Chiral N(H)-tBu and N(H)-Ad NiII complexes of glycine schiff bases: Deduction of a mode of kinetic diastereoselectivity

Article abstract of DOI:10.1002/ejoc.201402145

The results reported herein have led to the discovery of a novel mode of kinetic diastereoselectivity in the alkylation of N-tert-butyl- and N-(1-adamanyl)-containing Ni^II complexes of glycine Schiff bases. It arises from a significant differen

Full text of DOI:10.1002/ejoc.201402145

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FULL PAPER
DOI: 10.1002/ejoc.201402145
Chiral N(H)-tBu and N(H)-Ad NiII Complexes of Glycine Schiff Bases:
Deduction of a Mode of Kinetic Diastereoselectivity
Miguel A. Maestro,[a] Fernando Avecilla,[a] Alexander E. Sorochinsky,[b,c,d] Trevor K. Ellis,[e]
José Luis Aceña,[b] and Vadim A. Soloshonok*[b,c]
Keywords: Asymmetric synthesis / Schiff bases / Nickel / Diastereoselectivity
The results reported herein have led to the discovery of a
novel mode of kinetic diastereoselectivity in the alkylation of
N-tert-butyl- and N-(1-adamanyl)-containing NiII complexes
of glycine Schiff bases. It arises from a significant difference
in the steric shielding between the N-H and N-tBu/Ad sides
of the NiII coordination plane, directing the incoming electro-
phile towards the former.
Mannich,[8] and Michael[9] addition reactions can be con-
ducted at ambient temperature under scalable and opera-
Introduction
From the very beginning of organic chemistry as a scien- tionally convenient reaction conditions.[10]
tific discipline, the synthesis of α-amino acids (α-AAs) has
been a topic of significant interest.[1,2] The special appeal of
α-AAs as synthetic targets stems from their multidiscipli-
nary applications ranging from the origin of life to the de-
sign of modern pharmaceuticals. Over the years, the study
of chemistry associated with α-AAs has resulted in an enor-
mous wealth of methodologies addressing numerous as-
pects of α-AAs synthesis, particularly in enantiomerically
pure form.[3,4] The asymmetric synthesis of α-AAs by alkyl-
ation of glycine derivatives provides one of the most gener-
alized and robust approaches to the preparation of structur-
ally and functionally diverse tailor-made α-AAs.[2] Among
numerous chiral glycine derivatives developed in this area,
the NiII complexes of glycine Schiff base 1a and its deriva-
tives offer some attractive features, especially with regards
to practicality, rendering this type of glycine template of
special interest (Scheme 1).[2a–2c] For example, the homolo-
gation of 1a and its analogues by alkylation,[5,6] aldol,[7]
Scheme 1. Stereochemical outcome of the kinetically controlled
alkylation of chiral NiII complexes 1a,b.
The alkylation of complex (S)-1a is usually conducted
under homogeneous thermodynamically controlled condi-
tions resulting in 90–95% diastereomeric excess of the
major (S,S)-configured product 2a.[11] On the other hand,
kinetically controlled alkylation, for example, PTC alkyl-
ation of 1a occurs with a noticeably lower stereochemical
outcome of around 65% de.[12] Furthermore, PTC alkyl-
ation of the acetophenone-derived complex 1b is not stereo-
selective, giving rise to the product 2b with virtually equal
amounts of (S,S) and (S,R) diastereomers. These data are
clearly pointing to the benzophenone phenyl group as a ste-
reocontrolling feature in the alkylation of glycine derivative
1a.
