Reactions of n-arylsulfonyl-2,3-cis- and n-arylsulfonyl-2,3-frans-3-alkyl-2-vinylaziridines with organocopper reagents: importance of 2,3-cis-stereochemistry in controlling regio- and stereoselectivity

Article abstract of DOI:10.1021/jo9810157

Although reactions of 2,3-trans-N-arylsulfonyl-3-alkyl-2-alkenylaziridines with organocopper reagents give a mixture of two or three products, the corresponding 2,3-cis-isomers provide a highly efficient route to synthetically important nonracemic CE)-allylamines. It is also found that the reaction proceeds via the well-known anti-S_N2′ pathway.

Full text of DOI:10.1021/jo9810157

J . Org. Chem. 1998, 63, 7053-7061
7053
Rea ction s of N-Ar ylsu lfon yl-2,3-cis- a n d
N-Ar ylsu lfon yl-2,3-tr a n s-3-a lk yl-2-vin yla zir id in es w ith
Or ga n ocop p er Rea gen ts: Im p or ta n ce of 2,3-cis-Ster eoch em istr y in
Con tr ollin g Regio- a n d Ster eoselectivity
Ayako Toda, Hiroshi Aoyama, Norio Mimura, Hiroaki Ohno, Nobutaka Fujii, and
Toshiro Ibuka*
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606, J apan
Received May 28, 1998
Although reactions of 2,3-trans-N-arylsulfonyl-3-alkyl-2-alkenylaziridines with organocopper re-
agents give a mixture of two or three products, the corresponding 2,3-cis-isomers provide a highly
efficient route to synthetically important nonracemic (E)-allylamines. It is also found that the
reaction proceeds via the well-known anti-SN2′ pathway.
Development of synthetic methods that provide ready
access to nonracemic allylamines from alkenylaziridines
with a high level of regio- and (E)-stereoselectivity as well
as high chemical yields represents a challenge to syn-
thetic organic chemists. Recently, great advances have
been reported in the ring opening of activated and
unactivated aziridines1 by both carbon (e.g., enolates,2
enediolates,3 malonates and related reagents,4 organo-
lithiums,5 Grignard reagents,6 organocopper reagents,7
and Wittig reagents8) and heteroatom nucleophiles (e.g.,
amines,9 thiols or thiophenolates,10 and alcohols11). Al-
though extensive stereochemical and mechanistic studies
by Marshall12 and Marino13 on the ring-opening reaction
of vinyloxiranes and related compounds with organo-
copper reagents have shown that an anti-SN2′ pathway
is highly favored for substitution, until recently SN2′ ring-
opening reactions of vinylaziridines14,15 and their deriva-
tives16 with organocopper reagents for the synthesis of
various synthetically useful allylamines had been rare.
We now detail a regio- and (E)-stereoselective SN2′
ring-opening strategy involving organocopper reagents
for converting nonracemic N-protected 2,3-cis- and 2,3-
trans-3-alkyl-2-alkenylaziridines to the synthetically im-
portant N-protected allylamines in high yields. Synthesis
of a nonracemic vinylglycine derivative is also pre-
sented.
(11) (a) Nakajima, K.; Neya, M.; Yamada, S.; Okawa, K. Bull. Chem.
Soc. J pn. 1982, 55, 3049. (b) Bodenan, J .; Chanet-Ray, J .; Vessiere, R.
Synthesis 1992, 288. (c) For an aziridine ring-opening reaction with
acetic acid, see: Atkinson, R. S.; Ayscough, A. P.; Rattrell, W. T.;
Raynham, T. M. Tetrahedron Lett. 1998, 39, 4377.
(12) (a) Marshall, J . A.; Audia, V. H.; J enson, T. M.; Guida, W. C.
Tetrahedron 1986, 42, 1703. (b) Marshall, J . A.; Audia, V. H. J . Org.
Chem. 1987, 52, 1106. (c) Marshall, J . A.; Trometer, J . D. Tetrahedron
Lett. 1987, 28, 4985. (d) Marshall, J . A.; Trometer, J . D.; Clearly, D.
G. Tetrahedron 1989, 45, 391. (e) Marshall, J . A. Chem. Rev. 1989,
89, 1503. (f) Marshall, J . A.; Blough, B. E. J . Org. Chem. 1990, 55,
1540. (g) Marshall, J . A.; Blough, B. E. J . Org. Chem. 1991, 56, 2225.
(h) Marshall, J . A.; Crute, T. D., III.; Hsi, J . D. J . Org. Chem. 1992,
57, 115.
(13) Marino, J . P.; Floyd, D. M. Tetrahedron Lett. 1979, 675. Marino,
J . P.; Hatanaka, N. J . Org. Chem. 1979, 44, 4467. Marino, J . P.; Abe,
H. Synthesis 1980, 872. Marino, J . P.; Abe, H. J . Org. Chem. 1981, 46,
5379. Marino, J . P.; Abe, H. J . Am. Chem. Soc. 1981, 103, 2907. Marino,
J . P.; J ae´n, J . C. J . Am. Chem. Soc. 1982, 104, 3165. Marino, J . P.;
Ferna´ndez de la Pradilla, R.; Laborde, E. J . Org. Chem. 1984, 49, 5279.
Marino, J . P.; Ferna´ndez de la Pradilla, R.; Laborde, E. J . Org. Chem.
1987, 52, 4898. Ferna`ndez de la Pradilla, R.; Rubio, M. B.; Marino, J .
P. Viso, A. Tetrahedron Lett. 1992, 33, 4985. Marino, J . P.; Viso, A.;
Ferna´ndez de la Pradilla, R.; Ferna`ndez, P. J . Org. Chem. 1991, 56,
1349. Marino, J . P.; Anna, L. J .; Ferna´ndez de la Pradilla, R.; Mart´ınez,
M. V.; Montero, C.; Viso, A. Tetrahedron Lett. 1996, 37, 8031.
(14) Cantrill, A. A.; J arvis, A. N.; Osborn, H. M. I.; Ouadi, A.;
Sweeney, J . B. Synlett 1996, 847.
(15) A preliminary communication of this work has appeared:
Aoyama, H.; Mimura, N.; Ohno, H.; Ishii, K.; Toda, A.; Tamamura,
H.; Otaka, A.; Fujii, N.; Ibuka, T. Tetrahedron Lett. 1997, 38, 7383.
(16) (a) Ibuka, T.; Nakai, K.; Habashita, H.; Hotta, Y.; Fujii, N.;
Mimura, N.; Miwa, Y.; Taga, T.; Yamamoto, Y. Angew. Chem., Int. Ed.
Engl. 1994, 33, 652. (b) Wipf, P.; Fritch, P. C. J . Org. Chem. 1994, 59,
4875. (c) Fujii, N.; Nakai, K.; Tamamura, H.; Otaka, A.; Mimura, N.;
Miwa, Y.; Taga, T.; Yamamoto, Y.; Ibuka, T. J . Chem. Soc., Perkin
Trans. 1 1995, 1359. (d) Ibuka, T.; Akaji, M.; Mimura, N.; Habashita,
H.; Nakai, K.; Tamamura, H.; Fujii, N.; Yamamoto, Y. Tetrahedron
Lett. 1996, 37, 2849. (e) Ibuka, T.; Mimura, N.; Ohno, H.; Nakai, K.;
Akaji, M.; Habashita, H.; Tamamura, H.; Miwa, Y.; Taga, T.; Fujii,
N.; Yamamoto, Y. J . Org. Chem. 1997, 62, 2982. (f) Wipf, P.; Henninger,
T. C. J . Org. Chem. 1997, 62, 1486.
* Phone: 81-75-753-4528. Fax: 81-75-753-4570. E-mail: tibuka@
pharmsun.pharm.kyoto-u.ac.jp.
(1) For reviews of syntheses and reactions of activated and unacti-
vated aziridines, see: Pawda, A.; Woolhouse, A. D. In Comprehensive
Heterocyclic Chemistry; Lwowski, W., Ed.; Pergamon: Oxford, 1984;
Vol. 7, pp 47-93. Kasai, M.; Kono, M. Synlett 1992, 778. Tanner, D.
Angew. Chem., Int. Ed. Engl. 1994, 33, 599. Osborn, H. M. I.; Sweeney,
J . Tetrahedon: Asymmetry 1997, 8, 1693. Rayner, C. M. Synlett 1997,
11. Ibuka, T. Chem. Soc. Rev. 1998, 27, 145.
(2) Stamm, H.; Weiss, R. Synthesis 1986, 392.
(3) (a) Stamm, H.; Weiss, R. Synthesis 1986, 395. (b) Brigaud, T.;
Laurent, E.; Tardivel, R.; Cebulska, Z.; Bartnik, R. J . Chem. Res.,
Synop. 1994, 330. (c) Matsumoto, K.; Iida, H.; Uchida, T.; Yabe, Y.;
Kakehi, A. Chem. Express 1993, 8, 609.
(4) Stamm, H.; Assithianakis, P.; Buchholz, B.; Weiss, R. Tetrahe-
dron Lett. 1982, 23, 5021.
(5) Howson, W.; Osborn, H. M. I.; Sweeney, J . J . Chem. Soc., Perkin
Trans. 1 1995, 2439.
(6) Oppolzer, W.; Flaskamp, E. Helv. Chim. Acta 1977, 60, 204.
(7) (a) Eis, M. J .; Ganem, B. Tetrahedron Lett. 1985, 26, 1153. (b)
Dure´ault, A.; Greck, C.; Depezay, J . C. Tetrahedron Lett. 1986, 27,
4157. (c) Dure´ault, A.; Tranchepain, I.; Depezay, J .-C. J . Org. Chem.
1989, 54, 5324. (d) Kozikowski, A. P.; Ishida, H.; Isobe, K. J . Org. Chem.
1979, 44, 2788. (e) Church, N. J .; Young, D. W. Tetrahedron Lett. 1995,
36, 151. (f) Tanner, D.; Groth, T. Tetrahedron 1997, 53, 16139. (g)
Tanner, D.; Birgersson, C.; Dhaliwal, H. K. Tetrahedron Lett. 1990,
31, 1903. (h) Tanner, D.; Somfai, P. Tetrahedron 1988, 44, 619.
