Novel synthesis of chiral unactivated 2-aryl-1-benzylaziridines

Article abstract of DOI:10.1055/s-0028-1088125

Chiral (R_S,R)- and (R_S,S)-N-(tert-butylsulfinyl)-2- aryl-aziridines were transformed into (R)- and (S)-2-aryl-1-benzylaziridines via a short three-step procedure. Deprotection and ring opening of (R _S,R)- and (R_S

Full text of DOI:10.1055/s-0028-1088125

LETTER
1265
Novel Synthesis of Chiral Unactivated 2-Aryl-1-benzylaziridines
N
ovel Synthesis
r
of Chir
i
a
l
U
nac
k
tivate
d
2-A
r
a
yl-1-benzylazirid
L
ines eemans, Sven Mangelinckx,1 Norbert De Kimpe*
Department of Organic Chemistry, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium
Fax +32(9)2646243; E-mail: norbert.dekimpe@ugent.be
Received 6 February 2009
ring opening to chiral biologically and synthetically im-
portant phenylethylamines,14,15 is described with chiral 2-
aryl-1-(tert-butanesulfinyl)aziridines as starting material.
This transformation from chiral ‘activated’ aziridines to
Abstract: Chiral (RS,R)- and (RS,S)-N-(tert-butylsulfinyl)-2-aryl-
aziridines were transformed into (R)- and (S)-2-aryl-1-benzylaziri-
dines via a short three-step procedure. Deprotection and ring open-
ing of (RS,R)- and (RS,S)-N-sulfinyl-2-arylaziridines (95–99% de) in
acid medium afforded 2-aryl-2-chloroethylamine hydrochlorides in the corresponding enantiomerically pure ‘unactivated’
high yield (83–90%). These intermediates were converted into the
corresponding chiral N-(benzylidene)-b-aryl-b-chloro-amines in
good yield (78–85%). Subsequent reduction of the synthesized ald-
and the corresponding N-(benzylidene)-b-aryl-b-chloro-
imines afforded chiral 2-aryl-1-benzylaziridines in good to excel-
aziridines involves the efficient synthesis of two interme-
diates, namely 2-aryl-2-chloroethylamine hydrochlorides
amines.
lent yield (74–94%) and enantiomeric excess (83–99% ee). The
enantiomeric purity of the chiral aldimines and aziridines was estab-
lished by NMR spectroscopy using Pirkle alcohol as the chiral sol-
vating agent.
Chiral (RS,R)-N-(tert-butylsulfinyl)aziridines 2a–e were
prepared by reduction of (RS)-N-tert-butanesulfinyl a-
haloimines 1 with LiBHEt3 in dry THF and subsequent
treatment with KOH as reported earlier.11a,16 These chiral
Key words: chiral aziridines, asymmetric synthesis, ring opening,
ring closure, haloimines
aziridines 2a–e were obtained highly diastereomerically
enriched (dr 98:2 up to >99:1 as determined by 1H NMR
analysis) after recrystallization from Et2O in 62–80%
Chiral aziridines are important target compounds in or-
ganic chemistry and their synthesis remains a major chal-
lenge. Aziridines are divided into the class of ‘activated’
aziridines which have an electron-withdrawing N-substit-
uent and ‘unactivated’ aziridines, such as N-alkyl- or N-
benzylaziridines, which need to be quaternized to undergo
ring-opening reaction.2 ‘Activated’ and ‘unactivated’
aziridines can behave differently in terms of regioselectiv-
ity during nucleophilic ring-opening reactions,3 and,
therefore, the development of methodologies to transform
chiral activated aziridines into unactivated aziridines with
retention of the enantiomeric purity is of importance.4
yield. The aziridines (RS,R)-2 were deprotected and regio-
selectively ring-opened by treatment with a saturated so-
lution of dry HCl in dioxane while stirring for one hour at
room temperature which afforded the (S)-2-aryl-2-chloro-
ethylamine hydrochlorides 3 in high yield (83–90%,
Scheme 1).11a,b,17 These hydrochlorides 3 were then trans-
formed into the corresponding (S)-N-(benzylidene)-2-
aryl-2-chloroethylamines 4 in 78–85% yield by treatment
with benzaldehyde in the presence of triethylamine and
magnesium(II) sulfate in dichloromethane (Scheme 1).18
The regiochemistry of the ring opening of aziridines 2 and
the correct characterization of 2-aryl-2-chloroethylamine
hydrochlorides 3 and the corresponding aldimines 4 was
chemically ascertained by the synthesis of 2-azadiene 5
upon treatment of aldimine 4c with potassium tert-but-
oxide in tert-butanol for one hour at room temperature
(Scheme 2).
