Asymmetric synthesis of (S)-2-amino-3-(1-naphthyl)propanoic acid via chiral nickel complex. Crystal structure, circular dichroism, 1H and 13C NMR spectra of the complex

Article abstract of DOI:10.1135/cccc20051397

The recently published environmentally friendly preparation of a glycine synthon 2 from regeneratable chiral auxiliary BPB ((S)-N-(2-benzoylphenyl)- N′-benzylprolinamide) was used for preparative asymmetric synthesis of the non-coded amino acid 3-(1-naphthyl)alanine (1). Full assignment of ¹H and ¹³C NMR of both intermediate complex 3 and 1 and X-ray structure determination of complex 3 were made. Cotton effects observed in circular dichroism spectrum of complex 3 are consistent with published empirical rules.

Full text of DOI:10.1135/cccc20051397

Asymmetric Synthesis of (S)-2-Amino-3-(1-naphthyl)propanoic Acid
1397
ASYMMETRIC SYNTHESIS OF (S)-2-AMINO-3-(1-NAPHTHYL)PROPANOIC
ACID VIA CHIRAL NICKEL COMPLEX. CRYSTAL STRUCTURE, CIRCULAR
1
13
DICHROISM, H AND C NMR SPECTRA OF THE COMPLEX
a,
b
c
d
Alexander POPKOV *, Ivana CÍSAŘOVÁ , Jana SOPKOVÁ , Josef JIRMAN ,
e
f,
Antonín LYČKA and Konstantin A. KOCHETKOV *
a
Faculty of Health and Social Studies, University of South Bohemia,
3
70 01 České Budějovice, Czech Republic; e-mail: sasha@jcu.cz
b
Department of Inorganic Chemistry, Faculty of Natural Sciences, Charles University,
Hlavova 2030, 128 40 Prague 2, Czech Republic; e-mail: cisarova@natur.cuni.cz
UFR des Sciences Pharmaceutiques, 5 rue Vaubénard, 14032 Caen, France
Research Institute for Pharmacy and Biochemistry,
c
d
U Kabelovny 130, 102 37 Prague 10, Czech Republic; e-mail: jirman@vufb.cz
Research Institute for Organic Syntheses, Rybitví 296,
e
f
5
32 18 Pardubice 20, Czech Republic; e-mail: antonin.lycka@vuosas.cz
A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
Vavilov Street 28, 117813 Moscow, Russia; e-mail: const@ineos.ac.ru
Received March 2, 2005
Accepted Jun e 6, 2005
Th e recen tly publish ed en viron m en tally frien dly preparation of a glycin e syn th on 2 from
regen eratable ch iral auxiliary BPB ((S)-N-(2-ben zoylph en yl)-N′-ben zylprolin am ide) was used
for preparative asym m etric syn th esis of th e n on -coded am in o acid 3-(1-n aph th yl)alan in e (1).
1
13
Full assign m en t of H an d C NMR of both in term ediate com plex 3 an d 1 an d X-ray struc-
ture determ in ation of com plex 3 were m ade. Cotton effects observed in circular dich roism
spectrum of com plex 3 are con sisten t with publish ed em pirical rules.
Keyw ord s: Am in o acids; Biom im etic syn th esis; BPB; Circular dich roism ; Ch iral auxiliaries;
Crystal structure determ in ation ; Naph th ylalan in e; Nickel; NMR spectroscopy; Sch iff bases.
Heavy en viron m en tal im pact of waste-water an d by-products released by
ch em ical an d ph arm aceutical in dustry requires developm en t of n ew
“
green ” syn th etic procedures for m an ufacture of active ph arm aceutical in -
term ediates. Efficien t catalytic approach es h ave been suggested for a big
1
n um ber of α-am in o acids . Developm en t of such catalytic syn th eses often
requires tim e-con sum in g screen in g for an optim al catalyst, precursor an d
reaction con dition s. Ch iral stoich iom etric α-am in o acids syn th on s are of-
ten th e optim al ch oice for preparation of sm all batch es of n ew α-am in o ac-
ids an d for special application like preparation of radiolabeled α-am in o ac-
Collect. Czech. Chem. Commun. (Vol. 70) (2005)
doi:10.1135/cccc20051397

