 5e was submitted to hydrogenation (H2, Pd/C, MeOH, 80%) and
hydrolysis (NaOH, MeOH) to furnish compounds 9e from which the two major isomers were
separated by column chromatography on silica gel giving pure 9e0 (major, 42%) and 9e00 (minor,
18%). These two isomers were separately treated with CBr4/PPh3 (THF, Et3N, rt). Surprisingly,
only 9e00 cyclized to compound 109 (52%) (Scheme 2), while the major amino lactam 9e0 was
found to be unreactive.
1
The examination of the H NMR spectrum of 10 clearly established the relative con®guration
of the chiral centers from which can be deduced the erythro con®guration of the corresponding

4370
Scheme 2.
compound 5e. The same erythro relative con®guration for the major isomer of 5e could be proposed
1
on the basis of similar H NMR behavior. This result is in sharp contrast with the major threo
con®guration found in the aldol reaction of 2 with aldehydes.
In summary, we found that chiral non-racemic silyloxypyrrole 2 can react with non-enolizable
aldimines in the presence of a catalytic amount of Yb(OTf)3 supplying a new short stereoselective
approach for the preparation of 5-aminomethyl pyrrolidones.
Acknowledgements
The authors are pleased to thank Professor H.-P. Husson for interest in this work and for
valuable and enjoyable discussions.
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4371
8. (a) Compound 5c (major isomer): white amorphous solid; [ꢀ]D ^84 (CHCl3, c 0.8); 1H NMR (300 MHz, CDCl3) ꢁ
(ppm): 4.0 (broad s, 1H), 4.65 (m, 2H), 5.0 (dd, 1H, J=6.0, 11.2 Hz), 5.35 (d, 1H, J=3.7 Hz), 5.95 (dd, 1H, J=6.0,
9.7 Hz), 6.15 (d, 2H, J=8.1 Hz), 6.35 (dd, 1H, J=1.7, 6.0 Hz), 6.65 (m, 2H), 6.9 (m, 3H), 7.2 (t, 1H, J=6.0 Hz),
7.3 (t, 2H, J=7.7 Hz), 7.6±7.4 (m, 9H), 7.75 (d, 1H, J=8.1 Hz), 7.85 (d, 1H, J=7.9 Hz), 8.05 (d, 2H, J=7.1 Hz);
13C (75.43 MHz, CDCl3) ꢁ (ppm): 53.2, 53.9, 63.8, 64.9, 113.5, 118.5, 121.4, 124.7, 125.6, 125.8, 126.6, 128.1, 128.3,
128.5, 128.7, 129.2, 129.4, 129.5, 129.8, 130.1, 133.1, 134.2, 136.1, 145.1, 145.7, 165.9, 172.4. (b) Compound 5c
(minor isomer): white amorphous solid; [ꢀ]D +91 (CHCl3, c 0.2); 1H NMR (300 MHz, CDCl3) ꢁ (ppm): 3.8 (broad
s, 1H), 4.85 (broad s, 1H), 4.95 (broad s, 1H), 5.15 (dd, 1H, J=5.6, 11.1 Hz), 5.35 (dd, 1H, J=9.5, 11.1 Hz), 5.9
(dd, 1H, J=5.6, 9.3 Hz), 6.1 (d, 2H, J=7.9 Hz), 6.3 (m, 2H), 6.6 (t, 1H, J=6.5 Hz), 6.8 (dd, 1H, J=1.4, 6.0 Hz),
6.9 (t, 2H, J=8.3 Hz), 8.0±7.0 (m, 16H); 13C (75.43 MHz, CDCl3) ꢁ (ppm): 52.9, 54.3, 63.6, 64.5, 113.8, 118.0,
121.5,124.9, 125.8, 126.7, 127.3, 128.4, 128.7, 128.8, 129.0, 129.7, 130.4, 133.1, 133.6, 134.3, 136.4, 133.1, 146.0,
166.2, 173.3.
1
9. Compound 10: white amorphous solid; [ꢀ]D ^112 (CHCl3, c 0.7); H NMR (CDCl3, 250 MHz) ꢁ (ppm): 1.45 (m,
1H), 2.0 (m, 2H), 2.35 (m, 1H), 3.05 (dd, 1H, J=3.4, 12.8 Hz), 3.2 (dd, 1H, J=5.4, 12.8 Hz), 3.4 (d, 1H, J=13.6
Hz), 3.5 (d, 1H, J=13.6 Hz), 3.85 (d, 1H, J=5.0 Hz,), 4.35 (m, 1H), 5.4 ( dd, 1H, J=3.6, 4.7 Hz), 7.2±7.5 (m,
13H), 7.55 (d, 2H, J=9.0 Hz); 13C NMR (CDCl3, 75.43 MHz) ꢁ (ppm): 19.7, 30.0, 47.6, 51.7, 55.7, 59.38, 65.6,
127.4, 128.1, 128.5, 129.0, 130.4, 135.8, 138.3, 140.2, 174.5; MS (IC): 383 (MH+); HRMS calcd. for C26H27N2O:
383.21232; found: 383.21044.