A selective access to amino hydroxy oxetanes

Full text of DOI:10.1021/jo9708607

J . Org. Chem. 1997, 62, 8557-8559
8557
A Selective Access to Am in o Hyd r oxy
Oxeta n es
Alessandro Mordini,* Michela Valacchi, Chiara Nardi,
Simona Bindi, Giovanni Poli, and Gianna Reginato
Centro CNR Composti Eterociclici, Dipartimento
di Chimica Organica “U. Schiff”, via G. Capponi 9,
I-50121 Firenze, Italy
Received May 14, 1997
following known procedures13,19,20 starting with the amino
acids valine, leucine, and serine. The (E)-oxiranes de-
rived from valine and leucine and the (Z)-oxirane derived
from serine were obtained via reduction to the corre-
sponding N-Boc-amino aldehyde,21-23 selective olefination
to the (E)-24 or (Z)-R,â-unsaturated25 ester, respectively,
reduction to the allylic alcohol,19 and epoxidation with
m-chloroperbenzoic acid.26,27 The oxidation step is highly
syn-selective for these three substrates whereas the (E)-
allylic alcohol derived from serine gives a 1:1 mixture of
syn- and anti-epoxy amines.20 The epoxy alcohols 5-7
were converted into the benzyl oxiranyl ethers 8-10 and
then submitted to treatment with LIDAKOR in tetrahy-
drofuran at -50 °C. Oxetanes 11-13 were obtained in
good yields and with a selectivity which is related to the
configuration of the starting benzyl oxiranyl ethers. E-8
and E-9 derived from valine and leucine, respectively,
afforded the anti-oxetanes 11 and 12 as the unique
detectable products.
Oxetanes constitute an interesting class of compounds,1
being found in a large variety of natural products such
as taxane alkaloids and the antiviral and antibiotic
nucleoside oxetanocin2-8 just to mention a few of them.
We have recently discovered an easy and selective
access to di- (2, R′ ) H) and trisubstituted (2, R′ ) CH3)
oxetanes via isomerization of suitably substituted oxira-
nyl ethers 1.9
Our method allowed us to get access to hydroxy-
substituted oxetanes which may represent the starting
point for the synthesis of more complex, oxetane-contain-
ing, molecules. Moreover, our interest in the base-
promoted isomerization of heterosubstituted oxiranes
led us to report an access to syn-amino alcohols 313
10-12
from amino acids via amino alkoxy oxiranes 4. When
the alkoxy group R′O is methoxymethoxy,14 treatment
with the equimolar mixture butyllithium/diisopropy-
lamine/potassium tert-butoxide (LIDAKOR10,15) led to the
corresponding amino alcohol 3 as the unique product.13
On the basis of our previous findings,14 we assumed
that the replacement of the methoxymethoxy group with
a benzyloxy substituent could allow us to access amino
alcohols bearing an oxetane moiety which we envisaged
as useful building blocks for the synthesis of peptide
isosteres.16-18 We then prepared the required substrates
(1) Searles, S. In Comprehensive Heterocyclic Chemistry; Lwowsky,
W., Ed.; Pergamon Press: Oxford, 1984; Vol. 7, p 363.
(2) Hambalek, R.; J ust, G. Tetrahedron Lett. 1990, 31, 5445.
(3) Nakamura, H.; Hasegawa, S.; Shimada, N.; Fujii, A.; Takita, T.;
Iitaka, Y. J . Antibiot. 1986, 39, 1629.
(4) Niitsuma, S.; Ichikawa, Y.; Kato, K.; Takita, T. Tetrahedron Lett.
1987, 28, 4713.
(5) Nishiyama, S.; Yamamura, S.; Kato, K.; Takita, T. Tetrahedron
Lett. 1988, 29, 4743.
(6) Norbeck, D. W.; Kramer, J . B. J . Am. Chem. Soc. 1988, 110, 7217.
(7) Shimada, N.; Hasegawa, S.; Harada, T.; Tomisawa, T.; Fujii, A.;
Takita, T. J . Antibiot. 1986, 39, 1623.
(8) Wilson, F. X.; Fleet, G. W. J .; Vogt, K.; Wang, Y.; Witty, D. R.;
Choi, S.; Storer, R.; Myers, P. L.; Wallis, C. J . Tetrahedron Lett. 1990,
31, 6931.