1
398
Popkov et al.:
2
ids . Man y stoich iom etric approach es lead to destruction of a ch iral auxil-
iary used. A syn th etic path way em ployin g ch iral n ickel com plexes prepared
from α-am in o acids an d ch iral auxiliary BPB ((S)-N-(2-ben zoylph en yl)-
N′-ben zylprolin am ide) is an exception . After preparation of desired α-am in o
3
acid, en an tiom erically pure BPB·HCl is regen erated in h igh yield (>90%) .
Th e com plexes provide easy gen eration of in term ediate carban ion due to
4
h igh acidity of α-h ydrogen of an am in o acid fragm en t (pK ≥ 19) . Un like
a
m an y oth er ch iral syn th on s, th ey en able asym m etric syn th esis of substi-
tuted prolin es from α,β-un saturated aldeh ydes an d keton s via 1,4-addition
5
followed by h ydrolysis of a com plex an d reduction of C=N bon d . An oth er
un ique feature of th e com plexes is a bis-alkylation of th e glycin e syn th on
with CH Cl followed by h ydrolysis wh ich lead to en an tiom erically pure
2
2
(
S,S)-2,4-diam in oglutaric acid. Th is diam in o dicarboxylic acid h as been pre-
6
pared by a n um ber of m ultistep syn th eses . Based on kn own alkylation of
th e glycin e syn th on with CH Br2 , we developed a very sim ple approach
7
2
for bis-alkylation of a glycin e syn th on wh ere CH Cl was used both as an
2
2
8
alkylatin g agen t an d as a solven t . Recen tly, a preparative m odification of
th is syn th esis was publish ed . Com plex of en an tiom erically pure (S,S)-2,4-
9
diam in oglutaric acid could be also prepared by on e-pot reaction of BPB
1
0
with n ickel n itrate an d S-(2-am in oeth yl)cystein e in MeONa/MeOH . In
th is article we describe a preparative asym m etric syn th esis of n on -coded
am in o acid 3-(1-n aph th yl)alan in e ((S)-2-am in o-3-(1-n aph th yl)propan oic
1
13
acid; 1) (Sch em e 1), full assign m en t of H an d C NMR spectra of both th e
in term ediate com plex 3 an d am in o acid 1, a com parison of X-ray structures
of sin gle crystals of glycin e syn th on 2 an d com plex 3 an d circular
dich roism spectra of th eir m eth an olic solution s. Th e syn th esis applies a re-
cen tly publish ed en viron m en tally frien dly preparation of th e startin g
m etallocom plex glycin e syn th on 2 (Sch em e 2)1
1–13
.
Preparative application s of th e syn th on were developed by several
1
4
groups . Most of th e syn th eses described in th e literature deal with am in o
acids soluble in water in a wide pH ran ge. Th is specific property requires
sorption –desorption on a cation -exch an ge resin for separation of am in o
acid an d n ickel cation s presen t in aqueous solution after h ydrolysis of a sin -
gle diastereom er of an alkylated com plex. Am in o acid 1 is n ot water-soluble
at pH 7. Th e isolation procedure used in th is work th us could be con sidered
a m odel approach for isolation of h igh ly lipoph ilic am in o acids (for an -
1
5
oth er exam ple, see ref. ). Earlier we fully assign ed NMR spectra of several
sim ilar com plexes bearin g H, NMe or Br substituen ts on th e α-carbon atom
2
1
6
on am in o acid fragm en t (C-19) . Th e spectra of com poun d 3 (presen ted
h ere) are m ore com plex due to overlap of a n um ber of arom atic h ydrogen
Collect. Czech. Chem. Commun. (Vol. 70) (2005)

Asymmetric Synthesis of (S)-2-Amino-3-(1-naphthyl)propanoic Acid
1399
an d carbon sign als. X-ray structure determ in ation of com plex 3 followed by
1
7
its com parison with th e publish ed structure of th e startin g syn th on 2
aim ed at deeper un derstan din g of in tra- m olecular in teraction s affected
H
O
2
CH Ph
N
O
O
H
N
HN
Ni
H
N
N
O
Ni(NO ) ·6H O
O
3
2
2
H
+
NaOMe/MeOH
Cl
COOH
2
2
H N
BPB
NaOH
DMF
2
CH Ph
2
CH Ph
O
N
O
O
N
O
Ni
Ni
+
N
N
N
N
O
O
H
Ph
4
filtration and
regeneration
of BPB
CH
2
Ph
2
CH Ph
N
O
O
N
O
O
H
Ni
Ni
N
N
N N
O
O
H
NaOMe
MeOH
3
5
separation of diastereomers
hydrolysis of L,L-diastereomer with 6
isolation of -amino acid
M
HCl
L
HOOC
H
NH
2
1
SCHEME 1
Syn th esis of 1
Collect. Czech. Chem. Commun. (Vol. 70) (2005)

