Synthesis of (Trifluoromethyl)aziridines
1363
tion of tetrah edral in term ediates by th e CF substituen t. Alth ough n ot well
3
un derstood, HFIP appeared to be essen tial to solve th is difficulty.
In con clusion , we h ave sh own th at th e Yb(OTf) - or BF ·Et O-catalyzed
3
3
2
th ree-com pon en t reaction of fluoral eth yl h em iacetal, an arom atic am in e,
an d eth yl diazoacetate is efficien t in 1,1,1,3,3,3-h exafluoropropan -2-ol as
solven t. (Trifluorom eth yl)aziridin es 2 could be prepared in good yields but
with m oderate diastereoselectivity. Th e role of HFIP is crucial in th e prod-
uct lim itin g step of th ese sequen tial reaction s wh ich is th e form ation of an
aldim in e an d th e reactivity of tetrah edral adducts. More in vestigation s are
required to determ in e param eters govern in g th e ch em ical an d stereo-
ch em ical course of differen t steps of th ese th ree-com pon en t reaction s.
EXPERIMENTAL
Gen eral Procedure for th e Aziridin ation of Im in es
To a solution of im in e 1 (1 m m ol) in HFIP (3 m l) were added th e Lewis acid (0.01 m m ol)
an d EDA (1.5 m m ol, 0.16 m l) at room tem perature. Th e reaction was followed by GC. Wh en
startin g m aterial was n o m ore detected, th e reaction m ixture was quen ch ed by addition of
saturated NaHCO3 solution (10 m l). Th e aqueous layer was extracted with dieth yl eth er (3 ×
5
m l), th en th e organ ic layers were wash ed with saturated NaCl solution , dried (Na SO ), fil-
2 4
tered an d evaporated un der reduced pressure. Th e products were purified by flash ch rom a-
tograph y on silica gel (petroleum eth er–eth yl acetate, 4 : 1).
trans-1-(4-Methoxyphenyl)-3-trifluoromethyl-2-ethoxycarbonylaziridine (2a): pale yellow liquid.
1
H NMR (CDCl , 200 MHz): 6.82 (4 H, m ); 4.08 (2 H, q, J = 7.0); 3.75 (3 H, s); 3.42 (2 H, m );
3
1
3
1
4
.14 (3 H, t, J = 7.0). C NMR (CDCl ): 166.1, 157.2, 140.4, 124.1, 121.4, 115.4, 62.9, 56.4,
3
1
9
3.4, 40.4, 14.8.
F NMR (CDCl , CFCl ): –71.4 (d, J = 4.0). IR: 1 736 (CO). For
3 3
C13H14F3NO3 calculated: 53.98% C, 4.88% H, 4.84% N; foun d: 53.88% C, 5.02% H, 4.83% N.
cis-1-(4-Methoxyphenyl)-3-trifluoromethyl-2-ethoxycarbonylaziridine (2a): pale yellow liquid.
1
H NMR (CDCl , 200 MHz): 6.96 (2 H, d, J = 9.0); 6.81 (2 H, d, J = 9.0); 4.32 (2 H, q, J =
3
7
7
.0); 3.77 (3 H, s); 3.07 (1 H, d, J = 6.5); 2.89 (1 H, q, J
= 4.5, JH-H = 6.5); 1.33 (3 H, t, J =
H-F
1
3
.0). C NMR (CDCl ): 166.7, 157.5, 144.1, 121.4, 123.2, 115.5, 62.9, 56.3, 43.9, 42.3, 14.8.
3
1
9
F NMR (CDCl , CFCl ): –68.3 (d, J = 4.5). IR (n eat): 1 753 (CO).
trans-1-Benzyl-3-trifluoromethyl-2-ethoxycarbonylaziridine (2b): pale yellow liquid. 1H NMR
3
3
(
(
3
CDCl , 200 MHz): 7.31 (4 H, m ); 4.14 (2 H, q, J = 7.0); 3.93 (2 H, q); 2.95 (2 H, m ); 1.21
3
1
3
3 H, t, J = 7.0). C NMR (CDCl ): 167.5, 138.6, 129.3, 129.1, 128.3, 124.2, 62.7, 55.2, 44.5,
3
8.5, 14.6. 19F NMR (CDCl , CFCl ): –68.3 (d, J = 5.0). IR: 1 732 (CO). For C13H14F3NO2 cal-
3 3
culated: 57.14% C, 5.16% H, 5.13% N; foun d: 56.95% C, 5.25% H, 5.10% N.
1
cis-1-Benzyl-3-trifluoromethyl-2-ethoxycarbonylaziridine (2b ): H NMR (CDCl , 200 MHz):
3
7
.35 (2 H, m ); 4.26 (2 H, m ); 3.77 (3 H, s); 2.56 (1 H, d, J = 6.5); 2.43 (1 H, q, J
= 5.5,
H-F
1
3
JH-H = 6.5); 1.26 (3 H, t, J = 7.0). C NMR (CDCl ): 166.9, 136.6, 129.5, 129.2, 128.8, 124.2,
6
3
3.1, 62.6, 43.9, 42.2, 14.8. 1 F NMR (CDCl , CFCl ): –67.3 (d, J = 5.5). IR: 1 751 (CO).
9
3
3
trans-1-Diphenylmethyl-3-trifluoromethyl-2-ethoxycarbonylaziridine (2c): wh ite powder, m .p.
1
1
36 °C. H NMR (CDCl , 200 MHz): 7.56 (2 H, d, J = 8.0); 7.44 (2 H, d, J = 8.0); 7.39–7.20
3
(
6 H, m ); 4.91 (1 H, s); 4.23 (2 H, q, J = 7.0); 3.13 (1 H, d, J = 2.0); 3.08 (1 H, q, JH-F = 3.5,
Collect. Czech. Chem. Commun. (Vol. 67) (2002)