The established mechanistic rationale for the origin of
stereocontrol in the alkylation of 1a is presented in Fig-
ure 1.[12a] According to crystallographic data available in
the literature for NiII complexes of this type,[13] all NiII-
bonded/coordinated atoms, three nitrogen and one oxygen
atom, are normally positioned in the square-planar NiII co-
ordination plane. On the other hand, the chelate rings A–C
[a] Dept. Química Fundamental, Fac. Ciencias, Universidade da
Coruña,
Campus da Zapateira, 15071 A Coruña, Spain
[b] Department of Organic Chemistry I, Faculty of Chemistry,
University of the Basque Country UPV/EHU,
Paseo Manuel Lardizábal 3, 20018 San Sebastián, Spain
E-mail: vadym.soloshonok@ehu.es
http://www.ikerbasque.net/vadym.soloshonok
[c] IKERBASQUE, Basque Foundation for Science,
Alameda Urquijo, 36-5 Plaza Bizkaia, 48011 Bilbao, Spain
[d] Institute of Bioorganic Chemistry & Petrochemistry, National
Academy of Sciences of Ukraine,
Murmanska 5, 02094 Kyiv, Ukraine
[e] Department of Chemistry and Physics, Southwestern
Oklahoma State University,
100 Campus Drive, Weatherford, OK 73096-3098, United
States of America
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201402145.
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FULL PAPER
are remarkably puckered. In the case of the enolate derived complexes 4 and 5 might result in a significantly enhanced
from (S)-configured proline, as in Figure 1, the proline five- puckering of the chelate rings leading, in turn, to a more
membered ring is bent down, rendering the corresponding pronounced steric shielding of the corresponding enolate by
stereogenic nitrogen atom of (R) absolute configuration. the benzophenone phenyl group.
Ring A, adjacent to the (S)-proline chelate, contains both
Intrigued by this extraordinary level of kinetically con-
stereogenic carbon and nitrogen atoms, and is also bent trolled diastereoselectivity, we decided to investigate its ori-
with the carbon atoms positioned below the NiII coordina- gin in greater detail as it may lead to the development of a
tion plane. As a result of the (S)-proline-induced geometry new generation of highly efficient NiII complexes for the
of ring A, the three carbon atoms of the six-membered general asymmetric synthesis of α-AAs. With this aim, we
ring B are above the NiII plane, with the phenyl group lo- conducted a crystallographic study of complexes 4 and 5.[15]
cated above the enolate ring C. For the origin of the dia- One of the unusual features of the structure of complex 4
stereoselectivity in question, this is the most important geo- (Figure 2) is the severe twisting of the N-tBu-containing
metrical feature, with the benzophenone phenyl ring located five-membered chelate ring with a torsion angle (N–Ni–
above the enolate Re face. Consequently, the incoming elec- NH–CH2) of 33.14°. As a possible consequence of that, the
trophile approaches the enolate from the sterically less NH nitrogen and the glycine oxygen atom are out of the
shielded Si side leading to the preferential formation of the NiII coordination plane by 2.44 and 7.28°, respectively.
α-(S)-configured product. This mode of kinetically con- However, the two other chelate rings are relatively flat. In
trolled diastereoselectivity is in agreement with the fact that particular, the most important for our study, the glycine-
alkylation of complex 1b (Scheme 1) occurs with a minute containing ring has a torsion angle of only 6.78°. Therefore,
diastereoselectivity [ca. 3% de of (S)-2b] due to the insignifi- to our surprise, the puckering of the chelate rings in the
cant shielding effect of the methyl group.
structure of N-tBu-containing glycine complex 4 is far from
unusual leading to quite an average position of the
stereocontrolling benzophenone phenyl group. Thus, al-
though the phenyl ring is tilted towards the pro-(S)-glycine
hydrogen atom, the corresponding torsion angle is only
76.58°. One may agree that, although the crystallographic
structure of complex 4 suggests some preference for the
(R*,R*) relative configuration following alkylation, it can-
not explain the experimentally observed complete kinetic
control of the stereochemical outcome. A similar set of
crystallographic features is found in the structure of the N-
Ad-derived complex 5 (Figure 3). For example, the N-Ad-
containing five-membered chelate ring is distorted by a
slightly larger torsion angle (N–Ni–NH–CH2) of 36.03°. On
the other hand, the NH nitrogen and the glycine oxygen
atom are noticeably less out of the NiII coordination plane,
at 0.42 and 5.51°, respectively. However, the position of the
benzophenone phenyl group, the most important in terms
of stereochemistry, is such that it has a torsion angle of only
89.61°. This almost perpendicular position of the phenyl
group in the N-Ad-containing complex 5 is quite dis-
appointing as in this position it would be difficult to signifi-
cantly influence the stereochemical outcome.