(8) Baldwin, J . E.; Adlington, R. M.; Robinson, N. G. J . Chem. Soc.,
Chem. Commun. 1987, 153.
(9) (a) Shigematsu, N.; Setoi, H.; Uchida, I.; Shibata, T.; Terano,
H.; Hashimoto, M. Tetrahedron Lett. 1988, 29, 5147. (b) Nakajima,
K.; Tanaka, T.; Morita, K.; Okawa, K. Bull. Chem. Soc. J pn. 1980, 53,
283. (c) Cernerud, M.; Adolfsson, H.; Moberg, C. Tetrahedron: Asym-
metry 1997, 8, 2655. (d) Maligres, P. E.; See, M. M.; Askin, D.; Reider,
P. J . Tetrahedron Lett. 1997, 38, 5253.
(10) (a) Tomalia, D. A.; Sheetz, D. P.; Ham, G. E. J . Org. Chem.
1970, 35, 47. (b) Nakajima, K.; Oda, H.; Okawa, K. Bull. Chem. Soc.
J pn. 1983, 56, 520. (c) Lin, P.-Y.; Bellos, K.; Stamm, H.; Onistschenko,
A. Tetrahedron 1992, 48, 2359. (d) Legters, J .; Thijs, L.; Zwanenburg,
B. Tetrahedron Lett. 1989, 30, 4881.
S0022-3263(98)01015-9 CCC: $15.00 © 1998 American Chemical Society
Published on Web 09/15/1998

7054 J . Org. Chem., Vol. 63, No. 20, 1998
Toda et al.
Sch em e 1
Sch em e 2
Resu lts a n d Discu ssion
As shown in Scheme 1, three different products from
the reaction of 2-vinylaziridine 1 with an organocopper
reagent could be envisioned. If an organocopper reagent
reacts with vinylaziridine 1 by an SN2 mechanism, it will
produce either 2 or 3. If the reagent attacks by an SN2′
mechanism, it will generate either (E)- or (Z)-allylamine
4 or a mixture of (E)- and (Z)-configurational isomers.
The regio- and stereoselectivity of the ring-opening
reaction is expected to be controlled by a delicate balance
of steric and electronic factors. Thus, it is not an easy
matter to predict whether path A, B, or C is the major
reaction pathway in the reaction of 2-alkenylaziridines
with organocopper reagents.
Syn th esis of Non r a cem ic 2,3-cis- a n d 2,3-tr a n s-3-
Alk yl-2-vin yla zir id in es. It is well documented that the
reactivity of N-unsubstituted- or N-alkylaziridines to-
ward nucleophiles is relatively low; hence, activation by
the introduction of an electron-withdrawing protecting
group on the nitrogen atom of the aziridine is required.
The term “activated aziridines” has been introduced by
Ham for aziridines that easily undergo nucleophilic SN2-
type ring opening.17 The N,N-diphenylphosphinoyl group
serves as a good activating group.18 Alternatively, aryl-
sulfonyl groups work as most effective activating groups.19
The N-arylsulfonyl groups can withstand a wide range
of chemical manipulations and yet be removed by the use
of HBr-AcOH,7e,20 SmI2,21 TFA-thioanisole,22 Na-Hg,23
or Na-liquid NH3.24
Experimental Section). The 2,3-cis or -trans stereochem-
istry of the aziridines 11 and 12 was inferred from 1H
NMR spectral analyses. The 2,3-cis-aziridine 11 shows
a J (Hab) value (J ) 6.5 Hz) larger than that of the 2,3-
trans-isomer 12 (J ) 3.2 Hz). The data are in good
1
agreement with H NMR data for related compounds.22,26
The 2,3-cis/ trans pair of N-tosylaziridines 13 and 14 was
readily synthesized by our published method22 from (S)-
threonine and (D)-allo-threonine, respectively. Other 2,3-
cis/ trans pairs of N-2,4,6-trimethylbenzenesulfonyl-
aziridines (15 and 16), (17 and 18), and (19 and 20) were
prepared from (S)-valinol, (S)-phenylalanine, and (R)-
serine, respectively, following literature procedure.22
Rin g-Op en in g Rea ction s of Activa ted 2-Alk en yl-
3-alkylazir idin es with Or gan ocopper Reagen ts. Syn -
th esis of Non r a cem ic Allyla m in es. The ring-opening
reaction of activated 2,3-trans-2-vinylaziridine with some
nucleophiles has been examined independently by
Sweeney and co-workers14 and our group.15 However, the
synthetic utility of this transformation remains unex-
plored. At first, we briefly studied the scope of the
methylcopper-mediated reaction by using the two stereo-
isomeric substrates 11 and 12 (Scheme 3 and Table 1).
To our initial dismay, reaction of the 2,3-cis-vinylaziri-
dine 11 with 4 molar equiv of methylcopper (MeCu‚LiI‚
LiBr) or lower-order cyanocuprate [MeCu(CN)Li‚LiBr]
recovered the starting material unchanged (Table 1,
entries 1 and 2). Similar results were obtained by
reaction of 2,3-trans-isomer 12 with MeCu‚LiI or MeCu-
(CN)Li (Table 1, entries 5 and 6). Although the N,N-
diphenylphosphinoyl (DPP) group is a potentially useful
The requisite 2,3-cis/ trans pair of N,N-diphenyl-
phosphinoyl-3-alkyl-2-vinylaziridines 11 and 12 were
prepared from the known (S)-valinol 525 by a sequence
of reactions as shown in Scheme 2 (for details, see
(17) Ham, G. E. J . Org. Chem. 1964, 29, 3052.
(18) (a) Osborn, H. M. I.; Sweeney, J . B. Synlett 1994, 145. (b) Berry,
M. B.; Craig, D.; J ones, P. S.; Rowlands, G. J . Chem. Commun. 1997,
2141. (c) Cantrill, A. A.; Osborn, H. M. I.; Sweeney, J . Tetrahedron
1998, 54, 2181. (d) Hou, X.-L.; Yang, X.-F.; Dai, L.-X.; Chen, X.-F.
Chem. Commun. 1998, 747.
(19) Greene, T. W.; Wuts, P. G. M. In Protective Groups in Organic
Synthesis; J ohn Wiley & Sons: New York, 1991.
(20) Baldwin, J . E.; Spivey, A. C.; Schofield, C. J .; Sweeney, J . B.
Tetrahedron 1993, 49, 6309.
(21) Vedejs, E.; Lin, S. J . Org. Chem. 1994, 59, 1602.
(22) Ibuka, T.; Mimura, N.; Aoyama, H.; Akaji, M.; Ohno, H.; Miwa,
Y.; Taga, T.; Nakai, K.; Tamamura, H.; Fujii, N.; Yamamoto, Y. J . Org.
Chem. 1997, 62, 999.
(23) Craig, D.; McCague, R.; Potter, G. A.; Williams, M. R. V. Synlett
1998, 55 and 58.
(24) Ibuka, T.; Nakai, K.; Akaji, M.; Tamamura, H.; Fujii, N.;
Yamamoto, Y. Tetrahedron 1996, 52, 11739.
(25) McKennon, M. J .; Meyers, A. I.; Drauz, K.; Schwarm, M. J . Org.
Chem. 1993, 58, 3568.
(26) (a) Coutrot, P.; Elgadi, A.; Grison, C. Heterocycles 1989, 28,
1179. (b) Davis, F. A.; Zhou, P. Tetrahedron Lett. 1994, 35, 7525. (c)
Davis, F. A.; Zhou, P.; Reddy, G. V. J . Org. Chem. 1994, 59, 3243. (d)
Ziegler, F. E.; Belema, M. J . Org. Chem. 1994, 59, 7962.

Reactions of Vinylaziridines with Organocopper Reagents
J . Org. Chem., Vol. 63, No. 20, 1998 7055
Sch em e 3
Sch em e 4
Ta ble 1. Meth ylcop p er -Med ia ted Rea ction s of
Vin yla zir id in es 11 a n d 12a
product combd
ratio
isoltd
entry substr
reagent
21:22
yld (%)
1
2
3
4
5
6
7
11
11
11
11
12
12
12
MeCu‚LiI‚LiBr (4 equiv)
MeCu(CN)Li‚LiBr (4 equiv)
Me2CuLi‚LiI‚2LiBr (4 equiv)
recovered
recovered
89:11 93
Me2Cu(CN)Li2‚2LiBr (4 equiv) 99:1
MeCu‚LiI‚LiBr (4 equiv)
99
recovered
recovered
93
MeCu(CN)Li‚LiBr (4 equiv)
Me2Cu(CN)Li2‚2LiBr (4 equiv) 99:1
a
All reactions were carried out in THF under a positive pressure
of argon at -78 °C for 30 min. All methylcopper reagents have
been prepared by treatment of CuI or CuCN with ethereal MeLi
as the LiBr complex. All product ratios were determined by HPLC.
(CN)Li2‚2LiBr, prepared from 2 equiv of methyllithium
as the LiBr complex and an equivalent of CuCN, is the
reagent of choice because with it the most (E)-selective
anti-SN2′ substitution reaction to the N-DPP-2-vinylaziri-
dine substrate occurs.
protecting and activating group, it is clear that activation
by the DPP group is considerably lower than that by
arylsulfonyl groups. However, the ring-opening reaction
was accomplished by using a Gilman-type reagent,
Me2CuLi‚LiI‚LiBr, to yield an 89:11 mixture of (E)- and
(Z)-allylamines 21 and 22 in favor of the (E)-isomer 21
(Table 1, entry 3). The (E)-allylamine 21 could be
isolated readily after flash chromatography. Thus, of the
three possible regioisomeric products, ring-opening prod-
ucts via path C (Scheme 1) were formed exclusively. It
should be clearly noted that while there is 1H NMR
spectroscopic evidence to support the presence of the (Z)-
allylamine 22, the (Z)-isomer 22 could not be isolated in
a pure state by various silica gel columns.
Next, the scope of the organocopper-mediated reaction
was determined by using the four 2,3-trans substrates
13, 15, 17, and 19 bearing an N-arylsulfonyl group.
As can be seen from Scheme 4 and Table 2 (entries
1-10), regardless of the type of organocopper reagent,
mixtures of two or three products were obtained from all
reactions of 2,3-trans-2-vinylaziridines. It is of interest,
however, that all of these ring-opening reactions exhibit
high levels of regioselectivity and (E)-stereoselectivity
(>85%). In all cases studied in the 2,3-trans series of
substrates, 3-15% yields of (Z)-allylamines 24, 26, 28,
31, and 33 were obtained after flash chromatography.
