Convenient preparation of tert-butyl β-(protected amino)esters

Article abstract of DOI:10.1021/jo0110810

Refluxing an aldehyde 1 with benzotriazole and benzylcarbamate in the presence of a catalytic amount of p-TsOH gave the corresponding benzyloxycarbonylamino-1-(1-benzotriazolyl)alkane 2 in good yields. Compounds 2 treated with substituted tert-butyl acetates 3 using LDA as a base afford smoothly and under mild conditions the N-2-protected 3-aminoalkanoic esters 4.

Full text of DOI:10.1021/jo0110810

SCHEME 1
Con ven ien t P r ep a r a tion of ter t-Bu tyl
â-(P r otected a m in o)ester s
Alan R. Katritzky,* Kostyantyn Kirichenko,
Ahamad M. Elsayed, Yu J i, and Yunfeng Fang‡
Center for Heterocyclic Compounds, University of Florida,
Department of Chemistry, Gainesville, Florida 32611-7200
Peter J . Steel§
Department of Chemistry, University of Canterbury,
Christchurch, New Zealand
SCHEME 2
katritzky@chem.ufl.edu
Received November 16, 2001
Abstr a ct: Refluxing an aldehyde 1 with benzotriazole and
benzylcarbamate in the presence of a catalytic amount of
p-TsOH gave the corresponding benzyloxycarbonylamino-
1-(1-benzotriazolyl)alkane 2 in good yields. Compounds 2
treated with substituted tert-butyl acetates 3 using LDA as
a base afford smoothly and under mild conditions the N-2-
protected 3-aminoalkanoic esters 4.
Two popular methods for the synthesis of â-amino acids
utilize formation of the CR-Câ bond1a,b (Scheme 1): (i)
the treatment of imines with ester enolates or ketene
acetals,2a-e which is particularly convenient for making
N-substituted â-amino acids, and (ii) the treatment of
N-alkoxycarbonyl-1-methoxyamines with esters,3a,b which
can be applied to prepare N-unsubstituted â-amino acids.
In an extension of our previous work on the synthesis
of â- amino acids,4a,b we have now shown that reactions
of benzyloxycarbonylamino-1-(1-benzotriazolyl)alkanes
2a -e with substituted tert-butyl acetates 3x-z using
LDA as a base afford smoothly and under mild conditions
the N-protected 3-aminoalkanoic esters 4a x-cz, 4d x-
d y, and 4ey (Scheme 2, Table 1).
TABLE 1. P r ep a r a tion of â-Am in o Acid Der iva tives 4
4
R1
R2
yield (%)
a x
a y
a z
bx
by
bz
cx
cy
cz
d x
d y
ey
benzyl
benzyl
benzyl
4-MeC6H4
4-MeC6H4
4-MeC6H4
Ph
Ph
Ph
H
H
H
63
53
t-BuOCO
Ph
H
t-BuOCO
Ph
H
t-BuOCO
Ph
H
45 (72:28)a
43
53
The starting benzotriazole derivatives 2a -e were
easily prepared according to our previously published
method.4a The reactions of intermediates 2a -e with tert-
butyl acetates 3x-z are discussed in two subsections
according to the reaction results.
67 (71:29)a
53
65
73 (82:18)a
35
59
70
(i) Rea ction s of In ter m ed ia tes 2a -e w ith ter t-
Bu tyl Aceta tes 3x,y. Treatment of a mixture of a benzyl
t-BuOCO
t-BuOCO
isopropyl
a
These yields are the total yield of anti and syn adducts; the
‡ Present address: Triad Therapeutics, 5820 Nancy Ridge Drive,
#200, San Diego, CA 92121.
ratios are anti/syn.
§ E-mail: p.steel@chem.canterbury.ac.nz.
(1) (a) J uaristi, E.; Quintana, D.; Escalante, J . Aldrichim. Acta 1994,
27, 3. (b) Cardillo, G.; Tomasini, C. Chem. Soc. Rev. 1996, 117.