1
400
Popkov et al.:
stereoch em ical outcom e of alkylation of com plex 2. Alth ough
n aph th ylalan in e 1 is a steric an alogue of L-tryptoph an , it is a poor substrate
for tryptoph an decarboxylases, deam in ases an d h ydroxylases. Wh en trypto-
ph an is replaced by n aph th ylalan in e in a peptide, am ide bon ds form ed by
n aph th ylalan in e are m uch m ore stable to en zym atic tran sform ation s. Th is
n on -coded am in o acid is m an ufactured by a n um ber of ven dors for design
1
8
of peptidom im etic drug can didates .
RESULTS AND DISCUSSION
Th e m ost com m on application of n ickel com plexes as ch iral am in o acids
syn th on s con sists of several stan dard steps (Sch em e 1): (i) Tem plate prepa-
ration of th e startin g com plex 2 from glycin e, n ickel salt an d re-usable
ch iral auxiliary BPB. (ii) Alkylation of com plex 2 with an electroph ile
(
1-(ch lorom eth yl)n aph th alen e in our case) in an aprotic solven t. (iii) Retro-
H
O
H
O
H2, 50 bar
N
H
OH
Ref. 11
N
OH
cat. (Ph3P)3RhCl
+
CHO
H
+
O
H
O
N
OH
NH2 O
N
SOCl2
NH
Ref. 12
O
H
O
CH2Ph
N
O
O
H
N
HN
Ni
H
Ref. 13
N
N
O
Ni(NO ) ·6H O
O
3
2
2
H
+
NaOMe/MeOH
COOH
2
H2N
SCHEME 2
Preparation of com plex 2
Collect. Czech. Chem. Commun. (Vol. 70) (2005)

Asymmetric Synthesis of (S)-2-Amino-3-(1-naphthyl)propanoic Acid
1401
racem isation of th e reaction m ixture in MeONa/MeOH 19. (iv) Separation of
diastereom ers of th e alkylated com plex 3 an d 5, startin g com plex 2 an d a
m in or am oun t of a product of bis-alkylation 4. (v) Option al retroracem is-
ation of th e un desired diastereom er 5 in MeONa/MeOH. (vi) Acid h ydroly-
sis of diastereom erically pure com plex 3, isolation of th e am in o acid an d re-
gen eration of BPB.
Preparation of th e startin g com plex was optim ised in order to reduce th e
1
3
am oun t of n ickel in aqueous-organ ic waste . Th e alkylation reaction was
perform ed un der h eterogen eous con dition s em ployin g m in im um am oun t
of (toxic) aprotic solven t DMF. High con cen tration s of reagen ts in crease th e
speed of th e reaction . Stereoch em istry of alkylation of such com plexes in
aprotic solven ts is usually kin etically con trolled. In order to in crease th e
diastereom eric purity of th e alkylated com plex, th e th erm odyn am ically
con trolled retroracem isation in MeONa/MeOH sh ould be used for th e crude
1
9
alkylation product . In th erm odyn am ically con trolled con dition s dia-
stereom eric excess of th e desired L,L-diastereom er is favored by repulsion
between ortho-proton s of th e ben zyl group an d equatorial substituen ts of
1
6a
C-19 . For separation of predom in an t diastereom er, flash ch rom atogra-
ph y of retroracem ised crude product was applied. L,L-Con figuration of th e
m ain product was con firm ed by X-ray structure determ in ation takin g in to
accoun t L-con figuration of BPB 17. Circular dich roism (CD) spectra were
em ployed for routin e determ in ation of con figuration at C-19. Th e differ-
en ce between CD spectrum of com plex 2 an d th ose of alkylated com plexes
(
e.g. com plexes 3–5) is due to ch rom oph ore distortion in troduced by C-19
substituen ts. In th e case of bulky n aph th alen -1-ylm eth yl substituen t th e
differen ce is very sign ifican t (Fig. 1, solid lin e correspon ds to 3, dash ed lin e
correspon ds to 2). In good agreem en t with th e previously publish ed em piri-
1
9,20
cal rules
, m eth an olic solution of com plex 3 dem on strates a positive
Cotton effect in th e ran ge 610–480 n m an d a n egative Cotton effect in th e
ran ge 370–480 n m . Retroracem isation decreased th e am oun t of L,D-dia-
stereom er 5 (n ickel com plex of a Sch iff base of (R)-2-am in o-3-(1-n aph th yl)-
propan oic acid an d BPB) to far less th an 1% in crude reaction m ixture.
Attem pts to isolate 5 by preparative TLC on silica gal failed. High -m eltin g
com plex 4, th e on ly by-product resultin g from bis-alkylation of C-19
(
n ickel com plex of th e Sch iff base of bis(1-n aph th ylm eth yl)glycin e an d
BPB), was isolated in 1% yield on ly. After h ydrolysis of 3, filtration of
BPB·HCl, and adjusting pH to 9–10, am ino acid 1 was filtered off (Schem e 1).
Th e am in o acid could be used for preparation of protected derivatives for
1
8
peptide syn th esis with out addition al purification . An alytical sam ple was
recrystallised from water–eth an ol.
Collect. Czech. Chem. Commun. (Vol. 70) (2005)