(9) Mordini, A.; Bindi, S.; Pecchi, S.; Capperucci, A.; Degl’Innocenti,
A.; Reginato, G. J . Org. Chem. 1996, 61, 4466.
(10) Mordini, A.; Ben Rayana, E.; Margot, C.; Schlosser, M. Tetra-
hedron 1990, 46, 2401.
(11) Degl’Innocenti, A.; Mordini, A.; Pecchi, S.; Pinzani, D.; Reginato,
G.; Ricci, A. Synlett 1992, 753 ()803).
This result agrees well with our previous findings on
the isomerization of trans-oxiranyl ethers14 where a
remarkable anti-selectivity was found. When the (Z)-
isomer derived from serine (Z-10) was submitted to base-
promoted isomerization, we found a lower selectivity with
a 30:70 (syn:anti) mixture of oxetane 13 being isolated.
We postulate this to be due to the steric interaction in
the transition state geometry required for the 4-exo ring
closure.
(17) Ng, J . S.; Przybyla, C. A.; Liu, C.; Yen, J . C.; Muellner, F. W.;
Weyker, C. L. Tetrahedron 1995, 51, 6397.
(18) Beaulieu, P. L.; Wernic, D.; Duceppe, J . S.; Guindon, Y.
Tetrahedron Lett. 1995, 36, 3317.
(19) Moriwake, T.; Hamano, S.; Miki, D.; Saito, S.; Torii, S. Chem.
Lett. 1986, 815.
(20) Sakai, N.; Ohfune, Y. J . Am. Chem. Soc. 1992, 114, 998.
(21) Feherentz, J . A.; Castro, B. Synthesis 1987, 676.
(22) Saari, W. S.; Fisher, T. E. Synthesis 1990, 453.
(23) McKillop, A.; Taylor, R. J . K.; Watson, R. J .; Lewis, N. Synthesis
1994, 31.
(12) Mordini, A.; Pecchi, S.; Capozzi, G.; Capperucci, A.;
Degl’Innocenti, A.; Reginato, G.; Ricci, A. J . Org. Chem. 1994, 59, 4784.
(13) Mordini, A.; Valacchi, M.; Pecchi, S.; Degl’Innocenti, A.; Regi-
nato, G. Tetrahedron Lett. 1996, 37, 5209.
(14) Mordini, A.; Bindi, S.; Pecchi, S.; Degl’Innocenti, A.; Reginato,
G.; Serci, A. J . Org. Chem. 1996, 61, 4374-4378.
(15) Margot, C.; Schlosser, M. Tetrahedron Lett. 1985, 26, 1035.
(16) Green, B. E.; Chen, X.; Norbeck, D. W.; Kempf, D. Synlett 1995,
613.
(24) Reetz, M. T.; Lautebach, E. H. Tetrahedron Lett. 1991, 32, 4477.
(25) Still, W. C.; Gennari, C. Tetrahedron Lett. 1983, 24, 4405.
(26) Asensio, G.; Mello, R.; Boix-Bernardini, C.; Gonza´lez-Nu´n˜ez,
M. E.; Castellano, G. J . Org. Chem. 1995, 60, 3692.
(27) Kocovsky, P.; Stary, I. J . Org. Chem. 1990, 55, 3236.
S0022-3263(97)00860-8 CCC: $14.00 © 1997 American Chemical Society

8558 J . Org. Chem., Vol. 62, No. 24, 1997
Notes
The anti-selectivity associated with the (E)-oxiranes is
due to the steric repulsions between the R and Y groups.
On the other hand, (Z)-oxiranes do not experience a
similar crowding. In fact, the R group being far from
substituent Y results in a mixture of syn- and anti-
oxetanes.
the regioisomeric enethers. LDA without potassium tert-
butoxide does not react at all. This simple and highly
selective access to amino hydroxy oxetanes seems prom-
ising in view of a subsequent application to the synthesis
of oxetane-containing molecules.