(2) (a) Iimori, T.; Ishida, Y.; Shibasaki, M. Tetrahedron Lett. 1986,
27, 2153. (b) Annunziata, R.; Cinquini, M.; Cozzi, F.; Molteni, V.;
Schupp, O. J . Org. Chem. 1996, 61, 8293. (c) Cozzi, P. G.; Simone, B.
D.; Umani-Ronchi, A. Tetrahedron Lett. 1996, 37, 1691. (d) Shankar,
B. B.; Kirkup, M. P.; McCombie, S. W.; Clader, J . W.; Ganguly, A. K.
Tetrahedron Lett. 1996, 37, 4095. (e) Baldoli, C.; Buttero, P. D.;
Licandro, E.; Papagni, A. Tetrahedron 1996, 52, 4849.
(3) (a) Shono, T.; Kise, N.; Sanda, F.; Ohi, S.; Yoshioka, K.
Tetrahedron Lett. 1989, 30, 1253. (b) Kise, N.; Ueda, N. J . Org. Chem.
1999, 64, 7511.
N-[1-(1-benzotriazol-1-yl)arylalkyl]carbamate 2a -d and
tert-butyl acetate 3x in THF with 2.5 equiv of LDA
ranging from -78 to 0 °C gave â-amino acid derivatives
4a x, 4bx, 4cx, and 4d x. Analogously, treatment of
carbamate 2a -e and tert-butyl acetate 3y gave 4a y, 4by,
4cy, 4d y, and 4ey. For each of these nine products, the
1H and 13C NMR spectra showed only a single set of
signals for the appropriate protons and carbons because
there is only one chiral center in each of these com-
pounds.
(4) (a) Katritzky, A. R.; Yannakopoulou, K. Synthesis 1989, 747. (b)
Katritzky, A. R.; Pernak, J .; Fan, W.-Q.; Saczewski, F. J . Org. Chem.
1991, 56, 4439.
10.1021/jo0110810 CCC: $22.00 © 2002 American Chemical Society
Published on Web 06/17/2002
J . Org. Chem. 2002, 67, 4957-4959
4957

109.8, 118.3, 119.4, 124.0, 127.1, 127.5, 127.8, 128.1, 128.3, 128.5,
129.0, 132.9, 134.8, 135.5, 145.3, 155.5.
(ii) Rea ction s of In ter m ed ia tes 2a -c w ith ter t-
Bu tyl Aceta te 3z. The intermediates 2a -c reacted with
tert-butyl acetate 3z under the same conditions as used
above to give 4a z, 4bz, and 4cz, each as a mixture of
two diastereoisomers. According to the integrated inten-
sities of the two singlets near 1.10-1.40 ppm (assigned
to the tert-butyl group) and the two doublets near 3.60-
4.00 ppm (assigned to the proton R to the carbonyl group),
the ratios are approximately 72:28, 71:29, and 82:18,
respectively. Two sets of signals were also found in the
13C NMR spectra. According to Kise’s mechanistic study,3b
the anti adducts were expected to be obtained preferen-
tially. We successfully separated mixtures of diastereo-
isomers to obtain these six pure compounds, including
Ben zyl N-[1-ben zotr ia zol-1-yl(4-m eth ylp h en yl)m eth yl]-
ca r ba m a te (2b): white plates (diethyl ether); mp 129-131 °C
(57%); 1H NMR δ 2.29 (s, 3H), 5.02, 5.14 (AB, J ) 12.0 Hz, 2H),
6.69 (d, J ) 12.0 Hz, 1H), 7.08-7.18 (m, 4H), 7.25-7.42 (m, J )