Although both (E)- and (Z)-products, e.g., (23 and 24) and
(25 and 26), are the result of an SN2′ reaction, the loss of
stereocontrol, though slight, is undesirable in synthesis.
In addition, minor products (29 and 34, 2-3% yield) that
would have originated via the SN2 pathway were also
isolated from the reactions of vinylaziridines 17 and 19.
The most regio- and (E)-selective SN2′ type ring-
opening reaction was realized by the reaction of 11 or
12 with a higher order cuprate, Me2Cu(CN)Li2‚2LiBr27
-
(Me2CuLi‚LiCN‚2LiBr28), to yield almost exclusively allyl-
amine 21 (Table 1, entries 4 and 7). Thus, the stereo-
selectivity markedly changes by use of the higher-order
cuprate, Me2Cu(CN)Li2‚2LiBr instead of the Gilman-type
reagent, Me2CuLi‚LiI‚2LiBr29 (compare entry 3 with 4,
Table 1). Thus, the higher-order cyanocuprate, Me2Cu-
In contrast, upon the exposure of 2,3-cis-3-alkyl-2-
vinylaziridines 14, 16, 18, and 20 to organocopper
reagents, the corresponding (E)-allylamines were exclu-
sively produced in very high yields (Scheme 5 and Table
2, entries 11-19). In all cases examined in the 2,3-cis
series of substrates, reaction products were shown to be
(27) Lipshutz, B. H.; Wilhelm, R. S.; Kozlowski, J . A. Tetrahedron
1984, 40, 5005. Lipshutz, B. H.; Sharma, S.; Ellsworth, E. L. J . Am.
Chem. Soc. 1990, 112, 4032. Although the organocopper reagent
prepared from CuCN and 2 equiv of MeLi‚LiBr may be represented
as Me2CuLi‚LiCN‚2LiBr by analogy to Gilman reagent, Me2CuLi‚LiI‚
2LiBr, for the cuprate prepared from CuI and 2 equiv of MeLi‚LiBr as
suggested by Dr. Bertz,28a-c the formula Me2Cu(CN)Li2‚2LiBr has been
used throughout this paper as a matter of convenience. We are not
concerned about the exact constitution, but watch the reactive species
as a reagent system. See also: Lipshutz, B. H. Synthesis 1987, 325.
Lipshutz, B. H. In Organometallic in Synthesis; Schlosser, M., Ed.;
Wiley: New York, 1994; p 283.
(28) (a) Bertz, S. H. J . Am. Chem. Soc. 1990, 112, 4031. (b) Bertz,
S. H.; Miao, G.; Eliksson, M. J . Chem. Soc., Chem. Commun. 1996,
815. (c) Bertz, S. H.; Dabbagh, G.; He, X.; Power, P. P. J . Am. Chem.
Soc. 1993, 115, 11640. See also: Stemmler, T.; Penner-Hahn, J . E.;
Knochel, P. J . Am. Chem. Soc. 1993, 115, 348. Synder, J . P.; Spangler,
D. P.; Behling, J . R.; Rossiter, B. E. J . Org. Chem. 1994, 59, 2665.
(29) Similar results were obtained by treatment of (2R,3S)-2,3-cis-
N,N-diphenylphosphinoyl-3-(1-methylpropyl)-2-vinylaziridine, pre-
pared from (S)-isoleucine, with methylcopper reagents.
1
a single (E)-allylamine by H NMR and HPLC analyses
(compare entries 1-10 with entries 11-19).
Thus, it is found that whereas N-arylsulfonyl-2,3-trans-
3-alkyl-2-vinylaziridines gave mixtures of two or three
products, 2,3-cis-isomers gave exclusively the correspond-
ing (E)-allylamines in high yields. Since 2,3-trans-3-
alkyl-2-vinylaziridines could be transformed into the
corresponding 2,3-cis-isomers by the Pd(0)-catalyzed
isomerization reactions,22 we believe that the present
organocopper chemistry could be used for the selective
synthesis of (E)-allylamines.

7056 J . Org. Chem., Vol. 63, No. 20, 1998
Ta ble 2. Or ga n ocop p er -Med ia ted Rea ction s of 2,3-tr a n s- a n d 2,3-cis-3-Alk yl-2-vin yla zir id in esa
Toda et al.
ratiob
mol
combd
entry
reactant
reagent
equiv
product(s)
yld (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
13
13
15
15
15
15
17
17
19
19
14
14
16
16
16
18
18
20
20
MeCu‚LiI‚LiBr
MeCu(CN)Li‚LiI
MeCu‚2LiI
MeCu(CN)Li‚LiI
Me2CuLi‚LiI‚LiBr
i-PrCu(CN)MgCl
MeCu‚LiI‚LiBr
MeCu(CN)Li‚LiI
MeCu‚2LiI
MeCu(CN)Li‚LiI
MeCu‚LiI‚LiBr
Me3SiCu(CN)Li
MeCu(CN)Li‚LiI
i-PrCu(CN)MgCl
Me3SiCu(CN)Li
MeCu(CN)Li‚LiI
Me3SiCu(CN)Li
MeCu(CN)Li‚LiI
MeCu‚2LiI
5
4
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
23 + 24
99
99
98
95
99
99
99
95
93
89
91
98
99
99
99
99
87
98
87
96:4
89:11
92:8
85:15
93:7
85:15
93:4:3
95:3:2
93:4:3
94:4:2
100
100
100
100
100
100
100
100
100
23 + 24
25 + 26
25 + 26
25 + 26
30 + 31
27 + 28 + 29
27 + 28 + 29
32 + 33 + 34
32 + 33 + 34
23
35
25
30
36
27
37
32
32
a
All reactions were carried out in dry THF under slight positive argon pressure. Product ratios were determined by reverse-phase
b
HPLC. All compounds were isolated by flash chromatography and fully characterized. Values correspond to the products in the same
order as given in column 5.
Sch em e 5
Sch em e 6
chromatography over silica gel gave 2,3-cis-isomer 20 in
80% yield, which was then treated with MeCu(CN)Li‚
LiI to yield exclusively the desired (E)-allylamine 32. The
(E)-allylamine 32 was transformed into the vinylglycine
analogue 38 following a well-established sequence of
reactions.
As can be seen from Table 2, there remains the
question of why only the 2,3-cis-aziridines were exclu-
sively transformed into the corresponding (E)-allyl-
amines.35 To facilitate ab initio calculations, the most
simple system, N-mesyl-2,3-cis-3-methyl-2-vinylaziridine
39 and its 2,3-trans-isomer 40, was chosen for investiga-
tion of the theoretical aspects.22 Ab initio calculations
suggest that the energy difference between the conform-
ers 39-A and 39-B of 39 is ca. 10.2 kcal mol-1 at the RHF/
6-31G** level (Scheme 7). In addition, consideration of
the nonbonded interactions in the conformers 39-A and
39-B reveals that in conformer 39-B, which could lead
to (Z)-allylamine 42, a substantial nonbonded interaction
exists to destabilize 39-B in comparison with 39-A. As
a result, the reaction of 2,3-cis-3-alkyl-2-vinylaziridine
39 with organocopper reagents would be expected to
afford exclusively the corresponding (E)-allylamine 41.
Thus, the exclusive formation of (E)-allylamines from 2,3-
cis-aziridines (Scheme 5 and Table 2, entries 10-19) may
be rationalized by assuming a similar preferred confor-
mation of type 39-A (Scheme 7).
Unsaturated amino acids such as vinylglycines30 are
of particular biological interest as receptor antagonists31
and enzyme inhibitors.32 Vinylglycinol33 and butadienyl-
glycine34 have also attracted much interest in recent
years. Vinylglycine analogue 38 was synthesized from
2,3-trans-ziridine 19 in the following manner. Exposure
of 19 to 4 mol % of Pd(PPh3)4 in THF followed by flash
(30) Dardenne, G.; Casimir, J .; Marlier, M.; Larsen, P. O. Phyto-
chemistry 1974, 13, 1897. Havl´ıcek, L.; Hanus, J . Collect. Czech. Chem.
Commun. 1991, 56, 1365.
(31) Fagg, G. E.; Olpe, H. R.; Pozza, M. F.; Baud, J .; Steinmann,
M.; Schmutz, M.; Portet, C.; Baumann, P.; Thedinga, K.; Bittiger, H.;
Allgeier, H.; Heckendorn, R.; Angst, C.; Brundish, D.; Dingwall, J . G.
Br. J . Pharmacol. 1990, 99, 791. Ibuka, T.; Suzuki, K.; Habashita, H.;
Otaka, A.; Tamamura, H.; Mimura, N.; Miwa, Y.; Taga, T.; Fujii, N.
J . Chem. Soc., Chem. Commun. 1994, 2151.
(32) Sufrin, J . R.; Lombardini, J . B.; Keith, D. D. Biochem. Biophys.
Res. Commun. 1982, 106, 251.
(33) Trost, B. M.; Bunt, R. C. Angew. Chem., Int. Ed. Engl. 1996,
35, 99.
(34) Cameron, S.; Khambay, B. P. S. Tetrahedron Lett. 1998, 39,
1987.
(35) For (E)-selective SN2′ reactions, see: Trost, B. M.; Klun, T. P.
J . Org. Chem. 1980, 45, 4256-4257.

Reactions of Vinylaziridines with Organocopper Reagents
J . Org. Chem., Vol. 63, No. 20, 1998 7057
Sch em e 7
Next, we investigated the SN2′ substitution to deter-
mine if the reaction proceeds via an anti- or syn-SN2′
pathway (Scheme 8).36 Both anti- and syn-SN2′ reactions
of a vinylaziridine like 43 (Scheme 8) with organocopper
reagents should lead to a single product 44. If the usual
preference for an anti-SN2′ pathway is assumed,37 an
organocopper reagent would be expected to approach 2,3-
cis-vinylaziridines such as 43 from the side anti to the
N(1)-C(2) bond (Scheme 8). However, the mechanism
of the SN2′ reaction has been a matter of some contro-
versy since its discovery.38 The intermolecular SN2′
reactions of allylic carbamates,39 ammonium salts,40 some
oxiranes,41 (allyloxy)benzothiazoles,42 and some γ-mesyl-
oxy-R,â-enoates43 with organocopper reagents take place
by via the syn-SN2′ pathway.
