Investigation on the weak interactions assembling the crystal structures of Betti bases

Article abstract of DOI:10.1039/c2ce06295j

The crystal structures of (S, S)-aminobenzylnaphthols, easily produced by a chromatography-free highly stereoselective Betti reaction, were investigated by means of single crystal X-ray diffraction analysis, and the main intra- and intermolecular interactions were described. The presence of a strong intramolecular hydrogen bond was confirmed, whereas the whole crystal building was found to be due mainly to other bondings, such as CH...O and CH...π interactions. As far as the last interactions were concerned, we observed many short distances from one hydrogen atom to an aryl plane, together with the appropriate geometric requirements for the assemblies. The observations suggest that these interactions can play a relevant role in the crystal building. The absence of similar short distance CH...π interactions in the crystal of a diastereomeric (R, S)-aminobenzylnaphthol could be a suggestion of the preferential crystallisation of the (S, S)-stereoisomer and, consequently, its prevalence as a product of the Betti reaction.

Full text of DOI:10.1039/c2ce06295j

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PAPER
Investigation on the weak interactions assembling the crystal structures of
Betti bases{{
Cosimo Cardellicchio,*a Maria Annunziata M. Capozzi,b Angel Alvarez-Larena,c Joan F. Piniellac and
Francesco Capitellid
Received 29th September 2011, Accepted 9th March 2012
DOI: 10.1039/c2ce06295j
The crystal structures of (S, S)-aminobenzylnaphthols, easily produced by a chromatography-free
highly stereoselective Betti reaction, were investigated by means of single crystal X-ray diffraction
analysis, and the main intra- and intermolecular interactions were described. The presence of a strong
intramolecular hydrogen bond was confirmed, whereas the whole crystal building was found to be
…
…
due mainly to other bondings, such as CH O and CH p interactions. As far as the last interactions
were concerned, we observed many short distances from one hydrogen atom to an aryl plane,
together with the appropriate geometric requirements for the assemblies. The observations suggest
that these interactions can play a relevant role in the crystal building. The absence of similar short
…
distance CH p interactions in the crystal of a diastereomeric (R, S)-aminobenzylnaphthol could be a
suggestion of the preferential crystallisation of the (S, S)-stereoisomer and, consequently, its
prevalence as a product of the Betti reaction.
this projection from the centroid of the aryl moiety is
minimal.2–5
…
Introduction
Crystal engineering is concerned both with the understanding of
the intermolecular interactions in the context of crystal packing,
and with the application of the relevant ideas to the design of
new solids having desired physical and chemical properties.1
Hydrogen bond, that is both strong and directional, is the most
reliable among such intermolecular interactions.1–3 In recent
In the C–H p interactions, the distances from the hydrogen
atom to the aryl plane were reported to occur in the range
between 2.6 and 3.0 A,7,8 whereas cases of shorter distances were
˚
also reported.9 The strength of these weak interactions could be
increased if both the donor and the acceptor component were
activated, for example by increasing the proton donating ability,
or the electron density of the p-system. In fact, shorter distances
from the hydrogen atom to the aryl plane were observed in these
times, the concept of hydrogen bond was extended also to
4–8
…
…
…
…
C–H O, C–H N, O–H p, and finally to C–H p interactions,
that could be considered the weakest form of the hydrogen bond,1–3
even if no general consensus6 has been expressed towards this
position. The main criticism is due to the multi-atom nature of
the p-acceptor and to the somehow missing directionality
requirements.2,3 Since each crystal structure is a result of many
compromises, weaker hydrogen bonds are more likely to be
bent. However, higher bonding energies were calculated when
the angle between the CH bond and the projection of the
H-atom on the aryl plane gets closer to 180u, and the offset of
circumstances,
a fact that suggests that a real bonding
interaction is occurring.2,3
Even if weaker with respect to the other hydrogen bonds, the
possibility of multiple co-operative interactions of the same kind
…
can lead to a considerable total energy.2–4,10 In fact, CH
p
interactions have been reported to play a crucial role in many
different areas, such as supramolecular assemblies, protein
folding and drug–receptor interactions.4,5 Theoretical investiga-
tions corroborated its relevance also in asymmetric synthesis,11
as reported, among others, by Noyori et al.12 in the enantiose-
lective hydrogen transfer to carbonyl compounds from a chiral
arene-ruthenium(II) complex, by Nishibayashi et al.13 in the
enantioselective propargylic substitution reaction with a chiral
ruthenium complex, by Dudding, Houk et al. in a hetero-Diels–
Alder reaction,14 and by some of us15,16 in the enantioselective
oxidation of aryl benzyl sulfides in the presence of a chiral
titanium complex.
aCNR Istituto di Chimica dei Composti OrganoMetallici, Dipartimento di
Chimica, via Orabona 4, 70125 Bari, Italy.
E-mail: cardellicchio@ba.iccom.cnr.it; Fax: +39-0805539596;
Tel: +39-0805442077
bDipartimento di Chimica, via Orabona 4, 70125 Bari, Italy
cDepartment of Geology, Universitat Auto`noma de Barcelona, Campus
Universitari UAB, 08193, Bellaterra, Spain
dCNR Istituto di Cristallografia, via Salaria km 29,300, 00015
Monterotondo (Roma), Italy
{ Electronic Supplementary Information (ESI) available: Table of the
dihedral angles between mean aryl planes; NMR spectra of already
reported compounds. See DOI: 10.1039/c2ce06295j/
{ Dedicated to Prof. Alfredo Ricci on the occasion of his retirement.
Another fruitful research theme was the investigation on the
relative stability of the diastereomeric couples employed in the
enantiomer resolutions.17 Usually, the less soluble salt melts at
3972 | CrystEngComm, 2012, 14, 3972–3981
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higher temperature and with a larger enthalpy of fusion.17 This
…
2-naphthol, benzaldehyde or p-halobenzaldehyde with (S)-1-
arylethylamine (Scheme 2).
stability was sometimes explained by invoking C–H p interac-
tions. Cases of particular interest were reported by Saigo et al.18–20
…
The aminobenzylnaphthols 1–9 are constituted by three
different aryl groups, i.e. the naphthyl and the phenyl moieties
(Fig. 1), and a further aryl group deriving from the employed
1-arylethylamine, i.e. phenyl (molecules 1–4), 1-naphthyl (mole-
cules 5–8), or 4-methoxyphenyl group (molecule 9). The last aryl
groups are indicated with a B label (see Fig. 1) to distinguish
them from the main naphthyl or phenyl groups.
For example, more effective C–H p interactions were found in
the crystal structures of the less soluble salts of 2-naphthylglycolic
acid with 1-arylethylamines.18 Another work investigates the salts
of 2-naphthylglycolic acid with 1-phenylethylamine derivatives,
or the salts of cis-1-aminoindan-2-ol with arylalkanoic acids.