7H), 7.55 (d, J ) 7.7 Hz, 1H); 7.64 (d, J ) 9.4 Hz, 1H), 8.05 (d,
J ) 8.4 Hz, 1H); 13C NMR δ 21.0, 67.3, 67.6, 109.8, 119.9, 124.1,
126.1, 126.6, 127.7, 128.1, 128.3, 128.5, 129.6, 132.4, 135.4, 139.2,
145.9, 155.3. Anal. Calcd for C22H20N4O2: C, 70.95; H, 5.41; N,
15.04. Found: C, 70.03; H, 4.99; N, 14.99.
Ben zyl N-[1-ben zotr ia zol-1-yl-ben zyl]ca r ba m a te (2c):
white needles (hexanes); mp 136-137 °C (91%) (mp 115-117
°C4a); 1H NMR δ 5.04, 5.13 (AB, J ) 12.0 Hz, 2H), 7.18-7.45
(m, 12H), 7.75 (d, J ) 8.1 Hz, 1H), 7.86 (d, J ) 9.0 Hz, 1H), 8.00
(d, J ) 8.1 Hz, 1H), 9.30 (d, J ) 9.3 Hz, 1H); 13C NMR δ 65.7,
67.3, 109.9, 118.3, 122.9, 125.4, 126.2, 126.9, 127.2, 127.5, 127.7,
130.7, 134.7, 134.8, 144.7, 154.9. Anal. Calcd for C21H18N4O2:
C, 70.38; H, 5.06; N, 15.63. Found: C, 70.44; H, 5.30; N, 15.71.
Ben zyl N-(1-b en zot r ia zol-1-ylm et h yl)ca r b a m a t e (2d ):
white crystals (toluene); mp 122-123 °C (69%) (mp 124 °C5);
1H NMR δ 5.12 (s, 2H), 6.02 (d, J ) 7.0 Hz, 2H), 6.43 (t, J ) 6.8
Hz, 1H), 7.26-7.40 (m, 6H), 7.42-7.53 (t, J ) 7.5 Hz, 1H), 7.89
(d, J ) 8.3 Hz, 1H), 8.00 (d, J ) 8.4 Hz, 1H); 13C NMR δ 53.3,
67.5, 110.7, 119.6, 124.2, 127.9, 128.1, 128.3, 128.5, 132.3, 135.5,
146.0, 156.1.
Ben zyl N-[1-(1-b en zot r ia zol-1-yl)-2-m et h ylp r op yl]ca r -
ba m a te (2e): white crystals (benzene); mp 171-172 °C (83%)
(mp 170-172 °C5); 1H NMR δ 0.75, (d, J ) 6.4 Hz, 3H), 1.19 (d,
J ) 6.6 Hz, 3H), 2.65-2.90 (m, 1H), 4.96 (d, J ) 12.2 Hz, 1H),
5.10 (d, J ) 12.2 Hz, 1H), 6.13 (t, J ) 9.6 Hz, 1H), 6.49 (d, J )
9.7 Hz, NH), 7.20-7.43 (m, 6H), 7.43-7.55 (m, 1H), 7.77 (d, J
) 8.2 Hz, 1H), 8.05 (d, J ) 9.5 Hz, 1H); 13C NMR δ 18.6, 19.0,
33.0, 67.2, 70.4, 109.8, 119.7, 124.1, 127.7, 127.9, 128.2, 128.4,
133.2, 135.6, 145.3, 155.8.
Gen er a l P r oced u r e for th e P r ep a r a tion of â-Am in o Acid
Der iva tives 4. A mixture of benzyloxycarbonylamino-1-(1-
benzotriazolyl)alkanes 2 (1 mmol) and tert-butyl esters 3 (1.1
mmol) in THF (5 mL) was added to a solution of LDA (2.5 mmol)
in THF (10 mL) at -78 °C and the mixture was stirred for 12 h.
The reaction temperature was raised to 0 °C and kept at this
temperature for several hours until compound 2 was consumed.
The mixture was quenched with water and extracted with ethyl
acetate. The organic layer was washed with brine and dried over
Na2SO4. The solvent was removed in vacuo, and the residue was
purified by column chromatography to afford the pure samples
of 4.