The following experiment shows how the above prob-
lem has been clarified. Thus, the reaction of (E)-aziridine
45 with a higher order diphenylcyanocuprate, Ph2Cu-
(CN)(MgCl)2, provided anti-SN2′-substitution product 47
as a single product. The absolute configuration at the
(36) Although the detailed mechanism of organocopper SN2′ substi-
tution is still a question, evidence shows the reversible formation of a
cuprate-substrate (d-π*) complex in the initial step (Goering, H. L.;
Kantner, S. S. J . Org. Chem. 1981, 46, 2144. Goering, H. L.; Seitz, E.
P., J r.; Tseng, C. C. J . Org. Chem. 1981, 46, 5304. Corey, E. J .; Boaz,
N. W. Tetrahedron Lett. 1984, 25, 3063.). To gain an understanding of
the relative stabilities of two methylcopper-substrate (d-π*) com-
plexes, we undertook ab initio calculations at the RHF/LANL1DZ level
of theory. Effective core potential (ECP) for Cu and double-ú were used
for other elements. To reduce the size, two model systems A and B of
methylcopper-substrate (d-π*) complexes were chosen. However, it
was found that the energy difference between geometries A and B was
predicted to be only 0.387 kcal/mol.
Sch em e 8
(37) (a) Lipshutz, B. H.; Sengupta, S. In Organic Reactions; Paquette,
L. A., Ed.; J ohn Wiley & Sons: New York, 1992; p 135. (b) Lipshutz,
B. H. In Comprehensive Organometallic Chemistry II; Abel, E. W.,
Stone, F. G. A., Wilkinson, G., Eds.; Pergamon Press: London, 1995;
Vol. 12, pp 59-130. (c) Ibuka, T.; Yamamoto, Y. In Organocopper
Reagents; Taylor, R. J . K., Ed.; Oxford Unversity Press: Oxford, 1994;
pp 154-157. (d) Ibuka, T.; Nakao, T.; Nishii, S.; Yamamoto, Y. J . Am.
Chem. Soc. 1986, 108, 7420. (e) Ibuka, T.; Tanaka, M.; Yamamoto, Y.
J . Chem. Soc., Chem. Commun. 1989, 967. (f) Ibuka, T.; Akimoto, N.;
Tanaka, M.; Nishii, S.; Yamamoto, Y. J . Org. Chem. 1989, 54, 4055.
(g) Ibuka, T.; Tanaka, M.; Nishii, S.; Yamamoto, Y. J . Am. Chem. Soc.
1989, 111, 4864. (h) Ibuka, T.; Habashita, H.; Funakoshi, S.; Fujii,
N.; Oguchi, Y.; Uyehara, T.; Yamamoto, Y. Angew. Chem., Int. Ed.
Engl. 1990, 29, 801. (i) Ibuka, T.; Habashita, H.; Otaka, A.; Fujii, N.;
Oguchi, Y.; Uyehara, T.; Yamamoto, Y. J . Org. Chem. 1991, 56, 4371.
(38) Magid, R. M. Tetrahedron 1980, 36, 1901.
(39) (a) Gallina, C.; Ciattini, P. G. J . Am. Chem. Soc. 1979, 101,
1035. (b) Ganilla, C. Tetrahedron Lett. 1982, 23, 3093. (c) Goering, H.
L.; Kantner, S. S.; Tseng, C. C. J . Org. Chem. 1983, 48, 715. (d)
Fleming, I.; Thomas, A. P. J . Chem. Soc., Chem. Commun. 1986, 1456.
(e) RajanBabu, T. V.; Nugent, W. A.; Taber, D. F.; Fagan, P. J . J . Am.
Chem. Soc. 1988, 110, 7128. (f) Greene, A. E.; Coelho, F.; Depres, J .-
P.; Brocksom, T. J . Tetrahedron Lett. 1988, 29, 5661. (g) Underiner,
T. L.; Goering, H. L. J . Org. Chem. 1989, 54, 3239.
On the other hand, the energy difference between
possible conformers 40-A and 40-B of 2,3-trans-aziridine
40 is predicted to be somewhat smaller (ca. 3.4 kcal/mol).
Consequently, formation of a mixture of (E)- and (Z)-
allylamines 41 and 42 would be expected. In actuality,
the treatment of N-arylsulfonyl-2,3-trans-3-alkyl-2-vinyl-
aziridines with organocopper reagents gave the corre-
sponding mixtures of (E)- and (Z)-allylamines (Table 2,
entries 1-10).
Needless to say, the ground state and the reactive
conformer are not necessarily the same. In addition, the
precise dihedral angle of the reactive conformer would
not be near 180° (e.g., 39-A and 40-A) or 0° (e.g., 39-B
and 40-B). Although it is difficult to explain the differ-
ences in regioselection (SN2 versus SN2′), the picture used
in Scheme 7 is representative of our current level of
understanding of the stereoselective organocopper-medi-
ated SN2′ ring-opening reactions of N-arylsulfonyl-3-
alkyl-2-vinylaziridines.
(40) Hutchinson, D. K.; Fuchs, P. L. J . Am. Chem. Soc. 1985, 107,
6137. Hutchinson, D. K.; Hardinger, S. A.; Fuchs, P. L. Tetrahedron
Lett. 1986, 27, 1425. Hutchinson, D. K.; Fuchs, P. L. Tetrahedron Lett.
1986, 27, 1429. Pan, V.; Hutchinson, D. K.; Nantz, M. H.; Fuchs, P. L.
Tetrahedron 1989, 45, 467. Berglund, R. A.; Braish, T. F.; J akubowski,
J . A. Fuchs, P. L. Bioorg. Med. Chem. 1991, 1, 649.
(41) Ziegler, F. E.; Cady, M. A. J . Org. Chem. 1981, 46, 122.
(42) Valverde, S.; Bernabe´, M.; Garcia-Ochoa, S.; Go´mez, A. M. J .
Org. Chem. 1990, 55, 2294.
(43) Ibuka, T.; Taga, T.; Habashita, H.; Nakai, K.; Tamamura, H.;
Fujii, N.; Chounan, Y.; Nemoto, H.; Yamamoto, Y. J . Org. Chem. 1993,
58, 1207.

7058 J . Org. Chem., Vol. 63, No. 20, 1998
Toda et al.
) 17.3, 10.8, 5.9 Hz, 1 H). Anal. Calcd for C12H23NO3: C,
phenylated carbon center was established by conversion
of 47 into the known (R)-2-phenylpropan-1-ol 4944 through
a two-step sequence of reactions illustrated in Scheme
8. In a similar manner, the isomeric (Z)-propenylaziri-
dine 46 was converted into the known (S)-2-phenylpro-
pan-1-ol 5045 via the anti-SN2′ intermediate 48. We have
shown unequivocally that organocopper reagents attack
alkenylaziridines to give overall anti-SN2′ products.
In summary, we have demonstrated that although
reactions of 2,3-trans-N-arylsulfonyl-3-alkyl-2-alkenyl-
aziridines with organocopper reagents give a mixture of
two or three products, the corresponding 2,3-cis-isomers
provide a highly efficient route to synthetically important
nonracemic (E)-allylamines. It is also found that the
reaction proceeds via a net anti-SN2′ pathway.
62.85; H, 10.11; N, 6.11. Found: C, 62.55; H, 10.15; N, 6.03.
(3S,4S)-4-(N-Diph en ylph osph in oyl)am in o-5-m eth ylh ex-
1-en -3-ol (9). Trifluoroacetic acid (2 mL) was added to 229
mg (1.0 mmol) of the alcohol 7 at 0 °C, and the mixture was
stirred for 1 h with warming to room temperature. The
mixture was concentrated under reduced pressure to an oily
residue, which was made alkaline with 28% NH4OH and
extracted with CHCl3. The extract was washed with brine and
concentrated under reduced pressure to leave a colorless oil.
To the oil in 2 mL of DMF were added successively 0.166 mL
(1.2 mmol) of Et3N and 260 mg (1.1 mmol) of diphenylphos-
phinoyl chloride in 5 mL of DMF. After the mixture was
stirred for 14 h at 0 °C, 3 mL of saturated NaHCO3 was added
with stirring. The mixture was made acidic with saturated
citric acid and extracted with EtOAc. The extract was washed
with water, 5% NaHCO3, and brine and dried over MgSO4.
Concentration followed by flash chromatography over silica
gel with n-hexane-EtOAc (1:2) gave 129 mg (39% yield) of
the title compound 9: colorless needles from Et2O; mp 159-
Exp er im en ta l Section
160 °C; [R]22 -73.67 (c 1.20, CHCl3); 1H NMR (270 MHz,
Gen er a l Meth od s. All reactions were carried out under a
positive pressure of argon. All glassware and syringes were
dried in an electric oven at 100 °C prior to use. All melting
points are uncorrected. For flash chromatographies, silica gel
60 H (silica gel for thin-layer chromatography, Merck) or silica
gel 60 (finer than 230 mesh, Merck) was employed.
D
CDCl3) δ 0.86 (d, J ) 6.8 Hz, 3 H), 0.91 (d, J ) 6.5 Hz, 3 H),
1.84-1.99 (m, 1 H), 2.68-2.79 (m, 1 H), 2.94 (dd, J ) 11.1,
4.2 Hz, 1 H), 3.97 (ddd, J ) 7.0, 7.0, 1.5 Hz, 1 H), 5.16 (dd, J
) 10.4, 1.0 Hz, 1 H), 5.30 (dd, J ) 13.0, 1.0 Hz, 1 H), 5.33 (s,
1 H), 5.77 (ddd, J ) 17.6, 10.4, 7.6 Hz, 1 H), 7.41-7.58 (m, 6
H), 7.88-8.01 (m, 4 H); LRMS (FAB), m/z 330 (MH+, base
peak). HRMS (FAB), m/z calcd for C19H25NO2P (MH+) 330.1623,
found 330.1620.