Figure 1. Mechanistic rationale for the diastereoselectivity in the
alkylation of the enolate (S)-3 derived from complex 1a.
Results and Discussion
In the course of our study of the chemistry of new NH-
type NiII complexes of amino acid Schiff bases, we have
discovered that, in sharp contrast to complexes 1a,b, their
alkylation can be conducted with virtually complete kinet-
ically controlled diastereoselectivity.[14] In particular, the
PTC benzylation of N-tBu- and N-(1-adamantyl)- (N-Ad)-
derived complexes 4 and 5, respectively (Scheme 2), gave
rise to a single diastereomer 6 or 7 in high chemical yields.
The relative configurations of products 6 and 7 were deter-
mined as (R*,R*), with the N-R and Bn groups in trans
positions relative to each other. It was suggested that the
presence of sterically bulky N-tBu and N-Ad groups in
Scheme 2. Kinetically controlled benzylation of NH-type com-
plexes 4 and 5.
Figure 2. Crystallographic structure of N-tBu-containing glycine
complex 4.
2
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Chiral NiII Complexes of Glycine Schiff Bases
heating ligands 11a,b in methanol in the presence of base,
glycine, and a source of NiII ions.
With complexes 12a,b in hand, we studied their PTC alk-
ylations, conducted under the standard conditions
(Scheme 4). The results were rather spectacular. Thus, the
benzylation of both 12a and 12b occurred with an impres-
sive diastereoselectivity to provide the major diastereomers
13a,b in high chemical yields and with dr values larger than
85:15. In addition to the minor diastereomers 14a,b, the
products 15a,b of benzylation of the acetophenone methyl
group were also observed in the reaction mixture (ca. 3–
5%).
Figure 3. Crystallographic structure of N-Ad containing glycine
complex 5.
Consequently, the previously suggested enhanced level of
the established mode of diastereoselectivity (Figure 1) in the
alkylation of 4 and 5 is clearly not supported by the results
of the crystallographic study. The structural features of
complexes 4 and 5 indicate that the benzophenone phenyl
group plays a rather insignificant role in controlling the
stereochemical outcome. Faced with this unexpected con-
clusion, we felt a critical need for some additional experi-
menta data. In particular, the decisive role of the phenyl
group in the previously established (Figure 1) mode of ste-
reocontrol is quite clear considering the outcome of PTC
alkylations of the acetophenone-derived complex (S)-1b
(Scheme 1), which occurs virtually without any diastereo-
selectivity. Accordingly, we decided to prepare and study
the benzylation reactions of the corresponding acetophe-
none-derived NH-type complexes bearing the same bulky
tBu and Ad groups.
Scheme 4. Benzylation of acetophenone-derived complexes 12a,b
under PTC conditions.
The new complexes 12a,b were synthesized according to
Scheme 3. The starting o-aminoacetophenone (8) was acyl-
ated with bromoacetyl bromide to give amido bromide 9,
which was treated with tert-butyl- (10a) or 1-adamantyl-
amine (10b) to give ligands 11a,b. The target complexes
12a,b were prepared according to the usual procedure[16] by
Thus, in accord with the crystallographic study, these ex-
periments have undoubtedly demonstrated that the phenyl
group in the benzophenone-derived complexes 4 and 5
plays a secondary role and that the key stereocontrolling
element is, most likely, the bulk of the N-tBu and N-Ad
groups. However, the phenyl group is still an important fac-
tor in providing complete diastereoselectivity in the alkyl-
ations of 4 and 5, presumably by delivering an additional
stereocontrolling effect that matches the stereochemical
preferences of the N-tBu and N-Ad substituents.