1
good crystals of one of the 4cz isomers, whose H NMR
spectrum shows the J value assigned to the proton R to
the carbonyl group to be 5.4 Hz. X-ray analysis of this
isomer confirmed that it is the anti stereoisomer, 4cz-
a n ti. We can deduce that the other isomer of 4cz (the J
value is 10.3 Hz) is the syn adduct, 4cz-syn .
Furthermore, from comparisons of the 1H NMR spectra
of the three pairs of diastereoisomers, we can deduce the
structure of 4a z and 4bz. Compound 4a z-a n ti clearly
has a J value 6.2 Hz and 4bz-a n ti of 5.9 Hz. These anti
adducts are the major products. The syn adducts are the
minor products: the J value of 4a z-syn is 8.7 Hz, and
the J value of 4bz-syn is 10.4 Hz. Using similar reaction
conditions, but in the presence of Ti(OPr-i)4, for the
preparation of 4cz, the yield is 73%, and the ratio of anti:
syn decreased to 66:34 from 82:18 without Ti(OPr-i)4. Our
ratios of anti:syn are a little higher than Kise’s;3b the
higher stereoselectivity may be due to the greater bulk
of tert-butyl acetates 3z.
The present work is conceptually similar to the in-
novative and successful method of Kise3a,b but avoids the
anodic oxidation. Our starting materials are stable,
cheap, and easy to prepare, and the yields are useful.
Moreover, we prepare â-amino acids with differential
protection at the amine and carboxyl group. The reactions
give anti adducts preferentially.
ter t-Bu t yl 3-[(b en zyloxy)ca r b on yl]a m in o-4-p h en ylb u -
ta n oa te (4a x): white needles (hexanes/ethyl acetate); mp 78-
79 °C (oil, no mp6) (63%); 1H NMR δ 1.44 (s, 9H), 2.29-2.46 (m,
2H), 2.77-2.96 (m, 2H), 4.15-4.24 (m, 1H), 5.06 (s, 2H), 5.39
(d, J ) 8.5 Hz, 1H), 7.16-7.36 (m, 10H); 13C NMR δ 28.0, 38.6,
40.2, 49.5, 66.4, 81.1, 126.5, 128.0, 128.4, 128.5, 129.3, 136.5,
137.6, 155.5, 170.8. Anal. Calcd for C22H27NO4: C, 71.52; H, 7.37;
N, 3.79. Found: C, 71.54; H, 7.69; N, 3.75.
Exp er im en ta l Section
Gen er a l Meth od s. Melting points were determined on a hot-
stage apparatus and are uncorrected. NMR spectra were re-
corded in CDCl3 or DMSO-d6 with TMS as the internal standard
for 1H (300 MHz) or a solvent as the internal standard for 13C
(75 MHz). Microanalyses were performed on a Carlo Erba-1106
elemental analyzer. Benzene and toluene were dried over
molecular sieves. Column chromatography was conducted with
silica gel 200-425 mesh.
Di-ter t-bu tyl 2-(1-[(ben zyloxy)ca r bon yl]a m in o-2-p h en yl-
eth yl)m a lon a te (4a y): white needles (hexanes/ethyl acetate);
1
mp 64-66 °C (53%); H NMR δ 1.46 (s, 9H), 1.58(s, 9H), 2.81-
Gen er a l P r oced u r e for th e P r ep a r a tion of Ben zyloxy-
ca r bon yla m in o-1-(1-ben zotr ia zolyl)a lk a n es 2. A mixture of
benzotriazole (5.95 g, 50 mmol), benzyl carbamate (7.55 g, 50
mmol), a catalytic amount of p-TsOH (0.95 g, 5 mmol), and the
corresponding aldehyde 1 (50 mmol) in toluene (70 mL) was
refluxed for 6-10 h. Water formed during the reaction was
removed azeotropically with a Dean-Stark apparatus. Toluene
was then removed in vacuo. The residue was poured into diethyl
ether/hexanes (1:2, v/v) and filtered to get the precipitate, which
was collected and recrystallized from the appropriate solvent.