(3S,4S)-4-(N-ter t-Bu toxyca r bon yl)a m in o-5-m eth ylh ex-
1-en -3-ol (7) an d (3R,4S)-4-(N-ter t-Bu toxycar bon yl)am in o-
5-m et h ylh ex-1-en -3-ol (8). To a stirred solution of oxalyl
chloride (12.5 mL, 0.13 mol) in 80 mL of n-hexane-CHCl3 (3:
2) at -78 °C under argon was added dropwise a solution of
DMSO (28.4 mL, 0.40 mol) in 50 mL of n-hexane-CHCl3 (3:
2). After 30 min, a solution of the alcohol 6 (20.3 g, 0.1 mol)
in 50 mL of n-hexane-CHCl3 (3:2) was added to the above
reagent at -78 °C, and the mixture was stirred for 30 min.
N,N-Diisopropylethylamine (86.9 mL, 0.50 mol) was added
dropwise to the above solution at -78 °C, and the mixture was
stirred for 30 min with warming to 0 °C. The mixture was
extracted with Et2O and the extract was washed successively
with 5% citric acid, water, 5% NaHCO3, and brine and dried
over MgSO4. Concentration under reduced pressure gave a
crude aldehyde. To a stirred solution of ZnCl2 (13.6 g, 0.10
mol) in 100 mL of dry THF at -78 °C was added vinyl-
magnesium chloride (187.5 mL, 1.6 M solution in THF, 0.30
mol). After the mixture was stirred at this temperature for
10 min, a solution of the above crude aldehyde in 50 mL of
dry THF was added dropwise to the organometallic reagent
and the mixture was stirred at this temperature for 2 h. The
mixture was quenched with 10 mL of saturated NH4Cl. The
mixture was extracted with Et2O-EtOAc (1:1), and the extract
was washed successively with 5% citric acid, water, 5%
NaHCO3, and brine and dried over MgSO4. The usual workup
led to a mixture of products as a colorless oil, which was
separated by flash chromatography over silica gel eluting with
n-hexane-EtOAc 5:1, yielding, in order of elution, 7 (6.63 g,
(3R,4S)-4-(N-Diph en ylph osph in oyl)am in o-5-m eth ylh ex-
1-en -3-ol (10). By use of a procedure identical with that
described for the preparation of 9 from 7, the alcohol 8 (1.374
g, 6.0 mmol) was converted into 1.081 g (55% yield) of the title
compound 10: colorless needles from Et2O; mp 113 °C; [R]21
D
-102 (c 1.00, CHCl3); 1H NMR (270 MHz, CDCl3) δ 0.95 (d, J
) 6.8 Hz, 3 H), 1.05 (d, J ) 6.8 Hz, 3 H), 1.53-1.67 (m, 1 H),
2.70 (dd, J ) 11.9, 3.2 Hz, 1 H), 2.78-2.89 (m, 1 H), 4.32-
4.37 (m, 1 H), 5.32 (ddd, J ) 10.5, 1.6, 1.6 Hz, 1 H), 5.51 (ddd,
J ) 17.0, 1.6, 1.6 Hz, 1 H), 5.76 (d, J ) 11.1 Hz, 1 H), 5.90
(ddd, J ) 17.0, 10.5, 4.9 Hz, 1 H), 7.42-7.57 (m, 6 H), 7.89-
7.98 (m, 4 H). Anal. Calcd for C19H24NO2P: C, 69.28; H, 7.43;
N, 4.25. Found: C, 69.14; H, 7.47; N, 4.13.
(2R,3S)-N-Dip h en ylp h osp h in oyl-3-isop r op yl-2-vin yl-
a zir id in e (11). Triphenylphosphine (2.46 g, 9.4 mmol) and
diethyl azodicarboxylate (1.60 mL, 10.1 mmol) were added to
a stirred solution of the alcohol 9 (1.28 g, 3.9 mmol) in 20 mL
of dry THF at 0 °C, and the mixture was stirred at this
temperature for 30 min. The mixture was concentrated under
reduced pressure to an oil, which was flash chromatographed
over silica gel with n-hexane-EtOAc (1:1) to give 938 mg
(77% yield) of the title compound 11: colorless crystals from
n-hexane-Et2O (5:1); mp 67-68 °C; [R]25 -11.0 (c 1.036,
D
1
CHCl3); H NMR (270 MHz, CDCl3) δ 0.57 (d, J ) 6.8 Hz, 3
H), 0.87 (d, J ) 7.0 Hz, 3 H), 1.43-1.58 (m, 1 H), 2.58 (ddd, J
) 16.2, 9.5, 6.5 Hz, 1 H), 3.29 (ddd, J ) 14.0, 7.3, 6.5 Hz, 1 H),
5.27 (dd, J ) 10.2, 1.4 Hz, 1 H), 5.39 (dd, J ) 17.0, 1.4 Hz, 1
H), 5.77 (ddd, J ) 17.0, 10.2, 7.3 Hz, 1 H), 7.39-7.52 (m, 6 H),
7.86-7.94 (m, 4 H). Anal. Calcd for C19H22NOP: C, 73.29;
H, 7.12; N, 4.50. Found: C, 73.21; H, 7.12; N, 4.45.
29% yield) and 8 (2.20 g, 10% yield). 7: colorless needles from
1
n-hexane; mp 41 °C; [R]23 -61.14 (c 0.99, CHCl3); H NMR
D
(300 MHz, CDCl3) δ 0.94 (d, J ) 6.8 Hz, 3 H), 0.99 (d, J ) 6.7
Hz, 3 H), 1.43 (s, 9 H), 1.91 (m, 1 H), 2.22 (d, J ) 4.1 Hz, 1 H),
3.27 (m, 1 H), 4.26 (m, 1 H), 4.75 (d, J ) 8.1 Hz, 1 H), 5.18
(ddd, J ) 10.5, 0.6, 0.6 Hz, 1 H), 5.29 (ddd, J ) 17.1, 1.4, 1.4
Hz, 1 H), 5.91 (ddd, J ) 17.1, 10.5, 5.8 Hz, 1 H). Anal. Calcd
for C12H23NO3: C, 62.85; H, 10.11; N, 6.11. Found: C, 62.81;
(2S,3S)-N-Diph en ylph osph in oyl-3-isopr opyl-2-vin ylazir -
id in e (12). By use of a procedure identical with that described
for the preparation of 11 from 9, the alcohol 10 (987 mg, 3.0
mmol) was converted into 481 mg (52% yield) of the title
compound 12 by treatment with PPh3 (4.56 g, 14.7 mmol) and
diethyl azodicarboxylate (3.88 mL, 24.6 mmol) in THF (10 mL)
at 0 °C for 14 h followed by the usual workup and flash
chromatography over silica gel with n-hexane-EtOAc (3:1).
12: colorless needles from n-hexane-Et2O (3:1); mp 68 °C;
H, 10.10; N, 6.06. 8: colorless needles from n-hexane-Et2O
1
(4:1); mp 69 °C; [R]24 -31.78 (c 1.076, CHCl3); H NMR (270
D
MHz, CDCl3) δ 0.94 (d, J ) 6.8 Hz, 3 H), 0.99 (d, J ) 6.8 Hz,
3 H), 1.45 (s, 9 H), 1.69-1.82 (m, 1 H), 2.71 (d, J ) 5.4 Hz, 1
H), 3.50 (m, 1 H), 4.27 (m, 1 H), 4.44 (d, J ) 7.8 Hz, 1 H), 5.25
(d, J ) 10.8 Hz, 1 H), 5.36 (d, J ) 17.3 Hz, 1 H), 5.87 (ddd, J
[R]21 -95.38 (c 1.04, CHCl3); 1H NMR (270 MHz, CDCl3) δ
D
0.67 (d, J ) 6.7 Hz, 3 H), 0.90 (d, J ) 6.8 Hz, 3 H), 1.55-1.73
(m, 1 H), 2.68 (ddd, J ) 15.7, 7.3, 3.2 Hz, 1 H), 3.01 (ddd, J )
12.3, 9.5, 3.2 Hz, 1 H), 5.03 (dd, J ) 10.0, 1.3 Hz, 1 H), 5.21
(dd, J ) 17.0, 1.3 Hz, 1 H), 6.04 (ddd, J ) 17.0, 10.0, 10.0 Hz,
1 H), 7.30-7.52 (m, 6 H), 7.80-7.99 (m, 4 H). Anal. Calcd
(44) Roger, R.; Neilson, D. J . J . Chem. Soc. 1960, 627. J ohnson, R.
A.; Hall, C. M.; Krueger, W. C.; Murray, H. C. Bioorg. Chem. 1973, 2,
99.
(45) Watson, M. B.; Youngson, G. W. J . Chem. Soc., Perkin Trans.
1 1972, 1597.

Reactions of Vinylaziridines with Organocopper Reagents
J . Org. Chem., Vol. 63, No. 20, 1998 7059
for C19H22NOP: C, 73.29; H, 7.12; N, 4.50. Found: C, 73.34;
H, 7.18; N, 4.56.
of MeLi‚LiI in Et2O at -78 °C, and the mixture was allowed
to warm to room temperature and stirred at this temperature
for 15 min. A solution of the 2,3-cis-vinylaziridine 16 (50 mg,
0.17 mmol) in dry THF (1 mL) was added dropwise to the
above reagent at -78 °C with stirring, and the stirring was
continued for 30 min followed by quenching with 4 mL of a
1:1 saturated NH4Cl-28% NH4OH solution. The mixture was
extracted with Et2O-EtOAc (1:1), and the extract was washed
(E,3S)-3-(N-Diph en ylph osph in oyl)am in o-2-m eth ylh ept-
4-en e (21). To a stirred suspension of CuCN (50 mg, 0.64
mmol) in 2 mL of dry THF under argon was added by a syringe
MeLi‚LiBr (0.86 mL, 1.1 M solution in THF) at -78 °C, and
the mixture was stirred at this temperature for 10 min. The
aziridine 11 (50 mg, 0.16 mmol) in 1 mL of dry THF was added
dropwise to the above reagent at -78 °C with stirring, and
the stirring was continued for 30 min followed by quenching
with 2 mL of a 1:1 saturated NH4Cl-28% NH4OH solution.
