An improved synthesis of enantiopure β-amino acids

Article abstract of DOI:10.1081/SCC-100105666

An improved method for the preparation of both the enantiopure β-amino acids is presented. The diastereomer benzyl β-amino esters, obtained by stereoselective reduction of β-enamino esters, were separated and hydrogenolyzed to the free enantiopure β-amino acids.

Full text of DOI:10.1081/SCC-100105666

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AN IMPROVED SYNTHESIS OF ENANTIOPURE β-AMINO
ACIDS
Cristina Cimarelli a , Gianni Palmieri b & Emanuela Volpini a
a Dipartimento di Scienze Chimiche , Università di Camerino , Via S. Agostino 1,
Camerino, 1-62032, Italy
b Dipartimento di Scienze Chimiche , Università di Camerino , Via S. Agostino 1,
Camerino, 1-62032, Italy
Published online: 16 Aug 2006.
To cite this article: Cristina Cimarelli , Gianni Palmieri & Emanuela Volpini (2001) AN IMPROVED SYNTHESIS OF
ENANTIOPURE β-AMINO ACIDS, Synthetic Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 31:19, 2943-2953, DOI: 10.1081/SCC-100105666
To link to this article: http://dx.doi.org/10.1081/SCC-100105666
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SYNTHETIC COMMUNICATIONS, 31(19), 2943–2953 (2001)
AN IMPROVED SYNTHESIS OF
ENANTIOPURE b-AMINO ACIDS
Cristina Cimarelli, Gianni Palmieri,* and
Emanuela Volpini
Dipartimento di Scienze Chimiche,
Universita di Camerino, Via S. Agostino 1,
1-62032 Camerino, Italy
ABSTRACT
An improved method for the preparation of both the enan-
tiopure b-amino acids is presented. The diastereomer benzyl
b-amino esters, obtained by stereoselective reduction of
b-enamino esters, were separated and hydrogenolyzed to the
free enantiopure b-amino acids.
The synthesis of enantiopure non-proteinogenic b-amino acids is an
area of current interest because this compounds are crucial structural fea-
tures of many biologically active compounds, as well as they are found in
natural products1 and serve as key building blocks for the preparation of
b-lactam antibiotics2 naturally occurring macrolides3 and b-peptides.4
In the past few years several methods have been described in literature
for the synthesis of racemic compounds, but only a few methods have been
reported for the preparation of enantiopure b-amino acids.5 Anyway these
methods suffer of some drawbacks, as limitations in the configuration of the
*Corresponding author.
2943
Copyright & 2001 by Marcel Dekker, Inc.
www.dekker.com

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CIMARELLI, PALMIERI, AND VOLPINI
Scheme 1.
final product, long and complex experimental procedures, need of anhy-
drous reaction conditions and inert atmosphere.
During the course of our studies on the reduction of enaminones we
have found that b-enamino esters can be easily and stereoselectively reduced
to b-amino esters with sodium triacetoxyborohydride in acetic acid.6 This
stereoselective reductive ammination is fast, in spite of the mild reaction
conditions, easy to perform and has been selected as suitable to a large
scale synthesis too.7 Moreover this method allows to prepare separately
both the enantiomers of the desired product, depending on the selected
enantiomer of the starting chiral amine, which is commercially available
and cheap in both enantiomeric forms.