Ben zyl N-[1-(1-ben zotr ia zol-1-yl)-2-p h en yleth yl]ca r ba m -
a te (2a ): white needles (hexanes); mp 118-120 °C (57%) (mp
117-120 °C4a); 1H NMR δ 3.60-3.77 (m, 2H), 4.91, 5.07 (AB, J
) 12.3 Hz, 2H), 6.64-6.72 (m, 1H), 6.86 (d, J ) 9.6 Hz, 1H),
7.06-7.28 (m, 11H), 7.35 (t, J ) 8.1 Hz, 1H), 7.59 (d, J ) 8.1
Hz, 1H), 7.96 (d, J ) 8.4 Hz, 1H); 13C NMR δ 40.6, 66.0, 67.2,
2.89 (m, 1H), 3.06-3.14 (m, 1H), 3.37 (d, J ) 4.2 Hz, 1H), 4.50-
4.60 (m, 1H), 5.13 (s, 2H), 6.09 (d, J ) 9.6 Hz, 1H), 7.20-7.40
(m, 10H); 13C NMR δ 27.7, 27.9, 39.9, 52.4, 54.7, 66.4, 82.2, 82.3,
126.6, 127.8, 127.9, 128.3, 128.5, 129.2, 136.5, 137.3, 155.2, 167.0,
167.9. Anal. Calcd for C27H35NO6: C, 69.06; H, 7.51; N, 2.98.
Found: C, 69.11; H, 7.56; N, 2.98.
ter t-Bu tyl 3-[(ben zyloxy)ca r bon yl]a m in o-2,4-d ip h en yl-
bu ta n oa te (4a z): two stereoisomers, 4a z-a n ti/4a z-syn ) 72:
28.
ter t-Bu tyl (2R*,3R*)-3-[(ben zyloxy)ca r bon yl]a m in o-2,4-
d ip h en ylb u t a n oa t e (4a z-a n ti): white powder (methylene
(5) Katritzky, A. R.; Urogdi, L.; Mayence, A. J . Org. Chem. 1990,
55, 2206.
(6) Evans, D. A.; Wu, L. D.; Wiener, J . J . M.; J ohnson, J . S.; Ripin,
D. H. B.; Tedrow, J . S. J . Org. Chem. 1999, 64, 6411.
4958 J . Org. Chem., Vol. 67, No. 14, 2002

chloride); mp 102-103 °C (32%); 1H NMR δ 1.41 (s, 9H), 2.70-
2.90 (m, 2H), 3.65 (d, J ) 6.2 Hz, 1H), 4.20-4.40 (m, 1H), 4.98
(s, 2H), 5.67 (d, J ) 9.5 Hz, 1H), 7.05-7.50 (m, 15H); 13C NMR
δ 27.9, 39.4, 54.2, 55.6, 66.3, 81.6, 126.5, 127.4, 127.9, 128.3,
128.4, 128.5, 128.6, 129.3, 136.4, 136.7, 137.7, 155.6, 171.8. Anal.
Calcd for C28H31NO4: C, 75.48; H, 7.01; N, 3.14. Found: C, 75.39;
H, 7.08; N, 3.22.
ter t-Bu tyl (2R*,3S*)-3-[(ben zyloxy)ca r bon yl]a m in o-2,4-
d ip h en ylbu ta n oa te (4a z-syn ): contains about 50% 4a z-a n ti;
white powder (methylene chloride) (13%); 1H NMR δ 1.44 (s, 9H),
2.90-3.00 (m, 2H), 3.76 (d, J ) 8.7 Hz, 1H), 4.40-4.53 (m, 1H),
4.90 (s, 2H), 5.67 (d, J ) 9.5 Hz, 1H), 7.04-7.30 (m, 15H); 13C
NMR δ 27.9, 39.3, 54.5, 56.1, 66.2, 81.4, 126.5, 127.4, 127.7,
127.9, 128.4, 128.5, 128.7, 129.6, 136.1, 136.7, 137.6, 155.4, 171.3.