Chiral aziridines are mainly synthesized by ring closure of
chiral amino alcohols,5 ring opening of chiral epoxides
with azide followed by ring closure,5c,6 asymmetric aza-
Darzens reaction,7 asymmetric addition to azirines,8 stereo-
selective nitrene addition to olefins,9 aza-Payne rear-
rangement of 2,3-epoxy amines,10 asymmetric addition of
nucleophiles across a-haloimines,11 and reaction of ylides
with chiral imines.12 Due to the ability of chiral aziridines
to undergo a variety of synthetically useful transforma-
tions a broad range of chiral functionalized compounds
can be obtained. Nucleophilic ring opening, the most thor-
oughly studied reaction of chiral aziridines,13 is facilitated
by the release of ring strain and affords enantiomerically
pure b-substituted ethylamines.
The enantiomeric purity of aldimines 4 was determined
via an NMR technique using the chiral solvating agents
(R)-6 and (S)-6 (Pirkle alcohol, Figure 1).19 All initial at-
tempts to use the recently developed macrocyclic chiral
shift reagent Chirabite-AR (7) to determine the enantio-
meric purities of aldimines 4 failed.20 No NMR spectra
showing chemical shift nonequivalences could by ob-
tained upon addition of Chirabite-AR (7) to racemic ald-
imines 4 in CDCl3. Compounds 4 were prepared in the
same way from racemic tert-butanesulfinamide via race-
mic N-tert-butanesulfinyl a-haloimines 1 as described be-
fore. However, if one equivalent of (R)-Pirkle alcohol 6
[(R)-1-(9-anthryl)-2,2,2-trifluoroethanol] is added to ra-
cemic aldimine 4b, a well-resolved spectral nonequiva-
lence of the signals from each CH2- and CH-proton of the
In this paper, the convenient synthesis of chiral 2-aryl-1-
benzylaziridines as potential precursors for nucleophilic
SYNLETT 2009, No. 8, pp 1265–1268
x
x.
x
x.
2
0
0
9
Advanced online publication: 08.04.2009
DOI: 10.1055/s-0028-1088125; Art ID: G05109ST
© Georg Thieme Verlag Stuttgart · New York

1266
E. Leemans et al.
LETTER
t-Bu
O
t-Bu
RS
SR
N
H
Cl
Cl
N
O
PhCHO (1 equiv)
Et3N (1.1 equiv)
1) LiBHEt3 (1.1 equiv)
THF, –78 °C, 1 h
dioxane⋅HCl
NH2
⋅HCl
N
(10 equiv)
R
S
S
dioxane, r.t., 1 h
2) KOH (3 equiv)
H2O–THF (1:1)
reflux, 16 h
MgSO4 (1.5 equiv)
CH2Cl2, 0 °C, 7 h
Cl
R
R
R
R
1a R = Cl
1b R = Br
1c R = F
1d R = Me
1e R = H
2a 66%, 98% de
2b 71%, 98.5% de
2c 79%, 96% de
2d 80%, 99% de
2e 62%, 99% de
3a 90%
3b 86%
3c 86%
3d 83%
3e 84%
4a 78%, 98% ee
4b 85%, 88% ee
4c 81%, 91% ee
4d 83%, 90% ee
4e 85%, 99% ee
Scheme 1
1
two aldimine enantiomers is observed in the H NMR with HCl or results from the small contribution of a SN1-
spectrum (300 MHz, CDCl3).