…
Numerous CH p interactions were present in the most stable
isomer of the diastereomeric couples,19,20 thus contributing to the
stability of the crystal. This result was also confirmed by
theoretical calculations.20
From a synthetic point of view, the aryl aldehyde and the (S)-
1-arylethylamine were first mixed without any solvent to yield
the corresponding imine. Then, 2-naphthol was added and the
reaction mixture was kept at 60 uC for two days. An analysis of
the crude reaction mixture shows many products, among which
the (S, S)-stereoisomers 1–9 and the corresponding unreacted
imines were predominant.
The research by some of us in the enantioselective synthesis of
sulfoxides15,16 was also accompanied by an investigation of their
crystal structures.21 Another research theme in asymmetric
synthesis deals with chiral nonracemic aminobenzylnaphthols,
easily produced by using the so-called Betti reaction.22 In this
straightforward procedure, three small components (2-naphthol,
ammonia or amines, and aryl aldehydes) condense to yield the
corresponding aminobenzylnaphthol, or Betti base. The amino-
benzylnaphthtols that were produced by using this procedure can
be easily resolved into their enantiomers.22
After our first papers on the Betti reaction,23,24 several
research groups22 applied this valuable procedure to prepare
new chiral nonracemic aminobenzylnaphthols. Among these
investigations, a new fruitful research line started with the
contemporary works of the groups of Palmieri,25,26 Forlani27
and Chan.28 In their research, 2-naphthol was reacted with an
aryl aldehyde and with (R)- or (S)-1-arylethylamine. (R, R)- or
(S, S)-aminobenzylnaphthols were obtained, when the (R)- or
the (S)-1-arylethylamine was employed, respectively. For
instance, the reaction of 2-naphthol with benzaldehyde
and (R)-1-phenylethylamine at 60 uC without any solvent
(Scheme 1)25 yielded the corresponding (R, R)-aminobenzyl-
After two days, the addition of small amounts of ethanol
caused the precipitation of a solid, that was collected and re-
crystallised to yield (S, S)-aminobenzylnaphthol 1–9 free from
significant amount of the (R, S)-stereoisomer (de . 98%). With
this easy, solventless and chromatography-free procedure,
isolated yields in the range 51-68% were obtained for the
(S, S)-aminobenzylnaphthol 1–9 (see Experimental section).
Additional material could be recovered from the mother liquor,
provided that a chromatographic separation was employed.
Since the high stereoselectivity of the reaction was reported to
be related with the crystallisation of a particular molecular
form,25 we reasoned that a comparison between the interactions
present in the crystal structures of the (S, S)- and of the (R, S)-
stereoisomers could shed light on the selectivity of the process.
However, the preparation of the crystals of the last species
appeared to be an uphill task with the previous experimental
procedure. First, we were not able to obtain satisfactory
amounts of the (R, S)-stereoisomers from the crude reaction
mixture and then, as already reported,25 spontaneous transfor-
mation into the (S, S)-counterparts occurred when the crystal
naphthol
1 in high yield (93%) and with a very high
diastereomeric ratio (. 99 : 1).
The Palmieri group explained this high stereoselectivity by
invoking an asymmetric transformation of the second kind, in
which the (R, R)-stereoisomer crystallises preferentially, and can
thus be obtained as diastereomerically pure.25 At this stage, we
decided to investigate the main interactions building the crystal
structures of a series of similar aminobenzylnaphthols 1–9,
looking for a plausible explanation of the high asymmetric
induction observed in the Betti reaction.
Results and discussion
1. Synthesis of aminobenzylnaphthols.
Scheme 2 Stereoselective Betti reaction between 2-naphthol, aryl
aldehydes and (R)- or (S)-1-arylethylamine.
(S, S)-Aminobenzylnaphthols 1,25,27 2, 3,25,29 4,29 5,30 and 6–9
were obtained by a Betti reaction of commercially available
Fig. 1 Naming of the aryl groups in the aminobenzylnaphthols 1–9.
CrystEngComm, 2012, 14, 3972–3981 | 3973
Scheme 1 The Betti reaction with nonracemic 1-phenylethylamine.
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was grown. Finally, we succeeded in producing small amounts of
only (R, S)-1 by using a variation of the method reported by
Forlani et al.,27 in which a mixture of almost equal amounts of
the two diastereoisomers was produced. The (R, S)-1 was
isolated after crystallisations (see Experimental section), and
soon analysed. We observed that the aminobenzylnaphthol (R,
S)-1 has a low melting point (135–137 uC against 155–156 uC for
(S, S)-1). A DSC analysis confirmed these values.
2. Crystal structures of the aminobenzylnaphthols
2.1 General considerations. A systematic synthetic work was
performed to prepare (S, S)-2–4 and 6–8 aminobenzylnaphthols,
in which the sequence fluorine–chlorine–bromine atoms was
added to the prototypal (S, S)-1 or (S, S)-5 compounds.
Molecule 9 completes the screening. The crystal structures of
(S, S)-aminobenzylnaphthols 2–4 and 6–9 were determined in
this work, whereas the crystal structures of (S, S)-1 and (R, R)-5,
reported by Forlani et al.27 and Szatmari et al.,30 respectively,
are considered herein for comparison.
The crystal structures of (S, S)-2–4 and 6–9 are orthorhombic
and their space group is P212121. The molecular representation
and the atomic numbering are reported in Fig. 2–8, whereas
crystallographic data are reported in Table 1. Intramolecular
Fig. 3 ORTEP plot of aminobenzylnaphthol (S, S)-3.
…
hydrogen bonds and intermolecular CH O interactions are
summarised in Table 2.
The common characteristic of the aminobenzylnaphthols 1–9
…
is a strong O–H N intramolecular hydrogen bond formed by a
hydroxyl group and a nitrogen atom, observed for the Betti base
since 1954 with IR spectroscopy.31 In structures (S, S)-1–9, the
˚
H???N distances are in the range 1.70–1.93 A (Table 2).
…
The O–H N angles are in the range 139–151u. In principle,
the presence of the nitrogen atom in the aminobenzylnaphthols
investigated herein could provide a further acceptor for donor-
H???N hydrogen bonds. However, we observed that this atom is
not involved into any interaction in the aminobenzylnaphthols
2–9, a situation that occurred also in an investigation on similar
structures reported by Alfonsov et al.32
The most interesting aspect of the aminobenzylnaphthols 1–9
…
is the presence of a series of short distance CH p interactions.
Fig. 4 ORTEP plot of aminobenzylnaphthol (S, S)-4.