Exp er im en ta l Section
Gen er a l. Air and moisture sensitive compounds were stored
in Schlenk tubes. They were protected by and handled under
an atmosphere of 99.99% pure nitrogen. Ethereal extracts were
dried with sodium sulfate. The temperature of dry ice-ethanol
baths is consistently indicated as -78 °C, that of ice bath as 0
°C, and “room temperature” as 25 °C. If no reduced pressure is
specified, boiling ranges were determined under ordinary at-
mospheric conditions (720 ( 35 mmHg). Purifications by flash
column chromatography29 were performed using glass columns
(10-50 mm wide); silica gel 230-400 mesh was chosen as the
stationary phase (15 cm high), with an elution rate of 5 cm/min.
Nuclear magnetic resonance spectra of hydrogen nuclei were
recorded at 200 or 500 MHz. Chemical shifts were determined
relative to the residual solvent peak (CHCl3: 7.26 ppm). Nuclear
magnetic resonance spectra of carbon-13 nuclei were recorded
at 50.3 or 75.5 MHz. Chemical shifts were determined relative
to the residual solvent peak (CHCl3: 77.0 ppm).
Ma ter ia ls. Starting materials were commercially available
unless otherwise stated. All commercial reagents were used
without further purification except diisopropylamine, which was
distilled over calcium hydride. Anhydrous tetrahydrofuran was
distilled from sodium diphenylketyl. Petroleum ether, unless
specified, was the 40-70 °C boiling fraction.
Compounds E-5, E-6, and Z-7 have been prepared according
This was confirmed by the isomerization of the (E)-
benzyl oxiranyl ether 17 derived from serine which was
prepared using a different approach. The amino alde-
hyde 14 was treated with the lithium enolate of ethyl
bromoacetate,28 and the (E)-epoxy ester 15 thus obtained
was selectively reduced with sodium borohydride in
tetrahydrofuran/water and benzylated.
When 17 was submitted to treatment with LIDAKOR,
the expected oxetane 18 was again obtained as pure anti-
isomer.
to our already reported procedures.13
P r ep a r a t ion of (2′S,3′S,4S)-(-)-(E)-2,2-Dim et h yl-3-N-
(t er t -b u t oxyca r b on yl)-4-[3′-(1′-h yd r oxy-2′,3′-e p oxyp r o-
p yl)]oxa zolid in e (16). (1′R,2′S,4S)-(E)-2,2-Dim eth yl-3-N-
(t er t -b u t oxyca r b on yl)-4-[3′-(1′-ca r b e t h oxy-1′,2′-e p oxy-
eth yl)]oxa zolid in e (15). A solution of butyllithium in hexane
(4.8 mmol, 3.4 mL of a 1.6 M solution) was evaporated under
reduced pressure and the residue dissolved at -78 °C in
precooled THF (7 mL). Then diisopropylamine (4.8 mmol, 0.48
g) was added and the mixture stirred for 30 min before being
slowly added to a solution of (S)-(-)-2,2-dimethyl-3-N-(tert-
butoxycarbonyl)-4-formyloxazolidine 14 (Garner’s aldehyde,30 3.0
mmol, 0.68 g) and ethyl bromoacetate (4.8 mmol, 0.80 g) in THF
(7 mL) at -78 °C. The mixture was then slowly warmed to 25
°C and, after 3 h, treated with H2O (20 mL) and extracted with
Et2O (3 × 20 mL). The organic layer was washed with saturated
NaCl and dried. After evaporation of the solvent, the residue
(1.28 g) was purified by flash column chromatography (petroleum
ether:ethyl acetate 6:1 + 4% triethylamine) affording pure 15
(0.58 g, 61%). 1H NMR (CDCl3, 200 MHz): 4.34-3.94 (5H, m);
3.60 (1H, d, J ) 4.0); 3.20 (1H, dd, J ) 4.0, 8.8); 1.65 (3H, s);
1.58 (3H, s); 1.44 (9H, s); 1.33 (3H, t, J ) 7.4). 13C NMR (CDCl3,
50.3 MHz): 167.89; 152.03; 93.85; 80.84; 80.40; 66.19; 61.55;
58.15; 53.65; 28.32; 27.72; 24.21; 14.02. MS (m/z %): 300 (1,
M+ - CH3); 242 (2); 200 (47); 86 (12); 84 (38); 57 (100).
