High kinetic resolution in the addition of a racemic allenylzinc onto enantiopure N-tert-butanesulfinimines: Concise synthesis of enantiopure trans-2-ethynylaziridines

Article abstract of DOI:10.1021/jo0490696

Enantiopure trans-ethynyl N-tert-butanesulfinylaziridines (R_S)-6 were prepared in good to excellent yields by the condensation of the racemic allenylzinc species 1 derived from 3-chloro-1-trimethylsilylpropyne onto the corresponding enantiopure

Full text of DOI:10.1021/jo0490696

High Kinetic Resolution in the Addition of a Racemic Allenylzinc
onto Enantiopure N-tert-Butanesulfinimines: Concise Synthesis of
Enantiopure trans-2-Ethynylaziridines1
Fabrice Chemla and Franck Ferreira*
UMR 7611, Laboratoire de Chimie Organique, Universite´ Pierre et Marie Curie,
Tour 44-45, Case 183, 4 Place Jussieu, 75252 Paris Cedex 05, France
ferreira@ccr.jussieu.fr
Received June 3, 2004
Enantiopure trans-ethynyl N-tert-butanesulfinylaziridines (RS)-6 were prepared in good to excellent
yields by the condensation of the racemic allenylzinc species 1 derived from 3-chloro-1-trimethyl-
silylpropyne onto the corresponding enantiopure N-tert-butanesulfinimines (RS)-5. The absolute
stereochemistry of enantiopure N-tert-butanesulfinylaziridines (RS)-6 was shown to be (RS,2R,3R)
and results from a chelate-type transition state in which the zinc atom of allenylzinc 1 is coordinated
by both the nitogen and the oxygen atoms of the imine. Further removal of the N-tert-butanesulfinyl
auxiliary of alkyl 3-substituted and 3,3-disubstituted ethynyl N-tert-butanesulfinylaziridines (RS)-6
could be achieved by treatment with HCl in MeOH affording the corresponding deprotected
aziridines (2R,3R)-9 and (2R)-9 respectively as enantiomerically pure compounds.
Introduction
been used as chiral carbon nucleophiles in a stereoselec-
tive indium(I)-mediated reductive coupling reaction cata-
lyzed by palladium(0) with aldehydes giving 1,3-amino
alcohols with three stereocenters.7 In contrast, despite
their great synthetic potential, relatively little investiga-
tion has been undertaken so far on both the synthesis
and the reactivity of alkynylaziridines in the literature.8
Racemic alkynylaziridines have been previously prepared
by the reaction of nitrenes or nitrene equivalents with
enynes,9 by the condensation of lithiated cinnamyl chlo-
ride onto imines10 or from the corresponding alkynylox-
iranes in a two-step procedure.11 As regards the synthesis
of enantiopure alkynylaziridines, only two methods have
been described. Recently, Dai and co-workers have
reported the synthesis of enantiopure cis-alkynylaziri-
dines by the asymmetric aziridination of N-tosylimines
with D-(+)-camphor derived sulfonium ylides in moderate
to good enantioselectivities (14-85% ee).12 Shortly after-
ward, Ibuka and co-workers disclosed two multistep
syntheses from (S)-R-amino acids. The key steps of these
syntheses were a dehydrobromination reaction of 2-(1-
Aziridines and more particularly alkenyl- and alkynyl-
aziridines constitute an interesting class of compounds
as their high electrophilicity enables them to undergo
stereoselective ring-opening reactions with a wide variety
of nucleophiles. For instance, alkenylaziridines have
proven to be valuable intermediates in carbon-carbon
forming reactions such as metal-mediated SN2′ reactions2
and opening aziridine ring rearrangements.3 The cis-
trans transition metal-mediated equilibration of alkenyl-
aziridines has also been well-studied.4 Recently, ethenyl-
aziridines have been involved in the synthesis of chiral
amino allenes (valuable intermediates in the synthesis
of six- or five-membered azacyles5) with high optical
purities by the organocopper-mediated anti-SN2′ substi-
tution reaction.6 More recently, those compounds have
(1) Propargylic Carbenoids, Part 4. For Part 3, see ref 30.
(2) (a) Anzai, M.; Yanada, R.; Fujii, N.; Ohno, H.; Ibuka, T.;
Takemoto, Y. Tetrahedron 2002, 58, 5231-5239. (b) Ohno, H.; Toda,
A.; Miwa, Y.; Taga, T.; Fujii, N.; Ibuka, T. Tetrahedron Lett. 1999, 40,
349-352. (c) Toda, A.; Aoyama, H.; Mimura, N.; Ohno, H.; Fujii, N.;
Ibuka, T. J. Org. Chem. 1998, 63, 7053-7061. (d) Aoyama, H.; Mimura,
N.; Ohno, H.; Ishii, K.; Toda, A.; Tamamura, H.; Otaka, A.; Fujii, N.;
Ibuka, T. Tetrahedron Lett. 1997, 38, 7383-7386. (e) Wipf, P.;
Henninger, T. C. J. Org. Chem. 1997, 62, 1586-1587.
(3) (a) Penkett, C. S.; Simpson, I. D. Tetrahedron Lett. 2001, 42,
3029-3032. (b) Paul, B. J.; Hobbs, E.; Buccino, P.; Hudlicky, T.
Tetrahedron Lett. 2001, 42, 6433-6435. (c) Butler, D. C. D.; Inman;
G. A.; Alper, H. J. Org. Chem. 2000, 65, 5887-5890. (d) Åhman; J.;
Somfai, P. Tetrahedron 1999, 55, 11595-11600. (e) Linstro¨m, U. M.;
Somfai, P. Synthesis 1997, 109-116.
(4) (a) Honda, A.; Ohno, H.; Ibuka, T. Synlett 1998, 969-970. (b)
Mimura, N.; Ibuka, T.; Akaji, M.; Miwa, Y.; Taga, T.; Nakai, K.;
Tamamura, H.; Fujii, N.; Yamamoto, Y. J. Chem. Soc., Chem. Commun.
1996, 351-352.
(5) Ohno, H.; Toda, A.; Miwa, Y.; Taga, T.; Osawa, E.; Yamaoka,
Y.; Fujii, N.; Ibuka, T. J. Org. Chem. 1999, 64, 2992-2993 and
references cited therein.
(6) Ohno, H.; Toda, A.; Fujii, N.; Takemoto, Y.; Tanaka, T.; Ibuka,
T. Tetrahedron 2000, 56, 2811-2820.
(7) (a) Ohno, H.; Hamaguchi, H.; Tanaka, T. J. Org. Chem. 2001,
66, 1867-1875. (b) Takemoto, Y.; Anzai, M.; Yanada, R.; Fujii, N.;
Ohno, H.; Ibuka, T. Tetrahedron Lett. 2001, 42, 1725-1728. (c) Ohno,
H.; Hamaguchi, H.; Tanaka, T. Org. Lett. 2000, 2, 2161-2163.
(8) For a recent review on alkynylaziridines see: Chemla, F.;
Ferreira, F. Curr. Org. Chem. 2002, 6, 539-569.
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Chem. Soc., Perkin Trans. 1 1973, 550-555. (b) Labeish, N. N.;
Porfir’eva, Y. I.; Petrov, A. A. Zh. Org. Khim. 1984, 20, 402-406.
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(b) Manisse, N.; Chuche, J. J. Am. Chem. Soc. 1977, 99, 1272-1273.
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36, 1317-1319. (c) Wang, D.-E.; Dai, L.-X.; Hou, X.-L. Chem. Commun.
1997, 1231-1232.
