Indium-mediated diastereoselective addition of allyl bromides to enantiomerically pure N-tert-butylsulfinyl aldimines

Article abstract of DOI:10.1016/j.tetasy.2004.10.031

The reaction of different N-tert-butylsulfinyl aldimines 1 with allyl bromides 2 and indium powder in THF at 60°C affords, after hydrolysis with water, the corresponding N-tert-butylsulfinylamines 3 with high chemical yields and diastereoselectivities.

Full text of DOI:10.1016/j.tetasy.2004.10.031

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 15 (2004) 3823–3825
Indium-mediated diastereoselective addition of allyl bromides to
enantiomerically pure N-tert-butylsulfinyl aldimines
Francisco Foubelo* and Miguel Yus
´ ´ ´
Departamento de Quımica Organica, Facultad de Ciencias and Instituto de Sıntesis Organica (ISO), Universidad de Alicante,
Apdo. 99, 03080 Alicante, Spain
´
Received 27 September 2004; accepted 27 October 2004
Available online 24 November 2004
Abstract—The reaction of different N-tert-butylsulfinyl aldimines 1 with allyl bromides 2 and indium powder in THF at 60°C
affords, after hydrolysis with water, the corresponding N-tert-butylsulfinylamines
diastereoselectivities.
3 with high chemical yields and
Ó 2004 Elsevier Ltd. All rights reserved.
1. Introduction
the first time as a mediating reagent in the addition of
allyl bromides to carbonyl compounds under Barbier-
type reaction conditions.8 Since then, it has been used
also for promoting the addition of other allylic systems
to different electrophilic functional groups and as a
reducing reagent.9 Other important advantages of in-
dium over other metals are that it tolerates aqueous sol-
vents and air exposure without oxidising, meaning there
is no need for specific activation, and that it shows low
toxicity. Recently, Cook et al. have reported the indium-
mediated diastereoselective allylation of hydrazones,
using oxazolidinones derived from aminoalcohols as
chiral auxiliaries with excellent diastereoselectivities.10
Taking into account these antecedents we considered it
of interest to study the indium-mediated addition of
allyl bromides to simple enantiopure N-tert-butylsulfinyl
aldimines. To the best of our knowledge, the only exam-
ples of allylindium intermediates addition to N-tert-but-
ylsulfinyl aldimines have been provided by Grigg and
co-workers in their study of three-component palla-
dium–indium-mediated diastereoselective cascade allyl-
ation of imines with allenes and aryl iodides.11 They
found excellent diastereoselectivities in these processes,
especially those which occurred intramolecularly, with
chiral highly substituted pyrrolidines and piperidines
being synthesised in this way.
The addition of allyl metal derivatives to imines1 is an
effective method for the synthesis of homoallylic amines,
which are compounds of interest themselves because
they can be intermediates in the synthesis of other nitro-
genated materials.2 The asymmetric version of these
processes can be achieved by using chiral auxiliaries or
under asymmetric catalysis, with either chiral amines
or amine derivatives (amino alcohols, amino esters, ami-
no sugars, hydrazines and oximes) being the chiral aux-
iliaries of choice. Imines are less electrophilic than
carbonyls meaning that they are less reactive towards
nucleophiles. However this can be overcome by either
using electrophilic imines or by modulating the strength
of the nucleophile by choosing the appropriate metal
bonded to the organic fragment.3 For instance, in the
case of N-sulfonyl aldimines the nucleophilic additions
take place smoothly.4 More recently, N-tert-butylsulfi-
nyl aldimines have found high applicability in synthesis5
as electrophiles because of the possibility of preparing
both enantiomers in large scale processes following the
methodology developed by Ellman and co-workers6
and also because the chiral auxiliary can be easily re-
moved under acidic conditions. In this context, Li and
Batey reported the highly diastereoselective allylation
of N-tert-butylsulfinyl aldimines with potassium allyltri-
fluoroborate in the presence of boron trifluoride ether-
ate.7 On the other hand, indium metal has attracted
considerable attention since 1988 when it was used for
2. Results and discussion
Starting materials (R)-N-tert-butylsulfinyl aldimines
1
were prepared in high yields from readily
available (R)-1,1-dimethylethanesulfinamide12 and the
*
Corresponding author. Fax: +34 965 909672; e-mail: foubelo@ua.es
0957-4166/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2004.10.031