(2′S,3′S,4S)-(-)-(E)-2,2-Dim eth yl-3-N-(ter t-bu toxyca r bo-
n yl)-4-[3′-(1′-h yd r oxy-2′,3′-ep oxyp r op yl)]oxa zolid in e (16).
Epoxy ester 15 (1.84 mmol, 0.58 g) was dissolved in THF (10
mL) and H2O (10 mL) and cooled to 0 °C. NaBH4 (2.76 mmol,
0.11 g) was then added and the mixture stirred 12 h at 25 °C
before it was treated with H2O (20 mL) and extracted with Et2O
(2 × 20 mL) and dried. After evaporation of the solvent under
vacuum, the residue (0.42 g) was purified by flash column
chromatography (petroleum ether:ethyl acetate 4:1 + 4% tri-
ethylamine), affording 0.28 g (54%) of pure 16. [R]22 ) -22.3°
D
(c ) 0.7, CHCl3). 1H NMR (CDCl3, 200 MHz): 4.56 (1H, dd, J
) 11.2, 3.0); 4.16-3.94 (3H, m); 3.79 (1H, ddd, J ) 9.6, 5.4, 1.7);
3.50 (1H, ddd, J ) 12.0, 9.6, 2.7); 3.29 (1H, dt, J ) 3.9, 10.0);
3.03 (1H, dd, J ) 9.6, 3.9); 1.61 (3H, s); 1.51 (3H, s); 1.49 (9H,
s). 13C NMR (CDCl3, 50.3 MHz): 153.00; 94.38; 81.87; 66.28;
59.47; 56.89; 56.38; 53.98; 28.33; 27.49; 24.27. MS (m/z %): 258
(2, M+ - CH3); 202 (8); 186 (6); 158 (28); 116 (17); 100 (14); 98
It is worth noting that the choice of the base is of great
importance for the stereo- and regiochemical outcome of
the reaction. When we submitted a benzyloxy oxirane
to treatment with a series of lithium amides and acti-
vated organolithium reagents, we found very different
results. Only LIDAKOR gives the oxetane, while all the
other lithium derivatives lead to mixtures of oxetanes and
(29) Still, W. C.; Mitra, A. J . Org. Chem. 1978, 43, 2923.
(30) Garner, P.; Park, J . M. Org. Synth. 1991, 70, 18.
(28) Newman, M. S.; Magerlein, B. J . Org. React. 1949, 4, 413.

Notes
J . Org. Chem., Vol. 62, No. 24, 1997 8559
(12); 84 (14); 69 (13); 59 (29); 57 (100); 56 (25). Anal. Calcd for
cording to the general procedure, 0.31 g (46%) of the oxetane
was obtained upon purification (petroleum ether:ethyl acetate
1:1); mp 105-107 °C. [R]21D ) +13.6° (c ) 1.1, CHCl3). 1H NMR
(CDCl3, 500 MHz): 7.45-7.36 (5H, m); 5.54 (1H, d, J ) 6.5);
4.80 (1H, app t, J ) 7.0); 4.73 (1H, d, J ) 9.0); 4.65 (1H, app t,
J ) 8.5); 4.07 (1H, bs); 3.22-3.17 (1H, m); 3.03 (1H, dd, J ) 7.0,
8.0); 1.94-1.90 (1H, m); 1.38 (9H, s); 0.97 (3H, d, J ) 6.5); 0.92
(3H, d, J ) 6.5). 13C NMR (CDCl3, 50.3 MHz): 156.35; 142.10;
128.51; 128.03; 125.67; 84.71; 79.59; 70.49; 69.13; 59.75; 48.38;
29.43; 28.27; 19.09; 19.28. MS (m/z %): 292 (0.2, M+ - C3H7);
236 (2); 192 (7); 172 (12); 116 (88); 77 (14); 72 (82); 57 (100).
Anal. Calcd for C19H29NO4: C, 68.06; H, 8.72; N, 4.18. Found:
C, 68.28; H, 8.69; N, 4.21.
C
13H23NO5: C, 57.13; H, 8.49; N, 5.13. Found: C, 57.23; H, 8.52;
N, 5.11.
P r otection of th e Hyd r oxyl Gr ou p a s Ben zyl Eth er .