type pathway during the nucleophilic ring opening.21
In the last step, the chiral (R)-2-aryl-1-benzylaziridines
8a–e were synthesized in good yield (74–94%) by reduc-
tion of chiral aldimines 4a–e with sodium borohydride in
methanol under reflux (Scheme 3).22,23 The b-chloro-
amines formed by nucleophilic addition of hydride were
subsequently ring-closed by an internal nucleophilic sub-
stitution with a Walden inversion. The enantiomeric puri-
ty of 2-phenylaziridines 8 (88–99% ee) was again
determined via NMR-experiments with (R)-6 or (S)-6.
H
Cl
N
KOt-Bu (3 equiv)
t-BuOH, r.t., 1 h
N
S
H
F
4c
5 78%
F
Scheme 2
OH
CF3
CF3
OH
H
H
H
Cl
NaBH4 (1 equiv)
N
N
MeOH, reflux, 3 h
S
(S)-6
(R)-6
R
R
R
HN
O
4a R = Cl
4b R = Br
4c R = F
4d R = Me
4e R = H
8a 93%, 98% ee
8b 94%, 88% ee
8c 90%, 91% ee
8d 92%, 90% ee
8e 74%, 99% ee
N
O
HN
HN
O
O
NO2
Scheme 3
N
O
O
These experiments demonstrated that the ring closure of
(S)-N-(benzylidene)-b-aryl-b-chloroamines 4 to (R)-2-
aryl-1-benzylaziridines 8 occurs via an SN2-type pathway
without further racemization. The absolute configuration
of (R)-1-benzyl-2-phenylaziridine 8e was confirmed by
comparison of the optical rotation {(R)-8e: [a]D –73.7 (c
HN
7
Figure 1 Chiral Pirkle alcohols 6 and Chirabite-AR® (7)
Analogously, upon addition of 5.5 equivalents of (R)-6 to
aldimine 4b, a good separation of the corresponding sig-
nals for the asymmetrically prepared major enantiomer
(S)-4b and its minor enantiomer (R)-4b was observed, al-
lowing determination of the enantiomeric purity [88% ee
for (S)-4b]. Similar NMR experiments with (R)- and (S)-
Pirkle alcohol 6 were also carried out with the chiral ald-
imines 4a,c–e for determination of the enantiomeric ex-
cess. In this way, it was observed that the unsubstituted
aldimine 4e (R = H) and the p-chloro-substituted deriva-
tive 4a were enantiomerically pure (>98% ee) within the
limits of the NMR technique, while some racemization
occurred for the other para-substituted compounds 4b–d
(>88% ee). It is not clear, however, if this reduced enantio-
meric purity is due to some racemization of the starting N-
sulfinylaziridines 2b–d prior to nucleophilic ring opening
24
0.76, EtOH)} with literature values {(S)-8e: [a]D +69.2
(c 2.0, EtOH);24 (R)-8e: [a]D20 –49.4 (c 2.0, EtOH)}.25
The analogous transformation of the new (RS,S)-N-(tert-
butylsulfinyl)aziridines 9a,b, prepared in high yields via
the intrinsically more diastereoselective reduction of (RS)-
N-tert-butanesulfinyl a-chloroimines 1c,d with NaBH4,11a
to chiral (S)-2-aryl-1-benzylaziridines 11 gave somewhat
less satisfying results (Scheme 4). Deprotection of aziri-
dines 9 and imination of the corresponding 2-aryl-2-chloro-
ethylamine hydrochlorides afforded the aldimines 10 with
a lower enantiomeric purity (83–85% ee) as determined
via NMR experiments with (R)-6. Reduction of aldimines
10 with sodium borohydride in methanol under reflux ef-
ficiently resulted in ring closure to (S)-2-aryl-1-benzyl-
aziridines 11 without further loss of the configurational
integrity.
