The isomeric structure of pentacoordinate chiral spirophosphoranes in solution by the combined use of NMR experiments and GIAO DFT calculations of NMR parameters

Article abstract of DOI:10.1039/c7dt01605k

The interplay of NMR experiments and DFT calculations of NMR parameters is a reliable method for determining the relative configurations of pentacoordinate chiral spirophosphoranes bearing two six- or five-membered rings at the phosphorus atom in solution. The major product of the Betti based derivatives corresponds to the isomers with both substituents at chiral carbons being opposite to the P-H proton. The next populated product corresponds to the isomer with different chiralities at carbons. The least populated isomer is one with both substituents being at the same side of the heterocycle as the P-H bond.

Full text of DOI:10.1039/c7dt01605k

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The isomeric structure of pentacoordinate chiral
spirophosphoranes in solution by the combined
use of NMR experiments and GIAO DFT calculations
of NMR parameters†
Cite this: DOI: 10.1039/c7dt01605k
Fedor M. Polyancev,
Kirill E. Metlushka, Dilyara N. Sadkova, Zilya R. Khisametdinova,
Olga N. Kataeva, Vladimir A. Alfonsov, Shamil K. Latypov * and Oleg G. Sinyashin
The interplay of NMR experiments and DFT calculations of NMR parameters is a reliable method for
determining the relative configurations of pentacoordinate chiral spirophosphoranes bearing two six- or
five-membered rings at the phosphorus atom in solution. The major product of the Betti based derivatives
corresponds to the isomers with both substituents at chiral carbons being opposite to the P–H proton.
The next populated product corresponds to the isomer with different chiralities at carbons. The least
populated isomer is one with both substituents being at the same side of the heterocycle as the
P–H bond.
Received 2nd May 2017,
Accepted 30th May 2017
DOI: 10.1039/c7dt01605k
rsc.li/dalton
good single crystals is often time consuming and sometimes
impossible. This point, coupled with the fact that most chemi-
Introduction
Chiral phosphorus compounds are widely used in stereo- cal reactions and biological processes occur in solution, makes
1
–5
selective synthesis.
For example, chiral phosphorus ligands it highly desirable to find an alternative, reliable, and easy way
are of importance in the design of catalysts for asymmetric to determine the relative configurations of such hypervalent
6
33–38
homogeneous catalysis. Pentacoordinate phosphorus com- chiral phosphorus compounds directly in solution.
pounds have drawn special attention for their role as inter- Progress in NMR correlation techniques and the state-of-
mediates in some biological processes (e.g. enzymatic phos- the-art density functional theory (DFT) calculations of NMR
7
–29
phoryl transfer reactions,
hydrolysis/formation of DNA, parameters has emerged in recent years as a very powerful tool
for fine structural analysis of organic compounds and bio-
3
0,31
RNA, cyclic AMP).
Their structural and dynamic properties strongly correlate molecules. There are a number of examples when DFT calcu-
1
13
15
with the reactivity/selectivity of the processes they are involved lations of NMR H, C and N parameters in the frame of the
in. Although the knowledge about the stereochemistry (the GIAO method allowed the establishment of tautomeric, isomeric
39–53
absolute and relative configurations) of these compounds is and conformational structures as well.
However applications
important in understanding these processes, very few struc- of similar approaches to analyze phosphorus compounds by
3
1
54–56
tural studies of pentacoordinate phosphorus systems have DFT calculations of P NMR parameters are very rare.
been published so far.
3
2–38
The study here shows that the interplay of the NMR experi-
Pentacoordinate phosphoranes with an asymmetric phos- ment and theory is a powerful method for determining
phorus atom and with several additional chiral chelate ligands the relative configurations of pentacoordinate chiral spiro-
are especially difficult to analyze, since these chiral centers phosphoranes. For the illustration several pentacoordinate
may generate a variety of stereoisomers and the determination spirophosphoranes bearing two six-membered (Betti based
of their fine structure is not straightforward. To this end X-ray derivatives) and five-membered (α-aminocarbonic acid deriva-
single crystal investigations could be helpful, but obtaining tives) rings at the phosphorus atom were used.