Anal. Calcd for C28H31NO4: C, 75.48; H, 7.01; N, 3.14. Found:
C, 75.39; H, 7.08; N, 3.22.
136.3, 140.8, 155.5, 170.0. Anal. Calcd for C22H27NO4: C, 71.52;
H, 7.37; N, 3.79. Found: C, 70.97; H 7.10; N 3.94.
Di-ter t-bu tyl 2-[[(ben zyloxy)ca r bon yla m in o)ben zyl]m a l-
on a te (4cy): white needles (hexanes/ethyl acetate); mp 167-
1
169 °C (87%); H NMR δ 1.30 (s, 9H), 1.40 (s, 9H), 3.75 (d, J )
4.2 Hz, 1H), 5.04, 5.13 (AB, J ) 12.3 Hz, 2H), 5.51 (brs, 1H),
6.61 (d, J ) 9.3 Hz, 1H), 7.22-7.36 (m, 10H); 13C NMR δ 27.5,
27.6, 53.8, 58.1, 66.6, 82.2, 82.5, 126.2, 127.3, 127.8, 128.0, 128.2,
136.3, 139.3, 155.5, 166.1, 167.3. Anal. Calcd for C27H35NO6: C,
69.06; H, 7.51; N, 2.98. Found: C, 68.54; H, 7.32; N, 3.08.
ter t-Bu tyl 3-[(ben zyloxy)ca r bon yl]a m in o-2,3-d ip h en yl-
p r op a n oa te (4cz): two stereoisomers, 4cz-a n ti/4cz-syn ) 82:
18.
ter t-Bu tyl (2R*,3S*)-3-[(ben zyloxy)ca r bon yl]a m in o-2,3-
d ip h en ylp r op a n oa te (4cz-a n ti): white needles (ethanol); mp
1
129-130 °C (60%); H NMR δ 1.30 (s, 9H), 3.98 (d, J ) 5.4 Hz,
ter t-Bu t yl 3-[(b en zyloxy)ca r b on yl]a m in o-3-(4-m et h yl-
p h en yl)p r op a n oa te (4bx): white needles (hexanes/ethyl ace-
1H), 4.86, 4.95 (AB, J ) 12.3 Hz, 2H), 5.18-5.24 (m, 1H), 6.40
(d, J ) 8.7 Hz, 1H), 7.20-7.35 (m, 15H); 13C NMR δ 27.7, 57.4,
57.9, 66.6, 81.9, 126.5, 127.3, 127.5, 127.9, 127.9, 128.2, 128.3,
128.4, 128.5,135.8, 136.5, 140.4, 155.7, 171.4.
1
tate); mp 79-81 °C (43%); H NMR δ 1.33 (s, 9H), 2.32(s, 3H),
2.69-2.78 (m, 1H), 5.05, 5.12 (AB, J ) 12.3 Hz, 2H), 5.68-5.76
(brs, 1H), 7.15 (dd, J ) 18.6, 7.8 Hz, 4H), 7.25-7.37 (m, 5H);
13C NMR δ 21.0, 27.9, 41.9, 51.6, 66.7, 81.2, 117.8, 126.1, 128.0,
128.4, 129.2, 136.5, 137.1, 137.9, 155.5, 170.1. Anal. Calcd for
C22H27NO4: C, 71.52; H, 7.37; N, 3.79. Found: C, 71.49; H, 7.60;
N, 3.81.