When these interactions involve aryl hydrogen atoms as donors,
a characteristic T-shape arrangement of the aryl groups is
observed. In Table 3, we have collected a selection of the most
relevant distances and angles describing these interactions.4–7
2.2 (S, S)-1 stereoisomer. The investigation on the crystal
structure of the prototypal aminobenzylnaphthol (S, S)-127
showed that two molecules are present in the asymmetric unit
…
and are bound together by a series of mutual C–H
p
interactions (Fig. 9). In fact, the Hortho and the Hmeta of the
phenylB group of one molecule interact with the naphthyl moiety
of the other molecule, the distances from these atoms to the
…
naphthyl plane being 2.49 A (Table 3, C21–H21 Np2) and
˚
…
˚
2.82 A (Table 3, C22–H22 Np1) respectively. The value of
˚
2.49 A is one of the shortest distances ever reported for this type
of interaction.4-5,9 The distance from the projection of this atom
Fig. 2 ORTEP plot of aminobenzylnaphthol (S, S)-2.
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Fig. 8 ORTEP plot of aminobenzylnaphthol (S, S)-9.
˚
to the centroid of the aryl group is 0.39 A and the angle between
Fig. 5 ORTEP plot of aminobenzylnaphthol (S, S)-6.
the C–H bond and the projection of the hydrogen atom in the
mean aryl plane is 153u. These geometric characteristics
corroborate the fact that this interaction should be relatively
strong.
The phenylB group is also the H-acceptor of a different
interaction with one hydrogen atom of the phenylB group of the
B
other molecule (Table 3, C25–H25 Ph ), the distance from the
…
…
˚
hydrogen atom to the aryl plane being 2.74 A (C–H Hp angle
of 172u). Finally, one hydrogen atom of the naphthyl group
interacts with the naphthyl moiety of the other molecule
…
(Table 3, C8–H8 Np2). The distance from the hydrogen atom
˚
˚
to the naphthyl plane is 2.69 A and a 0.10 A distance from the
projection of this atom to the centroid of the aryl group was
measured.
The contemporary measure of various short distances from
the hydrogen atoms to the aryl planes, together with suitable
…
orientation requirements, suggest that these CH p interactions
should give a large contribution to the stabilisation of the
structure.4–7
Fig. 6 ORTEP plot of aminobenzylnaphthol (S, S)-7.
2.3 (R, S)-1 stereoisomer. The crystal structure of (R, S)-1
stereoisomer is monoclinic and its space group is P21 (Fig. 10).
Only one molecule is hosted in the asymmetric unit. Only one
…
main CH p interaction was observed, involving the Hmeta of the
phenylB group, which is 2.81 A distant from the plane of the
˚
…
naphthyl group (Table 3, C17–H17 Np1). This distance is
much longer than the many distances hydrogen atom/aryl plane
observed in the (S, S)-stereoisomer, thus suggesting a weaker
interaction and a consequent less stable crystal, as indicated also
by a lower melting point.
…
The safest way to detect the presence of CH p interactions is
by far the measurement, in the analysis of the crystal structures,
˚
of distances in the range 2.6–3.0 A, or below, from the hydrogen
atom to the aryl planes, together with appropriate directionality
requirements.4–8
However, other confirmations could be obtained also by using
spectroscopic techniques.4,5 For example, we examined the IR
spectra of the couple (S, S)-1 and (R, S)-1. A low-frequency shift
(5–22 cm21) is expected when this type of interaction is present.5
In this respect, since the crystal structure analysis revealed the
Fig. 7 ORTEP plot of aminobenzylnaphthol (S, S)-8.
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Table 1 Crystallographic data
(S, S)-2
(S, S)-3
(S, S)-4
(S, S)-6
Code name
G15
C25H22FNO
Nonius Kappa CCD
COLLECTa
371.44
F9
F13
G11
C29H24FNO
Nonius Kappa CCD
COLLECTa
421.49
Empirical formula
Diffractometer
Data collection software
Formula weight
T/K
C25H22ClNO
Bruker SMART APEX
SMARTb
387.89
293(2)
C25H22BrNO
Bruker SMART APEX
SMARTb
432.35
293(2)
293(2)
293(2)
˚
Radiation, l/A
Mo-Ka, 0.71073
128, 3.21u–20.03u
Orthorhombic
P212121
Mo-Ka, 0.71073
2160, 2.53u–20.71u
Orthorhombic
P212121
Mo-Ka, 0.71073
4533, 2.29u–22.52u
Orthorhombic
P212121
Mo-Ka,0.71073
108, 3.11u–20.57u
Orthorhombic
P212121
Cell reflections, h range
Crystal system
Space group
˚
a/A
10.687(2)
12.122(2)
15.549(3)
90
2014.3(7)
4, 1.225
0.080
784
10.6982(8)
12.1633(9)
15.7632(12)
90
2051.2(3)
4, 1.256
10.6828(6)
12.1716(7)
15.9649(9)
90
2075.8(2)
4, 1.383
8.2095(5)
˚
b/A
14.0391(8)
19.7711(12)
90
2278.7(2)
4, 1.229
˚
c/A
b (u)
3
˚
V/A
Z, rc/Mg m23
m/mm21
F(000)
0.201
816
1.995
888
0.079
888
Crystal size/mm
Shape, Colour
Data collection h range
Refl. collected/unique
R(int)
0.56 6 0.34 6 0.20
prism, colourless
2.13–29.18u
14 042/4931
0.030
0.28 6 0.24 6 0.23
prism, colourless
2.11–29.03u
14 206/4998
0.036
0.58 6 0.52 6 0.50
block, colourless
2.10–29.02u
14 211/5019
0.027
0.40 6 0.40 6 0.20
prism, colourless
1.78–29.06u
15 886/5561
0.024
Max. and min. trans.
Refinement method
Data/restraints/param.
