Amano PS lipase-catalyzed acetylation of hydroxymethyl-
aziridines 1: general procedure
(ϩ)-trans-2b: 1H NMR spectroscopy showed the presence of
two invertomers (73 : 27), due to slow nitrogen inversion on the
NMR timescale.2 1H NMR major invertomer: δH 1.39 (3H, d,
J 6.0, CH3CH), 1.69–1.77 (1H, m, CHCH2), 1.97 (3H, s,
COCH3), 2.16 (1H, dq, J 2.9, 6.0, CH3CH ), 3.53 (1H, d, J 13.8,
CH2Ph), 3.84 (1H, dd, J 11.6, 7.5, CH2O), 3.86 (1H, d, J 13.8,
CH2Ph), 4.24 (1H, dd, J 11.6, 4.6, CH2O), 7.32–7.44 (5H, m,
aromatic); minor invertomer: δH 1.27 (3H, d, J 5.5, CH3CH),
1.59–1.69 (1H, m, CHCH2), 2.01 (3H, s, COCH3), 2.19–2.31
(1H, m, CH3CH ), 3.62 (1H, d, J 13.9, CH2Ph), 3.87 (1H, d,
J 13.9, CH2Ph), 4.20 (1H, dd, J 12.4, 8.2, CH2O), 4.53 (1H, dd,
J 12.4, 3.9, CH2O), 7.25–7.33 (5H, m, aromatic). MS, m/z: 218
([M Ϫ 1]ϩ, 2%), 204 (1), 176 (1), 160 (13), 132 (3), 128 (16), 91
(74), 86 (100), 77 (4), 65 (20), 58 (24), 43 (67). (Found: C, 71.1;
H, 7.8; N, 6.3. C13H17NO2 requires C, 71.2; H, 7.8; N, 6.4%).
The hydroxymethylaziridine 1 (1 mmol) was dissolved in the
minimum amount of THF (generally no more than 2 ml) and
diluted with n-hexane (20 ml). Vinyl acetate (5 mmol) and
Amano PS lipase (1 : 2 w/w with respect to the aziridine) were
added and the resulting suspension was vigorously stirred at
37 ЊC for the time reported in Table 1. Thereafter, the enzyme
was removed by filtration and carefully washed with anhydrous
diethyl ether; the organic phases were combined and con-
centrated under reduced pressure. Depending on the chromato-
graphic separation observed between the unreacted alcohol
and the product of the enzymatic acetylation, the crude residue
was directly chromatographed (method A) or treated with
TBDMSCl to convert the unreacted alcohol into the corre-
sponding TBDMS-ether (method B). In the latter case, the
crude residue was dissolved in anhydrous CH2Cl2 (5 ml) and
subsequently treated with DMAP (0.8 mmol) and TBDMSCl
(0.6 mmol) under magnetic stirring at rt for 30 min. The
mixture was diluted with further CH2Cl2 (5 ml), washed with
water (5 ml) and brine (3 ml), and dried over MgSO4. The
solvent was distilled in vacuo and the residue chromatographed
on silica gel [using the eluent reported below in square
brackets], affording the product of the enzymatic acetylation 2
and the unreacted substrate as the O-TBDMS ether 3.
trans-1-Benzyl-3-ethyl-2-hydroxymethylaziridine (trans-1c).
Resolution of ( )-trans-1c (method B) afforded [light
petroleum–diethyl ether 70 : 30] the unreacted substrate as
1-benzyl-2-(tert-butyldimethylsilyloxymethyl)-3-ethylaziridine
(ϩ)-trans-3c (17%), [α]D ϩ11.1 (c 2.0, CHCl3), ee 37%, along
with the acetylated product 1-benzyl-2-acetoxymethyl-3-
ethylaziridine (Ϫ)-trans-2c (37%), [α]D Ϫ15.4 (c 4.2, CHCl3),
ee 38%.