3824
F. Foubelo, M. Yus / Tetrahedron: Asymmetry 15 (2004) 3823–3825
corresponding aldehyde in dichloromethane at room
temperature, in the presence of excess anhydrous mag-
nesium sulfate (5equiv) and a catalytic amount of PPTS
(0.05equiv). During the condensation no racemisation
was observed the aldimines isolated exclusively as the
(E)-imine isomers.6c,13
1 and Table 1). It is noteworthy that enantiopure N-tert-
butylsulfinyl amines 3 can be separated from the diaste-
reomeric reaction mixture by using conventional silica
gel column chromatography.
A six-membered ring chelation control model (Fig. 1) is
consistent with a high level of stereocontrol as well as
with the configuration of the newly created stereogenic
centre. Coordination of indium to nitrogen increases
the reactivity of the electrophilic centre of the imine,
while the coordination of the metal to the oxygen of
the sulfinyl group is responsible for the face selectivity.
We assume that the nucleophilic attack takes place in
all cases to the Si face of the imino group. Similar tran-
sition states have been proposed by others in the case of
nucleophilic allylation to aldimines.18
We first investigated the reaction conditions for the allyl-
ation of the benzaldehyde derivative 1d by treatment
with allyl bromide 2a in the presence of indium metal.
Based on our previous experience with indium-mediated
allylation of aldimines,14 we used 1.3equiv of indium
metal and 1.3equiv of allyl bromide, THF being the sol-
vent of choice. It was supposed that in these processes
the formation of an allylindium intermediate15 was facil-
itated in aqueous media, although in the cases of using
water or a water/THF mixture, hydrolysis of the starting
(R)-N-tert-butylsulfinyl aldimine 1d occurred, yielding
benzaldehyde and other reaction products derived from
it. In contrast, the allylation of N-sulfonyl imines per-
formed in aqueous media16 has already been reported.
Regarding the temperature, although the reaction does
not progress significantly at room temperature while at
40°C it takes 12h to drive it to completion, complete
conversion was achieved at 60°C after 4h without loss
of stereoselectivity. The diastereomeric ratio of the reac-
tion product 3g was found to be 94:6 (Scheme 1, Table
1, entry 7), determined both by 300MHz 1H NMR
spectroscopy and GLC with a chiral capillary column
from the crude reaction mixture,17 both results being
coincident. Similar yields and diastereomeric ratios were
found for a variety of aldimines 1a–c using both allyl
and methallyl bromides 2a and 2b, respectively (Scheme
In order to determine the configuration of the newly cre-
ated stereogenic centre, the removal of the chiral auxil-
iary from sulfinamide 3g under acidic conditions
yielded the homoallylic amine 4g in almost quantitative
22
D
CH2Cl2)} was consistent with that provided in the liter-
yield (Scheme 2) its specific rotation f½aŠ ¼ ꢀ37 (c 0.74,
22
ature for (S)-1-phenylbut-3-en-1-amine f½aŠ ¼ ꢀ42 (c
D
0.5, CH2Cl2)}.19
H
..
R2
S
N
R1
[In]
O
Figure 1.
R2
O
S
O
S
R2
1. In, THF, 60ºC
2. H2O
R1
N
R1
+
Br
N
H
1a: R1 = i-Pr
2a: R2 = H
2b: R2 = Me
3a-h
1b: R1 = CH3(CH2)7
1c: R1 = Ph(CH2)2
1d: R1 = Ph
Scheme 1.
Table 1. Preparation of sulfinamides 3
Entry
Starting aldimine
Allylic bromide
Producta
20
½aŠ (c)d
No
R1
R2
drb
Rfc
Yield (%)e
D
1
2
3
4
5
6
7
8
1a
1a
1b
1b
1c
1c
1d
1d
2a
2b
2a
2b
2a
2b
2a
2b
3a
3b
3c
3d
3e
3f
i-Pr
i-Pr
H
Me
92:8
88:12
96:4
95:5
91:9
90:10
94:6f
93:7
0.31
0.36
0.32
0.39
0.25
0.26
0.28
0.29
ꢀ65 (0.59)
ꢀ89 (1.10)
ꢀ50 (0.42)
ꢀ59 (1.82)
ꢀ44 (0.68)
ꢀ69 (0.62)
ꢀ148 (0.85)
ꢀ147 (0.55)
84
82
91
86
79
83
94
91
CH3(CH2)7
CH3(CH2)7
Ph(CH2)2
Ph(CH2)2
Ph
H
Me
H
Me
H
3g
3h
Ph
Me
a All products were >95% pure (GLC and 300MHz 1H NMR).
b Diastereomeric ratio was determined by 1H NMR spectroscopy.
c Silica gel, hexane/ethyl acetate: 2/1.
d In CH2Cl2; in parenthesis concentration given in g/100mL.
e Isolated yield after column chromatography (silica gel, hexane/ethyl acetate) based on the starting material 1.
f Diastereomeric ratio was also determined by GLC with a chiral capillary column, see text above and Ref. 17.