GOF
0.9841 and 0.9564
FMLS on F2
4931/0/257
1.006
0.9552 and 0.9458
FMLS on F2
4998/0/257
1.1015
0.4353 and 0.3908
FMLS on F2
5019/0/257
0.898
0.9843 and 0.9689
FMLS on F2
5561/0/293
1.032
Final R indices [I . 2s(I)] R1 = 0.0471; wR2 = 0.0836 R1 = 0.0490; wR2 = 0.0887 R1 = 0.0356; wR2 = 0.0666 R1 = 0.0460; wR2 = 0.0994
R1 = 0.0919; wR2 = 0.0976 R1 = 0.0922, wR2 = 0.1060 R1 = 0.0552, wR2 = 0.0707 R1 = 0.0662, wR2 = 0.1080
Final R indices (all data)
Flack parameter
˚
Larg. diff. peak/hole/e A
0.3(11)
0.122 and 20.129
0.02(7)
0.120 and 20.193
0.008(7)
0.637 and 20.238
0.0(10)
0.129 and 20.149
23
(S, S)-7
(S, S)-8
(S, S)-9
(R, S)-1
Code name
FF4
C
FF3
F1
CB63
Empirical formula
Diffractometer
Data colletion software
Formula weight
T/K
29H24ClNO
C29H24BrNO
Nonius Kappa CCD
COLLECTa
482.40
C26H25NO2
Bruker SMART APEX
SMARTb
383.47
293(2)
C25H23NO
Nonius Kappa CCD
COLLECTa
353.44
Nonius Kappa CCD
COLLECTa
437.94
293(2)
293(2)
293(2)
˚
Radiation, l/A
Mo-Ka, 0.71073
147, 3.95u–20.03u
Orthorhombic
P212121
Mo-Ka, 0.71073
144, 4.32u–18.49u
Orthorhombic
P212121
Mo-Ka, 0.71073
3366, 2.17u–18.65u
Orthorhombic
P212121
Mo-Ka, 0.71073
95, 3.60u–20.28u
Monoclinic
P21
Cell reflections, h range
Crystal system
Space group
˚
a/A
10.7520(7)
13.3730(17)
16.005(3)
90
2301.3(5)
4, 1.264
0.187
920
10.7830(5)
13.4940(19)
15.938(2)
90
2319.1(5)
4, 1.382
1.794
992
15.510(3)
15.661(3)
17.891(4)
90
4345.5(15)
8, 1.172
0.073
7.1201(6)
8.2128(7)
17.3792(6)
101.64(1)
995.4(1)
2, 1.179
0.071
376
˚
b/A
˚
c/A
b (u)
3
˚
V/A
Z, rc/Mg m23
m/mm21
F(000)
1632
Crystal size/mm
Shape, colour
Data collection h range
Refl. collected/unique
R(int)
0.45 6 0.50 6 0.55
prism, colourless
5.03u–27.50u
16 091/5123
0.074
0.50 6 0.50 6 0.55
prism, colourless
5.01u–27.50u
21 983/5188
0.071
0.52 6 0.34 6 0.23
block, colourless
1.73u–29.02u
30 166/10 679
0.044
0.75 6 0.25 6 0.20
prism, colourless
5.07u–27.53u
11 734/4444
0.126
Max. and min. trans.
Refinement method
Data/restraints/param.
GOF
0.9121 and 0.9121
FMLS on F2
5123/0/293
1.062
0.4674 and 0.4387
FMLS on F2
5188/0/293
1.088
0.9833 and 0.9628
FMLS on F2
10 679/0/531
0.931
0.9859 and 0.9486
FMLS on F2
4444/1/248
1.008
Final R indices [I . 2s(I)]
Final R indices (all data)
Flack parameter
R1 = 0.0579; wR2 = 0.0968 R1 = 0.0517; wR2 = 0.1021 R1 = 0.0499; wR2 = 0.0849 R1 = 0.0719; wR2 = 0.1051
R1 = 0.1217; wR2 = 0.1191 R1 = 0.1258; wR2 = 0.1264 R1 = 0.1532; wR2 = 0.1114 R1 = 0.1836; wR2 = 0.1386
20.01(9)
0.167 and 20.272
0.046(12)
0.292 and 20.519
0.4(12)
0.106 and 20.093
0(3)
0.168 and 20.166
23
˚
Larg. diff. peak/hole/e A
a
b
Nonius, COLLECT and EVAL. 2002 Nonius BV, Delft, The Netherlands. Bruker, SMART. 2002 Bruker AXS Inc., Madison, Wisconsin,
USA.
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presence of some T-shape interactions between the aryl moieties,
we focused on the signals relative to these groups. In particular,
we detected the aryl CH-stretching. Among the others, we
observed in the IR spectra (KBr pellets) a sequence of signals of
3065, 3057, 3049 and 3031 cm21 for the (R, S)-1 compound,
whereas the same sequence moves to 3056, 3048, 3034 and
3023 cm21 for the (S, S)-1, as expected from the presence of these
On the other hand,
a
relevant intramolecular T-shape
arrangement is found between the phenyl and the naphthyl
…
group (Table 3, C18–H18 Np2). In particular, the distances
from the hydrogen atom of the phenyl group to the naphthyl
˚
plane are short in the case of compounds 3 and 4 (2.65 A and
˚
˚
2.60 A, Table 3) and slightly longer in molecule 2 (2.73 A
Table 3). The distances from the projections of the hydrogen
atoms to the centroid of the aryl groups are in the range 0.33–
interactions in the (S, S)-1 stereoisomer.
…
˚
0.46 A, another hint that these interactions are strong and
Usually, another confirmation of the presence of CH
p
should contribute largely to the stabilisation of the crystals.
interactions is the upfield variation of the chemical shifts of the
1
involved proton in the H-NMR spectra.4,5,33 In the case of the
Representative compound 4 and its interactions are depicted in
Fig. 13.
…
couple of stereoisomers (S, S)-1 and (R, S)-1, we observed a
clearly different pattern between the aryl hydrogen atoms of the
(S, S)-1 and those of (R, S)-1. Most of the aryl signals of (S, S)-1
moved upfield (see ESI),{ but the complexity of the spectra did
not allow to attribute each signal. However, it seems safer to
draw our conclusions on the unambiguous results deriving from
the structural data of the crystals and of the IR spectra, since
NMR spectra refer to samples in solution.
Another CH
p interaction drawn in Fig. 13 for the
representative compound 4 involves one hydrogen atom of the
naphthyl with the plane of the phenylB group (Table 3,
B
C8–H8 Ph ). The distances from this hydrogen atom to the
…
phenylB plane are in the range 2.72–2.78 A for compounds 2–4,
˚
…
slightly longer than the other ones, but having the C–H Hp
angles in the range 172–176u.
…
A further CH p interaction, characterised by a longer
2.4 (S, S)-Stereoisomers 2–9. Only one molecule is hosted in
the asymmetric unit of the (S, S)-2–8 molecules. The crystal
structures of compounds (S, S)-2, (S, S)-3, and (S, S)-4, differing
only in the type of halogen atom, are isostructural (Fig. 11). The
RMS of the distances between equivalent carbon, nitrogen, and
oxygen atoms after performing a best molecular fit (BMF) is
0.041 for 2 and 3, 0.050 for 3 and 4, and 0.079 for 2 and 4.
hydrogen atom/aryl plane distance, was found from one
hydrogen atom of the phenylB group (Table 3, C21–
…
H21 Np1) to the plane of the naphthyl moiety, the distances
˚
A
being in the range 2.78–2.91
for compounds 2–4.
A
representative example is depicted in Fig. 14 for aminobenzyl-
naphthol 2.
The crystal of (S, S)-6 results in being isostructural with (S, S)-
5, obtained by inverting the structure reported30 for (R, R)-5
(Fig. 15), the RMS of the BMF being 0.102. In this couple, the
ArB ring adopts a conformation that differs from the molecules
2–4 and 7, 8. In fact, in these last aminobenzylnaphthols, the
angles between the arylB plane and the naphthyl plane are in the
…
Beyond the cited strong O–H N hydrogen bond (Table 2), in
…
the 2–4 molecules an intermolecular C–H O interaction involving
the Hmeta of the phenyl group and the hydroxyl oxygen atom is
…
present (C15–H15 O1, Table 2). Fig. 12 shows a representative
example of these bondings in aminobenzylnaphthol 2.