10.1021/jo0490696 CCC: $27.50 © 2004 American Chemical Society
Published on Web 10/29/2004
8244
J. Org. Chem. 2004, 69, 8244-8250

Synthesis of Enantiopure trans-2-Ethynylaziridines
bromovinyl)aziridine intermediates and an aziridine ring
closure of amino alcohols bearing an ethynyl group under
Mitsunobu conditions, respectively.13 More recently, Tana-
ka’s group has developed a highly stereoselective syn-
thesis of cis-ethynylaziridines from (S)-R-amino acids via
the intramolecular amination of chiral bromoallene in-
termediates.14 In both Ibuka’s and Tanaka’s works, trans-
and cis-ethynylaziridines were obtained in enantiomeri-
cally pure forms (>98% ee). However, they could not be
prepared selectively since they were isolated from ster-
eoisomeric mixtures (at different steps of the syntheses)
by chomatographic separations. Moreover, a limited
number of aziridines could be obtained due to the
limitation of the starting materials available.
of R-amino ester zinc enolates.18 Unfortunately, in pre-
liminary works we have found that N-R-methylben-
zylimines 4, easily prepared in the two enantiomeric
forms from the cheap and commercially available (R)- and
(S)-R-methylbenzylamines, do not react at all with alle-
nylzinc 1 even overnight at room temperature, only
products from the carbenoidic decomposition of 1 being
observed (eq 2).
Thus, when starting our study and to the best of our
knowledge, no univocal and general synthesis of enan-
tiopure trans-alkynylaziridines was reported in the lit-
erature so that an efficient and concise diastereo- and
enantioselective access to such compounds still remained
a challenge. With this aim in mind, we have recently
described a stereoselective access to racemic 3-substituted
trans-N-H and -N-benzyl 2-trimethylsilylethynylaziri-
dines 3a and 3b by the reaction of racemic allenylzinc
reagent 1 derived from 3-chloro-1-trimethylsilylpropyne
with achiral N-trimethylsilyl- and N-benzylimines 2a and
2b, respectively (eq 1).15
Facing the lack of reactivity of N-R-methylbenzylimines,
we reasoned that the use of the presumed more reactive
N-sulfinimines would allow us to reach our goal since
both Davis’19 and Ellman’s20 groups have carried out
extensive studies on the stereoselective addition of or-
ganometallic reagents (including Grignard reagents, or-
ganolithiums, and enolates) to enantiomerically pure
N-p-toluene- and N-tert-butanesulfinimines, respectively.
We were particularly interested in Ellman’s N-tert-
butanesulfinimines since the N-tert-butanesulfinyl group
has often provided enhanced diastereofacial selectivity
compared to other N-sulfinyl auxiliaries such as the N-p-
toluenesulfinyl group.21 Furthermore, the N-tert-butane-
sulfinyl group has proven to be comparable in reactivity
to a Boc group and in this context would play the dual
role of a chiral directing and protecting group (it is easily
removed under acidic conditions) for further transforma-
tions. Moreover, Ellman and others have shown that the
N-tert-butanesulfinyl group induces high stereoselectivi-
ties in numerous nucleophile additions onto imines. For
instance, the asymmetric syntheses of trifluoromethyl-
ated vicinal ethylenediamines,22 1,2- and 1,3-amino
In a continuation of this work, we have undertaken to
develop a new synthesis of ethynylaziridines in a dias-
tereo- and enantioselective manner. However, since al-
lenylzinc 1 could not been prepared yet in an enantioen-
riched form, we have envisoned to use imines bearing a
chiral auxiliary on the nitrogen atom. At first, we thought
that the N-R-methylbenzyl substituent would play the
role of a good chiral directing group since it has proved
to induce high levels of stereoselectivity in some reactions
such as the addition of organometallic reagents onto N-R-
methylbenzylimines16,17 and the carbocylization reaction
(18) Lorthiois, E.; Marek, I.; Normant, J. F. J. Org. Chem. 1998,
63, 2442-2450.
(19) (a) Davis, F. A.; Yang, B. Org. Lett. 2003, 5, 5011-5014. (b)
Davis, F. A.; Prasad, K. R.; Nolt, M. B.; Wu, Y. Org. Lett. 2003, 5,
925-927. (c) Davis, F. A.; Wu, Y.; Yan, H.; McCoull, W.; Prasad, K. J.
Org. Chem. 2003, 68, 2410-2419. (d) Davis, F. A.; Chao, B.; Fang, T.;
Szewczyk, J. M. Org. Lett. 2000, 2, 1041-1043. (e) Davis, F. A.; Zhou,
P.; Chen, B.-C. Chem. Soc. Rev. 1998, 27, 13-18. (f) Davis, F. A.;
Fanelli, D. L. J. Org. Chem. 1998, 63, 1981-1985. (g) Davis, F. A.;
Zhou, P.; Chen, B.-C. Chem. Soc. Rev. 1998, 27, 13-18. (h) Davis, F.
A.; Szewczyk, J. M.; Reddy, R. E. J. Org. Chem. 1996, 61, 2222-2225.
(i) Davies, F. A.; Reddy, R. E.; Szewczyk, J. M. J. Org. Chem. 1995,
60, 7037-7039.
(13) (a) Ohno, H.; Toda, A.; Takemoto, Y.; Fujii, N.; Ibuka, T. J.
Chem. Soc., Perkin Trans. 1 1999, 2949-2961. (b) Ohno, H.; Toda, A.;
Fujii, N.; Ibuka, T. Tetrahedron: Asymmetry 1998, 3929-3933.
(14) (a) Ohno, H.; Ando, K.; Hamaguchi, H.; Takeoka, Y.; Tanaka,
T. J. Am. Chem. Soc. 2002, 124, 15255-15266. (b) Ohno, H.; Hamagu-
chi, H.; Tanaka, T. Org. Lett. 2001, 3, 2269-2271.
(20) (a) McMahon, J. P.; Ellman J. A. Org. Lett. 2004, 6, 1645-1647.
(b) Evans, J. W.; Ellman, J. A. J. Org. Chem. 2003, 68, 9948-9957. (c)
Tang, T. P.; Volkman, S. K.; Ellman, J. A. J. Org. Chem. 2001, 66,
8772-8778. (d) Borg, G.; Chino, M.; Ellman, J. A. Tetrahedron Lett.
2001, 42, 1433-1436. (e) Cogan, D. A.; Liu, G.; Ellman, J. A.
Tetrahedron 1999, 55, 8883-8904. (f) Liu, G.; Cogan, G. A.; Owens,
T. D.; Tang, T. P.; Ellman, J. A. J. Org. Chem. 1999, 64, 1278-1284.
(g) Tang, T. P.; Ellman, J. A. J. Org. Chem. 1999, 64, 12-13. (h) Liu,
G.; Cogan, D. A.; Ellman, J. A. J. Am. Chem. Soc. 1997, 119, 9913-
9914.
(15) (a) Chemla, F.; Hebbe, V.; Normant, J. F. Tetrahedron Lett.
1999, 40, 8093-8096. (b) Chemla, F.; Ferreira, F.; Hebbe, V.; Stercklen,
E. Eur. J. Org. Chem. 2002, 1385-1391.
(16) For reviews on the stereoselective addition of organometallic
reagents onto chiral imines see: (a) Bloch, R. Chem. Rev. 1998, 98,
1407-1438. (b) Enders, D.; Reinhold: U. Tetrahedron: Asymmetry
1997, 8, 1895-1946.