(Ϫ)-trans-2c: 1H NMR spectroscopy showed the presence of
two invertomers (54 : 46), due to slow nitrogen inversion on the
NMR timescale.2 1H NMR major invertomer: δH 1.1 (3H, t,
J 7.4, CH2CH3), 1.40–1.58 (2H, m, CH3CH2), 1.55–1.70 (1H,
m, CHCH2CH3), 1.95 (3H, s, COCH3), 2.20–2.31 (1H, m,
CHCH2O), 3.49 (1H, d, J 13.4, CH2Ph), 3.85 (1H, dd, J 11.6,
7.4, CH2O), 3.92 (1H, d, J 13.4, CH2Ph), 4.21 (1H, dd, J 11.6,
4.8, CH2O), 7.25–7.43 (5H, m, aromatic); minor invertomer: δH
0.85 (3H, t, J 7.5, CH2CH3), 1.68–1.86 (2H, m, CH3CH2), 1.55–
1.70 (1H, m, CHCH2CH3), 2.02 (3H, s, COCH3), 1.96–2.07
(1H, m, CHCH2O), 3.55 (1H, d, J 13.6, CH2Ph), 3.90 (1H, d,
J 13.6, CH2Ph), 4.24 (1H, dd, J 12.6, 5.2, CH2O), 4.53 (1H, dd,
J 12.6, 3.6, CH2O), 7.25–7.43 (5H, m, aromatic). MS, m/z: 174
([M Ϫ 59]ϩ, 4%), 160 (2), 142 (10), 100 (82), 91 (76), 72 (13), 65
(22), 54 (9), 43 (100). (Found: C, 72.2; H, 8.1; N, 6.0. C14H19NO2
requires C, 72.1; H, 8.2; N, 6.0%).
1-Benzyl-2-hydroxymethylaziridine (1a). Resolution of ( )-1a
(method B) afforded [diethyl ether–light petroleum 80 : 20]
the unreacted substrate as 1-benzyl-2-(tert-butyldimethylsilyl-
oxymethyl)aziridine (2R)-(ϩ)-3a (10%), [α]D ϩ4.6 (c 1.3,
CHCl3), ee > 97%, along with the acetylation product (2S)-(ϩ)-
2a (20%), [α]D ϩ11 (c 1.9, CHCl3), ee 36%.
1
(2S)-(ϩ)-2a: H NMR: δH 1.57 (1H, d, J 6.4, CH2 ring),
1.83 (1H, d, J 3.4, CH2 ring), 1.85–1.96 (1H, m, CH ring), 2.00
(3H, s, COCH3), 3.35 (1H, d, J 13.3, CH2Ph), 3.64 (1H, d,
J 13.3, CH2Ph), 3.85 (1H, dd, J 11.6, 7.3, CH2O), 4.23 (1H, dd,
J 11.6, 4.4, CH2O), 7.27–7.39 (5H, m, aromatic). MS, m/z: 205
(Mϩ, 5%), 204 (6), 190 (1), 175 (2), 162 (4), 146 (15), 144 (15),
132 (8), 114 (7), 91 (100), 77 (6), 72 (94), 65 (17), 43 (80).
(Found: C, 70.4; H, 7.3; N, 6.8; C12H15NO2 requires C, 70.2; H,
7.4; N, 6.8%).
cis-1-Benzyl-2-hydroxymethyl-3-phenylaziridine
(cis-1d).
Resolution of ( )-cis-1d (method A) gave [diethyl ether–light
petroleum 60 : 40] the unreacted substrate (2R,3R)-(Ϫ)-cis-1d
(49%), [α]D Ϫ91.3 (c 0.8, CHCl3), along with the acetylated
product (2S,3S)-(ϩ)-cis-2d (50%), [α]D ϩ85.6 (c 3.2, CHCl3),
ee > 97%. The ee of (2R,3R)-(Ϫ)-cis-1d was determined after
conversion into (2R,3R)-(Ϫ)-cis-2d with acetic anhydride and
DMAP at 60 ЊC for 40 min (93%), which showed [α]D Ϫ81.4
(c 4.0, CHCl3), ee > 97%.
cis-1-Benzyl-2-hydroxymethyl-3-methylaziridine
(cis-1b).
