Reactions of alkyl, benzyl and stannyl halides with Lewis acid complexed α-lithiated tertiary amines

Article abstract of DOI:10.1055/s-2001-12324

α-amino stannanes can be obtained readily from tertiary amines through BF₃ promoted deprotonation; in situ CsF treatment of BF₃ complexed stannanes followed by lithium-transmetalation can be used to procure those α-alkylation product

Full text of DOI:10.1055/s-2001-12324

LETTER
517
Reactions of Alkyl, Benzyl and Stannyl Halides with Lewis Acid Complexed
Lithiated Tertiary Amines
-
Satinder V. Kessar, Paramjit Singh,* Kamal N. Singh, Sandeep K. Singh
Department of Chemistry, Panjab University, Chandigarh-160014, India
Fax 91-172-545459; E-mail: paramjit26@usa.net
Received 13 February 2001
A priori it was not apparent whether the low reactivity of
b is inherent for non-stabilized primary -aminocarban-
ions or is caused by complexation of the nitrogen atom
Abstract: -Amino stannanes can be obtained readily from tertiary
5
amines through BF promoted deprotonation; in situ CsF treatment
3
of BF complexed stannanes followed by lithium-transmetalation
3
5
can be used to procure those -alkylation products which are not with the Lewis acid. However, when the uncomplexed -
available directly.
lithiated amine 2b derived from the stannane 2e by trans-
metalation with sec-butyllithium, was reacted with butyl
and benzyl bromides, substitution products were obtained
in very good yields (2e 2b 2c, 2d) (Table, entries 11
and 12). It was, therefore, clear that if a method of in situ
Key words: Lewis acid, non-stabilized -aminocarbanions, -ami-
no stannanes, transmetalation, alkylation
decomplexation (5b
in reactions of 5b may be overcome. For this purpose, CsF
seemed suitable because of its stability in highly alkaline
2b) can be devised, the problems
Lewis acid promoted -deprotonation provides a conve-
nient method for synthetic elaboration of tertiary amines
1
-3
(
Scheme). For instance, intermediates 4b and 5b can be
-
6
medium and the strong F ion affinity for boron. Howev-
er, prolonged stirring of 5b with CsF (1.2 equiv.) in THF
at 78 °C did not result in formation of any insoluble tet-
rafluoroborate. Only on raising the temperature to 0 °C,
did the expected fluffy precipitates start to appear but at
this temperature 2b was unstable. By adding the alkylat-
ing agent and CsF together at 78 °C and allowing the re-
action mixture temperature to rise slowly to 0 °C, the
desired product 2c could be obtained but in a modest yield
of 37% (Table, entry 13). In another approach, the effect
of HMPA was investigated since this additive is known to
easily derived from the parent amines (1a and 2a) and re-
act smoothly with electrophiles such as aldehydes, ke-
1
tones, nitriles and esters. We now report that reactions of
such intermediates with alkyl and benzyl halides are ca-
pricious; while 4b reacts well with both types of halides,
4
these reactions fail in case of 5b. Use of butyltriflate af-
fords 2c from 5b in a moderate yield (Table, entries 1, 2
and 8-10).
enhance the reactivity of lithiated intermediates and also
7
has good affinity for BF . In the event, addition of HMPA
3
(
2 equiv.) to the reaction mixture gave a good yield of the
substitution product with butyl bromide but not in case of
benzyl bromide (Table, entries 14 and 15). Addition of
Scheme Reagents and conditions: i) BF ·Et O (1.1 equiv.), 0 °C, 10
min, THF; ii) BuLi (1.2 equiv.), 78 °C, 1 h; iii) electrophile (1.2
equiv.), 78 °C, 30 min, 30 °C, 30 min, then HCl (10%).
8
3
2
s
TMEDA had no useful effect in either case (Table 1, entry
9
1
6).
We found that reactions of both 1b and 2b with tributyltin
chloride proceed efficiently and the corresponding -stan-
nyl amines (1e and 2e) can be obtained directly through a
careful non-acidic work-up (Table, entries 3 and 4).10
Similarly, N-ethylpyrrolidine (3a) can be stannylated on
the ring provided Schlosser base is used for deprotonation
2
of 6a (Table, entry 5). The present procedure is far supe-
rior to the method commonly used for accessing these im-
portant synthetic intermediates. For example, 2e can be
obtained from N-methylpiperidine (2a) in 94% yield in
one step whereas the reported procedure affords 2e from
piperidine in 30% overall yield in two steps (piperidine
11
N-phenylthiomethylpiperidine
2e). Moreover, in situ
decomplexation of 5e with CsF, followed by tin-lithium
exchange and reaction with organic halides gives alkyl-
ation and benzylation products in good yield in a three-
step one-pot procedure (2a 5e 2e 2c, 2d) (Table,
entries 6 and 7).12
Figure
Synlett 2001 No. 4, 517–518 ISSN 0936-5214 © Thieme Stuttgart · New York