F. Foubelo, M. Yus / Tetrahedron: Asymmetry 15 (2004) 3823–3825
3825
P.; Chen, B.-C.; Davis, F. A. Tetrahedron 2004, 60, 8003–
8030.
O
S
NH2
4 M HCl-dioxane
MeOH, 20ºC
N
H
6. (a) Liu, G.; Cogan, D. A.; Ellman, J. A. J. Am. Chem. Soc.
1997, 119, 9913–9914; (b) Cogan, D. A.; Ellman, J. A. J.
Am. Chem. Soc. 1999, 121, 268–269; (c) Liu, G.; Cogan, D.
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1999, 64, 1278–1284.
7. Li, S.-W.; Batey, R. A. Chem. Commun. 2004, 1382–1383.
8. Araki, S.; Ito, H.; Butsugan, Y. J. Org. Chem. 1988, 53,
1831–1833.
3g
4g
Scheme 2.
3. Conclusion
9. For reviews, see: (a) Cintas, P. Synlett 1995, 1087–1096;
´
(b) Li, C.-J. Tetrahedron 1996, 52, 5643–5668; (c) Laine,
D. Synlett 1999, 1331; (d) Chauhan, K. K.; Frost, C. G. J.
Chem. Soc., Perkin Trans. 1 2000, 3015–3019; (e) Ranu, B.
C. Eur. J. Org. Chem. 2000, 2347–2356; (f) Podlech, J.;
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Jayan, N. C.; Pillai, B. S. Tetrahedron 2004, 60, 1959–
1982.
In conclusion, we have reported herein that the indium-
mediated allylation of different (R)-N-tert-butylsulfinyl
aldimines takes place under mild reaction conditions
with high diastereoselectivity to yield homoallylic sulfin-
amides 3 while the sulfinyl group can be removed easily
under acidic conditions to give primary homoallylic
amines. Studies are currently in progress trying to ex-
tend this methodology to the synthesis of different nitro-
genated compounds by using other allylic, benzylic and
propargylic bromides.
10. Cook, G. R.; Maity, B. C.; Kargbo, R. Org. Lett. 2004, 6,
1741–1743.
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1372–1373; (b) Cooper, I. R.; Grigg, R.; Hardie, M. J.;
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Acknowledgements
This work was generously supported by the Generalitat
Valenciana (project no GV01-443).
15. For a mechanistic proposal involving an allylindium
intermediate see, for instance: Chen, T. H.; Yang, Y. J.
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