The starting b-enamino esters 1 can be easily obtained in a classical
way by direct condensation8 of (R)-1-phenylethylamine with the corre-
sponding benzyl b-keto esters 6 or, when benzyl ester is not available, by
acylation of lithium imines 7 with benzyl chloroformates.9 The b-enamino
ester (R)-1f was prepared by condensation of (R)-1-phenylethylamine with
benzyl 1-acetylcyclopropanecarboxylate.10
In this paper we have applied the diastereoselective reduction pro-
cedure6 on a wider range of substrates, finding a good diastereoselectivity
in this case too. Moreover a high cis diastereoselectivity in the reduction of
cyclic b-enamino esters was observed.6 Yields and products are reported in

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ENANTIOPURE b-AMINO ACIDS
2945
Table 1. In the subsequent step the presence of a benzylic group both on ester
and amino functionalities allows the easy preparation of the free b-amino
acids 3 by direct and quantitative hydrogenolysis of the benzyl b-amino esters
2 and 5. This procedure, although yet used occasionally by other research-
ers,11 has not been systematically studied and used before in the preparation
of b-amino acids. In our study the experimental conditions and procedures
are optimized to define a routine procedure for the preparation of b-amino
acids. Moreover the use of chiral (R)-1-phenylethylamine to prepare the
starting b-enamino esters makes possible to separate the diastereoisomeric
b-amino esters after the reduction step and to submit to catalytic hydrogena-
tion only the desired pure diastereoisomer. In this way the final free b-amino
acid is obtained in enantiopure form without any need of purification (Table 1;
entries 1 and 2). Really, after the catalytic hydrogenation step the experi-
mental procedure is very simple: it is enough to remove the Pearlman’s cat-
alyst by filtration and evaporate the mixture to dryness to have the desired
free b-amino acids 3. In this way the step of hydrolysis of the ester function-
ality is avoided, with the long, consequent and tedious workup procedure,
generally used for the isolation of the final zwitterionic product 3. The
b-amino acids 3 obtained and the relative yields are reported in Table 1.
At the same time our interest was in the study of direct chromato-
graphic resolution on a chiral stationary phase12 to separate b-amino acids
enantiomers, and we needed the corresponding raceme products to test our
method. So we have applied the overall procedure to the direct preparation
of (ꢀ)-b-amino acids 3 by hydrogenolysis of simple benzylamino benzyl
esters (ꢀ)-5a–f. Our results are reported in Table 1.
In conclusion this methodology represents an improved synthesis of
enantiopure b-amino acids with good overall yields, starting from ready
accessible and cheap reagents and through a simple procedure of practical
utility. Moreover our procedure allows to choose the suitable synthetic
pathway to reach separately both the enantiomers of the desired product
and makes possible the simple expeditious asymmetric synthesis of b-amino
acids with biological activity too, as 2-amino cyclopentane13 and 2-amino
cyclohexane7 carboxylic acids and derivatives.
EXPERIMENTAL SECTION
Reduction of b-EnaminoEsters 1 to b-AminoEsters 2.
General Procedure
A solution of NaBH(OAc)3 was prepared by adding NaBH4 (0.34 g,
9.0 mmol) to glacial acetic acid (5 mL), keeping temperature in the range

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CIMARELLI, PALMIERI, AND VOLPINI

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ENANTIOPURE b-AMINO ACIDS
2947
10–20ꢁC until hydrogen evolution ceased. Then acetonitrile (5 mL) was
added and the solution was cooled to 0ꢁC (ice bath). The b-enamino ester
1 or 4 (3.0 mmol) was added in one portion and the reaction mixture was
stirred for 2 h at 0ꢁC. Acetic acid and acetonitrile were evaporated in vacuo
at 50ꢁC, then the residue dissolved in CH2Cl2 and washed with Na2CO3
saturated aqueous solution. The organic layer was dried with anhydrous
Na2SO4 and, after evaporation under reduced pressure of the solvent,
b-amino ester 2 or 5 were obtained. The mixture was analysed by GC-MS
1
or H- and 13C-NMR to determine the yields of all the diastereoisomeric
b-amino esters and the d.e. obtained. Purification and diastereoisomer
separation were performed by flash chromatography or by preparative
HPLC on silica gel (10–20% ethyl acetate in hexane as eluent).