1
402
Popkov et al.:
Recrystallised recovered BPB was re-used for preparation of 2 th us justify-
in g biom im etic, en zym e-like ch aracter of th is syn th etic approach . We as-
sum e th at ch rom atograph ic purification of 3 is n ot n ecessary for h igh -scale
preparation of 1. After retroracem isation th e m ixture of com plexes (3 an d
n egligible am oun ts of 4 an d 5) could be h ydrolysed followed by on e or two
crystallisation s of am in o acid 1 in order to rem ove traces of D-en an tiom er
an d bis(1-n aph th ylm eth yl)glycin e.
NMR Spectroscopy
1
13
Th e H an d C ch em ical sh ifts were assign ed usin g gs (gradien t selected)-
1
13
1
H,H-COSY, 1D-gs-NOESY, gs-HSQC (optim ised for J( C, H) ≈ 160 Hz) an d
gs-HMBC (optim ised for 3J( C, H) = 7 Hz). H,H-COSY provided us with
13
1
proton -proton con n ectivity an d 1D-gs-NOESY sh owed th e th rough -space
1
3
in teraction of am in o acid proton s H-32 an d H-34. Th e C ch em ical sh ifts
2
1,22
assign m en t was straigh tforward usin g HSQC an d HMBC spectra
.
Main argum en ts for assign m en t of som e crucial sign als an d space direc-
tion of som e atom s of com plex 3 (for NMR n um berin g, see Fig. 2) are:
Proton s H-4, H-19 an d orth o proton s of ben zyl group (H-23 an d H-27)
h ave NOESY cross-peaks. It m ean s th ey h ave to be on upper site of th e com -
1
0
.0
.5
0
.0
–
–
0.5
1.0
3
00 350 400 450 500 550 600
Wavelength, nm
FIG. 1
Circular dich roism spectra of m eth an olic solution s of com plexes 2 (dash ed lin e) an d 3 (solid
lin e)
Collect. Czech. Chem. Commun. (Vol. 70) (2005)

Asymmetric Synthesis of (S)-2-Amino-3-(1-naphthyl)propanoic Acid
1403
plex plan e an d ben zyl group is rotated towards H-19. Proton H-37 of n aph -
th alen e rin g h as a NOESY cross-peak with H-18 proton . Proton H-37 of
n aph th alen e rin g h as a NOESY cross-peak with proton H-19 an d both
m eth ylen e proton s H-28. Proton H-19 h as a NOESY cross-peak with n aph -
th alen e rin g proton s H-36 an d H-37. Th ere are positive cross-peaks in
NOESY TPPI spectrum between pairs of proton s H-14 an d H-18 an d H-15
an d H-17. It m ean s slow rotation of ph en yl rin g aroun d th e bon d
1
6a
C-12/C-13. Such rotation h as been observed in sim ilar com plexes . H-19
an d H-28a sh ould be closer th rough space th en H-19 an d H-28b because
th ere exists bigger cross-peak in first pair in NOESY spectrum . It corre-
spon ds with its couplin g con stan ts th at in case of pair H-19/H-28b sh ows
h igh er dih edral an gle of bon ds C-19/H-19 an d C-28/H-28b.
1
3
1
Previously, C an d H NMR spectra were fully assign ed for n ickel com plex
1
6a
of th e Sch iff base of L-2-dim eth ylam in oglycin e an d BPB (L,L-DMGK)
.
Wh ile h avin g th e sam e stereoch em istry of all ch iral cen tres as com plex 3,
th is com plex bears a dim eth ylam in o substituen t at C-19. Un like th e
dim eth ylam in o group in L,L-DMGK, 1-n aph th ylm eth yl group in com plex 3
stron gly affects several sign als of th e n ucleus belon gin g to th e core of th e
com plex by its electron -rich arom atic rin gs, both H -3 an d H -3 sign als
a
b
were sh ifted 0.99 an d 0.73 ppm down field in 1H NMR spectrum of 3, re-
spectively. C-12 sign al is sh ifted 3.9 ppm upfield, C-19 sign al – 13.81 ppm
upfield an d C-20 sign al – 2.29 ppm down field. Th ese carbon atom s are
proxim ate to th ose of 1-n aph th ylm eth yl group; th e proxim ity of H-37 to
H-19 was also con firm ed by both NOE an d X-ray data. N-Ben zyl group in
CDCl solution is rotated towards C-19 an d th e n ickel atom . Th is arran ge-
3
m en t is con firm ed by NOE cross-peaks between pairs of proton s H-4 H-23
(
H-27) an d H-23 (H-27) H-19. In th e sin gle crystal th e ben zyl group is ro-
24
2
3
25
26
2
22
1
3
H
O
31
2
1
27
O 30
4
32
33
O 20
N
H
19
5
Ni
2
9
34
N
N
28
18
38
6
35
1
1
13
7
8
12
17 37
16
36
1
4
1
0
9
15
FIG. 2
NMR n um berin g sch em e for 3
Collect. Czech. Chem. Commun. (Vol. 70) (2005)