With these results in hand, we are now in a position to
re-examine the crystallographic structures of complexes 4
and 5 from the stand point of a specific steric effect of the
N-tBu and N-Ad groups. First, we needed to consider three
basic transition states (TSs) A–C (Figure 4) in the benz-
ylation of complexes 4, 5, and 12a,b.
According to the previous mechanistic postulations on
the alkylation of various NiII complexes of glycine Schiff
bases and the new experimental data revealed in this work,
we can suggest that only TS B fully accounts for the effect
of the steric bulk of the substituent R on the stereochemical
outcome. Thus, in the case of TSs A and C, the N-R group
is rather remote and cannot impose its steric effect directly
on the incoming electrophile. Furthermore, in the TSs A
and C, one can see some destabilizing repulsive interactions
Scheme 3. Synthesis of new acetophenone-derived complexes 12a,b. between the electrophilic phenyl group and the nBu4N+ cat-
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V. A. Soloshonok et al.
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ance 300 spectrometer using CDCl3 as internal standard. Chemical
shifts are given in ppm (δ). Coupling constants (J) are given in
Hertz (Hz). The letters br., m, s, d and t stand for broad, multiplet,
singlet, doublet and triplet, respectively. High-resolution mass spec-
tra (HRMS) were recorded with an Agilent Synapt G2 instrument
with an ESI ion trap mass spectrometer and a TOF (time-of-flight)
detector.
General Procedure for the Synthesis of Ligands 11a,b: The corre-
sponding primary amine 10a or 10b (5 equiv.) was added to a solu-
tion of 2-[(2-bromoacetyl)amino]acetophenone (9;[16] 1 equiv.) in
MeCN (0.3 m). After stirring at 60 °C for 3 h, the mixture was
cooled to room temperature, and H2O was added. The crude mix-
ture was extracted with EtOAc, dried with Na2SO4, and concen-
trated in vacuo to give the corresponding product, which was em-
ployed in the next reaction without further purification.
Figure 4. Possible transition states in the benzylation of complexes
4, 5, and 12a,b.
ion (TS A) or the benzophenone phenyl group (TS C). On
the other hand, in TS B, the electrophilic phenyl group can
be accommodated under the NiII coordination plane, pro-
vided of course that the electrophile approaches on the side
opposite the N-R group. As one can see from Figures 2 and
3, the tBu methyl as well as the Ad methylene groups effec-
tively block one side of the NiII plane directing the electro-
phile to the open opposite side. However, in the case of
acetophenone-derived complexes 12a,b, TS C can still be
2-{[2-(tert-Butylamino)acetyl]amino}acetophenone (11a): Colorless
oil, 95% yield. 1H NMR (300 MHz, CDCl3): δ = 1.21 (s, 9 H), 1.72
(br., 1 H), 2.69 (s, 3 H), 3.44 (s, 2 H), 7.15 (td, J = 7.6, 1.0 Hz, 1
H), 7.57 (td, J = 7.9, 1.5 Hz, 1 H), 7.91 (dd, J = 8.0, 1.5 Hz, 1 H),
8.86 (dd, J = 8.5, 0.9 Hz, 1 H), 12.56 (br., 1 H) ppm. 13C NMR
(75.5 MHz, CDCl3): δ = 28.7, 47.4, 50.9, 63.0, 120.8, 122.3, 122.9,
131.2, 134.4, 139.8, 173.5, 201.2 ppm. HRMS: calcd. for
realized as there may be less steric repulsion between the C14H21N2O2 [M + H]+ 249.1603; found 249.1604.
methyl and phenyl groups as compared with between two
phenyl groups. This consideration may explain the very
high, but incomplete diastereoselectivity of the benzylations
of complexes 12a,b.[17]
2-{[2-(1-Adamantylamino)acetyl]amino}acetophenone (11b): Color-
less oil, 91% yield. H NMR (300 MHz, CDCl3): δ = 1.67 (br., 6
1
H), 1.74 (br., 6 H), 2.11 (br., 3 H), 2.70 (s, 3 H), 3.47 (s, 2 H), 7.15
(t, J = 7.6 Hz, 1 H), 7.58 (t, J = 7.9 Hz, 1 H), 7.92 (dd, J = 7.9,
1.2 Hz, 1 H), 8.86 (dd, J = 8.5, 1.0 Hz, 1 H), 12.58 (br., 1 H) ppm.
13C NMR (75.5 MHz, CDCl3): δ = 28.2, 29.0, 36.1, 41.9, 45.1, 50.4,
120.3, 121.8, 122.5, 130.9, 134.0, 139.4, 173.3, 200.6 ppm. HRMS:
calcd. for C20H27N2O2 [M + H]+ 327.2073; found 327.2082.