Benzyl (3R)-{[(1R)-1-phenylethyl]amino}butanoate [(R,R)-2a]: Oil;
20
D
½aŠ þ 38.6 (c ¼ 1.1, EtOH); IR (neat) 3350, 1715, 1440, 1170 cmꢂ1
;
1H NMR (CDCl3): d 1.07 (d, 3H, J ¼ 6.5 Hz), 1.32 (d, 3H, J ¼ 6.5 Hz),
1.89 (br s, 1H), 2.44 (dd, 1H, J ¼ 4.7, 14.7 Hz), 2.53(dd, 1H, J ¼ 3.8, 14.7 Hz),
3.03 (sext, 1H, J ¼ 6.2 Hz), 3.88 (q, 1H, J ¼ 6.5 Hz), 5.13(s, 2H), 7.15–7.44
(m, 10H); 13C NMR(CDCl3):d21.26, 24.25, 40.61, 47.94, 55.27, 66.16, 126.59,
127.02, 128.23, 128.25, 128.48, 128.54, 135.90, 171.95; MS (EI, 70 eV): m/z
(%) ¼ 297 (Mþ, 1), 282 (91), 148 (38), 120 (94), 95 (96), 91 (100); Anal. Calcd.
for C19H23NO2: C, 76.73; H, 7.80; N, 4.71. Found C, 76.96; H, 8.03; N, 4.46.
Benzyl (3S)-3-{[(10R)-10-phenylethyl]amino}butanoate [(3S,10R)-2a]:
20
Oil; ½aŠ þ 16.8 (c ¼ 1.7, EtOH); IR (neat) 3320, 1715, 1440, 1165 cmꢂ1
;
D
1H NMR (CDCl3): d 1.08 (d, 3H, J ¼ 6.3 Hz), 1.33 (d, 3H, J ¼ 6.6 Hz),
1.95 (br s, 1H), 2.37 (dd, 1H, J ¼ 15.5, 5.8 Hz), 2.46 (dd, 1H, J ¼ 15.5,
7.2 Hz), 2.93(sext, 1H, J ¼ 6.2 Hz), 3.92 (q, 1H, J ¼ 6.6 Hz), 5.07 and 5.14
(two d, 2H, JAB ¼ 12.3Hz), 7.15–7.44 (m, 10H); 13C NMR (CDCl3): d 20.31,
25.59, 42.86, 47.61, 55.36, 66.66, 127.09, 127.38, 128.75, 128.92, 129.04,
136.40, 145.66, 172.62; MS (EI, 70 eV): m/z (%) ¼ 297 (Mþ, 1), 282 (86),
148 (32), 120 (89), 95 (94), 91 (100); Anal. Calcd. for C19H23NO2: C, 76.73;
H, 7.80; N, 4.71. Found: C, 76.83; H, 7.92; N, 4.51.
Benzyl 3-(benzylamino)butanoate [(6)-5a]: Oil; IR (neat) 3330, 1718,
1445, 1170 cmꢂ1; 1H NMR (CDCl3): d 1.19 (d, 3H, J ¼ 1.2 Hz), 2.49 (dd, 1H,
J ¼ 15.4, 6.2 Hz), 2.64 (dd, 1H, J ¼ 15.4, 6.7 Hz), 3.21 (sext, 1H, J ¼ 6.4 Hz),
3.78 and 3.89 (two d, 2H, JAB ¼ 13.1 Hz), 5.12 (s, 2H), 7.21–7.38 (m, 10H);
13C NMR (CDCl3): d 16.32, 38.68, 47.71, 49.34, 66.56, 128.31, 128.55, 128.8þ1,
129.04, 129.18, 129.60, 131.77, 175.30. MS (EI, 70 eV): m/z (%) ¼ 283(M
,
1), 268 (1), 192 (4), 134 (32), 106 (42), 91 (100); Anal. Calcd. for C18H21NO2:
C, 76.30; H, 7.47; N, 4.94. Found: C, 76.47; H, 7.69; N, 5.13.