The mixture was extracted with EtOAc, and the extract was
washed with brine and dried over MgSO4. Concentration
under reduced pressure gave an oily residue, which was flash
chromatographed over silica gel with EtOAc to give 52 mg
(99% yield) of a 99:1 mixture of 21 and 22 as a crystalline
mass. Recrystallization from n-hexane-EtOAc (5:1) gave
with
a saturated NaCl solution and dried over MgSO4.
Concentration under reduced pressure gave a colorless oil,
which was purified by flash chromatography over silica gel
eluting with n-hexanes-EtOAc (4:1) to give 52 mg of the title
compound 25 in 99% yield: colorless crystals from n-hexane-
Et2O (3:1); mp 87-88 °C; [R]20D +31.9 (c 0.97, CHCl3); 1H NMR
(270 MHz, CDCl3) δ 0.74 (t, J ) 7.3 Hz, 3 H), 0.81 (d, J ) 6.5
Hz, 3 H), 0.87 (d, J ) 6.5 Hz, 3 H), 1.64-1.81 (m, 3 H), 2.28
(s, 3 H), 2.61 (s, 6 H), 3.46 (td, J ) 7.6, 5.7 Hz, 1 H), 4.40 (d,
J ) 7.6 Hz, 1 H), 4.97 (dddd, J ) 15.3, 8.4, 1.4, 1.4 Hz, 1 H),
5.23 (dddd, J ) 15.3, 6.2, 6.2, 0.5 Hz, 1 H), 6.91 (s, 2 H). Anal.
Calcd for C17H27NO2S: C, 65.98; H, 8.79; N, 4.53. Found: C,
65.71; H, 8.75; N, 4.40.
(E,2S)-1-P h en yl-2-[N-(2,4,6-tr im eth ylben zen e)su lfon yl]-
a m in o-3-h exen e (27) (Table 2, entry 16). By use of a
procedure similar to that described for the preparation of 25
from 16, 50 mg (0.15 mmol) of the 2,3-cis-vinylaziridine 18
was converted into 52 mg (99% yield) of the title compound
27 as colorless needles from n-hexane-Et2O (3:1): mp 50-
51 °C; [R]19D -13.0 (c 1.04, CHCl3); 1H NMR (270 MHz, CDCl3)
δ 0.77 (t, J ) 7.4 Hz, 3 H), 1.76-1.86 (m, 2 H), 2.27 (s, 3 H),
2.50 (s, 6 H), 2.77 (m, 2 H), 3.89 (m, 1 H), 4.42 (d, J ) 6.2 Hz,
1 H), 5.10 (dddd, J ) 15.3, 7.6, 1.5, 1.5 Hz, 1 H), 5.36 (dddd,
J ) 15.3, 5.1, 5.1, 0.5 Hz, 1 H), 6.87 (s, 2 H), 7.02-7.08 (m, 2
H), 7.17-7.27 (m, 3 H). Anal. Calcd for C20H27NO2S: C, 70.55;
H, 7.61; N, 3.90. Found: C, 70.52; H, 7.68; N, 3.90.
pure 21 as colorless needles: mp 150-151 °C; [R]22 +12.14
D
(c 1.008, CHCl3); 1H NMR (270 MHz, CDCl3) δ 0.89 (d, J )
7.0 Hz, 6 H), 0.93 (t, J ) 7.8 Hz, 3 H), 1.78-1.92 (m, 1 H),
1.93-2.03 (m, 2 H), 2.89 (dd, J ) 9.2, 6.8 Hz, 1 H), 3.44 (m, 1
H), 5.31 (dd, J ) 15.4, 7.0 Hz, 1 H), 5.46 (dt, J ) 15.4, 5.9 Hz,
1 H), 7.38-7.50 (m, 6 H), 7.83-7.96 (m, 4 H); LRMS (FAB),
m/z 328 (MH+, base peak); HRMS (FAB), m/z calcd for C20H27
-
NOP (MH+) 328.1830, found 328.1835. The (Z)-isomer 22
could not be isolated. In a similar manner, the 2,3-trans-
aziridine 12 was converted into a 99:1 mixture of 21 and 22
in 93% combined yield (Table 1, entry 7).
(E,2S)-2-[N-(4-Met h ylb en zen e)su lfon yl]a m in o-3-h ex-
en e (23) a n d Its (Z,2S)-Isom er (24). (Table 2, entry 1). To
a stirred suspension of CuI (328 mg, 1.73 mmol) in THF (2
mL) at -78 °C was added dropwise a solution of MeLi‚LiBr
(1.16 mL, 1.73 mmol, 1.5M in Et2O), and the mixture was
allowed to warm to 0 °C. The mixture was cooled to -78 °C,
and a solution of the aziridine 13 (82 mg, 0.344 mmol) in THF
(2 mL) was added dropwise under stirring. After 30 min, 2
mL of a 1:1 solution of 28% NH4OH and saturated NH4Cl was
added to the mixture. The whole was extracted with Et2O,
and the extract was washed with water and dried over MgSO4.
Concentration under reduced pressure gave a 96:4 mixture of
23 and 24 in 99% combined yield as a colorless oil. The
mixture was chromatographed over silica gel with n-hexane-
CHCl3-EtOAc (80:120:1) to yield, in order of elution, 83.5 mg
(E,3S)-2,7-Dim eth yl-3-[N-(2,4,6-tr im eth ylben zen e)su lfon -
yl]a m in o-4-octen e (30) (Table 2, entry 14). To a stirred
slurry of CuCN (35 mg, 0.40 mmol) in 1 mL of dry THF under
argon was added by a syringe 0.28 mL (0.40 mmol) of a
solution of 1.4 M-PrMgCl in Et2O at -78 °C, and the mixture
was allowed to warm to 0 °C and stirred at this temperature
for 15 min. A solution of the 2,3-cis-vinylaziridine 16 (29 mg,
0.10 mmol) in dry THF (1 mL) was added dropwise to the
above reagent at -78 °C with stirring, and the stirring was
continued for 30 min followed by quenching with 6 mL of a
1:1 saturated NH4Cl-28% NH4OH solution. The mixture was
extracted with Et2O-EtOAc (1:5), and the extract was washed
of 23 and 3.5 mg of 24. 23: [R]25 -25 (c 0.55, CHCl3); 1H
D
NMR (300 MHz, CDCl3) δ 0.83 (t, J ) 7.4 Hz, 3 H), 1.16 (d, J
) 6.7 Hz, 3 H), 1.86 (m, 2 H), 2.41 (s, 3 H), 3.86 (m, 1 H), 4.55
(d, J ) 7.4 Hz, 1 H), 5.15 (dddd, J ) 15.4, 6.5, 1.6, 1.6 Hz, 1
H), 5.44 (dddd, J ) 15.4, 6.3, 6.3, 1.2 Hz, 1 H), 7.25-7.30 (m,
2 H), 7.72-7.76 (m, 2 H); LRMS (FAB), m/z 254 (MH+, base
peak); HRMS (FAB), m/z calcd for C13H20NO2S (MH+) 254.1215,
found 254.1212. 24: colorless oil; [R]19D +68.2 (c 0.355, CHCl3);
1H NMR (300 MHz, CDCl3) δ 0.85 (t, J ) 7.5 Hz, 3H), 1.17 (d,
J ) 6.8 Hz, 3 H), 1.82 (dddd, J ) 11.8, 7.5, 7.5, 1.6 Hz, 1 H),
1.89 (dddd, J ) 11.8, 7.5, 7.5, 1.6 Hz, 1 H), 2.42 (s, 3 H), 4.17
(dddd, J ) 9.0, 6.4, 6.4, 0.9 Hz, 1 H), 4.31 (d, J ) 6.4 Hz, 1 H),
5.06 (dddd, J ) 10.7, 9.0, 1.6, 1.6 Hz, 1 H), 5.26 (dtd, J ) 10.7,
7.5, 0.9 Hz, 1 H), 7.28 (d, J ) 8.4 Hz, 2 H), 7.73 (dt, J ) 8.4,
2.0 Hz, 2 H). LRMS (FAB), m/z 254 (MH+); HRMS (FAB), m/z
calcd for C13H20NO2S (MH+) 254.1215; found 254.1219.
(E,2S)-2-[N-(4-Met h ylb en zen e)su lfon yl]a m in o-3-h ex-
en e (23) (Table 2, entry 11). By use of a procedure similar to
that described for the preparation of 23 and 24 from 13, 47.4
mg (0.2 mmol) of the 2,3-trans-vinylaziridine 14 was converted
into 46 mg (91% yield) of the title compound 23 as a colorless
with
a saturated NaCl solution and dried over MgSO4.
Concentration under reduced pressure gave a colorless oily
residue, which was purified by flash chromatography over
silica gel eluting with n-hexane-EtOAc (4:1) to give the trans-
alkene 30 (33 mg, 99% yield) as a colorless oil: [R]21D -0.85 (c
1
3.79, CHCl3); H NMR (270 MHz, CDCl3) δ 0.74 (d, J ) 6.5
Hz, 3 H), 0.76 (d, J ) 6.5 Hz, 3 H), 0.82 (d, J ) 7.0 Hz, 3 H),
0.86 (d, J ) 7.0 Hz, 3 H), 1.39 (m, 1 H), 1.55-1.78 (m, 3 H),
2.28 (s, 3 H), 2.62 (s, 6 H), 3.46 (dd, J ) 8.1, 5.1 Hz, 1 H),
4.43 (d, J ) 7.8 Hz, 1 H), 5.01 (dddd, J ) 15.2, 7.8, 1.1, 1.1
Hz, 1 H), 5.18 (dt, J ) 15.2, 6.8 Hz, 1 H), 6.91 (s, 2 H); LRMS
(FAB), m/z 338 (MH+); HRMS (FAB), m/z calcd for C19H32NO2S
(MH+) 338.2154, found 338.2144.