1
404
Popkov et al.:
tated outside th e n ickel atom . Proxim ity of H-37 to H-18 observed in CDCl
3
1
3
solution does n ot occur in th e sin gle crystal. Differen ces between C an d
1
H NMR spectra of 1-n aph th ylm eth yl group in com plex 3 an d in am in o
acid 1 are m uch lower an d could be m ostly attributed to recordin g th e spec-
tra in differen t solven ts an d at differen t pH.
X-ray Crystallography of Complex 3
Structure description. Th e m olecular structures of th e Ni com plex of Sch iff
base of BPB an d two am in o acids (glycin e or 3-(1-n aph th yl)alan in e) were
com pared (Sch em e 1). Molecular structure of 3 with th e atom n um berin g
sch em e is sh own in Fig. 3. Th e structure of 2 h as been publish ed else-
1
7
wh ere . Th e core of th e title com poun ds, i.e. atom s in th e n eigh bourh ood
of Ni, h as in all structures an approxim ately plan ar arran gem en t. Root-
m ean -square deviation from th e least-square plan e fitted th rough th e five
cen tral atom s – O2, N1, N2, N3 (atom s th at co-ordin ate Ni1) an d Ni1 ca.
0
.065 Å for 3. Th e Ni1 atom lies in th e cen tre of a plan ar core of th e two
com poun ds, an d is co-ordin ated by four atom s, th ree n itrogen s (N1, N2
an d N3) an d on e oxygen (O2). Th e arran gem en t of Ni1 co-ordin ation is
FIG. 3
A perspective view of com plex 3 with th e atom labellin g sch em e for n on -h ydrogen atom s. Dis-
placem en t ellipsoids are sh own at th e 50% probability level
Collect. Czech. Chem. Commun. (Vol. 70) (2005)

Asymmetric Synthesis of (S)-2-Amino-3-(1-naphthyl)propanoic Acid
1405
square plan ar. Th e N–Ni1 an d O–Ni1 bon d len gth s are very close in th e two
com plexes (see Table I), but th ey are sligh tly sh orter th an th e publish ed
2
3
average values – 2.07 Å for th e N–Ni1 an d 2.06 Å for O–Ni1 . Furth er-
m ore, th e N1–Ni1 bon d len gth s are lon ger by ca. 0.1–0.07 Å th an th e oth er
th ree Ni co-ordin ated bon ds in both structures, wh ose bon d len gth s are
very close (1.84–1.87 Å).
Th e ph en yl group bon ded to th e C13 atom is orien ted approxim ately
perpen dicularly th e core plan e, takin g up a position perpen dicular to th e
ph en ylen e group wh ich is situated with th e Ni1 core (C6, C7, C8, C9, C10
an d C11). Th ese two arom atic rin gs form an acute an gle of 89.5° in th e
com plex 2, an d an acute an gle of 85.57(7)° in th e com plex 3. Ben zyl group
is orien ted in both com plexes above th e Ni(II) plan e approxim ately parallel
to th is cen tre plan e (see Fig. 3). However, its relative position with respect
to th e Ni1 atom ch an ges as a fun ction of th e com plex. In com plex 2 it lies
towards th e Ni1 atom , an d in com plex 3 it is orien ted away from th e Ni1
atom (see Fig. 3). Th e n aph th alen e rin g in th is com plex lies on th e oth er
side of th e Ni1 core plan e from th e N1 ben zyl group an d away from th e Ni1
(
see Fig. 3). Th e ben zyl an d th e n aph th alen e rin gs are both position ed par-
allel to th e Ni1 plan e. In both 2 an d 3 th e pyrrolidin e rin g (C1, C2, C3, C4
an d N1) is perpen dicular to th e Ni1 core plan e in th e direction below th e
core plan e with respect to th e N1 ben zyl group. It takes a h alf-ch air con for-
m ation .
π-Charge delocalization. We observed a ch arge delocalization in th e prox-
im ity of th e N2 atom due to th e free π-orbital of th is n itrogen atom . Th e
bon ds between th e N2 an d C6 an d C5 (N2–C6 1.406(2) Å; N2–C5 1.366(3) Å)
2
are sh orter th an th e publish ed average value for N–C(sp ) bon d (d
1
≈
C–N
2
3
.47(1) Å , an d we fin d also a sm all deviation of th e bon d len gth of C5–O1
TABLE I
Selected distan ces (in Å) an d an gles (in °) of atom s co-ordin atin g th e Ni atom
Distan ce
2
3
An gle
2
3
Ni1–O2
Ni1–N1
Ni1–N2
Ni1–N3
1.8357(12)
1.9229(12)
1.8384(12)
1.8357(12)
1.868(2)
1.936(2)
1 857(2)
1.845(2)
N1–Ni1–N2
N1–Ni1–N3
N1–Ni1–O2
N2–Ni1–N3
N2–Ni1–O2
N3–Ni1–O2
88.72(5)
168.84(5)
89.04(5)
95.33(5)
175.88(6)
87.50(5)
87.60(7)
176.78(8)
91.88(7)
94.53(7)
173.69(7)
86.27(7)
Collect. Czech. Chem. Commun. (Vol. 70) (2005)