Benzyl (3S)-4-methyl-3-{[(10R)-10-phenylethyl]amino}pentanoate [(3S,
10R)-2b]: Oil; ½aŠ þ 14.6 (c ¼ 1.3, EtOH); IR (neat) 3320, 1715, 1440,
20
D
1165 cmꢂ1
;
1H NMR (CDCl3): d 0.80 (d, 3H, J ¼ 6.8 Hz), 0.87 (d, 3H,

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2948
CIMARELLI, PALMIERI, AND VOLPINI
J ¼ 6.8 Hz), 1.28 (d, 3H, J ¼ 6.5 Hz), 1.55 (br s, 1H), 1.69 (sept d, 1H,
J ¼ 6.5, 5.1 Hz), 2.41 (dd, 1H, J ¼ 14.3, 6.6 Hz), 2.52 (dd, 1H, J ¼ 14.3,
5.3Hz), 2.70 (dt, 1H, J ¼ 6.5, 5.1 Hz), 3.84 (q, 1H, J ¼ 6.4 Hz), 5.14 (s,
2H), 7.15–7.48 (m, 10H); MS, m/z 325 (Mþ, 2), 282 (100), 178 (93), 106
(67); Anal. Calcd. for C21H27NO2: C, 77.50; H, 8.36; N, 4.30. Found: C,
77.32; H, 8.57; N, 4.11.
Benzyl 4-methyl-3-(benzylamino)pentanoate [(6)-5b]: Oil; IR (neat)
1
3325, 1720, 1440, 1165 cmꢂ1; H NMR (CDCl3): d 0.90 (d, 3H, J ¼ 6.7 Hz),
0.92 (d, 3H, J ¼ 6.7 Hz), 1.65 (br s, 1H), 1.90 (sept d, 1H, J ¼ 6.7, 4.6 Hz), 2.41
(dd, 1H, J ¼ 15.0, 8.2 Hz), 2.51 (dd, 1H, J ¼ 15.0, 4.6 Hz), 2.94 (dt, 1H, J ¼ 8.2,
4.6 Hz), 3.78 (s, 2H), 5.14 (s, 2H), 7.15–7.41 (m, 10H); Anal. Calcd. for
C20H25NO2: C, 77.14; H, 8.09; N, 4.50. Found: C, 77.38; H, 8.32; N, 4.31.
Benzyl (3R)-3-phenyl-3-{[(10R)-10-phenylethyl]amino}propanoate [(R,R)-
20
D
2c]: Oil; ½aŠ þ 53.8 (c ¼ 1.1, EtOH); IR (neat) 3330, 1720, 1435, 765 cmꢂ1
;
1H NMR (CDCl3): d 1.25 (d, 3H, J ¼ 6.6 Hz), 1.84 (br s, 1H), 2.53–2.79 (m,
2H), 3.48 (q, 1H, J ¼ 6.6 Hz), 3.80 (dd, 1H, J ¼ 8.8, 5.3Hz), 5.03 and 5.13
(two d, 2H, JAB ¼ 12.2 Hz), 7.10–7.40 (m, 15H); 13C NMR (CDCl3): d 25.61,
43.88, 55.34, 57.11, 66.75, 127.04, 127.24, 127.31, 127.56, 127.84, 128.80,
128.84, 128.95, 129.02, 136.32, 143.09, 145.60, 171.97; MS (EI, 70 eV): m/z
(%) ¼ 359 (Mþ, 1), 344 (11), 254 (13), 210 (29), 120 (29), 105 (74), 91 (100);
Anal. Calcd. for C24H25NO2: C, 80.19; H, 7.01; N, 3.90. Found: C, 79.79; H,
6.93; N, 3.81.
Benzyl 3-benzylamino-3-phenylpropanoate [(6)-5c]: Oil; IR (neat) 3320,
1
1715, 1440, 750 cmꢂ1; H NMR (CDCl3): d 2.30 (br s, 1H), 2.71 (dd, 1H,
J ¼ 15.5, 5.7 Hz), 2.83(dd, 1H, J ¼ 15.5, 8.4 Hz), 3.54 and 3.66 (two d, 2H,
JAB ¼ 14.2 Hz), 4.16 (dd, 1H, J ¼ 8.4, 5.7 Hz), 5.09 (s, 2H), 7.20–7.42 (m,
15H); 13C NMR (CDCl3): d 43.40, 51.68, 59.39, 66.85, 127.49, 127.72,
128.11, 128.48, 128.71, 128.86, 129.02, 129.15, 134.92, 136.21, 171.96; MS
(EI, 70 eV): m/z (%) ¼ 345 (Mþ, 2), 254 (36), 196 (92), 91, (100); Anal. Calcd.
for C23H23NO2: C, 79.97; H, 6.71; N, 4.05. Found: C, 79.69; H, 6.93; N, 3.81.