5
18
S. V. Kessar et al.
LETTER
Table Alkylation, benzylation and stannylation of tertiary amines
(4) Reactions of carbanions with halides are known to vary with
the nature of the substrate, the electrophile and the
countercation. Wakefield, B. J. The Chemistry of
Organolithium Compounds, Pergamon: Oxford, 1974;
Gawley, R. E.; Rein, K. Comprehensive Organic Synthesis,
Trost, B. M.; Fleming, I., Eds.; Pergamon: New York, 1991,
Vol.3, Chap. 12.
(
5) Adverse effect of dipole stabilization of carbanions on
alkylation reactions has been observed earlier. Beak, P.;
Zajdel, W. J. J. Am. Chem. Soc. 1984, 106, 1010. Beak, P.;
Meyers, A. I. Acc. Chem. Res. 1986, 19, 356. Beak P.; Siegel,
B. J. Am. Chem. Soc.,1974, 96, 6803.
(
6) Clark, J. H. Chem. Rev. 1980, 80, 429. Garnier, L.; Plunian,
B.; Mortier, J.; Vaultier, M. Tetrahedron Lett. 1996, 37, 6699.
7) Normant, H. Angew. Chem., Int. Ed. Engl. 1967, 6, 1046.
Meyers, A. I.; Edwards, P. D.; Reiker, W. F.; Bailey, T. R. J.
Am. Chem. Soc. 1984, 106, 3270. Ferey, V.; Vedrenne, P.;
Toupet, L.; Le Gall, T.; Mioskowski, C. J. Org. Chem. 1996,
(
61, 7244.
(8) It may be concluded that addition of HMPA does not cause
removal of BF from the nitrogen atom because otherwise the
3
benzyl bromide reaction should also proceed well (Table,
entry 15).
(
9) Collum, D. B. Acc. Chem. Res. 1992, 25, 448.
-
Amino stannanes decompose under acidic conditions and
a
Yields are for pure products isolated after chromatography/ distilla-
on chromatography on silica gel. 1e is more unstable and
decomposes rapidly in polar solvents like chloroform and
dichloromethane.
tion. b Loss of material upon chromatography ( H NMR yield was
~
tassium. Through the three-step one-pot procedure.
1
c
90% before chromatography). The counter-ion in 6b may be po-
d
12
(11) Peterson, D. J. J. Am. Chem. Soc. 1971, 93, 4027 [V1][V2].
For a recent approach to -amino stannanes, see : Ashweek, N.
J.; Coldham, I.; Vennall, G. P. Tetrahedron Lett. 2000, 41,
2235.
(
12) General Procedure: Into a flame-dried three necked round
bottomed flask equipped with a septum cap, a solid addition
bend containing freshly dried CsF (1.2 equiv.) and a stir bar, a
solution of 2a in THF (0.3M) was placed under nitrogen
atmosphere. BF Et O (1.1 equiv.) was added at 0 °C and the
In summary, we have developed a methodology for effi-
cient reaction of Lewis acid complexed azacarbanions
with alkyl and benzyl halides and also for an easy access
to -amino stannanes.
3
2
s
reaction mixture was further cooled to 78 °C. BuLi (1.2
equiv.) was added and the resulting yellow solution was
Acknowledgement
stirred at 78 °C for 1 h and Bu SnCl (1.2 equiv.) was added.
3
Financial support by the Dept. of Science and Technology, India is
gratefully acknowledged.
After this, CsF (1.2 equiv.) was introduced into the reaction
mixture and then it was warmed up to 0 °C. The reaction
s
mixture was recooled to –78 °C and BuLi (1.2 equiv.) was
introduced followed by alkyl halide (1.2 equiv.) after 1 h. The
temperature was maintained at –78 °C for 30 min and then
allowed to rise to –30 °C over a period of 30 min. The reaction
was quenched with 10% HCl and worked up. For stopping the
reaction at stannylation stage, the reaction was quenched by
addition of water (5 ml) at 0 °C. The organic material was
extracted with ether. The ether extract was washed with
diluted NaOH solution, water, brine and dried. Evaporation of
the solvent in vacuo followed by distillation of the residual oil
References and Notes
(
1) Kessar, S. V.; Singh, P.; Vohra, R.; Kaur, N. P.; Singh, K. N.
J.Chem. Soc., Chem. Commun. 1991, 568. Kessar, S. V.;
Singh, P. Chem. Rev. 1997, 97, 721. Katritzky, A. R; Qi, M.
Tetrahedron 1998, 54, 2647.
(
2) For applications of Lewis acid complexation methodology in
the generation of secondary -aminocarbanions, see: Ebden,
M. R.; Simpkins N. S.; Fox, D. N. A. Tetrahedron Lett. 1995,
11
afforded 2e (94%). Data For 2e: bp 110-112 °C/ 0.1 mm Hg.
36, 8697. Harmata, M.; Carter, K.W.; Jones, D.E.; Kohraman,
1
H NMR (CDCl3): 0.90-1.05 (t, 9H), 1.25-1.70 (m, 24H),
.18-2.58 (m, 6H). Data for 2c: bp 189-190 °C. H NMR
M. Tetrahedron Lett. 1996, 37, 6267. Vedejs, E.; Kendall, J.
T. J. Am. Chem. Soc. 1997, 119, 6941. Kessar, S. V.; Singh,
P.; Singh, K. N.; Singh, S. K. J. Chem. Soc., Chem. Commun.
1
2
(
CDCl ): 0.86-0.91 (t, 3H, J = 7.0 Hz), 1.19-1.36 (m, 4H),
3
1
.42-1.52 (m, 4H), 1.54-1.62 (m, 4H), 2.23-2.28 (m, 2H), 2.36
1999, 1927.
13
(
brs, 4H). C NMR : 14.0 (CH ), 22.6 (CH ), 24.4 (CH ),
3 2 2
(
3) For gas phase thermochemical data and theoretical studies on
Lewis acid complexed -aminocarbanions, see : Ren, J.;
Workman, D. B.; Squires, R. R. J. Am. Chem. Soc. 1998, 120,
2
5.9 (2CH ), 26.6 (CH ), 29.9 (CH ), 54.6 (2CH ), 59.6 (CH ).
2 2 2 2 2
10511. Kuck, D. Angew. Chem., Int. Ed. 2000, 39, 125.
Article Identifier:
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Synlett 2001, No. 4, 517–518 ISSN 0936-5214 © Thieme Stuttgart · New York