(17) For some examples see: (a) De Vitis, L.; Florio, S.; Granito, C.;
Ronzini, L.; Troisi, L.; Capriati, V.; Luisi, R.; Pilati, T. Tetrahedron
2004, 60, 1175-1182. (b) Bertrand, M. P.; Coantic, S.; Feray, L.;
Nouguier, R.; Perfetti, P. Tetrahedron 2000, 56, 3951-3961. (c) Roland,
S.; Mangeney, P. Eur. J. Org. Chem. 2000, 611-616. (d) Gao, Y.; Sato,
F. J. Org. Chem. 1995, 60, 8136-8137. (e) Yamamoto, Y.; Ito, W.
Tetrahedron 1988, 44, 5415-5423. (f) Yamamoto, Y.; Nishii, S.;
Maruyama, K.; Komatsu, T.; Ito, W. J. Am. Chem. Soc. 1986, 108,
7778-7786.
(21) (a) Jacobsen, M. F.; Skrydstrup, T. J. Org. Chem. 2003, 68,
7112-7114. (b) Sorochinsky, A.; Voloshin, N.; Markovsky, A.; Belik,
M.; Yasuda, N.; Uekusa, H.; Ono, T.; Berbasov, D. O.; Soloshonok, V.
A. J. Org. Chem. 2003, 68, 7448-7454. (c) Staas, D. D.; Savage, K. L.;
Homnick, C. F.; Tsou, N. N.; Ball, R. G. J. Org. Chem. 2002, 67, 8276-
8279. (d) Prakash, G. K. S.; Mandal, M.; Ohla, G. A. Angew. Chem.,
Int. Ed. 2001, 40, 589-590. (e) Davis, F. A.; Lee, S.; Zhang, H. M.;
Fanelli, D. L. J. Org. Chem. 2000, 65, 8704-8708. (f) Kawecki, R. J.
Org. Chem. 1999, 64, 8724-8727. (g) Davis, F. A.; McCoull, W. J. Org.
Chem. 1999, 64, 3396-3397.
(22) Prakash, G. K. S.; Mandal, M. J. Am. Chem. Soc. 2002, 124,
6538-6239.
J. Org. Chem, Vol. 69, No. 24, 2004 8245

Chemla and Ferreira
SCHEME 1
FIGURE 1. NOE experiments on racemic major and minor
aziridines 6f.
TABLE 1. Reaction of Racemic Allenylzinc 1 with
Racemic N-tert-Butanesulfinimines 5a-f (Scheme 1)
equiv
trans:
yieldc
(%)
entry imine R1
R2
of 1 aziridine cisa
dra,b
1
2
3
4
5
6
rac-5a
rac-5b
rac-5c
rac-5d
rac-5e
H
H
H
H
H
n-Pr
1.5
3.0
6.0
rac-6a
rac-6b
rac-6c
rac-6d
rac-6e
rac-6f
90:10 >98:2
70
67
64
56
58
54
crotyld
i-Pr
94:6
96:4
>98:2
>98:2
c-hexyl 6.0
Ph
rac-5f Me Ph
90:10 >98:2
6.0
6.0
91:9
91:9
>98:2
>98:2
a Selectivities measured by 1H NMR on the crude reaction
mixtures. b dr values of the major isomers. c Isolated yields in
purified major isomers. d The E:Z ratio of the C-C double bond
of the starting imine was 95:5.
FIGURE 2. ORTEP drawing of racemic trans aziridine 6e.
ature, racemic trans-ethynyl aziridines 6a-e were ob-
tained with excellent diastereoselectivities as determined
by 1H NMR (the cis isomers being characterized by
greater coupling constants between the two aziridinyl
protons than the trans isomers). Moreover, only single
trans stereoisomers were detected by 1H NMR (>98:2 dr).
With aziridine 6f containing a quaternary stereogenic
carbon, the same trans stereochemistry for the major
isomer was deduced from NOE experiments, while the
minor isomer was shown to be cis (Figure 1).
alcohols,20c,23 R- and â-amino acid derivatives,20d,f nonra-
cemic amines,20e,24 R-aminoorganostannanes,25 and P,N-
sulfinyl iridium catalysts26 have been recently reported
in the literature. Thus, we reasoned that enantiopure
N-tert-butanesulfinimines could give a straightforward
access to the corresponding ethynylaziridines in diaste-
reo- and enantiomerically pure forms through the reac-
tion with allenylzinc 1. We report herein our recent
results about this topic.
The excellent trans diastereoselectivity observed in
these reactions clearly indicated a high induction of the
chiral N-tert-butanesulfinyl group of the imine on the
stereochemical outcome of the reaction. After chroma-
tography over silica gel, all racemic trans aziridines 6a-f
were isolated as diastereomerically pure compounds.
Their stereochemistry was deduced from the single-
crystal X-ray analysis30 of racemic aziridine 6e (Figure
2). On the other hand, the stereochemistry of the cis
isomers could not be assigned.
The reaction was also examined with pure E racemic
N-p-toluenesulfinimines 7a-e readily available in high
yields (85-94%) from racemic N-p-toluenesulfinamide
according to Davis’ procedure32 (eq 3).
Results and Discussion
Pure E racemic N-tert-butanesulfinimines 5a-f were
easily accessible in high yields (64-82%) from racemic
N-tert-butanesulfinamide27 according to Ellman’s proce-
dure.20h,28 Their reaction with racemic allenylzinc 1,
generated by dropwise addition of n-BuLi to an equimolar
mixture of 3-chloro-1-trimethylsilypropyne and TMEDA
at -95 °C in Et2O,29,30 was examined (Scheme 1).
In all cases, racemic imines 5a-f exhibited little
reactivity with racemic 1 (much less reactivity than the
corresponding N-trimethylsilyl- and N-benzyl ones) giv-
ing low conversions below 0 °C. Excesses of allenylzinc 1
needed to be used for a complete reaction at room
temperature because of the competitive carbenoidic
decomposition of this organometallic species. However,
when performing the reaction in Et2O at room temper-
(23) (a) Kochi, T.; Tang, T. P.; Ellman, J. A. J. Am. Chem. Soc. 2003,
125, 11276-11282. (b) Kochi, T.; Tang, T. P.; Ellman, J. A. J. Am.
Chem. Soc. 2002, 124, 6518-6519.
(24) (a) Shaw, A. W.; deSolms, S. J. Tetrahedron Lett. 2001, 42,
7173-7176. (b) Cogan, D. A.; Ellman, J. A. J. Am. Chem. Soc. 1999,
121, 268-269. (c) Borg, G.; Cogan, D. A.; Ellman, J. A. Tetrahedron
Lett. 1999, 40, 6709-6712.
(25) Kells, K. W.; Chong, J. M. Org. Lett. 2003, 5, 4215-4218.
(26) Schenkel, L. B.; Ellman, J. A. J. Org. Chem. 2004, 69, 1800-
1802.
(27) Netscher, T.; Prinzbach, H. Synthesis 1987, 683-688.
(28) (a) Weix, D. J.; Ellman, J. A. Org. Lett. 2003, 5, 1317-1320.
(b) Cogan, D. A.; Liu, G.; Kim, K.; Backes, B. J.; Ellman, J. A. J. Am.
Chem. Soc. 1998, 120, 8011-8019.
(29) Ferreira, F.; Bejjani, J.; Denichoux, A.; Chemla, F. Synlett 2004,
6, 2051-2065.
(30) Chemla, F.; Ferreira, F. Synlett 2004, 6, 983-986.
All these imines exhibited a much higher reactivity
than racemic N-tert-butanesulfinimines 5a-f. In most
(31) (a) Davis, F. A.; Ramachandar, T.; Wu Y. J. Org. Chem. 2003,
68, 6894-6898. (b) Koriyama, Y.; Nozawa, A.; Hayakawa, R.; Shimizu,
M. Tetrahadron 2002, 58, 9621-9628. (c) Davis, F. A.; Liu, H.; Zhou,
P.; Fang, T.; Reddy, G. V.; Zhang, Y. J. Org. Chem. 1999, 64, 7559-
7267. (d) Davis, F. A.; Prasad, K J. Org. Chem. 2003, 68, 7249-7253.