Gen er a l P r oced u r e. NaH (4.0 mmol, 60% in oil) was washed
with pentane (3 × 5 mL) and vacuum-dried. Freshly distilled
THF (2 mL) was added and the resulting suspension cooled to
0 °C before the oxiranyl alcohol (2.0 mmol in 8 mL THF) was
added and the mixture stirred for 1 h at 25 °C. Benzyl bromide
(2.4 mmol) was then added at 0 °C, and the reaction mixture
was stirred for 12-15 h at 25 °C. The reaction was then
quenched with ice/H2O (8 mL) and extracted with ether (3 × 8
mL), and the organic layer was washed with saturated NaCl
and dried. After evaporation of the solvent, the residue was
purified by flash column chromatography.
(1′S ,2′S ,2S ,3R )-2-P h e n y l-3-[[1′-(4′-m e t h y l-2′-N -(t er t -
bu toxycar bon yl)am in o]-1′-h ydr oxypen tyl]oxetan e (12). Ac-
cording to the general procedure, 0.53 g (76%) of the oxetane
was obtained upon purification (petroleum ether:ethyl acetate
(2R,3R,4S)-(E)-4-[N-(ter t-Bu toxycar bon yl)am in o]-5-m eth -
yl-1-(ben zyloxy)-2,3-ep oxyh exa n e (8). According to the gen-
eral procedure, 0.35 g (52%) of the benzyl ether was obtained
upon purification (petroleum ether:ethyl acetate 3:1). 1H NMR
(CDCl3, 200 MHz): 7.40-7.23 (5H, m); 4.56 (2H, m, AB system);
4.50 (1H, m); 3.80 (1H, dd, J ) 11.8, 2.2 Hz); 3.68 (1H, dd, J )
11.8, 3.0 Hz); 3.48-3.39 (1H, m); 3.03-2.99 (2H, m); 1.98-1.81
(1H, m); 1.43 (9H, s); 1.00 (3H, d, J ) 4.6 Hz); 0.97 (3H, d, J )
4.6 Hz). 13C NMR (CDCl3, 50.3 MHz): 155.72; 137.00; 128.38;
127.87; 127.51; 79.18; 73.19; 69.55; 58.63; 55.20; 53.36; 31.19;
28.20; 19.02; 18.22. MS (m/z %): 292 (2, M+ - C3H7); 266 (3);
236 (5); 192 (7); 91 (100); 57 (100).
(2R,3R,4S)-(E)-4-[N-(ter t-Bu toxycar bon yl)am in o]-6-m eth -
yl-1-(ben zyloxy)-2,3-ep oxyh ep ta n e (9). According to the
general procedure, 0.43 g (62%) of the benzyl ether was obtained
upon purification (petroleum ether:ethyl acetate 3:1). 1H NMR
(CDCl3, 200 MHz): 7.38-7.28 (5H, m); 4.56 (2H, m, AB system);
4.40 (1H, m); 3.98 (1H, m); 3.80 (1H, app d, J ) 12.0); 3.46 (1H,
m); 3.06 (1H, m); 2.91 (1H, m); 1.71 (1H, hept, J ) 6.6); 1.42
(9H, s); 1.4 (2H, m); 0.94 (6H, d, J ) 6.6). 13C NMR (CDCl3,
50.3 MHz): 155.32; 137.58; 128.12; 127.42; 127.39; 78.95; 72.94;
69.41; 57.09; 54.20; 46.72; 41.93; 28.07; 24.36; 22.79; 21.84. MS
(m/z %): 318 (6); 300 (5); 232 (6); 218 (10); 192 (11); 176 (14);
130 (26); 129 (42); 106 (14); 91 (100); 86 (35); 85 (50); 68 (16); 57
(100).
(2′S,3′R,4S)-(Z)-2,2-Dim eth yl-3-[N-(ter t-bu toxycar bon yl)]-
4-[3′-(1′-(ben zyloxy)-2′,3′-ep oxyp r op yl)]oxa zolid in e (Z-10).
