Reductive BOC-amination of aldehydes

Article abstract of DOI:10.1016/S0040-4039(01)00895-4

Base-assisted elimination-reduction of α-amidoalkyl sulfones with sodium borohydride proceeds in tetrahydrofuran at room temperature leading to the corresponding BOC-amines in good yields.

Full text of DOI:10.1016/S0040-4039(01)00895-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 5093–5094
Reductive BOC-amination of aldehydes
Elz; bieta Bernacka, Anna Klepacz and Andrzej Zwierzak*
:
Institute of Organic Chemistry, Technical University (Politechnika), Zeromskiego 116, 90-924 Lodz, Poland
Received 29 March 2001; accepted 24 May 2001
Abstract—Base-assisted elimination–reduction of a-amidoalkyl sulfones with sodium borohydride proceeds in tetrahydrofuran at
room temperature leading to the corresponding BOC-amines in good yields. © 2001 Elsevier Science Ltd. All rights reserved.
The N-protection of amino functions is essential in
many synthetic transformations.1 Among a wide variety
of protecting groups the t-butoxycarbonyl group
(BOC) is of fundamental importance due to its
availability, useful protection and ready cleavage.2
Although many reagents and methods are available to
introduce BOC groups novel, operationally simple, and
effective procedures are still in demand.
The similar utilization of a-amidoalkyl sulfones 2 as
N-acylimine equivalents has been described previ-
ously.5–8 The reaction of a-amidoalkyl sulfones 2 with
an excess of sodium borohydride in tetrahydrofuran
afforded N-BOC amines 4 in good yields and excellent
purity (1H NMR).
The following typical conditions were used. Finely
powdered sodium borohydride (1.13 g, 30 mmol) was
suspended in THF (40 ml). Solid crude a-amidoalkyl
sulfone 29 was added portionwise with stirring for ca.
15 min. The resulting mixture was then stirred for 2 h
at room temperature, cooled to 5°C, and quenched with
satd aq. NH4Cl (15 ml). Stirring was then continued for
0.5 h. The organic layer was separated and the aqueous
phase extracted with CH2Cl2 (2×15 ml). The combined
extracts and organic phase were dried over MgSO4 and
evaporated to give spectroscopically pure 4. Yields, mps
and literature mps of 2 and 4 are listed in Table 1.
Incidental to our studies on potential synthetic applica-
tions of N-BOC imines 3 we tried to prepare these
compounds by base-assisted elimination3 of p-toluene-
sulfinic acid from easily available a-amidoalkyl sulfones
2.3,4 Unexpectedly it was found that in addition to the
desired imine 3 considerable amounts of N-BOC
amines 4 were formed when the elimination was per-
formed with stoichiometric amounts of sodium boro-
hydride in tetrahydrofuran at room temperature.
This result suggests that sodium borohydride ini-
tially acts as a base inducing elimination and then
immediately reduces the CꢀN bond of the N-BOC
imine 3 to give the respective N-BOC amine 4
(Scheme 1).
In conclusion, we have disclosed a simple and conve-
nient variant of the reductive amination of aldehydes
leading directly to BOC-amines.
Scheme 1.
Keywords: a-amidoalkyl sulfones; N-BOC imines; reductive amination.
* Corresponding author. Fax: (48-42)636-55-30.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00895-4

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E. Bernacka et al. / Tetrahedron Letters 42 (2001) 5093–5094
Table 1. a-Amidoalkyl sulfones 2 and BOC-amines 4a
Entry
R
2 Yield (%)b
2 Mp (°C)
4 Yield (%)b
4 Mp (°C)c
a
b
c
d
e
f
g
h
i
Ph
65
77
68
77
54
76
69
76
80
177–178 (–)
174–175 (–)
179–180 (–)
183–185 (–)
148–150 (–)
88–90 (–)
73
71
87
91
82
77
87.5
82
73
52–53 (52–53)12
71–74 (75–76)13
48–50 (50–50.5)14
65–68 (72.5–73)13
48–51 (–)
p-Cl-C6H4
p-MeO-C6H4
p-Me-C6H4
2-Furyl
Me
Et
i-Pr
c-C6H11
d
(–)
(–)
(–)
d
114–6 (114–115)11
109–111 (–)
151–154 (–)
d
41–44 (50–51)15
a All new compounds were fully characterized by MS, IR and 1H NMR spectra.
b Yields of crude products.
c Mps of crude products. Literature mps are given in parentheses.
d Low-melting solid.
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ethyl acetate (2a–c), ethyl acetate-hexane (2d,e,h), etha-
nol–hexane (2i), and ether–hexane (2f,g).
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