8246 J. Org. Chem., Vol. 69, No. 24, 2004

Synthesis of Enantiopure trans-2-Ethynylaziridines
TABLE 2. Reaction of Racemic 1 with
cases, smaller amounts of racemic allenylzinc reagent 1
were needed to achieve the completion of the reaction at
room temperature, i.e., 1.5 and 3.0 equiv for imines
7a,b,e and 7c,d, respectively. Nevertheless, except with
imines 7c and 7d, poor levels of diastereoselection were
observed since complex stereoisomeric mixtures of trans
and cis aziridines were obtained. The drop in selectivity
with some sulfinimines 7 could presumably be attributed
to an enhancement of their reactivity toward allenylzinc
1 so that no facial stereodifferentiation could take place.
Unfortunately, lowering the temperature did not permit
the stereoselectivity of the reaction to be improved. As
mentioned above, sulfinimines 7c and 7d led to the
corresponding trans-ethynyl N-p-toluenesulfinylaziri-
dines 8c and 8d in 56% and 50% yield, respectively, as
single stereoisomers (>98:2 trans:cis and >98:2 dr). The
relative stereochemistry of the latter was reasonably
postulated to be the same as that of N-tert-butanesulfi-
nylaziridines 6a-f [i.e. (S*S,2S*,3S*)].
N-tert-Butanesulfinimines (RS)-5a-g (eq 4)
equiv
trans:
yieldc
entry imine
R1
R2
of rac-1 aziridine cisa dra,b (%)
1
2
3
4
5
6
7
8
9
(RS)-5a
rac-5a
(RS)-5a
(RS)-5be
(RS)-5c
(RS)-5d
(RS)-5e
H
H
H
H
H
H
H
n-Pr
n-Pr
n-Pr
crotyl
i-Pr
1.5
1.5
6.0
6.0
6.0
6.0
6.0
6.0
6.0
(RS)-6a 79:21 >98:2
d
rac-6a 90:10 >98:2 70
(RS)-6a 89:11 >98:2 61
(RS)-6b 90:10 >98:2 64
(RS)-6c 94:6 >98:2 69
(RS)-6d 90:10 >98:2 58
(RS)-6e 86:14 >98:2 50
(RS)-6f
(RS)-6g
c-hexyl
Ph
(RS)-5f Me
(RS)-5g n-pent n-pent
Ph
90:10 >98:2 69
>98:2 87
a Selectivities measured by 1H NMR on the crude reaction
mixtures. b dr values of the major isomers. c Isolated yields in
purified major isomers. d Not determined. e The E:Z ratio of the
C-C double bond of the starting imine was 95:5.
allenylzinc 1 could be regarded as at least partially
configurationally stable with respect to the time scale
defined by the reaction rate. Under these conditions, as
predicted by Hoffmann, using a large excess of racemic
allenylzinc 1 (6 equiv) allowed the stereoselectivity to be
improved up to a trans:cis ratio of 89:11, very close to
the theorical upper 90:10 ratio obtained with the racemic
imine 5a (Table 2, entry 3).
The same condition reactions were applied to the other
enantiopure N-tert-butanesulfinylaldimines and ketimines
(RS)-5b-f. After chromatography over silica gel, trans-
ethynylaziridines (RS)-6a-f were then isolated as dias-
tereomerically (>98:2 dr) and enantiomerically (>99% ee)
pure compounds in good isolated yields ranging from 50%
to 69%. In all cases, enantiopure imines (RS)-5a-f
afforded the corresponding aziridines (RS)-6a-f with
trans:cis stereoselectivities close to those observed with
the series of racemic aziridines 6a-f (Table 2, entries
3-8).
The high trans selectivity could not reasonably be
explained through a thermodynamical process since cis-
sulfonylaziridines have been described to be thermody-
namically favored.4 In fact, overall these results strongly
suggested that the trans isomers (RS)-6 could result from
the matched (RS)-5/(aS)-1 pairs via the chelate type
transition state TS-1 analogous to those evoked by others
in the additition of lithium or titanium enolates and of
potassium dialkyl phosphites onto sulfinimines.20c,f,31
Similarly, the cis isomers (RS)-6 could result from the
mismatched (RS)-5/(aR)-1 pairs via the open transition
state TS-2 with reference to N-sulfonylimines15b and
aromatic aldehydes29 (Scheme 2). Under the same condi-
tions, the symmetrical ketimine (RS)-5g gave aziridine
(RS)-6g in excellent yield (87%) and as a single isomer
(Table 2, entry 9). The stereochemical outcome of this
reaction simply reflects a high facial selectivity since, in
this particular case (R1 ) R2 in Scheme 2), the notion of
matched and mismatched pairs does not make any sense.
Having in hand an efficient method for preparing
trans-ethynyl N-tert-butanesulfinylaziridines in highly
diastereo- and enantioselective fashion, we have then
undertaken their conversion into the corresponding N-H
aziridines. The N-tert-butanesulfinyl auxiliary is de-
scribed to be comparable in reactivity to the Boc group
and to be easily removed under acidic conditions. How-
ever, in the case of 2-phosphonate N-tert-butanesulfinyl-
aziridines it has been recently reported by Davis that no
deprotection could occur without aziridine ring opening.31a
Thus, our method proved to be valuable only for
preparing a series of diastereomerically pure racemic
trans-ethynyl N-tert-butanesulfinylaziridines. We have
then undertaken its extension to the synthesis of enan-
tioenriched trans-N-tert-butanesulfinylaziridines (RS)-
6a-g. Pure E enantiopure N-tert-butanesulfinimines
(RS)-5a-g were easily prepared in excellent yields
(76-90%) from enantiopure N-tert-butanesulfinamide
(>99% ee as determibed by chiral GC analysis on a
Lipodex E capillary column) following the procedure
reported by Ellman.20h,28 Imines (RS)-5c,e,f exhibited the
same specific optical rotations as those reported in the
20h,28
literature
so that they were considered to be
enantiopure (>99% ee). By analogy, unknown imines
(RS)-5a,b,d,g were reasonably presumed to have the
same optical purity. Since the procedure for the prepara-
tion of allenylzinc 1 allows only the formation of a racemic
mixture we were confronted by the reaction between this
racemic nucleophile 1 and enantiopure sulfinimines
(RS)-5 (eq 4).
When carried out in Et2O at room temperature with
1.5 equiv of racemic allenylzinc 1, enantiopure imine (RS)-
5a gave a mixture of trans and cis aziridines (RS)-6a with
a selectivity of 79:21 in favor of the trans isomer (Table
2, entry 1). The trans:cis selectivity significantly deviated
from that obtained when racemic imine 5a was reacted
with 1.5 equiv of racemic 1 (Table 2, entries 1 vs 2). In
this context, according to Hoffmann’s works on the
configurational stability of organometallic reagents,33,34
(32) Davis, F. A.; Zhang, Y.; Andemichael, Y.; Fang, T.; Fanelli, D.
L.; Zhang, H. J. Org. Chem. 1999, 64, 1403-1406.
(33) (a) Hoffmann, R. W.; Julius, M.; Chemla, F.; Ruhland, T.;
Frenzen, D. Tetrahedron 1994, 50, 6049-6060. (b) Hirsch, R.; Hoff-
mann, R. W. Chem. Ber. 1992, 125, 975-982.
(34) For a recent review on the configurational stability of enan-
tioenriched organolithium reagents see: Basu, A.; Thayumanavan, S.