Synlett 2009, No. 8, 1265–1268 © Thieme Stuttgart · New York

LETTER
Novel Synthesis of Chiral Unactivated 2-Aryl-1-benzylaziridines
1267
(7) (a) Sweeney, J. B.; Cantrill, A. A.; Drew, M. G. B.;
t-Bu
S
t-Bu
O
R
SR
McLaren, A. B.; Thobhani, S. Tetrahedron 2006, 62, 3694.
(b) Sweeney, J. B.; Cantrill, A. A.; McLaren, A. B.;
Thobhani, S. Tetrahedron 2006, 62, 3681. (c) Kim, D. Y.;
Suh, K. H.; Choi, J. S.; Mang, J. Y.; Chang, S. K. Synth.
Commun. 2000, 30, 87. (d) Cantrill, A. A.; Hall, L. D.;
Jarvis, A. N.; Osborn, H. M. I.; Raphy, J.; Sweeney, J. B.
Chem. Commun. 1996, 2631.
1) NaBH4 (2 equiv)
MeOH (2 equiv)
THF, –78 °C, 1 h
N
O
N
S
Cl
2) KOH (3 equiv)
H2O–THF (1:1)
reflux, 16 h
R
R
1c R = F
1d R = Me
9a R = F 86%, 97% de
9b R = Me 76%, 95% de
(8) (a) Atkinson, R. S.; Coogan, M. P.; Lochrie, I. S. T. Chem.
Commun. 1996, 789. (b) Roth, P.; Somfai, P.; Andersson,
P. G. Chem. Commun. 2002, 1752. (c) Sjöholm-Timén, Å.;
Somfai, P. J. Org. Chem. 2003, 68, 9958. (d) Risberg, E.;
Andreas, F. B.; Somfai, P. Chem. Commun. 2004, 2088.
(e) Risberg, E.; Fischer, A.; Somfai, P. Tetrahedron 2005,
61, 8443.
1) dioxane⋅HCl
2) PhCHO (1 equiv)
Et3N (1.1 equiv)
MgSO4 (1.5 equiv)
CH2Cl2, 0 °C, 7 h
(10 equiv)
dioxane, r.t., 1 h
(9) (a) Watson, I. D. G.; Yu, L.; Yudin, A. K. Acc. Chem. Res.
2006, 39, 194. (b) Ma, L.; Jiao, P.; Zhang, Q.; Xu, J.
Tetrahedron: Asymmetry 2005, 16, 3718. (c) Atkinson,
R. S.; Tughan, G. J. Chem. Soc., Chem. Commun. 1987, 456.
(10) (a) Bilke, J. L.; Dzuganova, M.; Fröhlich, R.; Würthwein,
E.-U. Org. Lett. 2005, 7, 3267. (b) Bouyacoub, A.;
Volatron, F. Eur. J. Org. Chem. 2002, 4143. (c) Hudlicky,
T.; Rinner, U.; Gonzalez, D.; Akgun, H.; Schilling, S.;
Siengalewicz, P.; Martinot, T. A.; Pettit, G. R. J. Org. Chem.
2002, 67, 8726. (d) Ibuka, T. Chem. Soc. Rev. 1998, 27, 145.
(11) (a) Denolf, B.; Leemans, E.; De Kimpe, N. J. Org. Chem.
2007, 72, 3211. (b) Denolf, B.; Leemans, E.; De Kimpe, N.
J. Org. Chem. 2008, 73, 5662. (c) Denolf, B.; Mangelinckx,
S.; Törnroos, K. W.; De Kimpe, N. Org. Lett. 2006, 8, 3129.
