The first catalytic Mannich-type reaction of N-alkoxycarbonylamino sulfones with silyl enolates

Article abstract of DOI:10.1002/adsc.200606222

Bismuth inflate was found to be an efficient catalyst in the Mannich-type reaction of silyl enolates with N-alkoxycarbonylamino sulfones. The reaction proceeded smoothly with a low catalyst loading of bismuth triflate (0.5-1.0 mol%) to afford the correspo

Full text of DOI:10.1002/adsc.200606222

COMMUNICATIONS
DOI: 10.1002/adsc.200606222
The First Catalytic Mannich-Type Reaction of N-Alkoxycarbonyl-
amino Sulfones with Silyl Enolates
Thierry Ollevier,a,* Etienne Nadeau,a and Jean-Christophe Eguillona
a
DØpartement de Chimie, UniversitØ Laval, QuØbec, QuØbec G1K 7P4, Canada
Fax : (+1)-418-656-7916; e-mail: thierry.ollevier@chm.ulaval.ca
Received: May 11, 2006; Accepted: July 24, 2006
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: Bismuth triflate was found to be an effi-
cient catalyst in the Mannich-type reaction of silyl
enolates with N-alkoxycarbonylamino sulfones. The
reaction proceeded smoothly with a low catalyst
loading of bismuth triflate (0.5–1.0 mol%) to afford
the corresponding protected b-aminocarbonyl com-
pound in very good yields (up to 96%).
Recently, several laboratories have disclosed signifi-
cant advances regarding rare-earth and lanthanide tri-
flates as catalysts for Mannich-type reactions.[3] High
catalytic activity, low toxicity, moisture- and air-toler-
ance make lanthanide triflates valuable catalysts.
However, the high cost of these catalysts restricts
their use. Bismuth compounds are of interest as less
toxic and cheaper alternatives to the latter.[4] Bismuth
salts have been reported as catalysts for opening of
epoxides,[5] Mukaiyama-aldol reactions,[6] formation
and deprotection of acetals,[7] Friedel–Crafts reac-
tions,[8] Fries and Claisen rearrangements,[9] and Sa-
Keywords: N-alkoxycarbonylamino sulfones; bis-
muth; green chemistry; Mannich bases; Mannich
reaction; silyl enolates
kurai reactions.[10] Bi
(OTf)3 is particularly attractive
A
because it is commercially available or can be easily
prepared from commercially available starting materi-
The development of new methods for the synthesis of als.[11] We recently reported the Bi
(OTf)3-catalyzed
U
b-aminocarbonyl derivatives is an important area of Mannich-type reaction of a variety of aldimines gen-
synthetic efforts. b-Aminocarbonyl compounds are erated in situ using aldehydes, amines, and silyl eno-
extremely important as biologically active molecules. lates in a three-component reaction.[12] This method
Among the variety of synthetic methods reported so was very efficient with anilines but using Cbz carba-
far, Lewis acid-catalyzed reactions of imines with silyl mate instead of an aniline gave only a moderate yield
enolates provide an efficient route for the synthesis of of the Cbz-protected b-aminocarbonyl compound.[12b]
b-amino ketones and esters. Therefore, the develop- These results encouraged us to pursue a different ap-
ment of new catalytic methods for their preparation is proach to the bismuth
of prime importance in organic synthesis. Catalytic reaction.
ACHTREUNG
Mannich-type reactions have been reported by sever-
As a part of our ongoing interest in bismuth
ACHTREUNG
al groups as an efficient method to prepare b-amino- catalyzed reactions involving silyl nucleophiles, we
carbonyl compounds.[1] However, many imines tend to report herein a general bismuth triflate hydrate
be unstable during the purification process, such as [Bi(OTf)3·4H2O] catalyzed method for the addition of
N
distillation, chromatography, or prolonged storage. silyl enolates to N-alkoxycarbonylamino sulfones.[13]
Thus, methods involving the in situ generation of the Scheme 1 illustrates the preparation of the N-acyl-
imine are highly attractive, among which is the one- imine or -iminium precursor from the corresponding
pot preparation of imines formed in situ from alde- aldehydes.[14] N-Alkoxycarbonyl imines have been
hydes and amines, have been proposed.[2] Neverthe- prepared from the basic treatment of the N-alkoxy-
less, most Lewis acids cannot be used in this reaction carbonylamino sulfones 1;[15] the corresponding N-al-
because they deactivate or decompose in the presence koxycarbonyliminium derivatives have been prepared
of the amine and water produced during imine forma- by the use of a Lewis acid with 1 (Scheme 1).