Conclusions
The crystallographic study of complexes 4 and 5 as well
as alkylation reactions of acetophenone-derived complexes
12a,b allowed us to discover a novel mode of stereocontrol
in the reactions of NH-type NiII complexes of glycine Schiff
bases. It involves the steric shielding of one side of the NiII
coordination plane by the N-R group, forcing the approach
of the incoming electrophile to the opposite, quite open N-
H side. This mode of stereocontrol can provide complete
diastereoselectivity (Ͼ99% de) if the following conditions
are met: (1) the N-R groups are sterically bulky (tBu, Ad),
and (2) the NiII complexes are derived from o-aminobenzo-
phenone. In the latter case, the benzophenone phenyl group
provides an additional steric effect, matching the stereo-
directing pressure of the N-R group. Taking into account
that these NiII complexes, which contain a stereogenic
nitrogen atom, are inherently chiral, an understanding and
appreciation of this novel mode of stereocontrol is of great
importance in the creative structural design of new types of
NiII complexes.
General Procedure for the Synthesis of Complexes 12a,b: Glycine
(5 equiv.), Ni(NO3)2·6H2O (2 equiv.), and KOH (10 equiv.) were
added to a solution of ligand 11a or 11b (1 equiv.) in MeOH
(0.04 m). After stirring at 60 °C for 3 h, the mixture was cooled to
room temperature, and 5% aq. AcOH and ice were added. The
precipitate was collected by filtration to give the corresponding
product, which was employed in the next reaction without further
purification.
NiII Complex 12a of the Glycine Schiff Base with 11a: Red solid,
1
85% yield. H NMR (300 MHz, CDCl3): δ = 1.48 (s, 9 H), 2.44 (s,
3 H), 2.60 (d, J = 6.5 Hz, 1 H), 3.33 (d, J = 16.9 Hz, 1 H), 3.96 (d,
J = 19.5 Hz, 1 H), 4.13 (dd, J = 16.9, 7.4 Hz, 1 H), 4.29 (d, J =
19.5 Hz, 1 H), 7.06 (td, J = 7.7, 1.1 Hz, 1 H), 7.40 (td, J = 7.8,
1.4 Hz, 1 H), 7.66 (dd, J = 8.3, 1.3 Hz, 1 H), 8.25 (dd, J = 8.5,
0.9 Hz, 1 H) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 18.9, 27.9,
51.0, 58.1, 59.2, 121.6, 124.5, 126.9, 129.4, 132.2, 141.6, 169.4,
177.0, 177.8 ppm. HRMS: calcd. for C16H22N3NiO3 [M + H]+
362.1015; found 362.1014.
NiII Complex 12b of the Glycine Schiff Base with 11b: Red solid,
1
88% yield. H NMR (300 MHz, CDCl3): δ = 1.69 (br., 6 H), 2.07
(br., 6 H), 2.16 (br., 3 H), 2.42 (s, 3 H), 2.81 (d, J = 6.5 Hz, 1 H),
3.40 (d, J = 16.9 Hz, 1 H), 3.95 (d, J = 19.5 Hz, 1 H), 4.04 (dd, J
= 16.9, 7.4 Hz, 1 H), 4.29 (d, J = 19.4 Hz, 1 H), 7.04 (ddd, J = 7.7,
7.1, 1.1 Hz, 1 H), 7.38 (ddd, J = 7.8, 7.1, 1.4 Hz, 1 H), 7.64 (dd, J
= 8.3, 1.3 Hz, 1 H), 8.24 (dd, J = 8.5, 0.9 Hz, 1 H) ppm. 13C NMR
(75.5 MHz, CDCl3): δ = 18.9, 29.3, 35.8, 40.8, 49.1, 58.3, 59.2,
121.5, 124.5, 126.9, 129.4, 132.0, 141.6, 169.2, 177.3, 178.1 ppm.