1
406
Popkov et al.:
(
1.225(3) Å) from th e publish ed value dC=O ≈ 1.19(1) Å 23. Th e situation in
th e proxim ity of N3 is m ore com plicated an d we observed on ly sm all devia-
tion s wh ich are n ot sign ifican t, with th e exception of th e N3=C12 bon d
(
1.296(3) Å) wh ich is sh orter th an th e referen ce value dN=C ≈ 1.34 Å.
Crystal packing. In both th e com plexes th e usual h ydrogen bon d don ors
N–H, O–H are absen t, th e h ydrogen is in volved on ly in on e “h ydrogen
bon d”, C(18)–H18···O1 (C···O 3.288(3) Å, H···O 2.51 Å, C–H···O 142°),
wh ich is sign ifican tly sh orter th an th e sum of van der Walls radii. Neith er
stron g in term olecular in teraction of π system of arom atic rin gs n or an y
electron don ation to Ni1 atom was foun d in com plex 3, th erefore, its crys-
tal packin g is probably con trolled by weak van der Walls in teraction s. De-
tailed description of in ter- an d in tram olecular in teraction s in crystals of 2
was publish ed elsewh ere17b,17c.
CONCLUSIONS
Th e described procedure for asym m etric syn th eses of α-am in o acids is an
optim al approach for preparation of sm all batch es of n ew α-am in o acids for
research an d in dustrial purposes. Stereoch em istry of in term ediate ch iral
com plexes could be disclosed by circular dich roism , X-ray crystallograph y
1
or by NOE in teraction s in H NMR spectra. For extrem ely dem an din g appli-
1
1
cation s like preparation of en an tiom erically pure [ C]am in o acids for posi-
tron em ission tom ograph y, n ext gen eration ch iral auxiliaries could be used
2
4
in stead of BPB
.
EXPERIMENTAL
Optical rotation was m easured with a Perkin –Elm er M241 polarim eter. Circular dich roism
1
3
1
spectra were recorded on Jasco J-715 in strum en t. Th e C (125.76 MHz) an d H (500.13 MHz)
NMR spectra of com poun ds 3 an d 1 were m easured at am bien t tem perature on a Bruker
Avan ce 500 spectrom eter equipped with a 5-m m broadban d probe with z-sh ieldin g an d a
SGI O2 com puter. Ch em ical sh ifts are given in ppm (δ-scale), couplin g con stan ts (J) in Hz.
Am in o acid 1 (4 m g) was dissolved in a m ixture of D O (0.6 m l) an d two drops of
2
1
3
1
13
1
CF COOD. Th e C an d H NMR ch em ical sh ifts were referred to DSS (δ( C) 0.00, δ( H)
.00 in D O). Com plex 3 (30 m g) was dissolved in CDCl (0.5 m l). Th e 13C an d 1H NMR
ch em ical sh ifts were referred to TMS (δ( C) 0.00, δ( H) 0.00 in CDCl ). Two-dim en sion al
3
0
2
3
1
3
1
3
gs-H,H-COSY, 1D-gs-NOESY, gs-HSQC, an d gs-HMBC spectra were m easured usin g stan dard
m icroprogram s provided by Bruker.
Structure Determ in ation
Crystal data for 3: C38H33N NiO , M = 638.38, m on oclin ic, P2 (No. 4), a = 10.3270(2) Å, b =
3
3
1
3
–3
8
.8190(2) Å, c = 17.4540(3) Å, β = 102.748(1)°, V = 1550.42(3) Å , Z = 2, Dx = 1.367 Mg m
.
Collect. Czech. Chem. Commun. (Vol. 70) (2005)

