Stereospecific synthesis of 2,3-disubstituted aziridines from β- alkylamino phenylselenides

Article abstract of DOI:10.1016/S0040-4039(99)02159-0

Reduction of α-phenylselanyl imines derived from β-phenylselanyl α- oxoesters or PhSeCl assisted nucleophilic addition of primary amines to α,β-unsaturated esters have led to β-alkylamino phenylselenides 4, 5, 12 and 13 which were cyclised into aziridines

Full text of DOI:10.1016/S0040-4039(99)02159-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 663–666
Stereospecific synthesis of 2,3-disubstituted aziridines from
β-alkylamino phenylselenides
Stéphane Boivin, Francis Outurquin and Claude Paulmier ∗
Laboratoire de Synthèse Thio- et Séléno-organique, IRCOF-Université de Rouen, F-76821 Mont Saint Aignan Cedex, France
Received 12 October 1999; accepted 16 November 1999
Abstract
Reduction of α-phenylselanyl imines derived from β-phenylselanyl α-oxoesters or PhSeCl assisted nucleophilic
addition of primary amines to α,β-unsaturated esters have led to β-alkylamino phenylselenides 4, 5, 12 and 13
which were cyclised into aziridines 8, 9 and 14 after selenium activation. threo-Amino selenides led stereospeci-
fically to cis-2,3-disubstituted aziridines. Depending on the structure, non-functionalised amino selenides 19–20
were also cyclised into aziridines 21–22. © 2000 Elsevier Science Ltd. All rights reserved.
The aziridine nucleus is included in some natural substances which present antitumour and antibiotic
activity. Synthetic chiral aziridines have also shown biological properties and are pivotal targets for the
synthesis of chiral functionalised compounds. Efficient methods have been proposed for the stereocontro-
lled preparation of mono, di and trisubstituted optically active aziridines. Two recent reviews report on the
synthetic routes and on the principal reactions in relation with stereoselective ring opening processes.1,2
A convenient and efficient aziridine synthesis is based on the SN2 cyclisation of amino alcohols after
derivation of the hydroxy group. Enantiomerically pure starting materials are: amino acids, carbohy-
drates, and hydroxy acids. Catalysed asymmetric reactions of alkenes with nitrenoid compounds or
imines with carbenes have been proposed. The synthesis of optically active aziridines via an internal
SN2 displacement of a sulfonium group has been also studied. Sulfonamides and carbamates are used as
nucleophilic nitrogen groups and activated aziridines were obtained after basic treatment.3–5
The formation of epoxides from β-hydroxy selenides through internal SN2 displacement of a methyl
selenonium group is well known.6–8 The cis or trans stereochemistry of 2,3-disubstituted epoxides allows
the determination of the threo or erythro nature of the substrates. The absolute configuration of 3-
phenylselanyl 1,2-diol derivatives was assigned by this way.9
We describe here the first synthesis of aziridines from β-alkylamino selenides.The reduction of the
unstable imines 2 (R3=benzyl), derived from β-phenylselanyl α-oxoesters 1,10 gave the amino selenides
4. The ester group controls the stereochemistry of the reaction and one diastereoisomer was formed
∗
Corresponding author. Fax : 02-35-52-29-59; e-mail: claude.paulmier@univ-rouen.fr (C. Paulmier)
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(99)02159-0
tetl 16087

664
Scheme 1. (i) R3NH2 (4 equiv.), TiCl4 (0.66 equiv.), Et2O, rt, 5 h. (ii) NaBH3CN (1.5 equiv.), AcOH (1 equiv.), EtOH, 0°C, 1
−
h. (iii) Me3O+BF4 (2 equiv.), CH2Cl2, rt, then 1N NaOH aq. solution. (iv) PhSeCl (1.2 equiv.), ZnCl2 (0.3 equiv.), CH2Cl2, rt,
0.5 h, then BnNH2 (2.5 equiv.), rt, 14 h
Table 1
Amino selenides 4, 5, 12 and 13 and aziridines 8, 9 and 14
(Scheme 1, Table 1, entries 1–5). The trimethyloxonium tetrafluoroborate treatment of compounds 4
(R2=H) followed by addition of aq. NaOH has allowed cyclisation into aziridines 8.
The reduction of imines 2 occurred with partial deselenenylation of the substrate (5–9%) as for
imines 2 (R3=isopropyl, allyl)12 and those derived from α-phenylselanyl aldehydes.13 The JH H coupling
2
3