A.E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center,
Results
Synthesis
Russian Academy of Sciences, Arbuzov str. 8, Kazan, 420088, Russian Federation.
E-mail: lsk@iopc.ru
†
Electronic supplementary information (ESI) available: 1D/2D NMR spectra and
Three chiral elements (two centres and one axis) lead to the
four possible combinations. In order to obtain the full set of
calculated data for 4–6. CCDC 1542633 and 1542634. For ESI and crystallo-
graphic data in CIF or other electronic format see DOI: 10.1039/c7dt01605k
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via crystallization. It is interesting that after about 4–6 hours in
the NMR spectrum of the individual product that was major in
3
1
the initial reaction mixture (δ P = −75.4 ppm), additional
signals appeared which can also be attributed to the structure
3
1
of high symmetry (δ P = −80.7 ppm) with two spiro-connected
1
six-membered heterocycles being equivalent in the H NMR
spectra.
Scheme 1
In a similar manner for 5 the formation of two isomers was
observed which were separated and analyzed (Fig. 1a and b).
1
9
In this case the F NMR is particularly useful and allows
stereoisomers we used racemic Betti bases. The synthesis
of P–H-spirophosphoranes was carried out by substituting
the amino groups in the hexaethyltriamidophosphite by
-(α-aminobenzyl)-2-naphthols (Scheme 1). For example, in the
P{ H} NMR spectra of the reaction mixture of 4 there are two
signals with the chemical shifts (CS) characteristic of phos-
phoranes (−75.4 (65%) and −76.7 (35%) ppm) that may be
attributed to the formation of two isomers.
In contrast to the dominant product (δ P = −75.4 ppm),
the H spectra of which correspond to the high symmetry
19
distinguishing symmetrical (one singlet, δ F = −116 ppm)
19
and non-symmetrical (two singlet’s of equal intensity, δ F =
19
−
115.8 and δ F = −116.6 ppm) isomers. The monitoring of
1
1
31
the major isomer 5a via the H and P NMR showed that after
3
1
1
some time an additional product appeared (10%) in solution
19
31
(
δ F = −115.5 and δ P = −81.0 ppm) which presumably
corresponds to another symmetrical isomer (Fig. 1c).
For compound 6 very similar spectra and their evolution
were observed (ESI†).
3
1
1
structure, the second component apparently has no symmetry,
and two spiro halves of phosphorane 4 differ in the H NMR
1
Structure determination
spectrum. When diethylamine hydrochloride is used as the
Chemical structure and assignment. A variety of NMR corre-
catalyst, these two isomers could be obtained in an about 1 : 1 lations allows one to prove the chemical structure of two main
ratio and their isolation in individual form becomes possible stereoisomers practically directly. For example, first, starting
1
Fig. 1 H spectra of 5 in CDCl
3
at 303 K. (a) Major product (fresh, 5a); (c) the same product after 24 h; (b) second product; (d) structure of com-
1
1
1
13
1
31
1
15
pound 5a with principal NMR correlations: H– H COSY and H– C HMBC (black arrows), H– P HMBC (red arrows), H– N HMBC (blue arrows),
F– H HETCOR (orange arrows).
19
1
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a
Table 1 Some experimental and calculated NMR parameters for compounds 4–6
b
δ 31
1
3
Comp.