Table 2 Distance and angles of hydrogen bond type interactions in aminobenzylnaphthols 1–9
˚
D–H (A)
˚
H??A(A)
˚
D??A (A)
D–H???A
D–H??A(u)
Symmetry
(S, S)-1a
(R,S)-1
O1–H1 N1
O2–H2 N2
0.82
0.82
0.82
0.93
0.96
0.82
0.93
0.82
0.93
0.82
0.93
0.94
0.82
0.93
0.82
0.93
0.82
0.82
0.82
0.93
0.93
0.93
0.93
0.93
0.96
1.90
1.88
1.85
2.79
2.81
1.86
2.52
1.86
2.54
1.85
2.53
1.70
1.83
2.69
1.90
2.96
1.93
1.84
1.85
2.70
2.51
2.57
2.57
2.62
2.57
2.585
2.581
140
142
147
172
135
145
139
146
139
147
140
151
148
122
144
123
139
147
146
148
163
156
158
162
158
…
…
…
O1–H4 N1
2.574(4)
3.718(5)
3.552(5)
2.575(2)
3.281(3)
2.579(3)
3.306(3)
2.577(3)
3.296(3)
2.562
2.562(2)
3.274(3)
2.609(3)
3.553(4)
2.611(4)
2.565(2)
2.568(3)
3.522(3)
3.411(3)
3.441(3)
3.454(3)
3.520(3)
3.476(5)
…
C14–H14 O1
…
x21, +y, +z
2x+2,+y21/2,2z+1
C19–H19A O1
…
O1–H4 N1
…
(S, S)-2
(S, S)-3
(S, S)-4
C15–H15 O1
x+1/2,2y+1/2+1,2z+2
x+1/2,2y+1/2+1,2z+2
x+1/2,2y+1/2+1,2z+2
…
O1–H4 N1
…
C15–H15 O1
…
O1–H4 N1
…
C15–H15 O1
(R, R)-5b
(S, S)-6
O1–H1 N12
…
…
O1–H4 N1
…
C15–H15 O1
x+1, +y, +z
…
O1–H4 N1
…
(S, S)-7
C15–H15 O1
x21/2, 2y+1/2, 2z
…
O1–H4 N1
(S, S)-8
(S, S)-9
…
…
…
…
O1A–H4A N1A
O1B–H4B N1B
C5A–H5A O1B
C5B–H5B O1A
…
C9A–H9A O2B
x,+y21,+z
…
C22A–H22A O1B
…
x+1/2,2y21/2,2z+2
x,+y+1,+z
x21,+y+1,+z
C9B–H9B O2A
…
C26B–H26F O2A
a
Reported by Forlani et al.27 b Reported by Szatmari et al.30
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…
Table 3 Selected CH p interactions in aminobenzylnaphthols 1–9
a
b
c
d
…
D–H Ar
…
CH Ar(u)
˚
h (A)
˚
d (A)
˚
d (A)
(S, S)-1 molecule Ie,f
…
C8–H8 Np2
2.69
2.74
2.69
2.77
145
172
0.10
0.43
B
…
C25–H25 Ph
(S, S)-1 molecule IIe,f
…
C21–H21 Np2
2.49
2.82
2.52
2.82
153
139
0.39
0.21
…
C22–H22 Np1
(R,S)-1f
C17–H17 Np1
…
2.81
2.85
146
0.48
(S, S)-2f
C18–H18 Np2
…
2.73
2.78
2.78
2.77
3.26
2.93
146
176
150
0.46
1.71
0.91
B
…
C8–H8 Ph
…
C21–H21 Np1
(S, S)-3f
C18–H18 Np2
…
2.65
2.78
2.85
2.68
3.08
2.97
144
175
147
0.42
1.33
0.83
B
…
C8–H8 Ph
…
C21–H21 Np1
(S, S)-4f
C18–H18 Np2
…
2.60
2.72
2.91
2.62
2.86
2.99
144
172
147
0.33
0.87
0.70
B
…
C8–H8 Ph
…
…
Fig. 9 CH p interactions in aminobenzylnaphthol (S, S)-1.
C21–H21 Np1
(R, R)-5f,g,h
…
C21–H21 Np1
2.71
2.75
2.88
2.76
133
135
0.97
0.20
B
…
C27–H27 Np 1
(S, S)-6f
C21–H21 Np1
…
…
2.79
2.82
2.97
2.83
133
137
1.02
0.18
B
C27–H27 Np 1
(S, S)-7f
B
C8–H8 Np 1
…
2.68
2.69
2.86
2.70
2.73
2.88
159
145
176
0.27
0.43
0.36
…
…
C19–H19C Np2
C19–H19B Ph
(S, S)-8f
B
C8–H8 Np 1
…
2.70
2.71
2.79
2.73
2.75
2.81
159
145
177
0.36
0.46
0.30
…
…
C19–H19C Np2
C19–H19B Ph
(S, S)-9 Molecule If
…
C21–H21 Np1
2.74
2.81
2.87
2.83
149
0.86
0.35
(S, S)-9 Molecule IIf
…
C21–H21 Np1
145
a
b
Distance from the H-atom to the mean aryl plane. Distance from
…
c
the H-atom to the aryl ring centroid. C–H Hp angle, in which Hp is
d
the projection of the H-atom in the mean aryl plane. Distance
from the Hp to the aryl ring centroid. Reported by Forlani et al.27
The two rings of the naphthyl moiety were indicated as Np1 and
Np2, Np1 being the rings bonded to the methine carbon atoms.
e
f
Fig. 10 ORTEP plot of aminobenzylnaphthol (R, S)-1.
g
Reported by Szatmari et al.30 h The reported structure was relabelled
according to our numeration.
range 43.93–47.02u, whereas in compounds 5 and 6 the same
angles are 71.20 and 75.35u respectively (see Table A, ESI).{
…
The most relevant CH p interaction deals with the C21–
…
˚
H21 Np1 assembly, as depicted in Fig. 14 (Table 3, 2.71–2.79 A
distance from the hydrogen atom to the aryl plane).
The crystal structures of (S, S)-7 and (S, S)-8, in which ArB
=
1-naphtyl, are isostructural, the RMS of the BMF being 0.025
(Fig. 16).
Fig. 11 Best fit of (S, S)-2, (S, S)-3 and (S, S)-4 structures (including
…
The most interesting CH p interactions found in these
B
compounds deal with the C8–H8 Np 1 assembly already
25 carbon, 1 nitrogen and 1 oxygen atoms).