Benzyl cis-2-(benzylamino)cyclopentane-1-carboxylate [cis-(6)-5d]: Oil;
1
IR (neat) 3330, 1715, 1445, 1155 cmꢂ1; H NMR (CDCl3): d 1.48–2.17 (m,
7H), 2.95–3.10 (m, 1H), 3.33 (q, 1H, J ¼ 6.8 Hz), 3.74 and 3.80 (two d, 2H,
JAB ¼ 13.4 Hz), 5.15 (s, 2H), 7.17–7.40 (m, 10H); 13C NMR (CDCl3): d
22.27, 27.47, 31.55, 47.56, 52.19, 61.38, 66.17, 126.87, 128.06, 128.15,
128.29, 128.31, 128.52, 135.92, 139.75, 174.58; MS (EI, 70 eV): m/z
(%) ¼ 309 (Mþ, 2), 218 (34), 146 (57), 106 (94), 91 (100); Anal. Calcd. for
C20H23NO2: C, 77.64; H, 7.49; N, 4.53. Found: C, 77.46; H, 7.67; N, 4.81.
Benzyl 2-(benzylamino)cyclopentanecarboxylate [trans-(6)-5d]: Oil; IR
(neat) 3310, 1710, 1440, 1140 cmꢂ1; 1H NMR (CDCl3): d 1.40–2.15 (m, 7H),
2.70 (q, 1H, J ¼ 8.0 Hz), 3.37 (q, 1H, J ¼ 7.2 Hz), 3.70 and 3.79 (two d, 2H,
JAB ¼ 13.1 Hz), 5.10 and 5.17 (two d, 2H, JAB ¼ 12.4 Hz), 7.20–7.40 (m, 10H);

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ENANTIOPURE b-AMINO ACIDS
2949
13C NMR (CDCl3): d 23.99, 29.18, 33.55, 51.34, 52.91, 63.23, 66.77, 127.48,
128.61, 128.63, 128.68, 128.90, 129.06, 136.55, 140.41, 175.94; Anal. Calcd. for
C20H23NO2: C, 77.64; H, 7.49; N, 4.53. Found: C, 78.88; H, 7.33; N, 4.31.
Benzyl (1S,2R)-2-{[(10R)-10-phenylethyl]amino}cyclohexanecarboxylate
(1S,2R,10R)-2e: Oil; ½aŠ þ 48.4 (c ¼ 1.4, EtOH); IR (neat) 3325, 1705,
20
D
1
1420, 755 cmꢂ1; H NMR (CDCl3): d 1.19 (d, 3H, J ¼ 6.5 Hz), 1.24–1.79
(m, 9H), 2.76–2.93(m, 2H), .380 (q, 1H,
J ¼ 6.5 Hz), 5.18 (s, 2H),
7.15–7.48 (m, 10H); 13C NMR (CDCl3): d 23.18, 23.79, 24.96, 25.90,
30.30, 45.28, 53.85, 55.52, 66.39, 127.09, 127.22, 128.66, 128.72, 128.80,
129.05, 136.79, 146.96, 174.75; MS (EI, 70 eV): m/z (%) ¼ 337 (Mþ, 2),
322 (35), 160 (26), 120 (39), 105 (100), 91 (81); Anal. Calcd. for
C22H27NO2: C, 78.30; H, 8.06; N, 4.15. Found: C, 78.09; H, 7.83; N, 3.97.
