Ar-H); J4Јα,4Јβ 8.8, J6Јα,6Јβ 8.9, J4a,4b 12.4; 13C NMR δ: 8.2 (C-3Љ),
14.0 (OCH2CH3), 48.4 (C-5Ј), 61.1 (OCH2CH3), 64.6 (C-2Љ),
70.4 (C-1Ј), 70.9 (C-4), 72.1 (C-4Ј), 73.5 (C-1Љ), 73.8 (C-6Ј), 77.3
(C-2), 83.0 (C-8Ј), 118.8 (C-6), 125.7, 126.5, 127.0, 128.0, 128.3
3485, 2972, 2929, 1742 cmϪ1; 1H NMR (300 MHz) see Table 3.
Additional data, δ: 1.03 (s, 3H, CH3), 1.04 (s, 3H, CH3), 2.0
(s, 2H, OH), 3.33 (d, 1H, J1Љa,1Љb 10.8, 1Љa-H), 3.55 (d, 1H,
J1Љa,1Љb 10.8, 1Љb-H); J4Јα,4Јβ 8.2, J6Јα,6Јβ 8.9; 13C NMR δ: 14.1
(C-OCH2CH3), 17.9 (CH3), 23.3 (CH3), 50.6 (C-5Ј), 62.1 (C-2Љ),
62.3 (C-OCH2CH3), 66.5 (C-1Ј), 70.1 (C-1Љ), 71.3 (C-2), 72.8
(Ar), 133.3 (C-5), 140.5 (Ar), 170.0 (C᎐O); Anal. Calc. for
᎐
C21H29NO6 (343.4): C, 64.43; H, 7.47; N, 3.58. Found: C, 64.64;
H, 7.36; N, 3.89%.
(C-4Ј), 73.5 (C-6Ј), 85.5 (C-8Ј), 172.7 (C᎐O).
᎐
In the case of the reaction with unsubstituted hydroxylamine
the mixture of compounds 11h, 12h and 13h was refluxed in
toluene. The formation of a mixture of products was shown by
TLC (100% EtOAc; Rf 9h = 0.55, 14 = 0.22, 10h = 0.16,
8h = 0.07). Separation of four compounds (8h, 9h, 10h and 14)
was achieved by column chromatography [silica gel; EtOAc–
light petroleum (bp 40–60 ЊC), 1:1] and traces of another two
products could not be isolated. Spectral and other data of com-
pounds 8h and 14 are given in reference 8.
Ethyl (1ЈS,2R,2ЉS,5ЈR,8ЈS)-2-[2Ј-(1Љ,1Љ-diphenyl-1Љ-hydroxy-
propan-2Љ-yl)-3Ј,7Ј-dioxa-2Ј-azabicyclo[3.3.0]octan-8Ј-yl]-3-
oxahex-5-enoate 9g
Yield: 17%; [α]D19 Ϫ28.5 (c 0.34, CHCl3); H NMR see Table 3.
1
Additional data, δ: 0.91 (d, 3H, J2Љ,3Љ 6.6, 3Љ-H), 4.07 (q, 1H,
J2Љ,3Љ 6.6, 2Љ-H), 7.0–7.5 (m, Ar-H); J4Јα,4Јβ J6Јα,6Јβ 9.0; 13C NMR
δ: 14.3 (OCH2CH3), 14.7 (CH3), 49.3 (C-5Ј), 61.2 (OCH2CH3),
64.6 (C-2Љ), 68.7 (C-1Ј), 71.1 (C-4Ј), 72.2 (C-4), 73.9 (C-6Ј), 77.3
(C-2), 79.7 (C-1Љ), 83.6 (C-8Ј), 118.8 (C-6), 125.9–128.01 (Ar),
Ethyl (1ЈS,2R,5ЈR,8ЈS)-2-(3Ј,7Ј-dioxa-2Ј-azabicyclo[3.3.0]-
octan-8Ј-yl)-3-oxahex-5-enoate 9h
133.6 (C-5), 145.7, 148.0 (Ar), 170.2 (C᎐O).
᎐
(1ЈS,1ЉS,2S,5ЈR,8ЈS)-2-[2Ј-(1Љ-Phenylethyl)-3Ј,7Ј-dioxa-2Ј-
azabicyclo[3.3.0]octan-8Ј-yl]-3-oxahex-5-en-1-ol 10c
Yield: 9%, mp 65–68 ЊC; [α]D19 ϩ76.4 (c 1.0, CHCl3); νmax(KBr)
3395, 2965, 2935, 1738 cmϪ1; 1H NMR (500 MHz) see Table 3.