…
˚
represented in Fig. 13 (Table 3, 2.68 and 2.70 A distances from
˚
˚
and 2.71 A, with a 0.43 and 0.46 A distance from the projection
of the hydrogen atom to the centroid (Fig. 17).
the hydrogen atom to the aryl plane, with a distance from the
projection of the hydrogen atom to the centroid of 0.27 and
˚
0.36 A).
Compound 9 differs from the 2–8 aminobenzylnaphthols
because two molecules are hosted in the asymmetric unity. As far
…
…
Another CH p interaction involves the hydrogen atoms of
the methyl group that interact with the naphthyl groups (Table 3,
C19–H19–Np2). In the case of the couple of molecules 7 and 8,
the distances from the hydrogen atom to the aryl plane are 2.69
as the hydroxyl oxygen is concerned, two CH O interactions
were observed between the oxygen atom and one hydrogen
˚
…
atom of the naphthyl group (Table 2, 2.51 A distance,
…
˚
C5B–H5B O1A, and 2.70 A distance C5A–H5A O1B). The
3978 | CrystEngComm, 2012, 14, 3972–3981
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Fig. 15 Best fit of (S, S)-5 and (S, S)-6 structures (including 31 carbon,
1 nitrogen and 1 oxygen atoms).
presence of a further oxygen atom, belonging to the 4-methox-
…
yphenyl group, originates some further CH O interactions. The
first of these interactions is found between one hydrogen atom of
the methyl group and the oxygen atom of the methoxy group
…
…
˚
(Table 2, 2.57 A distance, C26B–H26F O2A), whereas the
Fig. 12 Intramolecular hydrogen bonds and intermolecular CH
interaction in aminobenzylnaphthol (S, S)-2.
O
second one occurs between a hydrogen atom of the naphthyl
˚
group and the other methoxy oxygen atom (Table 2, 2.57 A
…
distance, C9A–H9A O2B).
In the presence of these interactions involving the oxygen atom,
…
CH p assemblies are limited to the interaction of the Hmeta of the
B
phenyl group with the naphthyl group (Table 3, C21–H21 Np1,
…
˚
2.81 A distance from the hydrogen atom to the aryl plane).
Conclusions
The useful, highly stereoselective solvent- and chromatography-
free Betti reaction of 2-naphthol with aryl aldehydes and
nonracemic amines originated a class of interesting aminobenzyl-
naphthols, whose crystal structures were investigated by means of
X-ray diffraction experiments. The aminobenzylnaphthols
obtained by substituting a hydrogen atom with the sequence
fluorine–chlorine–bromine atom could be grouped into three
classes of isostructural molecules. In the investigated structures,
the presence of the known intramolecular hydrogen bonding was
…
Fig. 13 CH p interactions in aminobenzylnaphthol (S, S)-4.
…
confirmed, whereas CH p interactions appear to play an
important role in the intermolecular interactions building the
crystals structure. Some cases of very short distances from the
hydrogen atoms to the planes of the aryl groups were reported,
together with appropriate geometric requirements for these
interactions. The missing of the crystal structures of many
less accessible (R, S)-stereoisomers suggests to avoid speculations,
but the presence of these interactions only in the crystals of the (S,
S)-aminobenzylnaphthols could be considered a sound hint of a
…
Fig. 14 A CH p interaction in aminobenzylnaphthol (S, S)-2 invol-
ving the phenylB group.
Fig. 16 Best fit of (S, S)-7 and (S, S)-8 structures (including 29 carbon,
1 nitrogen and 1 oxygen atoms).
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1-[(1S)-(4-Fluorophenyl)-((19S)-19-naphthalen-1-yl-ethylamino)-
methyl]-naphthalen-2-ol (6). Isolated yield 53%. Mp 157–159 uC
(from ethanol). [a]D25 = + 313.1 (c = 1.0 in CHCl3). Anal. Calcd
for C29H24FNO: C 82.63; H 5.74; N 3.32. Found : C 82.67; H
1
5.81; N 3.43. H-NMR (500 MHz, CDCl3) dH 14.19–13.38 (1H,
br s, OH), 7.90–7.84 (2H, m, HAr), 7.80–7.76 (1H, m, HAr), 7.74–
7.46 (4H, m, HAr), 7.42–7.29 (2H, m, HAr), 7.26–6.95 (6H, m,
HAr), 6.92–6.87 (2H, m, HAr), 5.49 (1H, s, CHAr2), 5.01–4.77
(1H, m, CHMe), 2.66–2.37 (1H, br s, NH), 1.66 (3H, d, 3JHH 6.6
Hz, CH3). 13C-NMR (125 MHz, CDCl3) dC 162.2 (d, 1JCF 247.4
Hz, CAr-F), 157.0 (CAr), 139.9–139.0 (br s, CAr), 137.2 (CAr),
3
133.8 (CAr), 132.4 (CAr), 131.4 (CAr), 129.9 (CAr), 129.5 (d, JCF
8.0 Hz, CAr), 128.9 (CAr), 128.6 (CAr), 128.2 (CAr), 126.3 (CAr),
126.2 (CAr), 125.8 (CAr), 125.5 (CAr), 122.4 (CAr), 121.0 (CAr),
2
120.0 (CAr), 115.9 (d, JCF 20.9 Hz, CAr), 113.2 (CAr), 60.3
(CHAr2), 52.1–51.0 (br s, CHMe), 23.0 (CH3).
…
Fig. 17 A CH p interaction involving the methyl group in aminoben-
zylnaphthol (S, S)-7.
1-[(1S)-(4-Chlorophenyl)-((19S)-19-naphthalen-1-yl-ethyla-
mino)-methyl]-naphthalen-2-ol (7). Isolated yield 56%. Mp 142–
144 uC (from ethanol). [a]D25 = + 329.8 (c = 0.8 in CHCl3). Anal.
Calcd for C29H24ClNO: C 79.53; H 5.52; N 3.2. Found : C 79.51;
H 5.63; N 3.47. 1H-NMR (500 MHz, CDCl3) dH 14.10–13.30
(1H, br s, OH), 7.94–7.82 (2H, m, HAr), 7.79–7.35 (5H, m, HAr),
7.32–6.98 (10H, m, HAr), 5.45 (1H, s, CHAr2), 4.94–4.74 (1H, m,
more stable and, as a consequence, of a preferentially formed
crystal.
Experimental
Chemicals were purchased from Sigma-Aldrich and were used as
received. NMR spectra were recorded using a Bruker AM500
spectrometer. Elemental analyses were performed on a Carlo
Erba CHNS-O EA1108 Elemental Analyzer.