HRMS: calcd. for C22H28N3NiO3 [M + H]+ 440.1484; found
440.1487.
Experimental Section
General: All reagents and solvents are commercially available and
were used as received. The reactions were monitored with the aid
of thin-layer chromatography (TLC) on precoated silica gel plates,
and visualization was carried out with UV light. Flash column
chromatography was performed with the indicated solvents on sil-
ica gel (particle size 0.040–0.063 mm). 1H and 13C NMR spectra
were recorded at 300 and 75 MHz, respectively, with a Bruker Av-
General Procedure for the Benzylation of Complexes 12a,b: A 30%
aq. solution of NaOH (40 equiv.) was added to a solution of NiII
4
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Chiral NiII Complexes of Glycine Schiff Bases
complex 12a or 12b (1 equiv.) in (CH2Cl)2 (0.25 m) followed by
tetra-n-butylammonium iodide (TBAI; 10 mol-%) and BnBr
(1.5 equiv.). After stirring at room temperature for 2 h, the mixture
was diluted with H2O, and the crude mixture was extracted with
CH2Cl2, dried with Na2SO4, concentrated in vacuo, and purified
by column chromatography on silica (CH2Cl2/acetone, 4:1 to 1:5).
2 H), 7.11 (t, J = 7.3 Hz, 1 H), 7.31–7.36 (m, 3 H), 7.43 (ddd, J =
7.7, 7.1, 1.2 Hz, 1 H), 7.67 (d, J = 8.3 Hz, 1 H), 8.19 (d, J = 8.6 Hz,
1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 19.9, 29.3, 35.6, 39.6,
40.5, 48.7, 58.1, 70.2, 121.7, 125.2, 127.3, 128.4, 128.8, 129.5, 130.2,
131.9, 135.1, 141.2, 170.8, 177.5, 179.9 ppm.
1
Data for the Major Isomer of 15b: H NMR (300 MHz, CDCl3): δ
Benzylation of 12a: The reaction afforded the (R*,R*)-NiII complex
13a of the phenylalanine Schiff base with 11a in 77% yield, the
corresponding (S*,R*)-NiII complex 14a in 9% yield, and the
(R*,R*)- and (S*,R*)-NiII complexes 15a of the phenylalanine
Schiff base with 1-(2-{[(2-tert-butylamino)acetyl]amino}phenyl)-3-
phenylpropan-1-one in 5% yield as a mixture of isomers.
= 1.62 (br., 6 H), 1.83 (br., 6 H), 2.09 (br., 3 H), 3.00–3.18 (m, 5
H), 3.20–3.35 (m, 2 H), 3.61 (dd, J = 13.4, 3.2 Hz, 1 H), 4.84 (dd,
J = 4.6, 3.7 Hz, 1 H), 7.10 (ddd, J = 7.6, 7.2, 0.8 Hz, 1 H), 7.27–
7.44 (m, 8 H), 7.56–7.61 (m, 3 H), 7.79 (d, J = 7.5 Hz, 1 H), 8.27
(dd, J = 8.5, 0.8 Hz, 1 H) ppm. 13C NMR (75.5 MHz, CDCl3): δ
= 29.2, 32.3, 34.7, 35.6, 40.5, 40.6, 49.0, 57.8, 70.4, 121.4, 124.0,
125.7, 127.1, 127.8, 127.9, 128.7, 129.0, 129.4, 131.4, 132.4, 135.8,
138.8, 142.6, 169.8, 176.2, 178.2 ppm. HRMS: calcd. for
C36H40N3NiO3 [M + H]+ 620.2423; found 620.2422.