Additional data, J4Јα,4Јβ J6Јα,6Јβ 8.8; 13C NMR δ: 14.0 (CH3), 49.3
(C-5Ј), 60.9 (OCH2CH3), 67.2 (C-1Ј), 71.9 (C-4), 73.7 (C-6Ј),
75.9 (C-4Ј), 77.6 (C-2), 84.1 (C-8Ј), 118.1 (C-6), 133.6 (C-5),
OH
O-Allyl
Ph
Me
1
1′′
H1′
2
169.9 (C᎐O); MS (EI) m/z (rel. int.) 257 (Mϩ, 5%), 41 (100);
᎐
N
Anal. Calc. for C12H19NO5 (257.3): C, 56.02; H, 7.44; N, 5.44.
Found: C, 56.34; H, 7.69; N, 5.21%.
O
O
H5′
(1ЈS,2S,5ЈR,8ЈS)-2-(3Ј,7Ј-Dioxa-2Ј-azabicyclo[3.3.0]octan-8Ј-
yl)-3-oxahex-5-en-1-ol 10h
Yield: 14% mp 74–78 ЊC; [α]D19 Ϫ14.62 (c 0.13, CHCl3); νmax(KBr)
1
3495, 2934, 1459 cmϪ1; H NMR δ: 1.39 (d, 3H, J 6.5, CH3),
1
Yield: 9%; [α]D19 ϩ47.76 (c 0.67, CHCl3); H NMR δ: 3.16 (m,
3.30 (m, 1H, 5Ј-H), 3.56 (m, 3H, 2-H, 4Јα-H, 6Јα-H), 3.93 (m,
5H, 6Јβ-H, 8Ј-H, 1Љ-H, 1-H), 4.09 (dd, 1H, J 12.7, 6.6, 4a-H),
4.12 (dd, 1H, J 8.3, 6.3, 1Ј-H), 4.24 (dd, 1H, J 12.7, 5.5, 4b-H),
4.29 (dd, 1H, J 8.1, 8.7, 4Јβ-H), 5.17 (m, 2H, 6-H), 5.84 (m, 1H,
5-H), 7.26–7.37 (m, Ar-H); 13C NMR δ: 21.7 (q), 48.3 (d), 62.4
(t), 63.0 (d), 70.3 (t), 70.5 (d), 71.3 (t), 74.0 (t), 78.1 (d), 84.8 (d),
117.0 (t), 127.2–128.4 (Ar), 134.9 (d); MS (EI) m/z (rel. int.) 319
(3.5%), 104 (100); Anal. Calc. for C18H25NO4 (319.4): C, 67.69;
H, 7.89; N 4.39. Found: C, 67.23; H, 7.45; N, 4.48%.
1H, J 8.6, 8.6, 7.4, 7.2, 5Ј-H), 3.4 (dd, 1H, J 8.6, 7.4, 6Јβ-H),
3.51 (dt, 1H, J 4.8, 4.4, 2-H), 3.53 (dd, 1H, J 8.9, 7.2, 4Јβ-H),
3.62 (dd, 1H, J 6.5, 4.8, 8Ј-H), 3.74 (ddd, 2H, J 10, 4.4, 4.8,
1-H), 3.87 (d, 1H, J 8.9, 4Јα-H), 4.01 (dd, 1H, J 8.6, 6.5, 1Ј-H),
4.1 (m, 2H, 4-H), 4.24 (t, 1H, J 8.6, 6Јα-H), 5.15 (m, 2H, 6-H),
5.86 (m, 1H, 5-H); 13C NMR δ: 49.1 (C-5Ј), 62.1 (C-1), 67.9
(C-1Ј), 71.6 (C-4), 73.6 (C-6Ј), 75.9 (C-4Ј), 78.7 (C-2), 84.8
(C-8Ј), 117.4 (C-6), 134.8 (C-5); MS (EI) m/z 215 (Mϩ); Anal.
Calc. for C10H17NO4 (215.2): C, 55.80; H, 7.96; N, 6.50. Found:
C, 55.44; H, 7.62; N, 6.34%.