tion. Very reactive N-acyliminium species, which can
We report the first catalytic Mannich-type reaction
easily be prepared from stable precursors, provide an of N-alkoxycarbonylamino sulfones with silyl eno-
attractive alternative.
lates. Alkoxycarbonyl protected b-aminocarbonyl de-
rivatives are obtained efficiently in the presence of
2080
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2006, 348, 2080 – 2084

Mannich-Type Reaction of N-Alkoxycarbonylamino Sulfones with Silyl Enolates
COMMUNICATIONS
choice. Other carbamate protecting groups on 1 led to
very good yields of the desired products 3 (Table 1,
entries 5 and 6). N-Benzyloxycarbonylamino phenyl
sulfones were chosen as model substrates for the fol-
lowing studies.
Several examples of Bi(OTf)3-catalyzed Mannich-
N
type reactions of various N-benzyloxycarbonylamino
sulfones 1 with silyl enol ethers are summarized in
Table 2. N-Benzyloxycarbonylamino sulfones 1 de-
rived from differently substituted benzaldehydes were
reacted with trimethyl(1-phenylvinyloxy)silane in di-
chloromethane at room temperature. The correspond-
ing b-amino ketones 3 were obtained in very good to
excellent yields (Table 2, entries 1–6). The reaction
was efficient using electron-deficient benzaldehyde-
Scheme 1. Alkoxycarbonylamino sulfones as precursors of
N-alkoxycarbonylimine derivatives.
0.5–1.0 mol% of Bi(OTf)3·4H2O. To the best of our derived sulfones and the corresponding b-amino ke-
N
knowledge, a catalytic version of this reaction has tones 3 were obtained with very good yields (Table 2,
never been reported. The only published Mannich- entries 1 and 2). Sulfones derived from several elec-
type reactions from N-alkoxycarbonylamino sulfones tron-rich aromatic aldehydes led to the desired prod-
involve a Lewis acid-like TiCl4 or SnCl4 used in a stoi- ucts in good yields (Table 2, entries 3–6). For selected
chiometric amount or in large excess.[16]
substrates, a slightly better yield was obtained when
Initially, we screened various solvents for the Man- using a catalyst loading of 1 mol% instead of 0.5
nich-type reaction of N-alkoxycarbonylamino sulfones mol% (Table 2, compare entries 5 and 6). N-Benzyl-
1 with trimethyl(1-phenylvinyloxy)silane 2a in the oxycarbonylamino sulfones derived from aliphatic al-
presence of Bi
ACHTREUNG
latter was treated with 0.5 mol% Bi
AHCTREUNG
THF for 7 h at 228C, the corresponding Cbz-protect- yloxy)silane afforded b-amino ketone 3m in good
ed b-amino ketone was isolated in moderate yield yield (Table 2, entry 10). Silyl enol ethers derived
(51%) (Table 1, entry 1). Among various polar sol- from 3-pentanone, cyclopentanone, or 2,4-dimethyl-3-
vents tested, acetonitrile and dichloromethane gave pentanone afforded smoothly b-amino ketones 3n, 3o,
the best yields of the expected product (Table 1, en- and 3p, respectively (Table 2, entries 11–13).[17]
tries 2 and 3). The catalyst loading had to be in-
A further investigation with various silyl ketene
creased to 1 mol% for some substrates (Table 1, acetals is summarized in Table 3. Silyl ketene acetals
entry 4). Because of the poor solubility in acetonitrile 4 derived from various esters were reacted with N-
of many N-alkoxycarbonylamino sulfones 1 presented benzyloxycarbonylamino sulfones 1 in the presence of
here, dichloromethane was selected as the solvent of 0.5–1 mol% Bi(OTf)3·4H2O. The corresponding b-
G
Table 1. Bi
C
Entry
R1
R2
x (mol%)
Solvent
3
Yield of 3 [%][b]
1
2
3
4
5
6
Et
Et
Et
Ph
Ph
Ph
Cbz
Cbz
Cbz
Cb
Boc
CO2Et
0.5
0.5
0.5
z
1
0.5
THF
3a
3a
3a
51
90
94
MeCN
CH2Cl2
2Cl2
CH2Cl2
CH2Cl2
1
CH3b
3c
85
80[c]
85
3d
[a]
Conditions: N-alkoxycarbonylamino phenylsulfone (1.0 equiv.), trimethyl(1-phenylvinyloxy)silane 2a (1.3 equivs.),
Bi(OTf)3·4H2O (0.005–0.01 equivs.).