According to the general procedure, 0.45 g (60%) of the benzyl
ether was obtained upon purification (petroleum ether:ethyl
acetate 3:1). 1H NMR (CDCl3, 200 MHz): 7.40-7.26 (5H, m);
4.46 (2H, s); 4.00-3.90 (2H, m); 3.76-3.54 (3H, m); 3.19-3.05
(2H, m); 1.62 (3H, s); 1.49 (12H, bs). 13C NMR (50.3 MHz):
152.09; 137.52; 128.75; 128.09; 127.47; 93.96; 79.98; 73.10; 67.84;
65.70; 58.31; 56.58; 51.46; 28.10; 26.70; 24.23. MS: (m/z %): 348
(2; M+ - CH3); 248 (27);186 (10); 91 (100); 57 (100).
1:1). [R]21 ) +4.2° (c ) 1.2, CHCl3). 1H NMR (CDCl3, 200
D
MHz): 7.50-7.26 (5H, m); 5.60 (1H, d, J ) 7.0); 4.83 (1H, app
t, J ) 6.6); 4.66 (1H, dd, J ) 8.4, 6.2); 4.53 (1H, d, J ) 8.8); 3.86
(1H, m); 3.51 (1H, m); 3.10 (1H, m); 1.66 (3H, m); 1.40 (9H, s);
1.38 (1H, m); 0.91 (3H, d, J ) 6.6); 0.89 (3H, d, J ) 6.6). 13C
NMR (CDCl3, 50.3 MHz): 156.60; 142.64; 129.05; 128.58; 126.21;
85.32; 80.11; 73.60; 69.40; 52.73; 48.49; 41.49; 28.78; 25.18; 23.62;
22.54. MS (m/z %): 292 (2, M+ - C4H9); 236 (2); 186 (10); 174
(4); 133 (13); 130 (89); 117 (24); 107 (22); 105 (22); 91 (17); 86
(100); 84 (15); 77 (15); 57 (95). Anal. Calcd for C20H31NO4: C,
68.74; H, 8.94; N, 4.01. Found: C, 68.64; H, 8.79; N, 4.07.
(2R,3S,4′S,5S)- a n d (2S,3S,4′S,5S)-2-P h en yl-3-[[4′-(2′,2′-
d im e t h yl-3′-N -(t er t -b u t oxyca r b on yl)oxa zolid in yl)]h y-
d r oxym eth yl]oxeta n e (13). According to the general proce-
dure, 0.47 g (65%) of the oxetane was obtained (petroleum ether:
ethyl acetate 1:1) as a mixture of 2,3-syn/2,3-anti diastereoisomers
(30:70). An additional purification (dichloromethane: ethyl
acetate 8:1) led to pure isomers.
2,3-Syn isom er : [R]21 ) +30.7° (c ) 0.7, CHCl3). 1H NMR
D
(CDCl3, 200 MHz): 7.54-7.28 (5H, m); 5.95 (1H, d, J ) 8.0);
4.88 (1H, dd, J ) 8.0, 6.5); 4.48 (1H, app t, J ) 6.4); 4.12-4.01
(1H, m); 3.99-3.78 (3H, m); 3.54-3.36 (1H, m); 1.53 (3H, s); 1.49
(9H, s); 1.42 (3H, s). MS (m/z %): 348 (0.1, M+ - CH3); 250 (7);
200 (23); 144 (53); 133 (11); 117 (18); 107 (42); 105 (44); 100 (98);
91 (22); 84 (15); 83 (25); 79 (18); 77 (31); 57 (100); 55 (24). Anal.
Calcd for C20H29NO5: C, 66.09; H, 8.04; N, 3.85. Found: C,
66.04; H, 8.07; N, 3.81.
(2′S,3′S,4S)-(E)-2,2-Dim eth yl-3-N-(ter t-bu toxyca r bon yl)-
4-[3′-(1′-(ben zyloxy)-2′,3′-ep oxyp r op yl)]oxa zolid in e (17). Ac-
cording to the general procedure, 0.51 g (70%) of the benzyl ether
was obtained upon purification (petroleum ether:ethyl acetate
7:1 + 4% triethyl amine). 1H NMR (CDCl3, 200 MHz): 7.39-
7.24 (5H, m); 4.70-4.53 (2H, m); 4.23 (1H, d, J ) 11.6); 4.12
(1H, dd, J ) 9.2, 2.2); 4.00-3.93 (1H, m); 3.70-3.63 (1H, m);
3.57-3.47 (1H, m); 3.36-3.32 (1H, m); 3.05 (1H, dd, J ) 8.8,
4.4); 1.59 (3H, s); 1.47 (12H, s). 13C NMR (CDCl3, 50.3 MHz):
152.23; 138.20; 128.32; 127.72; 127.55; 94.07; 80.51; 73.16; 69.30;
66.19; 57.77; 56.35; 55.07; 28.38; 27.65; 24.50. MS (m/z %): 308
(16); 250 (12); 248 (19); 186 (18); 142 (15); 128 (21); 112 (11);
107 (17); 105 (12); 100 (43); 98 (21); 91 (100); 89 (14); 85 (12); 84
(26); 79 (13); 77 (9); 65 (30); 57 (98); 56 (24); 55 (11).