Angew. Chem., Int. Ed. 2002, 41, 716-738.
J. Org. Chem, Vol. 69, No. 24, 2004 8247

Chemla and Ferreira
SCHEME 2. Origin of trans- and
cis-N-tert-Butanesulfinylaziridines (RS)-6
3). In the other cases, i.e., with trans-ethenyl and
aromatic aziridines, (RS)-6b,e,f, only products resulting
from the aziridine ring opening reaction with MeOH were
observed. With such substrates the formation of a
stabilized allylic or benzylic carbocation, which under-
went subsequent reaction with MeOH, would certainly
be evoked to explain the aziridine ring opening reaction.
Conclusion
In summary, we have developed a concise and efficient
synthesis of enantiopure trans-ethynyl N-tert-butane-
sulfinylaziridines by the condensation of the allenylzinc
species derived from 3-chloro-1-trimethylsilylpropyne
onto N-tert-butanesulfinylaldimines and ketimines at
room temperature in Et2O. The excellent stereoselectivity
was shown to result from a high kinetic resolution in the
reaction of the racemic allenylzinc with enantiopure
N-tert-butanesulfinimines. This kinetic resolution was
proven to be the consequence of the zinc being coordi-
nated by both the oxygen and the nitrogen atoms of the
sulfinimine in a chelate-type transititon state. The
formation of certain enantiopure acetylenic N-H aziri-
dines could also be achieved through deprotection under
acidic conditions. The extension of this method to other
γ-functionalized allenylzincs, in the aim of preparing
nonracemic 1,2-amino alcohols or diamines for instance,
and the synthetic use of 2-ethynylsulfinylaziridines are
currently under investigation in our group and will be
reported in due course.
TABLE 3. Removal of the N-tert-Butanesulfinyl
Auxiliary from (RS)-6a,d,g (eq 5)
sulfinyl-
entry aziridine
invertomer - yield -
R1
R2
product
ratioa
(%)
1
2
3
(RS)-6a
(RS)-6d
(RS)-6g
H
H
n-Pr
(2R,3R)-9a
80:20
96:4
97:3
66b
82b
c-hexyl (2R,3R)-9d
n-pent n-pent (2R)-9g
100c
Experimental Section
a Invertomer ratios measured by 1H NMR on the purified
products. b Isolated yields in purified products. c No purification
was necessary.
General. See the Supporting Information.
Preparation of Enantiopure N-tert-Butanesulfinimines
(RS)-5a-g. The literature procedure20h,28 was followed. The 1H
and 13C values and the specific optical rotations obtained for
N-tert-butanesulfinimines (RS)-5c,e,f correspond to those re-
ported.
However, we have tried to deprotect trans aziridines (RS)-
6a,b,d-g by treatment with HCl (eq 5).
(RS,E)-(-)-N-Butylidene-tert-butanesulfinamide, (RS)-
5a. The literature procedure20h,28 was followed. Under a
nitrogen atmosphere, a suspension of butyraldehyde (0.68 mL,
7.50 mmol), (RS)-(+)-tert-butanesulfinamide (>99% ee by chiral
GC analysis on a Lipodex E capillary column, 605 mg, 5.00
mmol), PPTS (65 mg, 0.25 mmol), and anhydrous MgSO4 (3.00
g, 25.00 mmol) in CH2Cl2 (8 mL) was stirred for 24 h at room
temperature. The mixture was filtered over a pad of Celite
and concentrated in vacuo. The residual oil was purified by
filtration over a pad of silica gel (eluant: CH2Cl2) yielding
enantiopure E sulfinimine (RS)-5a as a colorless oil (705 mg,
4.32 mmol, 87%). [R]D -305.0 (c 0.94, CHCl3, 20 °C); IR (ATR
To our great delight and in contrast to the results
previously reported by Davis, when performing the
reaction with 5 equiv of HCl in MeOH, the deprotection
could be achieved within 30 min at room temperature
but only from alkyl 3-substituted and 3,3-disubstituted
aziridines (RS)-6a,d and (RS)-6g, respectively (Table 3).
The corresponding N-H aziridine was accompanied by
a small amount of opened aziridine ring products (about
15%) in the case of the little hindered trans aziridine (RS)-
6a. Deprotected aziridines were formed as single products
from the more hindered trans aziridine (RS)-6d and the
alkyl 3,3-disubstituted (RS)-6g one. Thus aziridines
(2R,3R)-9a,d and (2R)-9g were isolated in good to excel-
lent yields (ranging from 66% to 100%) as mixtures of
the two possible invertomers in ratios depending upon
the difference of steric hindrance between the two sides
of the aziridine ring (Table 3, entry 1 vs entries 2 and
Diamand) 2873 (m), 1621 (w), 1082 (s) cm-1 1H NMR (400
;
MHz, CDCl3) δ 8.06 (1H, t, J ) 4.8 Hz), 2.50 (2H, m), 1.67
(2H, m), 1.20 (9H, s), 0.99 (3H, t, J ) 7.6 Hz); 13C NMR (100
MHz, CDCl3) δ 170.0, 56.8, 38.4, 22.7, 19.3, 14.2. Anal. Calcd
for C8H17NOS: C, 54.81; H, 9.78; N, 7.99. Found: C, 54.75;
H, 9.85; N, 7.89.
(RS,E,E)-(-)-N-(But-2-enylidene)-tert-butanesulfina-
mide, (RS)-5b. The literature procedure20h,28 was followed as
above from crotonaldehyde (95:5 E:Z, 0.62 mL, 7.50 mmol)
yielding enantiopure E sulfinimine (RS)-5b as a yellow oil (705
mg, 4.08 mmol, 82%). [R]D -589.0 (c 0.94, CHCl3, 20 °C); IR
(ATR Diamand) 3034 (w), 1645 (s), 1580 (s), 1078 (s) cm-1; 1H
NMR (400 MHz, CDCl3) δ 8.19 (1H, d, J ) 9.2 Hz), 6.58 (1H,
qd, J ) 15.4, 6.5 Hz), 6.46 (1H, qdd, J ) 15.4, 9.2, 1.5 Hz),
1.99 (3H, dd, J ) 6.5, 1.5 Hz), 1.22 (9H, s); 13C NMR (100 MHz,
CDCl3) δ 163, 146.5, 130.2, 57.0, 22.3, 18.8. Anal. Calcd for
C8H15NOS: C, 55.45; H, 8.73; N, 8.08. Found: C, 55.22; H,
8.78; N, 8.01.
8248 J. Org. Chem., Vol. 69, No. 24, 2004

Synthesis of Enantiopure trans-2-Ethynylaziridines
(RS,E)-(-)-N-Cyclohexylmethylidene-tert-butanesulfi-
namide, (RS)-5d. The literature procedure20h,28 was followed
as above from cyclohexanecarboxaldehyde (0.91 mL, 7.50
mmol) yielding enantiopure E sulfinimine (RS)-5d as a color-
less oil (946 mg, 4.40 mmol, 88%). [R]D -232.5 (c 0.98, CHCl3,
0.50 mmol) in anhydrous Et2O (2 mL) was cannulated to a
solution of racemic allenylzinc 1 (3.0 mmol) at room temper-
ature. After being stirred for 4 h at room temperature, the
solution was quenched by 30% aqueous NH3:saturated aqueous
NH4Cl (1:2 solution). The layers were separated and the
aqueous layer was extracted with Et2O (3×). The combined
organic layers were washed with water and brine, dried over
anhydrous Na2SO4, and concentrated in vacuo. The residual
oil was purified by flash chromatography (gradient eluant:
5-20% Et2O in pentane) yielding enantiopure trans aziridine
(RS)-6a as a colorless oil (87 mg, 0.30 mmol, 61%). [R]D -158.8
(c 1.02, CHCl3, 20 °C); IR (ATR Diamand) 2175 (w), 1249 (m),
1099 (m), 840 (s), 759 (m) cm-1; 1H NMR (400 MHz, CDCl3) δ
2.76 (1H, d, J ) 3.8 Hz), 2.57 (1H, td, J ) 7.9, 3.8 Hz), 1.91
(1H, m), 1.51-1.37 (3H, m), 1.31 (9H, s), 0.98 (3H, t, J ) 7.3
Hz), 0.20 (9H, s); 13C NMR (50 MHz, CDCl3) δ 100.7, 91.1, 57.2,
47.0, 33.1, 32.8, 22.8, 20.2, 14.2, 0.1. Anal. Calcd for C14H27-
NOSSi: C, 58.89; H, 9.53; N, 4.91. Found: C, 58.89; H, 9.49;
N, 4.85.