665
constant values14 have confirmed the formation of cis-2,3-disubstituted aziridines 8 and led us to assign a
threo configuration to the amino selenides 4 (R2=H, JH H =4 Hz). No isomerisation occurred after basic
2
3
treatment of the amino selenonium salts 6. The same two-step sequence was applied to imine 3b derived
from (S)-1-phenylethylamine (Table 1, entry 8). The two threo amino selenides 5b and 5b0, formed in
25
equal amounts, were separated by silica gel chromatography and cyclised into cis-aziridines 9b {[α]
D
−50 (c 0.75 in CHCl3)} and 9b0 {[α]25 +23 (c 1.0 in CHCl3)}, respectively.
D
The alkyl aziridine-2-carboxylates 8e and 14 were also obtained by cyclisation of the β-benzylamino
α-phenylselanyl esters 12 (R0=Et) and 13 (R0=Me). These esters were prepared as erythro/threo mixtures
from (E)-enoates 10 and 11, respectively, by conjugated addition of benzylamine in the presence of
PhSeCl and ZnCl2, as recently described15 (Scheme 1, Table 1, entries 9–11). Cis/trans mixtures of
aziridines 8e and 14 were obtained in ratios reflecting those of the substrates taking into account the
modest yields. The prior methylation of the amino group, preventing the cyclisation, was never observed.
Scheme 2. (i) BnNH2 (1 equiv.), MgSO4, CH2Cl2, rt, 3 h (for 15a); BnNH2 (1.1 equiv.), C6H6 reflux Dean–Stark, 12 h (for
15b). (ii) BnNH2 (4 equiv.), TiCl4 (0.66 equiv.), Et2O, rt, 5 h (for ketones 16). (iii) NaBH3CN (1.5 equiv.), AcOH (1 equiv.),
−
EtOH, 0°C, 1 h. (iv) Me3O+BF4 (2 equiv.), CH2Cl2, rt, 12 h, then 1N NaOH aq. solution
Table 2
Amino selenides 19–20 and aziridines 21–22
The situation was found to be more complex with non-functionalised amino selenides 19–20 prepared
by reduction of imines 1713 derived from α-phenylselanyl aldehydes 1516,17 and imines 18 formed
from α-phenylselanyl ketones 1617 (Scheme 2). A threo selectivity occurred in the reduction of imines
18b, 18d and 18e (Table 2). The threo isomer of 18d, although formed with a modest yield, was the
only one isolated. The cyclisation process carried out on 19a led to a 30/70 mixture of 1-benzyl-2-
isopropylaziridine 21a and methylamino phenylselenide 23, resulting from a competitive methylation
of the amino group. With R1 and R2=H (19b, R1=R2=Me), the N-methylation occurred first and the

666
methylselenonium group underwent hydrolysis giving the amino alcohol 24 (54% yield). The formation
of aziridines 22 (Table 2, entries 3–6) was achieved from amines 20 derived from ketimines 18. The
amino selenide 20e (20/80 erythro/threo mixture), however, has led to the N-methyl amine 25 (59%
yield). The cyclisation into aziridine was prevented if two substituents are linked to the selenenylated
carbon as for the synthesis of epoxides from β-hydroxy selenides.7
In conclusion, this work describes the first stereospecific synthesis of aziridines from β-alkylamino
methylselenonium salts derived from β-amino phenylselenides. A total stereocontrol was observed
during the reduction of imines 2 and 3 as for the reduction of the corresponding α-oxoesters 1.12 Work
is in progress to study the scope and limitations of the cyclisation, the efficiency of other activation
processes and the access to optically active aziridines.
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