Cr ysta l d a ta for 4cz-a n ti: C27H29NO4, MW 431.51, orthor-
hombic, Pca21, a ) 10.238(6) Å, b ) 12.267(7) Å, c ) 38.013(22)
Å, V ) 4774(5) Å3, Z ) 8, T ) -105 °C, F(000) ) 1840, µ(Mo
KR) ) 0.080 mm-1, Dcalcd ) 1.201 g‚cm-3, 2θmax 45° (CCD area
detector, 99.9% completeness), wR(F2) ) 0.1178 (all 6224 data),
R ) 0.0505 (2867 data with I > 2σI).
ter t-Bu tyl (2R*,3R*)-3-[(ben zyloxy)ca r bon yl]a m in o-2,3-
d ip h en ylp r op a n oa te (4cz-syn ): white needles (ethanol); mp
180-181 °C (13%); 1H NMR δ 1.16 (s, 9H), 3.86 (d, J ) 10.3 Hz,
1H), 4.82-5.00 (m, 3H), 5.26-5.40 (m, 1H), 7.07-7.16 (m, 2H),
7.23-7.44 (m,13H); 13C NMR δ 27.6, 57.3, 58.9, 66.6, 81.4, 127.4,
127.8, 127.9, 127.9, 128.4, 128.4, 128.7, 128.7,135.5, 136.3, 140.5,
155.3, 170.0. Anal. Calcd for C27H29NO4: C, 75.15; H, 6.77; N,
3.25. Found: C, 75.47; H, 6.69; N 3.25.
Di-ter t-b u t yl 2-[[(b en zyloxy)ca r b on yl]a m in o(4-m et h -
ylp h en yl)m eth yl]m a lon a te (4by): white needles (hexanes/
ethyl acetate); mp 74-76 °C (78%); 1H NMR δ 1.32 (s, 9H), 1.40
(s, 9H), 2.30 (s, 3H), 3.70 (s, 1H), 5.04, 5.12 (AB, J ) 12.3 Hz,
2H), 5.43 (brs, 1H), 6.54 (d, J ) 8.4 Hz, 1H), 7.10 (d, J ) 7.5 Hz,
4H), 7.19 (d, J ) 7.2 Hz, 2H), 7.24-7.36 (m, 5H); 13C NMR δ
21.0, 27.7, 53.8, 58.3, 66.6, 82.3, 82.6, 126.2, 127.9, 128.0, 128.3,
129.0, 136.4, 137.0, 155.6, 166.3, 167.5. Anal. Calcd for C27H35
-
NO6: C, 69.06; H, 7.51; N, 2.98. Found: C, 69.41; H, 7.82; N,
3.00.
ter t-Bu tyl 3-[[(ben zyloxy)ca r bon yl]a m in o]p r op a n oa te
1
ter t-Bu tyl3-[(ben zyloxy)car bon yl]am in o-3-(4-m eth ylph en -
yl)-2-p h en ylp r op a n oa te (4bz): two stereoisomers, 4bz-a n ti/
4bz-syn ) 71:29.
(4d x): colorless oil7 (35%); H NMR δ 1.43 (s, 9H), 2.43 (t, J )
6.1 Hz, 2H), 3.35-3.48 (m, 2H), 5.08 (s, 2H), 5.42 (bs, 1H), 7.25-
7.40 (m, 5H); 13C NMR δ 27.9, 35.4, 36.6, 66.4, 80.8, 127.9, 128.3,
136.4, 156.2, 171.5.
ter t-Bu tyl (2R*,3S*)-3-[(ben zyloxy)ca r bon yl]a m in o-3-(4-
m eth ylph en yl)-2 ph en ylpr opan oate (4bz-a n ti): white needles
Di-ter t-bu tyl 2-([[(ben zyloxy)ca r bon yl]a m in o]m eth yl)-
m a lon a te (4d y): colorless oil (59%); 1H NMR δ 1.44 (s, 18H),
3.44 (t, J ) 6.2 Hz, 1H), 3.62 (t, J ) 6.2 Hz, 2H), 5.08 (s, 2H),
5.46 (bs, 1H), 7.25-7.40 (m, 5H); 13C NMR δ 27.7, 39.5, 53.4,
66.5, 81.9, 127.9, 128.3, 136.3, 156.0, 167.3. Anal. Calcd for
C20H29NO6: C, 63.31; H, 7.70; N, 3.69. Found: C, 63.68; H, 8.08;
N, 4.28.