(E,2S)-1-(ter t-Bu tyld im eth ylsiloxy)-2-[N-(2,4,6-tr im eth -
ylben zen e)su lfon yl]a m in o-3-h exen e (32) (Table 2, entry
18). By use of a procedure similar to that described for the
preparation of 25 from 16, 515 mg (1.3 mmol) of the 2,3-cis-
vinylaziridine 20 was converted into 526 mg (98% yield) of the
title compound 32 by treatment with MeCu(CN)Li‚LiI followed
by flash chromatography over silica gel eluting with n-hex-
oil: [R]25 -26 (c 0.407, CHCl3); 1H NMR (300 MHz, CDCl3) δ
D
0.83 (t, J ) 7.4 Hz, 3 H), 1.16 (d, J ) 6.7 Hz, 3 H), 1.86 (m, 2
H), 2.41 (s, 3 H), 3.86 (m, 1 H), 4.55 (d, J ) 7.4 Hz, 1 H), 5.15
(dddd, J ) 15.4, 6.5, 1.6, 1.6 Hz, 1 H), 5.44 (dddd, J ) 15.4,
6.3, 6.3, 1.2 Hz, 1 H), 7.25-7.30 (m, 2 H), 7.72-7.76 (m, 2 H).
LRMS (FAB), m/z 254 (MH+, base peak). HRMS (FAB), m/z
calcd for C13H20NO2S (MH+) 254.1215, found 254.1218.
(E,3S)-2-Meth yl-3-[N-(2,4,6-tr im eth ylben zen e)su lfon yl]-
a m in o-4-h ep ten e (25) (Table 2, entry 13). To a stirred slurry
of CuCN (61 mg, 0.68 mmol) in 1 mL of dry THF under argon
was added by a syringe 0.17 mL (0.68 mmol) of a 1.0 M solution
anes-EtOAc (8:1): colorless needles from n-hexane-Et2O (2:
1
1); mp 67-68 °C; [R]21 +19.7 (c 1.03, CHCl3); H NMR (270
D
MHz, CDCl3) δ 0.03 (s, 6 H), 0.79 (t, J ) 7.3 Hz, 3 H), 0.87 (s,
9 H), 1.77-1.87 (m, 2 H), 2.29 (s, 3 H), 2.61 (s, 6 H), 3.44 (dd,
J ) 9.9, 5.9 Hz, 1 H), 3.53 (dd, J ) 9.9, 4.3 Hz, 1 H), 3.62-
3.71 (m, 1 H), 5.03-5.13 (m, 2 H), 5.49 (dddd, J ) 15.4, 5.9,
5.9, 0.6 Hz, 1 H), 6.92 (s, 2 H). Anal. Calcd for C21H37NO3-
SSi: C, 61.27; H, 9.06; N, 3.40. Found: C, 61.36; H, 9.06; N,
3.43.

7060 J . Org. Chem., Vol. 63, No. 20, 1998
Toda et al.
(E,4S)-1-Tr im eth ylsilyl-4-[N-(4-m eth ylben zen e)su lfon yl]-
a m in o-2-p en ten e (35) (Table 2, entry 12). To a stirred
solution of THF-HMPA (3:1; 4 mL) under argon were added
by syringe 0.20 mL (1.00 mmol) of Me3SiSiMe3 and 0.62 mL
(1.00 mmol) of 1.6 M n-BuLi in n-hexane at -78 °C, and the
mixture was stirred for 1 h. To a slurry of CuCN (89 mg, 1.00
mmol) in 1 mL of dry THF was added a solution of the above
reagent, and the mixture was allowed to warm to -30 °C and
stirred at -78 °C for 5 min. A solution of the 2,3-cis-
vinylaziridine 14 (24 mg, 0.10 mmol) in dry THF (1 mL) was
added dropwise to the above reagent at -78 °C with stirring,
and the stirring was continued for 30 min followed by quench-
ing with 4 mL of a 1:3 saturated NH4Cl-28% NH4OH solution.
The mixture was extracted with EtOAc, and the extract was
washed with saturated brine and dried over MgSO4. Concen-
tration under reduced pressure gave a colorless oil, which was
purified by flash chromatography over silica gel eluting with
n-hexane-EtOAc (8:1) to give the title compound 35 (31 mg,
ature for 30 min. To the above mixture was added 357 mg of
(E,2S,)-2-N-[(2,4,6-trimethylbenzene)sulfonyl]amino-3-hexen-
1-ol in 2 mL of CHCl3 at -78 °C. After 30 min, N,N-
diisopropylethylamine (86.9 mL, 0.50 mol) was added at -78
°C under stirring, and the mixture was stirred at this tem-
perature for 30 min. The mixture was made acidic with
saturated citric acid and the whole was extracted with Et2O.
The extract was washed with water and 5% NaHCO3 and dried
over MgSO4. Concentration under reduced pressure gave a
crude aldehyde as a colorless oil. The oily crude aldehyde in
acetone (3 mL) was oxidized with J ones’ reagent. Methylation
with diazomethane followed by the usual workup and flash
chromatography over silica gel with n-hexane-EtOAc (5:1)
gave 78 mg (20% yield) the title compound 38 as a colorless
oil: [R]27 +42.1 (c 0.737, CHCl3); 1H NMR (270 MHz, CDCl3)
D
δ 0.85 (t, J ) 7.4 Hz, 3 H), 1.92 (m, 1 H), 2.29 (s, 3 H), 2.63 (s,
6 H), 3.58 (s, 3 H), 4.44 (dddd, J ) 8.1, 8.1, 1.5, 1.5 Hz, 1 H),
5.21 (dddd, J ) 15.1, 8.1, 1.5, 1.5 Hz, 1 H), 5.33 (d, J ) 8.1
Hz, 1 H), 5.73 (ddd, J ) 15.1, 6.5, 1.5 Hz, 1 H), 6.94 (s, 2 H);
LRMS (FAB), m/ z 326 (MH+); HRMS (FAB), m/ z calcd for
98% yield) as a colorless oil: [R]17 -48.5 (c 0.231, CHCl3); 1H
D
NMR (270 MHz, CDCl3) δ -0.07 (s, 9 H), 1.16 (d, J ) 6.6 Hz,
3 H), 1.32 (m, 2 H), 2.42 (s, 3 H), 3.83 (m, 1 H), 4.33 (d, J )
7.3 Hz, 1 H), 5.05 (dddd, J ) 15.7, 8.1, 0.8, 0.8 Hz, 1 H), 5.42
(dddd, J ) 15.7, 8.4, 8.4, 1.0 Hz, 1 H), 7.26-7.30 (m, 2 H),
7.72-7.76 (m, 2 H). LRMS (FAB), m/z 312 (MH+); HRMS
(FAB), m/z calcd for C15H26NO2SSi (MH+) 312.1453, found
312.1442.
C
16H24NO4S (MH+) 326.1426, found 326.1432.
(E,2S,5S)-7-Meth yl-2-p h en yl-5-N-[(2,4,6-tr im eth ylben -
zen e)su lfon yl]a m in ooct-3-en e (47). To a stirred solution
of CuCN (172 mg, 1.92 mmol) and LiCl (189 mg, 3.84 mmol)
in 3 mL of dry THF under argon was added by a syringe 3 mL
(3.84 mmol) of PhMgBr (1.3 M solution in THF) at - 78 °C,
and the mixture was stirred at this temperature for 30 min.
The aziridine 45 (154 mg, 0.48 mmol) in 4 mL of dry THF was
added dropwise to the above reagent at -78 °C with stirring,
and the stirring was continued for 30 min followed by quench-
ing with 4 mL of a 3:5 mixture of saturated NH4Cl-28%
NH4OH. The mixture was extracted with Et2O, and the
extract was washed with brine and dried over MgSO4. Con-
centration under reduced pressure gave an oily residue, which
was flash chromatographed over silica gel with n-hexane-
EtOAc (9:1) to give 90 mg (47% yield) of the title compound
(E,4S)-5-Meth yl-1-tr im eth ylsilyl-4-[N-(2,4,6-tr im eth yl-
ben zen e)su lfon yl]a m in o-2-h exen e (36) (Table 2, entry 15).
By use of a procedure similar to that described for the
preparation of 35 from 14, 29 mg (0.10 mmol) of the 2,3-trans-
vinylaziridine 16 was converted into 36 mg (99% yield) of the
title compound 36 as a colorless oil: [R]17 -46.3 (c 0.468,
D
1
CHCl3); H NMR (270 MHz, CDCl3) δ -0.09 (s, 9 H), 0.80 (d,
J ) 6.8 Hz, 3 H), 0.86 (d, J ) 6.8 Hz, 3 H), 1.20 (m, 2 H),
1.66-1.78 (m, 1 H), 2.28 (s, 3 H), 2.62 (s, 6 H), 3.44 (m, 1 H),
4.39 (d, J ) 7.4 Hz, 1 H), 4.88 (ddd, J ) 15.1, 8.1, 1.4 Hz, 1
H), 5.21 (ddd, J ) 15.1, 7.5, 7.5 Hz, 1 H), 6.91 (s, 2 H). LRMS
47: colorless needles from n-hexane; mp 82-83 °C; [R]19
D
(FAB), m/ z 368 (MH+). HRMS (FAB), m/ z calcd for C19H34
-
-18.15 (c 0.981, CHCl3); 1H NMR (300 MHz, CDCl3) δ 0.83
(d, J ) 6.5 Hz, 3 H), 0.85 (d, J ) 6.8 Hz, 3 H), 1.07 (d, J ) 6.8
Hz, 3 H), 1.21-1.45 (m, 2 H), 1.62 (m, 1 H), 2.27 (s, 3 H), 2.57
(s, 6 H), 3.11 (m, 1 H), 3.75 (m, 1 H), 4.52 (d, J ) 7.3 Hz, 1 H),
4.95 (ddd, J ) 15.2, 7.8, 1.4 Hz, 1 H), 5.44 (ddd, J ) 15.2, 5.9,
0.5 Hz, 1 H), 6.86 (s, 2 H), 6.94-6.97 (m, 2 H), 7.15-7.28 (m,
3 H). Anal. Calcd for C24H33NO2S: C, 72.14; H, 8.32; N, 3.51.
Found: C, 71.86; H, 8.37; N, 3.36.
NO2SSi (MH+) 368.2079; found 368.2087.
(E,4S)-5-P h en yl-1-tr im eth ylsilyl-4-[N-(2,4,6-tr im eth yl-
ben zen e)su lfon yl]a m in o-2-p en ten e (37) (Table 2, entry 17).