[(RS,2R,3R)-(E)]-(-)-N-tert-Butanesulfinyl-3-(prop-1-
enyl)-2-trimethylsilylethynylaziridine, (RS)-6b. The above
procedure was followed with enantiopure E sulfinimine (RS)-
5b (86 mg, 0.50 mmol). Flash chromatography (gradient
eluant: 5-20% Et2O in pentane) yielded enantiopure trans
aziridine (RS)-6b as a colorless oil (90 mg, 0.32 mmol, 64%).
[R]D -99.8 (c 1.01, CHCl3, 20 °C); IR (ATR Diamand) 2171 (w),
1249 (m), 1101 (m), 841 (s), 759 (m) cm-1; 1H NMR (400 MHz,
CDCl3) δ 5.85 (1H, qd, J ) 15.4, 6.6 Hz), 5.24 (1H, ddd, J )
15.4, 8.3, 1.5 Hz), 3.02 (1H, dd, J ) 8.3, 3.8 Hz), 2.88 (1H, d,
J ) 3.8 Hz), 1.69 (3H, dd, J ) 6.6, 1.5 Hz), 1.22 (9H, s), 0.13
(9H, s); 13C NMR (100 MHz, CDCl3) δ 132.6, 125.7, 99.6, 91.0,
57.1, 48.4, 33.4, 22.5, 17.9, -0.3; HRMS found 284.1498,
C14H26NOSSi [MH+] requires 284.1504.
1
20 °C); IR (ATR Diamand) 1618 (s), 1083 (s) cm-1; H NMR
(400 MHz, CDCl3) δ 7.97 (1H, d, J ) 4.6 Hz), 2.47 (1H, m),
1.92-1.68 (7H, m), 1.67-1.35 (3H, m), 1.20 (9H, s); 13C NMR
(100 MHz, CDCl3) δ 173.2, 56.8, 44.4, 29.7, 26.2, 25.7, 22.7.
Anal. Calcd for C11H21NOS: C, 61.35; H, 9.83; N, 6.50.
Found: C, 61.32; H, 9.85; N, 6.22.
(RS)-(-)-N-r-Pentylhexylidene-tert-butanesulfina-
mide, (RS)-5g. The literature procedure20h,28 was followed.
Under a nitrogen atmosphere, a stirred solution of 6-unde-
canone (1.13 mL, 5.50 mmol), (RS)-(+)-tert-butanesulfinamide
(>99% ee by chiral GC analysis on a Lipodex E capillary
column, 605 mg, 5.00 mmol), and Ti(OEt)4 (technical grade,
2.30 mL, 11.00 mmol) in THF (11 mL) was refluxed for 18 h.
After cooling to room temperature, the solution was poured
into vigorously stirred saturated aqueous NaCl (15 mL). The
mixture was filtred over a pad of Celite and the solid rinced
with AcOEt (4 × 30 mL). The organic layer was washed with
brine and the resulting aqueous layer was extracted once with
AcOEt. The combined organic layers were dried over anhy-
drous Na2SO4 and concentrated in vacuo. The residual oil was
purified by flash chromatography (gradient eluant: 20-25%
Et2O in pentane) yielding enantiopure sulfinimine (RS)-5g as
a pale yellow oil (1.100 g, 4.03 mmol, 82%). [R]D -132.8 (c 1.01,
1
CHCl3, 20 °C); IR (ATR Diamand) 1619 (s), 1075 (s) cm-1; H
NMR (400 MHz, CDCl3) δ 2.64 (2H, m), 2.36 (2H, m), 1.55 (4H,
m), 1.28 (8H, m), 1.19 (9H, s), 0.85 (6H, t, J ) 7.2 Hz); 13C
NMR (100 MHz, CDCl3) δ 189.0, 56.1, 40.8, 36.4, 31.9, 31.3,
27.0, 25.2, 22.5, 22.3, 22.2, 13.9, 13.8. Anal. Calcd for C15H31-
NOS: C, 65.88; H, 11.43; N, 5.12. Found: C, 65.80; H, 11.56;
N, 5.03.
(RS,2R,3R)-(-)-N-tert-Butanesulfinyl-3-isopropyl-2-tri-
methylsilylethynylaziridine, (RS)-6c. The above procedure
was followed with enantiopure E sulfinimine (RS)-5c (87 mg,
0.50 mmol). Flash chromatography (eluant: 3% Et2O in CH2-
Cl2) yielded enantiopure trans aziridine (RS)-6c as a colorless
oil (99 mg, 0.34 mmol, 69%). [R]D -233.5 (c 1.08, CHCl3, 20
°C); IR (ATR Diamand) 2176 (w), 1249 (m), 1049 (m), 840 (s),
Preparation of Racemic N-p-Toluenesulfinimines 7a-
e. The literature procedure32 was followed. The 1H and 13C
spectral data obtained for racemic N-p-toluenesulfinimines
7a-c,e correspond to those reported.
(SS*,E)-N-Cyclohexylmethylidene-p-toluenesulfina-
mide, 7d. The literature procedure32 was followed. Under a
nirogen atmosphere, a solution of cyclohexanecarboxaldehyde
(0.49 mL, 7.50 mmol), racemic p-toluenesulfinamide (621 mg,
4.00 mmol), and Ti(OEt)4 (technical grade, 4.20 mL, 20.00
mmol) in CH2Cl2 (60 mL) was refluxed for 1 h. After cooling
to 0 °C, the mixture was quenched with H2O (60 mL) and
filtred over a pad of Celite and the solid was rinced with
CH2Cl2 (3 × 60 mL). The layers were separated and the
aqueous layer was extracted once with CH2Cl2. The combined
organic layers were dried over anhydrous Na2SO4 and con-
centrated in vacuo. The residual oil was purified by filtration
over a pad of silica gel (eluant: CH2Cl2) yielding racemic E
sulfinimine 7d as a colorless oil (849 mg, 3.41 mmol, 85%). IR
(ATR Diamand) 1615 (s), 1092 (s), 1072 (s) cm-1; 1H NMR (400
MHz, CDCl3) δ 8.13 (1H, d, J ) 4.4 Hz), 7.56 (2H, d, J ) 8.1
Hz), 7.32 (2H, d, J ) 8.1 Hz), 2.44 (1H, m), 2.42 (3H, s), 1.91-
1.60 (5H, m), 1.37-1.27 (5H, m); 13C NMR (100 MHz, CDCl3)
δ 170.1, 142.1, 141.4, 129.7, 124.5, 43.6, 29.0, 25.8, 25.2, 21.3.
Anal. Calcd for C14H19NOS: C, 67.43; H, 7.68; N, 5.62.
Found: C, 67.31; H, 7.79; N, 5.50.