(d) Denolf, B.; Mangelinckx, S.; Törnroos, K. W.; De
Kimpe, N. Org. Lett. 2007, 9, 187. (e) Malkov, A. V.;
Stončius, S.; Kočovský, P. Angew. Chem. Int. Ed. 2007, 46,
3722. (f) Hodgson, D. M.; Kloesges, J.; Evans, B. Org. Lett.
2008, 10, 2781. (g) Chen, Q.; Li, J.; Yuan, C. Synthesis
2008, 2986.
H
N
Cl
NaBH4 (1 equiv)
MeOH, reflux, 3 h
S
N
R
R
R
11a 86%, 85% ee
11b 87%, 83% ee
10a 74%, 85% ee
10b 80%, 83% ee
Scheme 4
In conclusion, a short synthesis of the unactivated (R)- and
(S)-2-aryl-1-benzylaziridines 8 and 11 was developed in
high yield and good to excellent enantiomeric purity via a
three-step sequence from the activated (RS,R)- and (RS,S)-
N-(tert-butylsulfinyl)-2-arylaziridines 1 and 9. The enan-
tiomeric purity of the intermediate N-(benzylidene)-b-
aryl-b-chloroamines and aziridines was influenced by the
para-substituent of the aryl group. The synthesis of chiral
N-unactivated aziridines 8 and 11 is complementary to the
access towards chiral N-activated aziridines 2 and 9.
(12) Li, A.-H.; Dai, L.-X.; Aggarwal, V. K. Chem. Rev. 1997, 97,
2341.
(13) (a) McCoull, W.; Davis, F. A. Synthesis 2000, 1347.
(b) Hu, X. E. Tetrahedron 2004, 60, 2701.
Acknowledgment
(14) (a) Cossy, J.; Bellosta, V. FR 2821354, 2002, Chem. Abstr.
2003, 138, 169957. (b) Allan, R. D.; Tran, H. W. Aust. J.
Chem. 1990, 43, 1123. (c) Ghorai, M. K.; Das, K.; Shukla,
D. J. Org. Chem. 2007, 72, 5859. (d) Ghorai, M. K.; Ghosh,
K. Tetrahedron Lett. 2007, 48, 3191. (e) Ghorai, M. K.;
Das, K.; Kumar, A.; Ghosh, K. Tetrahedron Lett. 2005, 46,
4103.
The authors are indebted to Ghent University (GOA) and the Re-
search Foundation-Flanders (FWO-Vlaanderen) for financial sup-
port of this research.
The authors are indebted to Prof. D. M. Hodgson for addressing im-
portant suggestions regarding the ring opening of chiral aziridines 2.
(15) For some reviews on the importance of phenylethylamines,
see: (a) Smith, T. A. Phytochemistry 1977, 16, 9.
(b) Juaristi, E.; Léon-Romo, J. L.; Reyes, A.; Escalante, J.
Tetrahedron: Asymmetry 1999, 10, 2441. (c) Juaristi, E.;
Escalante, J.; León-Romo, J. L.; Reyes, A. Tetrahedron:
Asymmetry 1998, 9, 715. (d) Bentley, K. W. Nat. Prod. Rep.
2006, 23, 444.
References and Notes
(1) Postdoctoral Fellow of the Research Foundation-Flanders
(FWO).
(2) Aziridines and Epoxides in Organic Synthesis; Yudin, A. K.,
Ed.; Wiley-VCH: Weinheim, 2006.
(3) For selected examples with N-nucleophiles, see:
(a) Karikomi, M.; De Kimpe, N. Tetrahedron Lett. 2000, 41,
10295. (b) D’hooghe, M.; Van Speybroeck, V.; Van
Nieuwenhove, A.; Waroquier, M.; De Kimpe, N. J. Org.
Chem. 2007, 72, 4733.
(4) For a recent example of enzymatic resolution of unactivated
aziridines and their study in nucleophilic ring opening
reactions, see: Moran-Ramallal, R.; Liz, R.; Gotor, V. Org.