Isolated yield.
ACHTREUNG
[b]
[c]
Product 3c slightly decomposed on silica gel chromatography and was contaminated by small quantities of deprotected b-
aminoketone.
Adv. Synth. Catal. 2006, 348, 2080 – 2084
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.asc.wiley-vch.de
2081

Thierry Ollevier et al.
COMMUNICATIONS
Table 2. Bi(OTf)3-catalyzed Mannich-type reactions with various N-benzyloxycarbonylamino phenyl sulfones and silyl enol
A
ethers.[a]
Entry
R1
Silyl enol ether 2
x (mol%)
3
Yield of 3 [%][b]
1
2
3
4
5
6
7
8
9
4-ClC6H4
4-FC6H4
4-MeC6H4
2-MeC6H4
4-MeOC6H4
4-MeOC6H4
2a
0.5
0.5
0.5
0.5
0.5
1
1
1
0.5
3e
3f
3g
3h
3i
84
92
89
88
83
87
87
96
85
3i
CH3
(CH3)2CH
c-C6H11
A
3j
3k
3l
H
10
11
CH3(CH2)2
G
0.5
1
3m
80
C6H5CH2
3n
77[c]
12
CH3
(CH2)2
0.5
0.5
3o
3p
81[d]
86
13
4-MeC6H4
[a]
Conditions: N-benzyloxycarbonylamino phenyl sulfone (1.0 equiv.), silyl enol ether (1.3 equivs.), Bi(OTf)3·4H2O (0.005–
A
0.01 equivs.).
Isolated yield.
[b]
[c]
Silyl enol ether was used as a mixture of stereoisomers (Z/E=87:13). Product 3n was isolated as a mixture of stereoiso-
1
mers (syn/anti=72:28) (ratio determined by H NMR).
Product 3o was isolated as a 57/43 mixture of diastereosisomers as determined by H NMR.
[d]
1
amino esters 5 were obtained in moderate to good reoselectivity [2 mol% Bi(OTf)3·4H2O, yield=84%,
E
R
G
H
C
A
T
N
yields (Table 3). Silyl enolates derived from esters as 3n/3nꢀ (syn/anti)=72:28] (Scheme 2). Reduction of
well as thioesters reacted smoothly to give the ad- the major diastereoisomer 3n with lithium tri-tert-bu-
ducts. The N-benzyloxycarbonylamino sulfone derived toxyaluminohydride afforded 6 as the only diastereo-
from n-butyraldehyde 1 led to moderate yields of b- isomer. Further cyclization of the latter with NaH af-
amino esters when reacted with acetate derived silyl forded 4-benzyl-6-ethyl-5-methyl-1,3-oxazinan-2-one
ketene acetals (Table 3, entries 1 and 2). A very good 7. The relative configuration of the six-membered car-
yield was obtained when the same sulfone was sub- bamate was established as cis-cis via NMR analysis.