1
Data for 13a: H NMR (300 MHz, CDCl3): δ = 1.25 (s, 9 H), 2.05
(br., 1 H), 2.49 (s, 3 H), 3.00 (d, J = 16.6 Hz, 1 H), 3.15 (dd, J =
13.4, 5.2 Hz, 1 H), 3.40 (dd, J = 16.6, 7.4 Hz, 1 H), 3.60 (dd, J =
13.5, 3.5 Hz, 1 H), 4.47 (dd, J = 5.0, 3.7 Hz, 1 H), 7.03 (t, J =
7.6 Hz, 1 H), 7.32–7.41 (m, 3 H), 7.53–7.59 (m, 3 H), 7.70 (dd, J
= 8.3, 1.0 Hz, 1 H), 8.21 (d, J = 8.5 Hz, 1 H) ppm. 13C NMR
(75.5 MHz, CDCl3): δ = 17.9, 27.6, 39.8, 50.8, 57.5, 70.6, 121.3,
123.6, 126.9, 127.7, 128.8, 129.4, 131.3, 132.3, 135.8, 141.8, 167.2,
176.2, 178.7 ppm. HRMS: calcd. for C23H28N3NiO3 [M + H]+
452.1484; found 452.1486.
Supporting Information (see footnote on the first page of this arti-
cle): NMR spectra of new compounds.
Acknowledgments
We thank IKERBASQUE, Basque Foundation for Science, the
Basque Government (SAIOTEK S-PE13UN098), the Spanish
Ministry of Science and Innovation (CTQ2010-19974) and Hamari
Chemicals (Osaka, Japan) for generous financial support. We also
thank SGIker (UPV/EHU) for HRMS analyses.
1
Data for 14a: H NMR (300 MHz, CDCl3): δ = 1.21 (s, 9 H), 2.38
(br., 1 H), 2.42 (s, 3 H), 3.14 (dd, J = 13.7, 4.8 Hz, 1 H), 3.20 (d,
J = 17.0 Hz, 1 H), 3.26 (dd, J = 13.8, 4.7 Hz, 1 H), 3.82 (dd, J =
16.9, 7.7 Hz, 1 H), 4.57 (t, J = 4.6 Hz, 1 H), 7.05–7.12 (m, 3 H),
7.31–7.37 (m, 3 H), 7.41 (ddd, J = 7.7, 7.1, 1.3 Hz, 1 H), 7.62 (dd,
J = 8.3, 1.3 Hz, 1 H), 8.18 (dd, J = 8.5, 0.9 Hz, 1 H) ppm. 13C
NMR (75.5 MHz, CDCl3): δ = 19.6, 27.7, 40.2, 50.4, 57.8, 70.2,
121.8, 125.2, 127.4, 128.7, 129.5, 130.3, 131.4, 132.0, 135.3, 141.1,
170.9, 177.4, 179.9 ppm.
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1
Data for the Major Isomer of 15a: H NMR (300 MHz, CDCl3): δ
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= 1.26 (s, 9 H), 1.77 (d, J = 6.8 Hz, 1 H), 2.97–3.16 (m, 5 H), 3.20–
3.31 (m, 1 H), 3.37 (dd, J = 16.6, 7.4 Hz, 1 H), 3.62 (dd, J = 13.4,
3.4 Hz, 1 H), 4.47 (dd, J = 4.8, 3.6 Hz, 1 H), 7.10 (ddd, J = 7.6,
7.1, 1.0 Hz, 1 H), 7.27–7.46 (m, 8 H), 7.55–7.62 (m, 3 H), 7.79 (dd,
J = 8.3, 1.0 Hz, 1 H), 8.26 (dd, J = 8.5, 1.0 Hz, 1 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 27.7, 32.4, 34.8, 40.5, 50.9, 57.6,
70.4, 121.5, 123.9, 125.7, 127.2, 127.8, 127.9, 128.8, 129.1, 129.5,
131.4, 132.5, 135.8, 138.8, 142.6, 169.9, 176.1, 178.2 ppm. HRMS:
calcd. for C30H34N3NiO3 [M + H]+ 542.1954; found 542.1956.