Asymmetric Synthesis of (S)-2-Amino-3-(1-naphthyl)propanoic Acid
1407
A red crystal 0.4 × 0.2 × 0.01 m m was m oun ted on a glass capillary with epoxy glue an d
m easured on a Non ius KappaCCD diffractom eter usin g m on och rom atised MoKα radiation
–
1
(
λ = 0.71073 Å) at 150(2) K. Absorption was n eglected (µ = 0.669 m m ). A total of 21 891
m easured reflection s in th e ran ge h = –13 to 13, k = –11 to 11, l = –22 to 2 (θm ax = 27.5°), of
wh ich 7099 were un ique (Rin t = 0.044), 6553 were observed accordin g to th e I > 2σ(I) crite-
rion . Cell param eters were obtain ed from 3745 reflection s (θ = 1–27.5°). Th e structure was
2
5
2
solved by direct m eth ods (SIR92) an d refin ed by full-m atrix least squares based on F
(
2
6
SHELXL97) . Th e h ydrogen atom s on carbon s were fixed in idealised position s (ridin g
m odel) an d assign ed tem perature factors Hiso(H) = 1.2 Ueq(pivot atom ). Th e refin em en t
con verged (∆/σm ax = 0.002) to R = 0.032 for observed reflection s an d wR = 0.071, GOF =
1
.040 for 406 param eters an d all 7099 reflection s. Th e fin al differen ce m ap displayed n o
–
3
peaks of ch em ical sign ifican ce (∆ρm ax = 0.324, ∆ρm in = –0.324 e Å ). CCDC 261140 con tain s
th e supplem en tary crystallograph ic data for th is paper. Th ese data can be obtain ed free of
ch arge via www.ccdc.cam .ac.uk/con ts/retrievin g.h tm l (or from th e Cam bridge Crystallo-
graph ic Data Cen tre, 12, Un ion Road, Cam bridge, CB2 1EZ, UK; fax: +44 1223 336033; or
deposit@ccdc.cam .ac.uk).
Th e m ass spectra of com poun d 4 were m easured on a ZAB-SEQ double-focusin g m ass
spectrom eter (VG An alytical). Th e fast atom beam used was gen erated from xen on ion s,
wh ich were accelerated to 8 kV. Th e liquid m atrix of bis(2-h ydroxyeth yl)disulfide (DS) was
used for m easurem en t. Th e sam ples were dissolved in ch loroform an d added to th e m atrix.
For h igh -resolution m easurem en ts th e in strum en t was tun ed to a resolution of 5000 (10%
valley defin ition ).
Note: High -purity argon atm osph ere sh ould be used in th e alkylation reaction . Argon -
vacuum lin e is stron gly recom m en ded. Th e use of tech n ical n itrogen in stead of h igh -purity
argon leads to oxidation of carban ion s.
Nickel(II) Com plex of th e Sch iff Base of (S)-N-(2-Ben zoylph en yl)-N′-ben zylprolin am ide
an d (S)-2-Am in o-3-(1-n aph th yl)propan oic Acid 3
To a stirred m ixture of 2 11–13 (10 g, 20 m m ol) an d powdered NaOH (3.6 g, 90 m m ol) in
DMF (30 m l) was added 1-(ch lorom eth yl)n aph th alen e (3.9 g, 22 m m ol) in two portion s un -
der Ar. After 1 h th e reaction m ixture was poured in to a 5% solution of citric acid (400 m l).
Th e red precipitate was filtered, wash ed with water an d air-dried for 15 h . Th e precipitate
was dissolved in MeONa/MeOH (0.5 m ol/l, 200 m l) un der Ar. After 2 h th e reaction m ixture
was poured in to 5% solution of citric acid (400 m l). Meth an ol an d a part of water were
evaporated in vacuum . Th e red precipitate was filtered off, wash ed with water an d air dried
for 15 h . Th e precipitate was purified by colum n ch rom atograph y on silica gel (80 × 5 cm ,
CHCl ). Th e first red fraction con tain s th e bis-alkylation product 4, th e secon d (m ain ) frac-
3
tion con tain s com plex 3. An alytical sam ples were addition ally purified by preparative TLC
on silica gel followed by gel ch rom atograph y on Seph adex LH-20 (toluen e/m eth an ol 2:1).
Com poun d 4: Red crystals. Yield 0.15 g (1% based on 2), m .p. 303–305 °C. EI-MS: 777.9
(
9
7
2.7%), 733.9 (18%), 636.8 (8.2%), 495.6 (10%), 439.5 (10%), 217.3 (13%), 160.3 (100%),
+
1.17 (73.6%). High resolution FAB-MS: 778.2496; for (C49H41N NiO + H ) calculated:
3 3
78.2579.
Com poun d 3: Red crystals. Yield 11 g (86% based on 2), m .p. 259–261 °C. 1H NMR
500 MHz, CDCl ): H1 1.94 H1b 3.17, H2a 1.94 H2b 3.00, H3a 2.44 H3b 2.46, H4 1.94 3Ja
(
1
=
3
a
3
0.1 Jb = 7.1, H7 8.16, H8 7.09, H9 6.60, H10 6.48, H14 7.12, H15 7.30, H16 7.20, H17
Collect. Czech. Chem. Commun. (Vol. 70) (2005)