jected to
a
tetrasubstituted silyl ketene acetal
In summary, we have found that the Mannich-type
(Table 3, entry 3). The latter afforded moderate to reaction of N-benzyloxycarbonylamino sulfones 1 pro-
good yields of b-amino esters 5d, 5e, and 5f with phe- ceeds smoothly with silyl enolates and a catalytic
nylacetaldehyde, p-tolualdehyde, and o-tolualdehyde amount of Bi
A
derived sulfones respectively (Table 3, entries 4–6). advantages including mild reaction conditions, very
The potential of this catalytic approach is further low catalyst loading (0.5–1 mol%), and no formation
demonstrated by the synthesis of a substituted 1,3-ox- of by-products such as deamination products. To the
azinan-2-one via
a reduction-cyclization strategy best of our knowledge, this is the first report of a cat-
(Scheme 2).[18] Optimization of the previously report- alytic Mannich-type reaction of N-alkoxycarbonylami-
ed Mannich-type reaction of trimethyl(pent-2-en-3- no sulfones with silyl enolates. Moreover, our process
yloxy)silane with the sulfone derived from phenylace- involves an environmentally benign, cheap, and easy
taldehyde (Table 2, entry 11) led to the corresponding to handle catalyst. The b-aminocarbonyl compound,
b-amino ketone in a good yield with moderate diaste- already protected as a Cbz derivative, is smoothly ob-
2082
www.asc.wiley-vch.de
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2006, 348, 2080 – 2084

Mannich-Type Reaction of N-Alkoxycarbonylamino Sulfones with Silyl Enolates
COMMUNICATIONS
Table 3. Bi(OTf)3-catalyzed Mannich-type reactions with various N-benzyloxycarbonylamino phenyl sulfones and silyl
N
ketene acetals.[a]
Entry
1
R1
CH3
CH3(CH2)2
Silyl ketene acetal 4
x (mol%)
0.5
5
Yield of 5 [%][b]
(CH2)2
5a
66
2
3
G
0.5
1
5b
5c
61
86
CH3(CH2)2
U
4
5
6
C6H5CH2
4-MeC6H4
2-MeC6H4
1
1
1
5d
5e
5f
67
78
73
[a]
Conditions: N-benzyloxycarbonylamino phenyl sulfone (1.0 equiv.), silyl ketene acetal (1.3 equivs.), Bi(OTf)3·4H2O
A
(0.005–0.01 equivs.).
Isolated yield.
[b]
Scheme 2. Synthesis of 1,3-oxazinan-2-ones via the N-alkoxycarbonylamino phenyl sulfone pathway.
1H NMR, tetramethylsilane (TMS) served as internal stan-
dard (d=0). For 13C NMR, CDCl3 was used as internal stan-
dard (d=77.0) and spectra were obtained with complete
proton decoupling. For 19F NMR, CFCl3 was used as internal
standard (d=0). Column chromatography was performed
on silica gel (230–400 mesh) and analytical thin-layer chro-
matography was carried out using 250 mm commercial silica
gel plates. Acetonitrile and dichloromethane were distilled
from calcium hydride (CaH2). Tetrahydrofuran was distilled
from sodium/benzophenone.
tained under mild conditions. Because of its numerous
benefits, the Bi(OTf)3·4H2O protocol should find util-
ity in the synthesis of biologically active compounds.
Research is under way to demonstrate other signifi-
ACHTREUNG
cant applications of this Bi
Mannich-type reaction.
A
Experimental Section
General Procedure for the Bismuth-Catalyzed
Mannich-type Reaction
General Remarks
Infrared spectra were recorded on an FT infrared spectrom-
eter and are reported in reciprocal centimeters (cmÀ1). H,
Under an inert atmosphere of argon, the silyl enolate
(0.65 mmol) in 0.5 mL of dry dichloromethane was added
1
13C, and 19F NMR spectra were recorded on a 400 MHz nu-
clear magnetic resonance spectrometer in CDCl3. For
dropwise to a solution of Bi(OTf)3·4H2O (0.0025 mmol,
A
Adv. Synth. Catal. 2006, 348, 2080 – 2084
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.asc.wiley-vch.de
2083

Thierry Ollevier et al.
COMMUNICATIONS
1.8 mg or 0.0050 mmol, 3.6 mg) and the N-alkoxycarbonyl-
amino sulfone (0.5 mmol) in 1 mL of dry dichloromethane.