3
CHMe), 2.66–2.38 (1H, br s, NH), 1.64 (3H, d, JHH 6.7 Hz,
CH3). 13C-NMR (125 MHz, CDCl3) dC 157.3 (CAr), 140.2 (CAr),
140.1–139.4 (br s, CAr), 134.1 (CAr), 134.0 (CAr), 132.6 (CAr),
131.7 (CAr), 130.3 (CAr), 129.4 (CAr), 129.2 (CAr), 128.9 (CAr),
128.5 (CAr), 126.6 (CAr), 126.5 (CAr), 126.1 (CAr), 125.8 (CAr),
122.7 (CAr), 122.6 (CAr), 121.2 (CAr), 120.3 (CAr), 113.2 (CAr),
60.6 (CHAr2), 52.1–51.1 (br s, CHMe), 23.3 (CH3).
Materials
(S, S)-Aminobenzylnaphthols 2–4 and 6–9 were synthesised by
reacting 2-naphthol, aryl aldehydes and (S)-1-arylethylamine for
two days at 60 uC without any solvent. After this time, the
addition of small amounts of ethanol caused the precipitation of
the desired product, that was collected and re-crystallised.
1-[(1S)-(4-Bromophenyl)-((19S)-19-naphthalen-1-yl-ethyla-
mino)-methyl]-naphthalen-2-ol (8). Isolated yield 51%. Mp 126–
128 uC (from ethanol). [a]D25 = + 226.8 (c = 1.1 in CHCl3). Anal.
Calcd for C29H24BrNO: C 72.20; H 5.01; N 2.90. Found : C
1-[(S)-(4-Fluorophenyl)-((19S)-19-phenylethylamino)-methyl]-
naphthalen-2-ol (2). Isolated yield 68%. Mp 108–110 uC (from
ethanol). [a]D = + 213.3 (c = 1.0 in CHCl3). Anal. Calcd for
1
72.41; H 5.16; N 3.07. H-NMR (500 MHz, CDCl3) dH 14.02–
13.43 (1H, br s, OH), 7.89–7.82 (2H, m, HAr), 7.73 (1H, d, 3JHH
25
3
8.6 Hz, HAr), 7.68 (1H, d, JHH 7.8 Hz, HAr), 7.65–7.43 (2H, m,
C25H22FNO: C 80.84; H 5.97; N 3.77. Found C 80.89; H 5.90; N
4.01. 1H-NMR (500 MHz, CDCl3) dH 13.40–12.37 (1H, br s,
OH), 7.82–7.72 (2H, m, HAr), 7.45–7.31 (4H, m, HAr), 7.29–7.16
(7H, m, HAr), 6.94–6.86 (2H, m, HAr), 5.49 (1H, s, CHAr2), 3.92
(1H, q, 3JHH 6.9 Hz, CHMe), 3.30–2.80 (1H, br s, NH), 1.53 (3H,
d, 3JHH 6.9 Hz, CH3). 13C-NMR (125 MHz, CDCl3) dC 162.4 (d,
1JCF 247.4 Hz, CAr-F), 156.6 (CAr), 142.1–141.6 (br s, CAr), 132.3
(CAr), 130.1 (CAr), 129.7 (d, 3JCF 8.0 Hz, CAr), 129.1 (CAr), 128.9
(CAr), 128.8 (CAr), 128.2 (CAr), 126.9 (CAr), 126.6 (CAr), 122.7
3
Ar), 7.39 (1H, d, JHH 7.4 Hz, HAr), 7.34–7.29 (2H, m, HAr),
H
7.24–7.20 (1H, m, HAr), 7.17–6.98 (7H, m, HAr), 5.41 (1H, s,
CHAr2), 4.96–4.76 (1H, m, CHMe), 2.69–2.30 (1H, br s, NH),
1.61 (3H, d, 3JHH 6.6 Hz, CH3). 13C-NMR (125 MHz, CDCl3) dC
157.1 (CAr), 140.6 (CAr), 139.5 (CAr), 133.9 (CAr), 132.4 (CAr),
132.2 (CAr), 131.5 (CAr), 130.1 (CAr), 129.5 (CAr), 129.0 (CAr),
128.7 (CAr), 128.3 (CAr), 126.3 (CAr), 125.9 (CAr), 125.6 (CAr),
122.5 (CAr), 122.4 (CAr), 122.0 (CAr), 121.0 (CAr), 120.1 (CAr),
113.0 (CAr), 60.5 (CHAr2), 52.0–51.0 (br s, CHMe), 23.1 (CH3).
2
(CAr), 120.8 (CAr), 119.9 (CAr), 115.9 (d, JCF 21.7 Hz, CAr),
112.3 (CAr), 59.4 (CHAr2), 56.9 (CHMe), 22.6 (CH3).
1-[(S)-(phenyl)-((19S)-19-49-methoxyphenylethylamino)-methyl]-
naphthalen-2-ol (9). Isolated yield 64%. Mp 127–129 uC (from
tert-butanol). [a]D = + 187.8 (c = 2.0 in CHCl3). Anal. Calcd
1-[(S)-(4-Chlorophenyl)-((19S)-19-phenylethylamino)-methyl]-
naphthalen-2-ol (3). Isolated yield 52%. Mp 149–150 uC (from
tert-butanol) (lit.,27 132–140 uC for the (R, R) stereoisomer).
25
for C26H25NO2: C 81.43; H 6.57; N 3.65. Found C 81.35; H 6.79;
1
N 3.94. H-NMR (500 MHz, CDCl3) dH 13.87–13.69 (1H, br s,
25
[a]D = + 205.1 (c = 2.0 in CHCl3) (lit.,27 = 2192.0 (c = 3.5 in
CHCl3) for the (R, R) stereoisomer).
OH), 7.76–7.71 (2H, m, HAr), 7.41–7.38 (1H, m, HAr), 7.26–7.16
(8H, m, HAr), 7.12–7.09 (2H, m, HAr), 6.95–6.91 (2H, m, HAr),
5.46 (1H, s, CHAr2), 3.88–3.81 (4H, m, CHMe + OCH3), 2.25–
1-[(S)-(4-Bromophenyl)-((19S)-19-phenylethylamino)-methyl]-
naphthalen-2-ol (4). Isolated yield 57%. Mp 138–140 uC (from
2.13 (1H, br s, NH), 1.48 (3H, d, JHH 6.7 Hz, CH3). 13C-NMR
31
3
25
tert-butanol). [a]D = + 190.1 (c = 1.0 in CHCl3).
(125 MHz, CDCl3) dC 159.3 (CAr), 157.0 (CAr), 141.0–140.3 (br s,
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Ramanan, Crystal Engineering.
Publishing, Singapore, 2011.
A
Textbook. World Scientific
CAr), 134.8–134.0 (br s, CAr), 132.5 (CAr), 129.9 (CAr), 129.0
(CAr), 128.8 (CAr), 128.1 (CAr), 128.0 (CAr), 127.8 (CAr), 126.4
(CAr), 122.5 (CAr), 121.1 (CAr), 120.0 (CAr), 114.3 (CAr), 112.8–
112.4 (br s, CAr), 60.1 (CHAr2), 55.9 (CHMe), 55.3 (OCH3), 22.8
(CH3).
