Tellurium-triggered formation of racemic and non-racemic allylic amines from aziridinemethanol derivatives

Article abstract of DOI:10.1016/S0040-4039(01)01124-8

Sharpless epoxidation, aminohydroxylation, and aziridination procedures provide substrates for the tellurium-triggered synthesis of racemic and non-racemic allylic amines under phase-transfer conditions.

Full text of DOI:10.1016/S0040-4039(01)01124-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 5789–5791
Tellurium-triggered formation of racemic and non-racemic allylic
amines from aziridinemethanol derivatives
Bin Chao and Donald C. Dittmer*
Department of Chemistry, Syracuse University, Syracuse, NY 13244, USA
Received 30 April 2001; accepted 19 June 2001
Abstract—Sharpless epoxidation, aminohydroxylation, and aziridination procedures provide substrates for the tellurium-triggered
synthesis of racemic and non-racemic allylic amines under phase-transfer conditions. © 2001 Elsevier Science Ltd. All rights
reserved.
Allylic amines, particularly non-racemic examples, are
useful synthetic intermediates because they embody
both a reactive amine and an alkene functionality. They
are used as antifungal agents,1 and as precursors to a-
and b-amino acids,2 chiral terpenoid-based perfumes,3
aminoepoxide intermediates for HIV protease inhibi-
tion,4 b-hydroxy-g-amino acids (renin inhibitors),5 a-
hydroxy-b-amino acids (immunopotentiators),6 and
peptide isosteres.7
1).14 This earlier synthesis was unusual because the
aziridine ring was readily opened by the nucleophilic
telluride despite the lack of activation of the aziridine
by an electron-withdrawing group on the nitrogen
atom. Under the conditions used, electron-withdrawing
substituents (e.g. N-tosyl) were actually unsatisfactory
in yielding allylic amines with telluride ion, probably
because the ring carbon atoms were attacked instead of
the carbon atom of the alcohol tosylate. Nucleophilic
opening of N-tosylaziridines is known to occur readily
with organometallic reagents15 and also internally
analogous to the Payne rearrangement.16 Since the con-
venient preparations of aziridinemethanols based on the
chemistry described by Sharpless and co-workers yield
N-tosyl derivatives, an adaptation of the telluride pro-
cess to these previously recalcitrant molecules is
desirable.
The starting materials for the tellurium-triggered syn-
thesis of allylic amines are allylic alcohols. These ver-
satile intermediates have been used previously in the
preparation of allylic amines by displacement reac-
tions,8 rearrangement reactions,9 and by formation of
p-allyl metal complexes followed by reaction with nitro-
gen nucleophiles.10 Methods for the synthesis of allylic
amines have been reviewed.11
We find that under phase-transfer conditions the tel-
lurium-triggered reaction works well with the electron-
withdrawing p-toluenesulfonyl group on the nitrogen
atom of the aziridine (Table 1).17 Tellurium powder
suspended in water (nitrogen atmosphere) is reduced
with sodium borohydride or with rongalite (sodium
hydroxymethanesulfinate dihydrate) under gentle heat-
ing (60°C) to give a purple to pink solution.26 The
aziridinemethanol derivative in toluene is added with a
Recent developments from the Sharpless group have
provided easy access to racemic aziridinemethanol
derivatives12 and to non-racemic b-N-tosylamino-a-
hydroxycarboxylic acid esters.13 These latter com-
pounds can be converted to aziridinemethanols, a class
of compounds that comprised the starting materials for
our previously reported synthesis of allylic amines via
the intervention of telluride ions (exemplified in Scheme
CPh3
Ph3C
Me
CPh3
Ph3C
Me
N
NH
N
N
Me
H
Te2 , rt, 24 h
CH2OTs
H
-Te
Me
CH2Te
(H+)
Te
H
(Te, NaBH4, DMF)
H
H
Scheme 1. Previous allylic amine synthesis via tellurium.14
* Corresponding author.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01124-8