The mixture was stirred at room temperature until the reac-
tion was complete as indicated by TLC. The reaction was
quenched with water (2 mL) and the mixture extracted with
ethyl acetate (3”10 mL). The organic phase was washed
with water (2 mL) and saturated aqueous sodium chloride
(2 mL), dried over magnesium sulfate, and concentrated
under vacuum (rotary evaporator). The crude product was
purified by silica gel chromatography (hexane/ethyl acetate/
triethylamine 75/24/1–96/3/1).
Tetrahedron Lett. 2004, 45, 49–52; c) T. Ollevier, G.
Lavie-Compin, Tetrahedron Lett. 2002, 43, 7891–7893.
[6] a) T. Ollevier, V. Desyroy, B. Debailleul, S. Vaur, Eur.
J. Org. Chem. 2005, 4971–4973; b) S. Kobayashi, T.
Ogino, H. Shimizu, S. Ishikawa, T. Hamada, K.
Manabe, Org. Lett. 2005, 7, 4729–4731; c) C. Le Roux,
L. Ciliberti, H. Laurent-Robert, A. Laporterie, J.
Dubac, Synlett 1998, 1249–1251.
[7] a) N. M. Leonard, M. C. Oswald, D. A. Freiberg, B. A.
Nattier, R. C. Smith, R. S. Mohan, J. Org. Chem. 2002,
67, 5202–5207; b) M. D. Carrigan, D. Sarapa, R. C.
Smith, L. C. Wieland, R. S. Mohan, J. Org. Chem. 2002,
67, 1027–1030.
[8] a) C. Le Roux, J. Dubac, Synlett 2002, 181–200; b) J. R.
Desmurs, M. Labrouill›re, C. Le Roux, H. Gaspard, A.
Laporterie, J. Dubac, Tetrahedron Lett. 1997, 38, 8871–
8874; c) S. RØpichet, C. Le Roux, J. Dubac, J. R. Des-
murs, Eur. J. Org. Chem. 1998, 2743–2746.
[9] a) T. Ollevier, V. Desyroy, M. Asim, M.-C. Brochu,
Synlett 2004, 2794–2796; b) T. Ollevier, T. M. Mwene-
Mbeja, Tetrahedron Lett. 2006, 47, 4051–4055; c) B.
Sreedhar, V. Swapna, C. Sridhar, Synth. Commun.
2004, 34, 1433–1440.
Acknowledgements
This work was financially supported by the Natural Sciences
and Engineering Research Council ofCanada (NSERC), the
Fonds QuØbØcois de la Recherche sur la Nature et les Tech-
nologies (FQRNT, QuØbec, Canada), the Canada Foundation
for Innovation, and UniversitØ Laval. E. N. thanks NSERC
for a postgraduate scholarship. J.-C. E. thanks the Office
Franco-QuØbØcois pour la Jeunesse (OFQJ) for an under-
graduate scholarship. We thank Rhodia (Lyon, France) and
Sidech s.a. (Tilly, Belgium) for generous gift of chemicals.
[10] a) T. Ollevier, T. Ba, Tetrahedron Lett. 2003, 44, 9003–
9005; b) B. Leroy, I. E. Markó, Org. Lett. 2002, 4, 47–
50.
[11] a) S. RØpichet, A. Zwick, L. Vendier, C. Le Roux, J.
Dubac, Tetrahedron Lett. 2002, 43, 993–995; b) M.
Labrouill›re, C. Le Roux, H. Gaspard, A. Laporterie, J.
Dubac, J. R. Desmurs, Tetrahedron Lett. 1999, 40, 285–
286; c) M. Peyronneau, C. Arrondo, L. Vendier, N.
Roques, C. Le Roux, J. Mol. Cat. A 2004, 211, 89–91;
References
[1] For reviews of catalytic Mannich-type reactions: a) S.
Kobayashi, M. Ueno, Comprehensive Asymmetric Cat-
alysis, Supplement, Springer, Berlin, 2004, 1, 143–150;
b) A. Córdova, Acc. Chem. Res. 2004, 37, 102–112;
c) M. Arend, B. Westermann, N. Risch, Angew. Chem.