LIDAKOR-In du ced Isom er ization of th e Oxir an yl Eth er s.
Gen er a l P r oced u r e. A solution of butyllithium in hexane (2.0
mmol) was evaporated under reduced pressure and the residue
dissolved at -78 °C in precooled THF (2.0 mL). Then diisopro-
pylamine (2.0 mmol) and potassium tert-butoxide (2.0 mmol) was
added and the mixture stirred for 30 min. After the addition of
the substrate (1.0 mmol) the reaction mixture was kept for 15 h
at -50 °C before it was treated with H2O (2.0 mL) and allowed
to reach 25 °C. The aqueous phase was extracted with Et2O (3
× 5 mL), and the organic layer was washed with saturated NaCl
and dried over Na2SO4: after evaporation of the solvent, the
residue was purified by flash column chromatography.
2,3-An ti isom er : [R]21D ) -32.6° (c ) 1.3, CHCl3). 1H NMR
(CDCl3, 200 MHz): 7.51-7.28 (5H, m); 5.81 (1H, d, J ) 6.2);
4.72-4.67 (2H, m); 4.48-4.38 (1H, m); 4.17-4.07 (1H, m); 3.94-
3.85 (1H, m); 3.76-3.67 (1H, m); 3.60-3.49 (1H, m); 3.04-2.90
(1H, m); 1.56 (3H, s); 1.51 (9H, s); 1.46 (3H, s). 13C NMR (CDCl3,
50.3 MHz): 154.67; 142.82; 128.48; 127.75; 125.50; 94.20; 84.17;
81.68; 74.83; 69.78; 64.33; 60.93; 47.41; 29.67; 28.34. MS (m/z
%): 200 (3, M+ - C10H11O2); 133 (4); 106 (5); 105 (35); 100 (7);
77 (17); 57 (100); 56 (44); 55 (13); 43 (24); 42 (13); 41 (54). Anal.
Calcd for C20H29NO5: C, 66.09; H, 8.04; N, 3.85. Found: C,
66.12; H, 8.09; N, 3.79.
(2S,3S,4′S,5R)-2-P h en yl-3-[[4′-(2′,2′-d im et h yl-3′-N-(ter t-
bu toxycar bon yl)oxazolidin yl)]h ydr oxym eth yl]oxetan e (18).
According to the general procedure, 0.43 g (60%) of the oxetane
was obtained upon purification (dichloromethane: ethyl acetate
8:1). [R]21 ) +17.4° (c ) 0.9, CHCl3). 1H NMR (CDCl3, 200
D
MHz): 7.51-7.27 (5H, m); 5.74 (1H, d, J ) 6.6); 4.69-4.54 (2H,
m); 4.38-4.22 (1H, m); 4.07-3.84 (3H, m); 3.58-3.44 (1H, m);
3.38-2.86 (1H, m); 1.61 (3H, s); 1.48 (9H, bs); 1.45 (3H, s). 13C
NMR (CDCl3, 50.3 MHz): 153.92; 142.56; 128.37; 127.62; 125.29;
94.34; 86.08; 83.64; 75.13; 70.05; 64.43; 61.10; 46.72; 29.69; 28.36;
26.54. MS (m/z %): 200 (6, M+ - C10H11O2); 144 (7); 133 (3);
105 (10); 100 (21); 77 (11); 57 (100); 55 (8).
(1′S,2′S,2S,3R)-2-P h en yl-3-[[1′-(3′-m et h yl-2′-[N-(ter t-b u -
toxyca r bon yl)a m in o]-1′-h yd r oxybu tyl]oxeta n e (11). Ac-
J O9708607