Resolution of ( )-cis-1b (method A) afforded [pure diethyl
ether and finally diethyl ether–ethyl acetate 80 : 20] the
unreacted substrate (2R,3R)-(Ϫ)-cis-1b (41%), [α]D Ϫ3.9 (c 1.4,
CHCl3), ee > 97%, along with the acetylated product 1-benzyl-
2-acetoxymethyl-3-methylaziridine (2S,3S)-(ϩ)-cis-2b (46%),
[α]D ϩ22.8 (c 2.6, CHCl3), ee 86%. The ee of (2R,3R)-(Ϫ)-cis-1b
was evaluated after conversion, under standard conditions,
into the corresponding 1-benzyl-2-(tert-butyldimethylsilyloxy-
methyl)-3-methylaziridine (2R,3R)-(ϩ)-cis-3b (84%), [α]D ϩ4.0
(c 2.7, CHCl3), ee > 97%.
1
(2S,3S)-(ϩ)-cis-2d. H NMR: δH 1.95 (3H, s, COCH3), 2.26
(1H, ddd, J 7.6, 6.6, 5.2, CHCH2), 2.93 (1H, d, J 6.6, PhCH ),
3.69 (1H, d, J 13.4, CH2Ph), 3.77 (1H, dd, J 11.8, 7.6, CH2O),
3.80 (1H, d, J 13.4, CH2Ph), 3.96 (1H, dd, J 11.8, 5.2, CH2O),
7.22–7.49 (10H, m, aromatic). MS, m/z: 222 ([M Ϫ 59]ϩ, 2%),
190 (66), 148 (84), 130 (12), 120 (23), 91 (100), 77 (10), 65 (18),
43 (57). (Found: C, 76.7; H, 6.8; N, 4.9. C18H19NO2 requires: C,
76.8; H, 6.8; N, 5.0%).
(2S,3S)-(ϩ)-cis-2b: 1H NMR: δH 1.25 (3H, d, J 5.6, CH3CH),
1.69–1.82 (1H, m, CH3CH ), 1.83–1.91 (1H, m, CHCH2), 2.01
(3H, s, COCH3), 3.45 (1H, d, J 13.5, CH2Ph), 3.65 (1H, d,
J 13.5, CH2Ph), 4.07 (1H, dd, J 11.7, 7.0, CH2O), 4.18 (1H, dd,
J 11.7, 5.5, CH2O), 7.27–7.38 (5H, m, aromatic). MS, m/z: 218
([M Ϫ 1]ϩ, 3%), 160 (16), 128 (22), 91 (64), 86 (100), 65 (15), 45
(49). (Found: C, 70.9; H, 7.7; N, 6.3. C13H17NO2 requires C,
71.2; H, 7.8; N, 6.4%).
trans-1-Benzyl-2-hydroxymethyl-3-phenylaziridine (trans-1d).
Resolution of ( )-trans-1d (method B) afforded [light
petroleum–diethyl ether 70 : 30] the unreacted substrate as 1-
benzyl-2-(tert-butyldimethylsilyloxymethyl)-3-phenylaziridine
(ϩ)-trans-3d (24%), [α]D ϩ8.5 (c 3.1, CHCl3), along with the
trans-1-Benzyl-2-hydroxymethyl-3-methylaziridine (trans-1b).
Resolution of ( )-trans-1b (method B) afforded [light
petroleum–diethyl ether 70 : 30] the unreacted substrate as 1-
benzyl-2-(tert-butyldimethylsilyloxymethyl)-3-methylaziridine
(Ϫ)-trans-3b (27%), [α]D Ϫ5.8 (c 3.1, CHCl3), ee 31%, along
with the acetylation product 1-benzyl-2-acetoxymethyl-3-
methylaziridine (ϩ)-trans-2b (37%), [α]D ϩ15.4 (c 3.1, CHCl3),
ee 24%.
acetylation
product
1-benzyl-2-acetoxymethyl-3-phenyl-
aziridine (Ϫ)-trans-2d (29%), [α]D Ϫ36.5 (c 3.0, CHCl3).
(Ϫ)-trans-2d: 1H NMR spectroscopy showed broad and
poorly resolved signals, indicating the presence of two
1
invertomers at nitrogen2 overlapped at the cohalescence. H
NMR: δH 2.00 (3H, s, COCH3), 2.58 (1H, ddd, J 7.8, 4.4, 3.3,
J. Chem. Soc., Perkin Trans. 1, 2002, 1948–1953
1951