Int. Ed. 1998, 37, 1044–1070; d) S. Kobayashi, M. Su-
giura, H. Kitagawa, W. W.-L Lam, Chem. Rev. 2002,
102, 2227–2302; e) S. Kobayashi, H. Ishitani, Chem.
Rev. 1999, 99, 1069–1094.
d) Bi(OTf)3·4H2O has been prepared from Bi2O3 ac-
N
cording to ref.[11a]
[12] a) T. Ollevier, E. Nadeau, Synlett 2006, 219–222; b) T.
Ollevier, E. Nadeau, J. Org. Chem. 2004, 69, 9292–
9295.
[13] For a recent review of N-alkoxycarbonylamino sulfones
as precursors of N-alkoxycarbonyl iminium derivatives:
M. Petrini, Chem. Rev. 2005, 105, 3949–3977.
[14] a) J. B. F. N. Engberts, J. Strating, Recl. Trav. Chim.
1965, 84, 942–950; b) T. Mecozzi, M. Petrini, J. Org.
Chem. 1999, 64, 8970–8972.
[15] a) N. Giri, M. Petrini, R. Profeta, J. Org. Chem. 2004,
69, 7303–7308; b) T. Mecozzi, M. Petrini, R. Profeta, J.
Org. Chem. 2001, 66, 8264–8267; c) C. Palomo, M.
Oiarbide, M. C. Gonzµlez-Rego, A. K. Sharma, J. M.
Garciµ, A. Gonzµlez, C. Landa, A. Linden, Angew.
Chem. Int. Ed. 2000, 39, 1063–1065.
[2] For reviews of multicomponent reactions: a) J. Zhu, H.
BienaymØ (Eds.), Multicomponent Reactions, Wiley-
VCH, Weinheim, 2005; b) M. Syamala, Org. Prep.
Proc. Int. 2005, 37, 103–171. For recent examples of
multicomponent reactions: c) S. Kobayashi, S. Iwamoto,
S. Nagayama, Synlett 1997, 1099–1101; d) T. Akiyama,
J. Takaya, H. Kagoshima, Synlett 1999, 1426–1428;
e) S. Iimura, D. Nobutou, K. Manabe, S. Kobayashi,
Chem. Commun. 2003, 1644–1645.
[3] a) S. Kobayashi, M. Araki, H. Ishitani, S. Nagayama, I.
Hachiya, Synlett 1995, 233–234; b) S. Kobayashi, M.
Araki, M. Yasuda, Tetrahedron Lett. 1995, 36, 5773–
5776; c) S. Kobayashi, T. Busujima, S. Nagayama, Syn-
lett 1999, 545–546; d) S. Kobayashi, M. Moriwaki, R.
Akiyama, S. Suzuki, I. Hachiya, Tetrahedron Lett. 1996,
37, 7783–7786.
[16] a) M. Petrini, E. Torregiani, Tetrahedron Lett. 2005, 46,
5999–6003; b) D. Enders, S. Oberbçrsch, Synlett 2002,
471–473; c) A. Giardinꢁ, T. Mecozzi, M. Petrini, J.
Org. Chem. 2000, 65, 8277–8282.
[17] Various b-amino ketones derivatives were found very
effective as bioactive compounds: H. Buschmann, C.
Puetz, D. Enders, S. Oberboersch, US Patent
0096361 A1, 2005.
[18] A related strategy has been disclosed in solid-phase
synthesis: S. Schunk, D. Enders, Org. Lett. 2001, 3,
3177–3180.
[4] a) H. Suzuki, Y. Matano
A
Chemistry, Elsevier, Amsterdam, 2001; b) H. Gaspard-
Iloughmane, C. Le Roux, Eur. J. Org. Chem. 2004,
2517–2532; c) N. M. Leonard, L. C. Wieland, R. S.
Mohan, Tetrahedron 2002, 58, 8373–8397.
[5] a) C. Ogawa, S. Azoulay, S. Kobayashi, Heterocycles
2005, 66, 201–206; b) T. Ollevier, G. Lavie-Compin,
2084
www.asc.wiley-vch.de
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2006, 348, 2080 – 2084