Preparation of Racemic Allenylzinc 1. Under a nitrogen
atmosphere, TMEDA (0.15 mL, 1.0 mmol) and n-BuLi (2.1 M
solution in hexanes, 0.48 mL, 1.0 mmol) were successively
added to a solution of 1-chloro-3-trimethylsilylpropyne (0.16
mL, 1.0 mmol) in anhydrous Et2O (13 mL) at -95 °C. After 5
min of stirring at -95 °C, a solution of ZnBr2 (1.0 M in Et2O,
1.0 mL, 1.0 mmol) was added dropwise to the yellow mixture.
The resulting white slurry mixture was then warmed to room
temperature and used immediately.
1
759 (m) cm-1; H NMR (400 MHz, CDCl3) δ 2.81 (1H, d, J )
4.0 Hz), 2.53 (1H, dd, J ) 6.8, 4.0 Hz), 1.85 (1H, m), 1.32 (9H,
s), 1.09 (3H, d, J ) 6.4 Hz), 0.92 (3H, d, J ) 6.8 Hz), 0.19 (9H,
s); 13C NMR (100 MHz, CDCl3) δ 100.4, 90.9, 56.8, 51.0, 30.1,
28.5, 22.6, 20.0, 17.9, -0.3. Anal. Calcd for C14H27NOSSi: C,
58.89; H, 9.53; N, 4.91. Found: C, 58.72; H, 9.72; N, 4.82.
(RS,2R,3R)-(-)-N-tert-Butanesulfinyl-3-cyclohexyl-2-
trimethylsilylethynylaziridine, (RS)-6d. The above proce-
dure was followed with enantiopure E sulfinimine (RS)-5d (107
mg, 0.50 mmol). Flash chromatography (gradient eluant:
5-20% Et2O in pentane) yielded enantiopure trans aziridine
(RS)-6d as a white solid (95 mg, 0.29 mmol, 58%). Mp (pentane)
70-71 °C. [R]D -140.8 (c 0.99, CHCl3, 20 °C); IR (ATR
Diamand) 2183 (w), 1242 (m), 1106 (m), 839 (s), 764 (m) cm-1
;
1H NMR (400 MHz, CDCl3) δ 2.82 (1H, d, J ) 4.0 Hz), 2.53
(1H, dd, J ) 6.3, 4.0 Hz), 1.95 (1H, m), 1.78-1.69 (4H, m),
1.49 (1H, m), 1.32 (9H, s), 1.28-1.08 (4H, m), 1.08-0.95 (m,
1H), 0.19 (9H, s); 13C NMR (100 MHz, CDCl3) δ 100.6, 90.9,
57.0, 50.4, 38.2, 30.8, 30.7, 28.9, 26.1, 25.7, 25.6, 22.7, -0.3.
Anal. Calcd for C17H31NOSSi: C, 62.71; H, 9.60; N, 4.30.
Found: C, 62.84; H, 9.61; N, 4.20.
(RS,2R,3R)-(-)-N-tert-Butanesulfinyl-3-phenyl-2-tri-
methylsilylethynylaziridine, (RS)-6e. The above procedure
was followed with enantiopure E sulfinimine (RS)-5e (104 mg,
0.50 mmol). Flash chromatography (gradient eluant: 5-20%
Et2O in pentane) yielded enantiopure trans aziridine (RS)-6e
as a white solid (80 mg, 0.251 mmol, 50%). Mp 124-127 °C
dec. [R]D -61.7 (c 0.95, CHCl3, 20 °C); IR (ATR Diamand) 2183
1
(w), 1248 (m), 1083 (m), 839 (s), 761 (m) cm-1; H NMR (400
(RS,2R,3R)-(-)-N-tert-Butanesulfinyl-3-propyl-2-trimeth-
ylsilylethynylaziridine, (RS)-6a. Under a nitrogen atmo-
sphere, a solution of enantiopure E sulfinimine (RS)-5a (87 mg,
MHz, CDCl3) δ 7.36-7.33 (3H, m), 7.28-7.26 (2H, m), 3.46
(1H d, J ) 3.5 Hz), 3.09 (1H, d, J ) 3.5 Hz), 126 (9H, s), 0.24
(9H, s); 13C NMR (100 MHz, CDCl3) δ 135.0, 128.8, 128.5,
J. Org. Chem, Vol. 69, No. 24, 2004 8249

Chemla and Ferreira
126.3, 98.7, 92.6, 57.2, 47.6, 36.7, 22.5, -0.3. Anal. Calcd for
C17H31NOSSi: C, 63.90; H, 7.89; N, 4.38. Found: C, 63.41; H,
8.16; N, 4.22.
29.3, 25.9, 25.5, 25.3, 21.6, -0.2. Anal. Calcd for C20H29-
NOSSi: C, 66.80; H, 8.13; N, 3.90. Found: C, 66.81; H, 8.30;
N, 3.78.
(RS,2R,3R)-(+)-N-tert-Butanesulfinyl-3-methyl-3-phen-
yl-2-trimethylsilylethynylaziridine, (RS)-6f. The above
procedure was followed with enantiopure E sulfinimine (RS)-
5f (111 mg, 0.50 mmol). Flash chromatography (gradient
eluant: 5-20% Et2O in pentane) yielded enantiopure trans
aziridine (RS)-6f as a white solid (115 mg, 0.34 mmol, 69%).
Mp (pentane) 111-133 °C. [R]D +15.7 (c 1.02, CHCl3, 20 °C);
IR (ATR Diamand) 2178 (w), 1246 (m), 1078 (m), 843 (s), 759
(2R,3R)-(+)-3-Propyl-2-trimethylsilylethynylaziri-
dine, (2R,3R)-9a. Under an argon atmosphere, to a stirred
solution of enantiopure trans-N-sulfinylaziridine (RS)-6a (142
mg, 0.50 mmol) in absolute MeOH (15 mL) was added at 0 °C
HCl (1 M etheral solution, 2.50 mL, 2.50 mmol) and the
resulting mixture was warmed to room temperature. After 30
min of stirring at this temperature, saturated aqueous NaH-
CO3 (30 mL) was added, the layers were partitioned, and the
aqueous layer was extracted with Et2O (3×). The combined
organic layers were dried over anhydrous MgSO4 and evapo-
rated in vacuo to give a pale yellow oil. After purification by
flash chromatography (eluant: 15% Et2O in pentane), enan-
tiopure trans-N-H aziridine (2R,3R)-9a was obtained as a
yellow oil (59 mg, 0.33 mmol, 66%). Invertomer ratio: 80:20.
[R]D +63.3 (c 1.26 CHCl3, 20 °C); IR (ATR Diamand) 2168 (m),
(m) cm-1 1H NMR (400 MHz, CDCl3) δ 7.53-7.50 (2H, m),
;
7.42-7.33 (3H, m), 3.24 (1H, s), 1.81 (3H, s), 1.29 (9H, s), 0.23
(9H, s); 13C NMR (100 MHz, CDCl3) δ 137.5, 128.9, 128.5,
128.4, 99.7, 91.0, 57.4, 52.5, 38.0, 23.0, 22.4, -0.2; HRMS found
334.1661, C18H28NOSSi [MH+] requires 334.1667.