1
408
Popkov et al.:
6
7
7
.79, H18 5.91, H19 4.42 3Ja = 7.7 3Jb = 5.0, H21 3.45 H21 4.31 2Ja = 12.7, H23 8.00, H24
a
b
3
3
3
3
.28, H25 7.12, H26 7.28, H27 8.00, H28a 3.82 Ja = 14.1 Jb = 5.0, H28b 4.05 J = 14.1 Jb
=
a
1
3
.7, H30 7.38, H31 7.76, H32 7.35, H34 7.76, H35 7.35, H36 7.19, H37 7.55. C NMR
(
125 MHz, CDCl ): C1 57.02, C2 23.63, C3 30.77, C4 70.44, C5 180.06, C7 123.18, C8
3
1
1
1
1
1
32.24, C9 120.47, C10 133.57, C11 126.11, C12 170.78, C13 134.50, C14 127.25, C15
a
28.40, C16 129.06 , C17 128.35, C18 127.49, C19 71.33, C20 178.58, C21 63.01, C22
a
33.16, C23 131.39, C24 128.76, C25 128.74 , C26 128.76, C27 131.39, C28 39.87, C29
b
c
b
c
32.55, C30 126.20, C31 128.26 , C32 125.45 , C33 131.85, C34 128.15 , C35 128.74 , C36
a, b,
c
25.75, C37 123.40, C38 133.11 (
Note: Som e assign m en ts of n aph th alen e rin g carbon s in 13C NMR spectrum of 3 h ave a
– assign m en t can be in terch an ged).
sm aller con fiden ce, because experim en ts were m ade in in version m ode an d resolution in F1
axis was n ot so good from poin t of view of very crowded spectrum area belon gin g to th e
n aph th alen e carbon s an d proton s (even in 125 an d 500 MHz spectra, respectively). For
C38H33N NiO (637.2) calculated: 71.49% C, 5.21% H, 6.58% N; foun d: 71.68% C, 5.22% H,
3
3
6
.52% N.
(
S)-2-Am in o-3-(1-n aph th yl)propan oic Acid 1
A m ixture of 3 (9.5 g, 15 m m ol), 50 m l MeOH an d 6 M HCl was refluxed for 1 h an d th en
evaporated to dryn ess. Water (50 m l) was added to th e residue an d th e in soluble m aterial
(
(
correspon din g to BPB·HCl) was filtered off, wash ed with water (4 × 50 m l), dried an d stored
sim ilar to ref.15). Un der stirrin g, pH of th e water solution was adjusted to 9–10 with aque-
ous NH , th e precipitate of 1 was filtered off, wash ed with ch loroform (40 m l), water (100 m l),
3
cold MeOH (40 m l), an d dried.
2
D
1
27
Am in o acid 1: Yield (73% based on 3), m .p. 229–231 °C. [α ] –15.0 (c 1, 0.3 M HCl), ref.
2
0
1
3
3
[
α ] –15.0 (c 0.97, 0.3 M HCl). H NMR (500 MHz, CDCl ): H19 4.56 Ja = 9.2 Jb = 5.9, H28a
D
3
3
.64 3Ja = 14.8 Jb = 5.9, H28b 4.05 Ja = 14.8 Jb = 9.2, H30 7.58, H31 7.63, H32 8.06, H34
3
3
3
1
3
8
.12, H35 7.73, H36 7.78, H37 8.22. C NMR (125 MHz, CDCl ): C19 56.05, C20 174.11,
3
C28 35.89, C29 136.53, C30 131.19, C31 128.52, C32 131.57, C33 132.82, C34 131.87, C35
1
6
29.15, C36 129.77, C37 125.63, C38 133.88. For C13H13NO2 (215.3) calculated: 72.54% C,
.09% H, 6.51% N; foun d: 72.67% C, 6.15% H, 6.40% N.
The authors thank Dr M. Durchan for assistance in circular dichroism spectra measurement and
Dr K. Ubik for recording the mass spectra. Access to Jasco J-715 (grant MSMT 123100002) is ac-
knowledged.
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2
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