Benzylation of 12b: The reaction afforded the (R*,R*)-NiII complex
13b of the phenylalanine Schiff base with 11b in 75% yield, the
corresponding (S*,R*)-NiII complex 14b in 13% yield, and the
(R*,R*)- and (S*,R*)-NiII complexes 15b of the phenylalanine
Schiff base with 1-(2-{[2-(1-adamantylamino)acetyl]amino}-
phenyl)-3-phenylpropan-1-one in 3% yield as a mixture of isomers.
Data for 13b: 1H NMR (300 MHz, CDCl3): δ = 1.59 (br., 6 H),
1.83 (br., 6 H), 1.94 (br., 1 H), 2.05 (br., 3 H), 2.48 (s, 3 H), 3.10
(d, J = 16.5 Hz, 1 H), 3.18 (d, J = 9.4 Hz, 1 H), 3.33 (dd, J = 16.3,
6.2 Hz, 1 H), 3.59 (d, J = 12.2 Hz, 1 H), 4.42 (br., 1 H), 7.02 (t, J
= 7.6 Hz, 1 H), 7.30–7.40 (m, 3 H), 7.50–7.57 (m, 3 H), 7.69 (d, J
= 8.1 Hz, 1 H), 8.22 (d, J = 8.4 Hz, 1 H) ppm. 13C NMR
(75.5 MHz, CDCl3): δ = 17.8, 29.1, 35.6, 39.4, 40.6, 48.9, 57.7, 70.1,
121.1, 123.6, 126.8, 127.6, 128.6, 129.4, 131.1, 132.1, 135.8, 141.8,
167.3, 176.3, 178.6 ppm. HRMS: calcd. for C29H34N3NiO3 [M +
H]+ 530.1954; found 530.1959.
1
Data for 14b: H NMR (300 MHz, CDCl3): δ = 1.60–1.75 (m, 12
H), 2.08 (br., 3 H), 2.16 (br., 1 H), 2.53 (s, 3 H), 3.10 (dd, J = 13.6,
4.9 Hz, 1 H), 3.23–3.31 (m, 1 H), 3.27 (d, J = 17.0 Hz, 1 H), 3.80
(dd, J = 16.8, 7.7 Hz, 1 H), 4.60 (t, J = 4.4 Hz, 1 H), 7.03–7.08 (m,
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Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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V. A. Soloshonok et al.
FULL PAPER
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[15]
[16]
CCDC-977565 (for 4) and -977566 (for 5) contain the supple-
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can be obtained free of charge from The Cambridge Crystallo-
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[17] The following possible explanation for the observed kinetic
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zation the alkylation would be expected to occur from the face
corresponding to the top of the pyramid. As Seebach had
shown,[18] even a slight pyramidalization may cause very high
levels of diastereoselectivity in such cases. The pyramidali-
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methylene unit to be alkylated can be classified in a pseudo-
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Thus the effect of the remote N-substituent would be the induc-
tion of a conformational bias of the square-planar complex
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Received: February 25, 2014
Published Online: ᭿
6
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Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O42145
/KAP1
Date: 26-05-14 17:46:20
Pages: 7
Chiral NiII Complexes of Glycine Schiff Bases
Schiff Base Ni Complexes
M. A. Maestro, F. Avecilla,
A. E. Sorochinsky, T. K. Ellis, J. L. Aceña,
V. A. Soloshonok* ............................. 1–7
Chiral N(H)-tBu and N(H)-Ad NiII Com-
plexes of Glycine Schiff Bases: Deduction
of a Mode of Kinetic Diastereoselectivity
The PTC alkylation of NiII complexes de-
rived from glycine and a primary amine
RNH2 proceeds predominantly in an anti
relationship with respect to the R group, as
demonstrated by crystallographic and syn-
thetic studies.
Keywords: Asymmetric synthesis / Schiff
bases / Nickel / Diastereoselectivity
Eur. J. Org. Chem. 0000, 0–0
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