(1ЈS,2S,5ЈR,8ЈS)-2-[2Ј-(1Љ-Hydroxy-2Љ-methylpropan-2Љ-yl)-
3Ј,7Ј-dioxa-2Ј-azabicyclo[3.3.0]octan-8Ј-yl]-3-oxahex-5-en-1-ol
10d
Catalysis of the reaction of diethylzinc with benzaldehyde
Yield: 14%; [α]D19 ϩ12.85 (c 0.07, CHCl3); νmax(neat) 3468, 2936,
Freshly distilled benzaldehyde (0.25 mL, 2.5 mmol) was added
to the catalyst (0.15 mmol) in a 10 mL flask under argon. The
clear solution was cooled to 0 ЊC, then a 1.0 M solution of
diethylzinc in hexane (3.75 mL, 3.75 mmol) was added within a
period of 20 min. The reaction mixture was stirred for 12 h at
0 ЊC, then the reaction was quenched with 1.5 M hydrochloric
acid (10 mL). Subsequently the mixture was extracted three
times with diethyl ether. The combined organic layer was dried
with MgSO4. After filtration and removal of the solvent at
30 ЊC/500 mm Hg, a non-racemic mixture of (R)- and (S)-1-
phenylpropan-1-ol 20 was obtained in the yields as presented in
Table 5. At this stage a small amount of the crude mixture was
analysed by 1H NMR spectroscopy to determine the degree of
conversion to 20 and benzyl alcohol. After this determination,
the mixture was concentrated in vacuo in order to remove excess
benzaldehyde and benzyl alcohol. Compound 20 was converted
to the ester 21 for ee determination as described below. In add-
ition, for some probes ee values were determined by GC on a
chiral column.
1
1468 cmϪ1; H NMR δ: 0.81 (s, 3H, CH3), 0.89 (s, 3H, CH3),
3.17 (m, 1H, 5Ј-H), 3.31 (d, 1H, J1Љa,1Љb 11.0, 1Љa-H), 3.52 (d, 1H,
J1Љa,1Љb 11.0, 1Љb-H), 3.58 (m, 2H, 4Јα/6Јα-H), 3.75 (dd, 1H, J1a,1b
11.3, J1a,2 3.7, 1a-H), 3.83 (dd, 1H, J1a,1b 11.3, J1b,2 4.8, 1b-H),
3.9 (m, 2H, 4Јβ or 6Јβ-H, 4a-H), 4.01 (m, 3H, 1Ј-H, 4Јβ or
6Јβ-H, 8Ј-H), 4.16 (m, 2H, 4b-H, 2-H), 5.18 (m, 2H, 6-H), 5.86
(m, 1H, 5-H); 13C NMR δ: 18.4 (q), 23.2 (q), 50.3 (d), 61.9 (s),
62.0 (t), 66.9 (d), 70.1 (t), 71.2 (t), 72.9 (t), 73.1 (t), 77.8 (d), 86.1
(d), 117.4 (t), 134.0 (d).
(1ЈS,2S,2ЉR,5ЈR,8ЈS)-2-[2Ј-(1Љ-Hydroxybutan-2Љ-yl)-3Ј,7Ј-
dioxa-2Ј-azabicyclo[3.3.0]octan-8Ј-yl]-3-oxahex-5-en-1-ol 10e
Yield: 11%; [α]D19 ϩ13.50 (c 0.23, CHCl3); 1H NMR δ: 0.92 (t, 3H,
J 7.5, 4Љ-H), 1.54 (m, 1H, 3Љa-H), 1.70 (m, 1H, 3Љb-H), 2.63 (m,
1H, 1Љa-H), 3.28 (m, 1H, 1Љb-H), 3.57–4.26 (m, 13H), 5.23 (m,
2H, 6-H), 5.91 (m, 1H, 5-H); 13C NMR δ: 10.5, 19.9, 48.7, 61.1,
62.3, 65.6, 70.6, 70.7, 71.4, 73.6, 78.1, 84.2, 117.7, 134.4; MS
(EI) m/z 287 (Mϩ); Anal. Calc. for C14H25NO5 (287.4): C, 58.52;
H, 8.77; N, 4.87. Found: C, 58.23; H, 8.55; N, 4.38%.
Determination of the enantiomeric excess of 1-phenylpropanol 20
by preparation of diastereomeric esters 21 obtained by reaction
with (S)-(؉)-O-acetylmandelic acid
Ethyl (1ЈS,2R,5ЈR,8ЈS)-hydroxy[2Ј-(1Љ-hydroxy-2Љ-methyl-
propan-2Љ-yl)-3Ј,7Ј-dioxa-2Ј-azabicyclo[3.3.0]octan-8Ј-yl]-
acetate 17
Yield: 52% mp 104–106 ЊC; [α]D19 Ϫ4.3 (c 0.28, CHCl3); νmax(KBr)
1-Phenylpropan-1-ol, 20 (from the above concentrated mixture)
(94.3 mg, 0.69 mmol) was dissolved in dichloromethane (10
J. Chem. Soc., Perkin Trans. 1, 1998, 3717–3724
3723