By use of a procedure similar to that described for the
preparation of 35 from 14, 34 mg (0.10 mmol) of the 2,3-cis-
vinylaziridine 18 was converted into 36 mg (87% yield) of the
title compound 37 as colorless needles: mp 69-70 °C; [R]20
D
1
-39.4 (c 0.966, CHCl3); H NMR (270 MHz, CDCl3) δ -0.13
(E,2R,5S)-7-Met h yl-5-(2,4,6-t r im et h ylb en zen esu lfon -
yl))a m in o-2-p h en yloct-3-en e (48). By use of a procedure
identical with that described for the preparation of 47 from
45, the aziridine 46 (321 mg, 1.0 mmol) was converted into
(s, 9 H), 1.24 (m, 2 H), 2.28 (s, 3 H), 2.52 (s, 6 H), 2.74 (dd, J
) 13.5, 7.3 Hz, 1 H), 2.81 (dd, J ) 13.5, 6.2 Hz, 1 H), 3.87 (m,
1 H), 4.39 (d, J ) 6.2 Hz, 1 H), 4.99 (dddd, J ) 15.1, 7.6, 1.4,
1.4 Hz, 1 H), 5.31 (dddd, J ) 15.1, 8.6, 1.0, 1.0 Hz, 1 H), 6.88
(s, 2 H), 7.03-7.07 (m, 2 H), 7.14-7.26 (m, 3 H); LRMS (FAB),
m/z 416 (MH+). HRMS (FAB), m/z calcd for C23H34NO2SSi
(MH+) 416.2079, found 416.2075.
233 mg (58% yield) of the title compound 48 as a colorless oil:
1
[R]23 - 27.5 (c ) 0.898, CHCl3); H NMR (270 MHz, CDCl3)
D
δ 0.81 (d, J ) 6.8 Hz, 6 H), 1.12 (d, J ) 7.0 Hz, 3 H), 1.19-
1.42 (m, 2 H), 1.58 (m, 1 H), 2.29 (s, 3 H), 2.61 (s, 6 H), 3.18
(m, 1 H), 3.74 (m, 1 H), 4.39 (d, J ) 7.8 Hz, 1 H), 5.02 (ddd, J
) 15.4, 8.1, 1.4 Hz, 1 H), 5.43 (ddd, J ) 15.4, 10.0, 7.0 Hz, 1
H), 6.92 (s, 2 H), 6.90-7.02 (m, 2 H), 7.14-7.29 (m, 3 H); LRMS
Meth yl (E,2S)-2-[N-(2,4,6-Tr im eth ylben zen e)su lfon yl]-
a m in o-3-h exen -1-en oa te (38). To a stirred solution of the
alkene 32 (502 mg, 1.22 mmol) in 4 mL of MeCN were added
3 mL of 46% HF and 2 mL of H2O at 0 °C, and the mixture
was stirred for 16 h at room temperature and for 4 h at 50 °C.
The mixture was made basic with 3 mL of 28% NH4OH and
extracted with EtOAc. The extract was washed with brine
and dried over MgSO4. Concentration under reduced pressure
gave an oily residue, which was purified by flash chromatog-
raphy over silica gel with n-hexane-EtOAc (3:1) to give
(E,2S)-2-N-[(2,4,6-trimethylbenzene)sulfonyl]amino-3-hexen-
1-ol as a colorless oil (347 mg, 96% yield): [R]23D +14.1 (c 1.01,
(FAB), m/ z 400 (MH+); HRMS (FAB), m/ z calcd for C24H34
-
NO2S (MH+) 400.2310, found 400.2314.
(R)-2-P h en ylpr opan -1-ol (49) an d (S)-N-[(2,4,6-Tr im eth -
ylben zen e)su lfon yl]leu cin ol. Ozone was bubbled through
a solution of the alkene 47 (80 mg, 0.20 mmol) in 6 mL of
n-hexane-CHCl3 (1:1) at - 78 °C until a blue color persisted.
Zinc powder (5 g) was added to the mixture, and the mixture
was stirred for 10 min, during which time it was allowed to
warm to 0 °C. To the above mixture at -78 °C was added
dropwise 10.0 mL (10.0 mmol) of a 1.0 M toluene solution of
DIBAL, and the mixture was allowed to warm to room
temperature. Saturated NH4Cl (3 mL) was added with vigor-
ous stirring at -78 °C. The mixture was extracted with Et2O-
EtOAc (1:1), and the extract was washed successively with 5%
citric acid, water, 5% NaHCO3, and brine and dried over
MgSO4. The usual workup and flash chromatography over
silica gel with n-hexane-EtOAc (5:1) gave, in order of elution,
(2R)-2-phenylpropan-1-ol 49 (20 mg, 73% yield) and (S)-N-
[(2,4,6-trimethylbenzene)sulfonyl]leucinol (44 mg, 73% yield).
1
CHCl3); H NMR (270 MHz, CDCl3) δ 0.80 (t, J ) 7.6 Hz, 3
H), 1.84 (m, 1 H), 2.17 (t, J ) 5.4 Hz, 3 H), 2.29 (s, 3 H), 2.63
(s, 6 H), 3.45-3.62 (m, 2 H), 3.67-3.79 (m, 1 H), 5.07 (d, J )
7.3 Hz, 1 H), 5.10 (dd, J ) 15.4, 7.3 Hz, 1 H), 5.45 (ddd, J )
15.4, 6.2, 6.2 Hz, 1 H), 6.94 (s, 2 H); LRMS (FAB), m/z 298
(MH+); HRMS (FAB), m/z calcd for C15H24NO3S (MH+) 298.1477,
found 298.1472. To a stirred solution of oxalyl chloride (0.12
mL, 3.6 mmol) in 70 mL of CH2Cl2 was added dropwise DMSO
(0.77 mL, 10.8 mmol) in 2 mL of n-hexane-CHCl3 (1:1) at -78
°C under argon, and the mixture was stirred at this temper-

Reactions of Vinylaziridines with Organocopper Reagents
J . Org. Chem., Vol. 63, No. 20, 1998 7061
49: a colorless oil; [R]23 +16.53 (c 1.471, CHCl3); 1H NMR
1H NMR (270 MHz, CDCl3) δ 0.65 (d, J ) 6.8 Hz, 3 H), 0.77
(d, J ) 6.8 Hz, 3 H), 1.22-1.34 (m, 1 H), 1.42 (m, 2 H), 1.42-
1.55 (m, 1 H), 2.07 (broad s, 1 H), 2.30 (s, 3 H), 2.66 (s, 6 H),
3.25 (m, 1 H), 3.44 (m, 1 H), 3.53-3.59 (m, 1 H), 4.78 (broad
s, 1 H), 6.96 (s, 2 H); LRMS (FAB), m/ z 300 (MH+, base peak).
HRMS (FAB), m/ z calcd for C15H26NO3S (MH+) 300.1633,
found 300.1636.
D
(270 MHz, CDCl3) δ 1.27 (d, J ) 6.9 Hz, 3 H), 1.45 (broad s, 1
H), 2.94 (qd, J ) 6.9, 6.9 Hz, 1 H), 3.68 (m, 2 H), 7.20-7.25
(m, 3 H), 7.30-7.36 (m, 2 H); LRMS (EI), m/ z 136 (M+), 106,
105 (base peak), 91, 79, 77. HRMS (EI), m/ z calcd for C9H12
O
(M+) 136.0888, found 136.0893. (S)-N-[(2,4,6-Trimethylben-
zene)sulfonyl]leucinol: colorless needles from n-hexanes-Et2O
(2:1); mp 112-113 °C; [R]20D -21.93 (c 0.963, CHCl3); 1H NMR
(270 MHz, CDCl3) δ 0.65 (d, J ) 6.8 Hz, 3 H), 0.77 (d, J ) 6.8
Hz, 3 H), 1.22-1.34 (m, 1 H), 1.42-1.50 (m, 1 H), 2.07 (broad
s, 1 H), 2.30 (s, 3 H), 2.66 (s, 6 H), 3.23-3.29 (m, 1 H), 3.40-
3.48 (m, 1 H), 3.53-3.59 (m, 1 H), 4.78 (broad s, 1 H), 6.94 (s,
2 H). Anal. Calcd for C15H25NO3S: C, 60.17; H, 8.42; N, 4.68.
Found: C, 59.97; H, 8.46; N, 4.59.
Ack n ow led gm en t. Financial support from a Grant-
in-Aid for Scientific Research from the Ministry of
Education, Science, Sports and Culture, J apan, is grate-
fully acknowledged. We are grateful to Professor T. Taga
and Dr. Y. Miwa, Kyoto University, for helpful discus-
sions.
(S)-2-P h en ylp r op a n -1-ol (50) a n d (S)-N-[(2,4,6-Tr im eth -
ylben zen e)su lfon yl]leu cin ol. By use of a procedure identi-
cal with that described for the preparation of 49 and (S)-N-
[(2,4,6-trimethylbenzene)sulfonyl]leucinol from 47, the alkene
48 (80 mg, 0.20 mmol) was converted into 20 mg (73% yield)
of (2S)-2-phenylpropan-1-ol 50 and 44 mg (73% yield) of (S)-
N-[(2,4,6-trimethylbenzene)sulfonyl]leucinol. 50: a colorless
oil; [R]21D -16.09 (c 0.513, CHCl3); 1H NMR (270 MHz, CDCl3)
δ 1.27 (d, J ) 6.9 Hz, 3 H), 1.34 (broad s, 1 H), 2.94 (qd, J )
6.9, 6.9 Hz, 1 H), 3.68 (m, 2 H), 7.20-7.25 (m, 3 H), 7.30-7.36
(m, 2 H). LRMS (CI), m/ z 137 (MH+, base peak); HRMS (CI),
m/ z calcd for C9H13O (MH+) 137.0966, found 137.0967. (S)-
N-[(2,4,6-Trimethylbenzene)sulfonyl]leucinol: colorless crys-
tals from n-hexane-CHCl3 (2:1); [R]21D -22.5 (c 0.845, CHCl3);
Su p p or tin g In for m a tion Ava ila ble: Experimental de-
tails of reactions of 15, 17, and 19 with organocopper reagents;
synthetic methods of compounds 26, 45, 46, and an authentic
sample of 50; and copies of 1H NMR spectra for compounds 9,
21, 23, 24, 26, 28-31, 33-38, 45, 46, and 48-50 that have
no combustion analysis (25 pages). This material is contained
in libraries on microfiche, immediately follows this article in
the microfilm version of the journal, and can be ordered from
the ACS; see any current masthead page for ordering
information.
J O9810157