Benzyl 2-(benzylamino)cyclohexane-1-carboxylate [cis-(6)-5e]: Oil; IR
1
(neat): n ¼ 3330, 1710, 1440, 1150 cmꢂ1; H NMR (CDCl3): d 1.25–2.05 (m,
9H), 2.77 (dt, 1H, J ¼ 8.8, 4.0 Hz), 3.06 (dt, 1H, J ¼ 6.6, 3.6 Hz), 3.71 and
3.83 (two d, 2H, JAB ¼ 13.2 Hz), 5.11 and 5.16 (two d, 2H, JAB ¼ 12.4 Hz),
7.17–7.43(m, 10H); 13C NMR (CDCl3): d ¼ 22.24, 24.35, 25.39, 28.93,
46.37, 51.49, 55.14, 66.46, 128.56, 128.59, 128.61, 128.63, 128.78, 129.02,
136.67, 141.08, 174.84; Anal. Calcd. for C21H25NO2: C, 77.99; H, 7.79; N,
4.33. Found: C, 78.26; H, 7.53; N, 4.57.
Benzyl 2-(benzylamino)cyclohexanecarboxylate [trans-(6)-5e]: Oil; IR
(neat): 3325, 1710, 1440, 1140 cmꢂ1; 1H NMR (CDCl3): d 0.85–2.23(m, 9H),
2.37 (ddd, 1H, J ¼ 11.6, 10.3, 3.7 Hz), 2.83 (td, 1H, J ¼ 10.6, 3.7 Hz),
3.71 and 3.89 (two d, 2H, JAB ¼ 12.9 Hz), 5.14 and 5.19 (two d, 2H,
JAB ¼ 12.4 Hz), 7.17–7.40 (m, 10H); 13C NMR (CDCl3): d 25.29, 25.64,
29.76, 32.27, 51.21, 51.40, 58.00, 66.59, 127.31, 128.57, 128.60, 128.64,
128.81, 129.03, 136.70, 141.14, 175.85; Anal. Calcd. for C21H25NO2: C,
77.99; H, 7.79; N, 4.33. Found: C, 78.19; H, 7.57; N, 4.14.
Benzyl (2R,3R)-2-methyl-1-[(10R)-10-phenylethyl]-3-pyrrolidinecarbo-
20
xylate [(R,R,R)-2f]: Oil; ½aŠ þ 42.6 (c ¼ 1.8, EtOH); oil; IR (neat):
D
n ¼ 1720, 1440, 1145, 750 cmꢂ1
;
1H NMR (CDCl3): dd 0.80 (d, 3H,
J ¼ 6.3 Hz), 1.36 (d, 3H, J ¼ 6.3 Hz), 1.77–3.25 (m, 4H), 3.01–3.25 (m, 1H),
3.72–3.40 (m, 2H), 5.13 (s, 2H), 7.15–7.43 (m, 10H); 13C NMR (CDCl3):
d ¼ 12.91, 21.18, 25.34, 48.05, 49.23, 57.59, 61.24, 66.81, 126.99, 128.10,
128.47, 128.53, 128.71, 128.93, 136.41, 145.32, 173.44; Anal. Calcd. for
C21H25NO2: C, 77.99; H, 7.79; N, 4.33. Found: C, 77.96; H, 7.52; N, 4.51.
Benzyl cis-(6)-1-benzyl-2-methylpyrrolidine-3-carboxylate [cis-(6)-5f]:
Oil; IR (neat): n 1725, 1445, 1145, 735 cmꢂ1; H NMR (CDCl3): d 1.03(d,
1
3H, J ¼ 6.3Hz), 1.80–2.02 (m, 1H), 2.12–2.42 (m, 2H), 2.87–3.05 (m, 2H),
3.12 (q, 1H, J ¼ 8.0 Hz), 3.38 and 3.90 (two d, 2H, J ¼ 13.2), 5.13 and 5.16
(two d, 2H, J ¼ 12.0), 7.18–7.41 (m, 10H); 13C NMR (CDCl3): d 14.60,
25.73, 47.37, 52.16, 57.27, 60.11, 66.27, 126.86, 128.16, 128.20, 128.40,

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2950
CIMARELLI, PALMIERI, AND VOLPINI
128.51, 128.78, 135.95, 139.04, 173.62; Anal. Calcd. for C20H23NO2: C,
77.64; H, 7.49; N, 4.53%. Found: C, 77.86; H, 7.34; N, 4.31%.