Di-ter t-b u t yl 2-(1-[[(b en zyloxy)ca r b on yl]a m in o]-2-m e-
th ylp r op yl)m a lon a te (4ey): colorless oil (70%); 1H NMR δ
0.92-1.00 (m, 6H), 1.39 (s, 9H), 1.47 (s, 9H), 1.67-1.82 (m, 1H),
3.52 (d, J ) 4.4 Hz, 1H), 3.94-4.05 (m, 1H), 5.07 (s, 2H), 5.96
(d, J ) 10.3 Hz, 1H), 7.24-7.40 (m, 5H); 13C NMR δ 19.2, 19.7,
27.6, 27.8, 32.2, 54.7, 56.6, 66.3, 82.1, 82.3, 127.8, 128.0, 128.3,
136.6, 156.1, 167.2, 168.2. Anal. Calcd for C23H35NO6: C, 65.53;
H, 8.37; N, 3.32. Found: C, 65.31; H, 8.70; N, 3.93.
1
(chloroform); mp 60-61 °C (48%); H NMR δ 1.31 (s, 9H), 2.29
(s, 3H), 3.96 (d, J ) 5.9 Hz, 1H), 4.94, 5.04 (AB, J ) 12.2 Hz,
2H), 5.16-5.22 (m, 1H), 6.33 (d, J ) 8.7 Hz, 1H), 7.07 (d, J )
8.0 Hz, 2H), 7.14 (d, J ) 8.0 Hz, 2H), 7.20-7.38 (m, 10H); 13C
NMR δ 21.0, 27.7, 57.4, 57.7, 66.5, 81.8, 126.4, 127.4, 127.9,
127.9, 128.3, 128.4, 128.5, 129.0, 135.9, 136.6, 136.9, 137.4, 155.7,
171.5. Anal. Calcd for C28H31NO4: C, 75.48; H, 7.01; N, 3.14.
Found: C, 75.20; H, 6.58; N, 3.22.
ter t-Bu tyl (2R*,3R*)-3-[(ben zyloxy)ca r bon yl]a m in o-3-(4-
m eth ylp h en yl)-2 p h en ylp r op a n oa te (4bz-syn ): white needles
(chloroform); mp 172-173 °C (19%); 1H NMR δ 1.18 (s, 9H), 2.33
(s, 3H), 3.84 (d, J ) 10.4 Hz, 1H), 4.80-5.00 (m, 3H), 5.22-5.37
(m, 1H), 7.05-7.20 (m, 4H), 7.20-7.45 (m, 10H); 13C NMR δ 21.1,
27.6, 57.0, 58.9, 66.5, 77.2, 81.3, 127.3, 127.8, 127.9, 128.3, 128.6,
128.7, 129.1, 135.6, 136.3, 137.4, 155.3, 170.0. Anal. Calcd for
C28H31NO4: C, 75.48; H, 7.01; N, 3.14. Found: C, 75.29; H, 7.11;
N, 3.08.
Su p p or tin g In for m a tion Ava ila ble: X-ray crystallo-
graphic data. This material is available free of charge via the
Internet at http://pubs.acs.org.
ter t-Bu tyl 3-[(ben zyloxy)ca r bon yl]a m in o-3-p h en ylp r o-
p a n oa te (4cx): white needles (hexanes/ethyl acetate); mp 89-
J O0110810
1
91 °C (53%); H NMR δ 1.31 (s, 9H), 2.69-2.78 (m, 2H), 5.04-
5.14 (m, 2H), 5.80 (brs, 1H), 7.23-7.40 (m, 10H); 13C NMR δ
(7) Muller, D.; Zeltser, I.; Bitan, G.; Gilon, C. J . Org. Chem. 1997,
62, 411.
27.8, 41.8, 51.8, 66.8, 81.3, 126.2, 127.5, 128.1, 128.4, 128.5,
J . Org. Chem, Vol. 67, No. 14, 2002 4959