Lett. 2007, 9, 521.
(16) (RS,R)-N-(tert-Butylsulfinyl)-2-(4-methylphenyl)-
aziridine (2d)
Prepared according to a previously described method, see
ref. 11a. 1H NMR (300 MHz, CDCl3): d = 1.29 (s, 9 H), 1.99
(d, J = 3.9 Hz, 1 H), 2.34 (s, 3 H), 2.97 (d, J = 7.2 Hz, 1 H),
3.09 (dd, J = 7.2, 3.9 Hz, 1 H), 7.13–7.20 (m, 4 H). 13C NMR
(75 MHz, CDCl3): d = 21.2, 22.8, 28.6, 34.7, 57.4, 126.3,
129.2, 134.6, 137.5. IR (ATR): nmax = 1063, 1362, 1457,
1681, 2960, 3346 cm–1. MS (ES, pos. mode): m/z (%) =
238(100) [M + H+]. [a]D –238.5 (c 1.15, CH2Cl2); mp 106.0–
107.0 °C. Anal. Calcd for C13H19NOS: C, 65.78; H, 8.07; N,
5.90; S, 13.51. Found: C, 65.44; H, 8.35; N, 6.11; S, 13.28.
(5) (a) Gabriel, S. Ber. Dtsch. Chem. Ges. 1888, 21, 1049.
(b) Wenker, H. J. Am. Chem. Soc. 1935, 57, 2328.
(c) Tanner, D. Angew. Chem., Int. Ed. Engl. 1994, 33, 599.
(6) Sinou, D.; Emziane, M. Tetrahedron Lett. 1986, 27, 4423.
Synlett 2009, No. 8, 1265–1268 © Thieme Stuttgart · New York

1268
E. Leemans et al.
LETTER
(17) (S)-2-Chloro-2-(4-methylphenyl)ethylamine
Hydrochloride (3d)
(20) Ema, T.; Tamida, D.; Sahai, T. J. Am. Chem. Soc. 2007, 129,
10591.
(21) Ghorai and co-workers have concluded, based on
experimental results, that the Lewis acid mediated
nucleophilic ring opening of activated 2-phenylaziridines
occurs via an SN2 pathway, see ref. 14c–e.
(22) (a) Galindo, A.; Orea, L. F.; Gnecco, D.; Enriquez, R. G.;
Toscano, R. A.; Reynolds, W. F. Tetrahedron: Asymmetry
1997, 8, 2877. (b) Van, N. T.; De Kimpe, N. Tetrahedron
2000, 56, 7299.
Prepared according to a previously described method, see
ref. 11a,b. 1H NMR (300 MHz, D2O): d = 2.31 (s, 3 H), 3.19
(dd, J = 12.7, 4.4 Hz, 1 H), 3.26 (dd, J = 12.7, 8.7 Hz, 1 H),
4.93 (dd, J = 8.7, 4.4 Hz, 1 H), 7.26–7.32 (m, 4 H). 13C NMR
(75 MHz, D2O): d = 20.8, 45.8, 70.0, 126.6, 130.1, 137.1,
139.6. IR (ATR): nmax = 1146, 1510, 1603, 2361, 2958 cm–1.
MS (ES, pos. mode): m/z (%) = 152/154(100), 170/172(20)
[M + H+]. [a]D +52.6 (c 1.01, MeOH); mp 173.6–174.6 °C.
Anal. Calcd for C9H13NCl2: C, 52.45; H, 6.36; N, 6.80.
Found: C, 52.52; H, 6.42; N, 6.57.
(23) Preparation of (R)-1-Benzyl-2-(4-methylphenyl)-
aziridine (8d)
(18) Preparation of (S)-N-Benzylidene-[2-chloro-2-(4-
methylphenyl)ethyl]amine (4d)
To a stirred solution of aldimine 4d (0.12 g, 0.47 mmol) in
MeOH (15 mL) was added NaBH4 (0.02 g, 0.47 mmol), and
the reaction mixture was brought to reflux for 3 h.