Hydrogenolysis of b-AminoEsters 2 and 5 to b-AminoEsters 3.
General Procedure
The b-amino esters 2 or 5 (3mmol) were dissolved in MeOH (20 mL)
in the presence of palladium hydroxide on charcoal (20%, 0.2 g), then placed
under hydrogen pressure (5 atm.) and stirred at r.t. overnight. After removal
of the catalyst by filtration and evaporation under reduced pressure of the
solvent, the pure b-amino ester 3 was obtained in 83–90% yield.
(R)-3-Aminobutanoic acid [(R)-3a]: M.p. 212–214ꢁC (EtOH, decomp.);
½aŠ2D0-35.6 (c ¼ 1.6, H2O); IR (nujol) 1573, 1458, 1392, 702 cmꢂ1; H NMR
1
(D2O): d ¼ 1.19 (d, 3H, J ¼ 6.6 Hz), 2.38 (d, 2H, J ¼ 6.4 Hz), 3.49 (sest, 1H,
J ¼ 6.5 Hz); 13C NMR (D2O): d ¼ 20.54, 43.50, 48.26, 180.97; Anal. Calcd. for
C4H9NO2: C, 46.59; H, 8.80; N, 13.58. Found: C, 46.77; H, 8.96; N, 13.41.
(3S)-3-Amino-4-methylpentanoic acid [(S)-3b]: M.p. 203–205ꢁC (EtOH,
decomp.); ½aŠ2D0-38.8 (c ¼ 2.6, H2O); IR (nujol) 1570, 1460, 1370, 845 cmꢂ1
;
1H NMR (D2O): d 0.86 (t, 3H, J ¼ 6.8 Hz), 0.88 (t, 3H, J ¼ 6.8 Hz), 1.82
(octet, 1H, J ¼ 6.7 Hz), 2.27 (dd, 1H, J ¼ 16.9, 9.1 Hz), 2.44 (dd, 1H,
J ¼ 16.9, 4.4 Hz), 3.20 (m, 1H); 13C NMR (D2O): d 20.14, 20.31, 32.82,
38.80, 57.61, 181.23; Anal. Calcd. for C6H13NO2: C, 54.94; H, 9.99; N,
10.68. Found: C, 55.21; H, 10.27; N, 10.45.
(3R)-3-Amino-3-phenylpropanoic acid [(R)-3c]: M.p. 234–237ꢁC (EtOH,
20
decomp.); ½aŠ þ 6.8 (c ¼ 1.3, H2O); IR (nujol) 1579, 1457, 1247, 696 cmꢂ1
;
D
1H NMR (D2O): d ¼ 2.74 (dd, 1H, J ¼ 16.1, 6.7 Hz), 2.83(dd, 1H, J ¼ 16.1,
7.9 Hz), 4.56 (t, 1H, J ¼ 7.3Hz), 7.20–7.48 (m, 5H); 13C NMR (D2O):
d ¼ 43.39, 55.58, 129.75, 132.09, 132.25, 138.93, 180.13; Anal. Calcd. for
C9H11NO2: C, 65.44; H, 6.71; N, 8.48. Found: C, 65.62; H, 6.86; N, 8.32.
Cis-(1S,2R)-2-Aminocyclopentanecarboxylic acid [cis-(1S,2R)-3d]: M.p.
225–227ꢁC (EtOH, decomp.); ½aŠ þ 8.6 (c ¼ 1.4, H2O); IR (nujol) 1458,
20
D
1
1377, 1335, 845 cmꢂ1; H NMR (D2O): d 1.53–1.81 (m, 4H), 1.87–2.09 (m,
2H), 2.73(td, 1H, J ¼ 8.4, 6.1 Hz), 3.59 (td, 1H, J ¼ 6.6, 4.2 Hz); 13C NMR
(D2O): d 24.01, 30.77, 32.24, 50.39, 55.77, 183.70; Anal. Calcd. for
C6H11NO2: C, 55.80; H, 8.58; N, 10.84. Found: C, 55.61; H, 8.51; N, 10.62.