(RS,2R)-(-)-N-tert-Butanesulfinyl-3,3-dipentyl-2-tri-
methylsilylethynylaziridine, (RS)-6g. The above procedure
was followed with enantiopure sulfinimine (RS)-5g (136 mg,
0.50 mmol). Flash chromatography (gradient eluant: 5-20%
Et2O in pentane) yielded enantiopure aziridine (RS)-6g as a
yellow oil (167 mg, 0.43 mmol, 87%). [R]D -77.3 (c 0.93, CHCl3,
20 °C); IR (ATR Diamand) 2166 (w), 1249 (m), 1099 (m), 841
1249 (m), 836 (s) cm-1 1H NMR (400 MHz, CDCl3) δ 2.26
;
(0.8H, br s), 2.07 (0.8H, br s: major invertomer), 1.76 (0.4H,
br s: minor invertomer), 1.55-1.30 (5H, m), 0.97 (2.4H, t, J
) 7.2 Hz: major invertomer), 0.61 (0.6H, br s: minor inver-
tomer), 0.16 (9H, s); 13C NMR (100 MHz, CDCl3) δ 105.9, 84.6,
40.3, 35.3 (br), 25.4, 20.3, 13.8, -0.1; HRMS found 182.1366,
C10H20NSi [MH+] requires 182.1365.
1
(s), 759 (m); H NMR (400 MHz, CDCl3) δ 2.67 (1H, s), 2.00
(1H, m), 1.69-1.33 (15H, m), 1.29 (9H, s), 0.91 (6H, m), 0.18
(9H, s); 13C NMR (100 MHz, CDCl3) δ 100.9, 89.2, 57.0, 53.2,
39.6, 32.3, 31.8, 31.5, 26.1, 24.4, 22.51, 22.49, 22.0, 14.1, 14.0,
-0.2; HRMS found 384.2757, C21H42NOSSi [MH+] requires
384.2756.
(2R,3R)-(+)-3-Cyclohexyl-2-trimethylsilylethynylaziri-
dine, (2R,3R)-9d. The above procedure was followed with
enantiopure trans-N-sulfinylaziridine (RS)-6d (162 mg, 0.50
mmol). Flash chromatography (eluant: 15% Et2O in pentane)
yielded enantiopure trans-N-H aziridine (2R,3R)-9d as a
yellow oil (89 mg, 0.41 mmol, 82%). Invertomer ratio: 96:4.
[R]D +84.4 (c 1.09 CHCl3, 20 °C); IR (ATR Diamand) 3152 (m),
(S*S,2S*,3S*)-(()-3-Isopropyl-N-p-toluenesulfinyl-2-tri-
methylsilylethynylaziridine, 8c. Under a nitrogen atmo-
sphere, a solution of racemic E sulfinimine 7c (104 mg, 0.50
mmol) in anhydrous Et2O (2 mL) was cannulated to a solution
of racemic allenylzinc 1 (1.5 mmol) at room temperature. After
being stirred for 1 h at room temperature, the solution was
quenched by Na2CO3/NaHCO3 buffer and diluted with H2O.
The layers were then separated and the aqueous layer was
extracted with Et2O (3×). The combined organic layers were
washed with water and brine, dried over anhydrous Na2SO4,
and concentrated in vacuo. The residual oil was purified by
flash chromatography over silica gel (eluant: 3% Et3N in 8%
Et2O/pentane) to yield racemic trans aziridine 8c as a viscous
colorless oil (89 mg, 0.28 mmol, 56%). IR (ATR Diamand) 2173
1
2161 (m), 837 (s) cm-1; H NMR (400 MHz, CDCl3) δ 2.11-
2.07 (2H, m), 1.87-1.67 (5H, m), 1.20-1.05 (5H, m), 0.86 (1H,
m), 0.21 (0.36H, s: minor invertomer), 0.16 (8.64H, s: major
invertomer), H on the nitrogen atom was not observed; 13C
NMR (100 MHz, CDCl3) δ 106.2, 84.4, 45.7, 41.6, 30.6, 30.3,
26.3, 25.8, 25.7, 24.3, -0.1; HRMS found 222.1673, C13H24Nsi
[MH+] requires 222.1678.
(2R)-(+)-3,3-Dipentyl-2-trimethylsilylethynylaziri-
dine, (2R)-9g. The above procedure was followed with enan-
tiopure N-sulfinylaziridine (RS)-6g (96 mg, 0.25 mmol) yielding
enantiopure N-H aziridine (2R)-9g as a white solid (70 mg,
0.25 mmol, 100%). Invertomer ratio: 97:3. Mp 87-89 °C. [R]D
+57.3 (c 1.10 CHCl3, 20 °C); IR (ATR Diamand) 2165 (w), 1249
1
(w), 1597 (w), 1249 (m), 1102 (m), 840 (s), 731 (m) cm-1; H
NMR (400 MHz, CDCl3) δ 7.75 (2H, d, J ) 8.4 Hz), 7.34 (2H,
d, J ) 8.4 Hz), 2.95 (1H, d, J ) 4.0 Hz), 2.44 (3H, s), 2.24 (1H,
dd, J ) 7.6, 4.0 Hz), 1.32 (1H, m), 0.82 (3H, d, J ) 6.8 Hz),
0.49 (3H, d, J ) 6.8 Hz), 0.22 (9H, s); 13C NMR (100 MHz,
CDCl3) δ 142.9, 142.5, 129.8, 125.9, 99.5, 92.9, 50.5, 34.8, 30.5,
21.8, 19.3, 19.0, 0.0. Anal. Calcd for C17H25NOSSi: C, 63.90;
H, 7.89; N, 4.38. Found: C, 63.48; H, 8.02; N, 4.07.
1
(m), 839 (s) cm-1; H NMR (400 MHz, CDCl3) δ 2.28 (0.03H,
br s: minor invertomer), 2.22 (0.97H, br s: major invertomer),
1.69 (1H, m), 1.37-1.28 (16H, m), 0.92 (3H, t, J ) 6.8), 0.90
(3H, t, J ) 7.1), 0.21 (0.27H, s: minor invertomer); 0.16 (8.73H,
s: major invertomer), H on the nitrogen atom was not
observed; 13C NMR (100 MHz, CDCl3) δ 104.4, 85.6, 45.3, 35.7,
34.2 (minor invertomer), 33.0 (minor invertomer), 32.1, 31.5
(minor invertomer), 30.3 (minor invertomer), 31.9, 25.5, 25.0,
22.7, 22.6, 14.1, 14.0, -0.1; HRMS found 280.2465, C17H34NSi
[MH+] requires 280.2461.
(S*S,2S*,3S*)-(()-3-Cyclohexyl-N-p-toluenesulfinyl-2-
trimethylsilylethynylaziridine, 8d. The above procedure
was followed with racemic E sulfinimine 7d (124 mg, 0.50
mmol). Flash chromatography (eluant: 3% Et3N in 8% Et2O/
pentane) yielded racemic trans aziridine 8d as a viscous pale
yellow oil (90 mg, 0.25 mmol, 50%). IR (ATR Diamand) 3038
(w), 2174 (w), 1596 (w), 1248 (m), 1103 (m), 841 (s), 759 (m)
Supporting Information Available: General methods
and 1H and 13C NMR spectra for compounds (RS)-5a,b,d,g,
(RS)-6a-g, rac-7d,8c,d, (2R,3R)-9a,d, and (2R)-9g. This mate-
rial is available free of charge via the Internet at http://pubs.
acs.org.
1
cm-1; H NMR (400 MHz, CDCl3) δ 7.63 (2H, d, J ) 8.4 Hz),
7.31 (2H, d, J ) 8.4 Hz), 2.94 (1H, d, J ) 4.0 Hz), 2.44 (3H, s),
2.28 (1H, dd, 3J ) 7.6, 4.0 Hz), 1.70-1.48 (4H, m), 1.13-0.88
(6H, m), 0.59 (1H, m), 0.21 (9H, s); 13C NMR (50 MHz, CDCl3)
δ 142.6, 142.1, 129.5, 125.6, 99.4, 92.6, 49.2, 39.6, 34.3, 29.6,
JO0490696
8250 J. Org. Chem., Vol. 69, No. 24, 2004