Afterwards, a sat. soln of NaHCO3 (10 mL) was added, and
the organic solvent was evaporated. The resulting mixture
was extracted with CH2Cl2 (3 × 15 mL), and the combined
organic layers were dried (MgSO4) and filtered to afford
1-benzyl-2-(4-methylphenyl)aziridine (8d, 0.09 g) in pure
form after removal of the solvent in vacuo; yield 92%. 1H
NMR (300 MHz, CDCl3): d = 1.82 (d, J = 6.6 Hz, 1 H), 1.97
(d, J = 3.3 Hz, 1 H), 2.32 (s, 3 H), 2.47 (dd, J = 6.6, 3.3 Hz,
1 H), 3.58 (d, J = 13.8 Hz, 1 H), 3.70 (d, J = 13.8 Hz, 1 H),
7.08–7.38 (m, 9 H). 13C NMR (75 MHz, CDCl3): d = 21.1,
37.8, 41.4, 64.8, 126.1, 126.9, 127.8, 128.3, 129.0, 136.5,
137.1, 139.2. IR (ATR): nmax = 1026, 1452, 1517, 2826,
3028 cm–1. MS (ES, pos. mode): m/z (%) = 224(100) [M +
H+]. [a]D –55.8 (c 1.01, CH2Cl2). Anal. Calcd for C16H17N:
C, 86.05; H, 7.67; N, 6.27. Found: C, 86.21; H, 7.83; N, 5.96.
(24) Tsuchiya, Y.; Kumamoto, T.; Ishikawa, T. J. Org. Chem.
2004, 69, 8504.
Triethylamine (0.09 g, 0.93 mmol) was added to a solution
of (S)-2-chloro-2-(4-methylphenyl)ethylamine hydro-
chloride (3d, 0.15 g, 0.88 mmol), MgSO4 (0.15 g, 1.27
mmol), and benzaldehyde (0.09 g, 0.88 mmol) in CH2Cl2 (15
mL). The reaction was stirred for 7 h at 0 °C. The suspension
was subsequently filtered, and the solvent was evaporated.
Diethyl ether (15 mL) was added and the obtained mixture
was again filtered and evaporated, yielding 4d which was
purified by recrystallization from Et2O (0.18 g); yield 83%.
1H NMR (300 MHz, CDCl3): d = 2.35 (s, 3 H), 4.02 (ddd,
J = 12.5, 8.5, 1.1 Hz, 1 H), 4.21 (ddd, J = 12.5, 5.0, 1.7 Hz,
1 H), 5.24 (dd, J = 8.5, 5.0 Hz, 1 H), 7.16–7.45 and 7.72–
7.76 (m, 9 H), 8.28 (s, 1 H). 13C NMR (75 MHz, CDCl3):
d = 21.2, 62.7, 69.0, 127.2, 128.3, 128.6, 129.3, 131.0,
135.8, 137.0, 138.3, 163.7. IR (ATR): nmax = 1449, 1514,
1645, 2361, 2916 cm–1. MS (ES, pos. mode): m/z (%): 258/
260(100) [M + H+]. [a]D +55.8 (c 0.70, CH2Cl2); mp 79.4–
80.4 °C. Anal. Calcd for C16H16NCl: C, 74.55; H, 6.26; N,
5.43. Found: C, 74.89; H, 6.37; N, 5.20.
(25) (a) Kawamoto, A. M.; Wills, M. Tetrahedron: Asymmetry
2000, 11, 3257. (b) Kawamoto, A. M.; Wills, M. J. Chem.
Soc., Perkin Trans. 1 2001, 1916.
(19) Pirkle, W. H.; Sikkenga, D. L.; Pavlin, M. S. J. Org. Chem.
1977, 42, 384.
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