Trans-(6)-2-aminocyclopentanecarboxylic acid (trans-(6)-3d): M.p.
245–248ꢁC (EtOH, decomp.); IR (nujol) 1462, 1381, 1315, 812 cmꢂ1
;
1H NMR (D2O): d 1.50–1.79 (m, 4H), 1.96–2.15 (m, 2H), 2.59 (q, 1H,
J ¼ 7.7 Hz), 3.68 (q, 1H, J ¼ 7.2 Hz); 13C NMR (D2O): d 25.53, 32.27,
33.13, 54.47, 57.75, 184.18; Anal. Calcd. for C6H11NO2: C, 55.80; H, 8.58;
N, 10.84. Found: C, 55.46; H, 8.48; N, 10.78.

ORDER
REPRINTS
ENANTIOPURE b-AMINO ACIDS
2951
Cis-(1S,2R)-2-aminocyclohexanecarboxylic acid [cis-(1S,2R)-3e]: M.p.
220–223ꢁC (EtOH, decomp.); ½aŠ þ 5.9 (c ¼ 1.1, H2O); IR (nujol) 1639,
20
D
1
1461, 1377, 824 cmꢂ1; H NMR (D2O): d 1.15–1.96 (m, 8H), 2.56 (dt, 1H,
J ¼ 6.7, 4.2 Hz), 3.37 (td, 1H, J ¼ 6.4, 4.0 Hz); 13C NMR (D2O): d 21.94,
22.42, 26.32, 27.11, 43.36, 50.12, 180.72; Anal. Calcd. for C7H13NO2: C,
58.72; H, 9.15; N, 9.78. Found: C, 58.61; H, 9.24; N, 9.42.
Trans-(6)-2-aminocyclohexanecarboxylic acid [trans-(6)-3e]: M.p.
220–223ꢁC (EtOH, decomp.); IR (nujol) 1622, 1478, 1213, 803 cmꢂ1
;
1H NMR (D2O): d 1.05–2.35 (m, 8H), 2.40–2.75 (m, 1H), 3.62 (td, 1H,
J ¼ 10.4, 4.7 Hz); 13C NMR (D2O): d 26.75, 27.57, 32.14, 32.59, 51.86,
55.13, 183.92; Anal. Calcd. for C7H13NO2: C, 58.72; H, 9.15; N, 9.78.
Found: C, 58.39; H, 9.18; N, 9.81.
(2R,3R)-2-Pyrrolidine-3-carboxylic acid [(R,R)-3f ]: M.p. 215–217ꢁC
(EtOH, decomp.); ½aŠ2D0-6.86 (c ¼ 0.2, H2O); IR (nujol) 1627, 1422, 781,
1
699 cmꢂ1; H NMR (D2O): d 1.27 (d, 3H, J ¼ 6.8 Hz), 2.00–2.23(m, 2H),
2.94 (q, 1H, J ¼ 6.4 Hz), 3.24 (dt, 1H, J ¼ 11.8, 7.5), 3.47 (dt, 1H, J ¼ 11.8,
8.1 Hz), 3.73 (quint, 1H, J ¼ 6.7 Hz); 13C NMR (D2O): d 15.92, 29.58, 46.82,
52.06, 60.33, 182.09; Anal. Calcd. for C6H11NO2: C, 55.80; H, 8.58; N,
10.84. Found: C, 55.63; H, 8.43; N, 10.69.
ACKNOWLEDGMENT
Financial support from Ministero dell’Universita e della Ricerca-
Scientifica e Tecnologica, Rome, and the University of Camerino (National
Project ‘‘Stereoselezione in Sintesi Organica. Metodologie ed applicazioni’’)
is gratefully acknowledged.
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Received in the UK September 20, 2000

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