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1-[(R)-(phenyl)-((19S)-19-phenylethylamino)-methyl]-naphtha-
len-2-ol (1). An almost equimolar mixture of (R, S)-1 and (S, S)-1
was obtained by reacting a solution of 2-naphthol, benzaldehyde
and (S)-1-phenylethylamine in THF for three days at room
temperature. The reaction mixture was crystallised from
n-hexane/diethyl ether 99 : 1, and then the recovered solid was
re-crystallised from n-hexane/diethyl ether 1 : 1. The mother
liquor of this crystallisation yielded some crystals of the (R, S)-
diastereomer upon slow evaporation of the solvent. Mp 135–137
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25
uC (from ethanol). [a]D = 2167.7 (c = 0.25 in CHCl3).
14 C. D. Anderson, T. Dudding, R. Gordillo and K. N. Houk, Org.
Lett., 2008, 10, 2749–2752.
X-Ray experiments
X-Ray data were collected at 293 K by means of single crystal
X-ray diffractometers. Unit cell parameters are reported in
Table 1. Data were corrected for Lorentz and polarisation
effects, and for absorption effects (3, 4, 7, 8 and 9).34 The
structures were solved by direct methods (SIR97)35 and refined
by full-matrix-least-square technique on F2 for all unique
measured data (SHELXL-97).36 Non-hydrogen atoms were
refined using anisotropic displacement parameters. Nitrogen-
bonded H atoms were located by means of Fourier maps
application, and had assigned a fixed isotropic displacement
parameter (Uiso(H) = 1.2 Uiso(N)); the other hydrogen atoms
were geometrically imposed with riding-model constraints
15 F. Naso, M. A. M. Capozzi, A. Bottoni, M. Calvaresi, V. Bertolasi,
F. Capitelli and C. Cardellicchio, Chem.–Eur. J., 2009, 15,
13417–13426.
16 M. A. M. Capozzi, C. Centrone, G. Fracchiolla, F. Naso and C.
Cardellicchio, Eur. J. Org. Chem., 2011, 4327–4334.
17 H. Suezawa, S. Ishihara, Y. Umezawa, S. Tsuboyama and M. Nishio,
Eur. J. Org. Chem., 2004, 4816–4822.
18 K. Kinbara, Y. Harada and K. Saigo, J. Chem. Soc., Perkin Trans. 2,
2000, 1339–1347.
19 T. Shimada, Y. Kobayashi and K. Saigo, Tetrahedron: Asymmetry,
2005, 16, 3807–3813.
20 K. Saigo and Y. Kobayashi, Chem. Rec., 2007, 7, 47–56.
21 F. Naso, C. Cardellicchio, M. A. M. Capozzi, F. Capitelli and V.
Bertolasi, New J. Chem., 2006, 30, 1782–1789.
22 C. Cardellicchio, M. A. M. Capozzi and F. Naso, Tetrahedron:
Asymmetry, 2010, 21, 507–517.
23 C. Cardellicchio, G. Ciccarella, F. Naso, E. Schingaro and F.
Scordari, Tetrahedron: Asymmetry, 1998, 9, 3667–3675.
24 C. Cardellicchio, G. Ciccarella, F. Naso, F. Perna and P. Tortorella,
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25 C. Cimarelli, A. Mazzanti, G. Palmieri and E. Volpini, J. Org. Chem.,
2001, 66, 4759–4765.
(C–HAr 0.93 A C21–HMethine
=
˚
˚
0.98 A with Uiso(H) =
˚
1.2Uiso(C); C–HMethyl 0.96 A with Uiso(H) = 1.5Uiso(C); O–H
˚
= 0.82 A with Uiso(H) = 1.5Uiso(0)). Complete crystallographic
data are available upon request from the Cambridge
Crystallographic Data Centre (12 Union Road, Cambridge,
CB2 1EZ, UK; email: deposit@ccdc.cam.ac.uk), by quoting the
depository numbers CCDC-822815 ((S, S)-2), 822816 ((S, S)-3),
822817 ((S, S)-4), 822818 ((S, S)-6), 822819 ((S, S)-7), 822820
((S, S)-8), 822821 ((S, S)-9), 822822 ((R, S)-1).
26 C. Cimarelli, G. Palmieri and E. Volpini, Tetrahedron: Asymmetry,
2002, 13, 2417–2426.
27 C. Boga, E. Di Martino, L. Forlani and F. Torri, J. Chem. Res., 2001,
43–45.
28 D.-X. Liu, L.-C. Zhang, Q. Wang, C.-S. Da, Z.-Q. Xin, R. Wang,
M. C. K. Choi and A. S. C. Chan, Org. Lett., 2001, 3, 2733–2735.
29 M. R. Saidi and N. Azizi, Tetrahedron: Asymmetry, 2003, 14,
389–392.
Acknowledgements
30 I. Szatmari, R. Sillanpaa and F. Fulop, Tetrahedron: Asymmetry,
2008, 19, 612–617.
31 V. Carassiti and G. B. Fabbri, Boll. Sci. Fac. Chim. Ind. Bologna,
1954, 12, 160–161, (Chem. Abstr., 49, 10744d).
32 V. A. Alfonsov, K. E. Metlushka, C. E. Mc Kenna, B. A.
Kashemirov, O. N. Kataeva, V. F. Zheltukhin, D. N. Sadkova and
A. B. Dobrynin, Synlett, 2007, 488–490.
33 W. B. Jennings, N. J. P. McCarthy, P. Kelly and J. F. Malone, Org.
Biomol. Chem., 2009, 7, 5156–5162.
This work was financially supported, in part, by the MIUR Rome
(PRIN Project: Stereoselezione in sintesi organica. Metodologie e
applicazioni) and by the University of Bari. We thank Dr
Gabriella Cannone and Dr Francesco Iannone (Dipartimento di
Chimica, Bari, Italy) for preliminary synthetic experiments, Mr
Giuseppe Chita (CNR, Istituto di Cristallografia, Bari, Italy) for
some X-ray data collection, Dr Francesca Benevelli (Bruker
Italia), and Prof. Francesco Naso for helpful discussions.
34 Bruker. SAINT and SADABS. 2001, Bruker AXS Inc., Madison,
Wisconsin, USA.
35 A. Altomare, M. C. Burla, M. Camalli, G. L. Cascarano, C.
Giacovazzo, A. Guagliardi, A. G. Moliterni, G. Polidori and R.
Spagna, J. Appl. Crystallogr., 1999, 32, 115–119.
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This journal is ß The Royal Society of Chemistry 2012
CrystEngComm, 2012, 14, 3972–3981 | 3981