5790
B. Chao, D. C. Dittmer / Tetrahedron Letters 42 (2001) 5789–5791
phase-transfer catalyst (Adogen 464) to the aqueous
solution of telluride cooled to room temperature. The
reaction to produce the allylic amine occurs relatively
rapidly as indicated by the formation of finely divided
black tellurium. It is not necessary to purify the
aziridinemethanol tosylates which are used directly in
the telluride reaction. Only with the N-tosylaziridine
derivative from cinnamyl alcohol did the tellurium pro-
cess deviate from the mechanism of Scheme 1, yielding
3 instead of 2f (Table 1). This behavior may be
attributed to attack by the telluride ion at C-3 favored
by phenyl stabilization of positive charge at that posi-
tion caused by electron withdrawal by the N-tosyl
group. However, the expected rearrangement occurs in
our telluride-oxazolidinonemethanol procedure to give
an analog of 2f in which the N-tosyl group is replaced
by n-hexyl.27
converted to (2R,3R)-3-amino-1,2-hexanediol [h]2D0=
+9.3 (CHCl3, c=1.5) by reduction with H2-Pd.18
The aminodiol (0.387 g, 2.90 mmol) in CH2Cl2 (10 mL)
at 0°C was treated with p-toluenesulfonyl chloride (2.21
g, 11.6 mmol), 4-N,N-dimethylaminopyridine (0.008 g),
and triethylamine (4.83 mL). The reaction mixture was
stirred at room temperature for 32 h, water (2 mL) was
added, and the phases were separated. The aqueous
phase was extracted with CH2Cl2 (10 mL), and the
combined organic phases were dried (MgSO4), concen-
trated, and chromatographed (silica gel, ethyl ace-
tate:hexane, 15:85) to give the crude aziridine
derivative, 1-(N-4-methylbenzenesulfonyl)-2-aziridine-
methyl p-toluenesulfonate, (2S,3R)-1a (0.920 g, 2.18
mmol, 75%) [1H NMR (CDCl3) l 7.82 (d, J=8.2 Hz,
2H), 7.72 (d, J=8.1 Hz, 2H), 7.32 (m, 4H), 4.07 (m,
2H), 2.90 (m, 1H), 2.72 (m, 1H), 2.42 (s, 6H), 1.58–1.42
(m, 2H), 1.26 (m, 2H), 0.85 (t, J=7.4 Hz, 3H); 13C
NMR (CDCl3) l 147.0, 144.2, 137.1, 132.3, 130.0,
129.6, 127.8, 127.3, 68.2, 47.5, 45.2, 31.0, 21.7, 21.5,
20.3, 13.5]. The aziridine tosylate (0.700 g, 1.65 mmol)
without further purification was treated with sodium
telluride [prepared by reduction of a suspension of
tellurium powder (0.42 g, 3.3 mmol) with aqueous
NaBH4 (0.25 g, 6.6 mmol) at 60°C for 2 h under argon
and cooled to room temperature] under phase-transfer
conditions [toluene, 0.2 M in aziridine, Adogen 464 (0.1
g)]. Black elemental tellurium began to precipitate even
at 0°C after about 15 min. The toluene–water mixture
was stirred for 3 h and the toluene layer was removed,
dried (MgSO4), filtered through a pipette of silica gel to
remove tellurium, and evaporated to give 4-methyl-N-
(1-propyl-2-propenyl)benzenesulfonamide20 (R)-2a(0.288
g, 1.21 mmol, 74%) as a colorless oil: [h]2D0=−3.5
The precursors of the non-racemic aziridine tosylates
(1a, 1b) of Table 1 were derived, respectively, from
aminodiols obtained via asymmetric epoxidation28 fol-
lowed by aminolysis with diphenylmethanamine,
hydrogenolysis, and exhaustive tosylation (see Experi-
mental)14,18,19 or from ethyl crotonate via aminohydroxy-
lation followed by reduction of the ester and exhaustive
tosylation.13 The racemic aziridine tosylates were pre-
pared by aziridination of known allylic alcohols.12
The conclusion is that the ready availability of both
racemic and non-racemic aminodiols and racemic N-
tosylaziridinemethanols enables a general synthesis of
racemic and non-racemic allylic amines to be performed
via a tellurium process under mild, phase-transfer con-
ditions which allow easy isolation of product and easy
recovery of tellurium which can be reused, thus avoid-
ing the loss of a key reagent.
1
(CHCl3, c=2.0); H NMR (CDCl3) l 7.79 (d, J=8.1
Hz, 2H), 7.21 (d, J=8.1 Hz, 2H), 5.67 (m, 1H), 5.06 (d,
J=17.1 Hz, 1H), 5.0 (d, J=11.2 Hz, 1H), 4.75 (d,
J=7.7 Hz, 1H), 3.80 (m, 1H), 2.42 (s, 3H), 1.58–1.42
(m, 2H), 1.27 (dt, J=14.0, 7.2 Hz), 0.86 (t, J=7.2 Hz,
3H). 13C NMR (CDCl3) 144.2, 137.1, 137.0, 129.6,
127.2, 115.5, 56.0, 37.5, 21.2, 19.0, 13.3. HRMS (FAB,
M++H) calcd for C13H19NO2S+H 254.1216. Found
254.1207.
Experimental tellurium procedure for (R)-2a
(2R,3R)-3-(a-Phenylbenzylamino)-1,2-hexanediol [h]2D0=
−20.0 (CHCl3, c=1.5), lit14 [h]D20=−24.2 (CHCl3, c=
4.4), prepared in 65% yield by reaction of diphenyl-
methylamine
with
(2S,3S)-3-n-propyl-2-oxirane-
methanol, as described by Perica`s and Riera,18 was
Table 1. N-Tosylallylic amines from N-tosylaziridinemethanol tosylates
Ts
R3
3
Te2-, H2O-PhMe
NHTs
R
R2
R1
N
+
Te
R2
Adogen 464, 0 o
OTs
rt
R1
2
1
R1
R2
R3
% Yield
(2S,3R)-1a14,18,19
n-Pr
H
Me
BnOCH2
H
Ph
H
Me
Me
H
-(CH2)3-
H
H
H
H
H
(R)-2a20,21a
(S)-2b22
2c21
74
81
85
88
95
0a
(2S,3S)-1b13
1c
1d
1e
1f
2d23
-(CH2)3-
H
2e20,21,24
2f
a The product is (E)-PhCHꢀCHCH2NHTs25 (3) (80%).

B. Chao, D. C. Dittmer / Tetrahedron Letters 42 (2001) 5789–5791
7920–7925.
5791
Acknowledgements
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Acknowledgement is made to the donors of The
Petroleum Research Fund, administered by the Ameri-
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research. We are indebted to Professor Franklin Davis
for the mass spectra and to Professor John Baldwin for
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