X at C11
H
R at C
4
Isomer
ΔE
P
δH
6
δH16,20
δH17,19
δH
4
δH
5
J
PH
J
PH4
c
4
Ph
I
Exp (a)
0
−75.4
−75.2
−76.7
−76.4
−80.7
−82.5
7.08
7.66
7.34
7.80
7.54
7.75
7.32
7.64
7.19
7.41
6.93, 7.29
7.21, 7.58
n/d
5.95
5.98
5.81, 5.87
5.81, 5.84
5.74
4.18
3.77
3.80, 4.00
3.46, 3.83
3.58
788.5
715.4
823.5
742.6
848.6
762.7
34.1
36.1
26.3, 33.1
27.6, 35.2
25.6
II
Exp (b)
7.02, 7.45
7.42, 7.88
0
.53
Exp (c)
.33
d
III
n/d
1
7.87
7.58
5.65
3.36
25.2
5
H
FC H
6 4
I
Exp (a)
0
Exp (b)
−75.2
−74.4
−76.6
−75.7
−80.5
−82.1
7.09
7.63
7.32
7.75
7.52
7.74
7.26
7.52
6.91, 7.39
7.37, 7.82
n/d
6.88
7.04
6.58, 6.95
6.81, 7.17
n/d
5.91
5.94
5.76, 5.82
5.77, 5.86
5.70
4.17
3.76
3.77, 3.95
3.48, 3.78
3.56
792.1
713.9
824.0
738.3
849.0
764.2
34.1
36.1
27.7, 33.6
27.6, 34.6
25.0
II
III
0
.47
Exp (a)
.33
1
7.82
7.15
5.63
3.33
24.7
6
Br
Ph
I
Exp (a)
0
Exp (b)
−76.4
−75.6
−77.7
−76.5
−81.4
−80.5
7.08
7.62
7.33
7.77
7.54
7.69
7.27
7.58
6.96, 7.28
7.20, 7.78
n/d
7.19
7.41
6.96, 7.28
7.18, 7.59
n/d
5.89
5.92
5.74, 5.78
5.68, 5.74
5.71
4.17
3.74
3.77, 3.95
3.34, 3.81
3.58
790.4
718.3
828.0
742.6
852.3
769.9
34.1
36.0
27.5, 33.7
27.6, 35.2
25.1
II
III
0
.44
Exp (c)
.67
0
7.78
7.59
5.60
3.25
24.1
a
Chemical shifts in ppm, spin–spin couplings in Hz. Relative energy, in kcal mol−1
b
c
d
.
Experimental data. No data.
1
15
from H– N HSQC connectivities the NH protons were centers are the same the last two isomers become equivalent
revealed, then the vicinal H protons were assigned based on in terms of NMR. Thus three main isomers were considered in
4
31
1
COSY data. Next, the H– P HMBC connectivities from the details: with both aryl substituents being opposite to the P–H
NH and H to phosphorus allowed the determination of the bond (Δ R R /Λ S S , I), with one aryl opposite to the P–H
4
P
c
c
P c c
structure of this central moiety (Fig. 1d). Further on, the bond and another one being on the same side of the cycle
1
13
1
1
H– C HSQC/HMBC and H– H COSY correlations allow with the P–H bond (Δ
P c c P c c
R S /Λ S R , II), in the third isomer both
establishing the structures of two aromatic fragments (ESI†). aryls are at the same side of the cycle with the P–H bond
1
9
1
In addition, for 5 the F– H HETCOR correlations help to (Λ
P
R
c
R
c
/Δ
P c c
S S , III) (Fig. 2).
establish connectivities up to fluorine atoms. As to the third
Qualitative consideration of these structures predicts some
(
minor) isomer due to its low population and extensive over- stereospecific features. There are different dihedral angles
1
lapping with the signals of the first isomer in the H NMR between H
4
–C and N–P in isomers I and III, that may lead to
spectra, only some principal resonances can be identified with different three bond SSCs. As to the II-nd isomer, the geome-
1
31
confidence (e.g. Fig. 1c). However, the 2D H– P HMBC experi- tries of its two spiro-halves are very similar to the halves of the
ments (ESI†) allow one to unambiguously reveal its signal in I-st and III-rd isomers, therefore two sets of signals are
3
1
1
13
19
the P spectra and also the PH, NH and H
e.g. for 5c Fig. 1c).
Isomeric structure. The analysis of the NMR parameters of symmetry considerations. Presumably, the “a” (major) pro-
4
proton resonances expected for its H ( C, F) spectra.
(
Thus, preliminary identification can be based on NOEs and
diastereomers of the phosphoranes 4–6 reveals some general ducts can be ascribed to the I isomer because there is no NOE
particularities – namely, there are notable differences in some between the ortho-aryl and P–H protons. Lack of symmetry in
CSs and spin–spin couplings (SSCs) of the isomers (ESI†). The the second product (“b”) may be indicative of the II-isomer. As
1
most spectacular are the values of direct JHP SSCs, that vary to the co-product (“c”) that appeared after some time in solu-
from ∼790 (a-product) up to ∼850 (c-product) Hz (Table 1), tion of the major isomer (“a”), there are no clear NOEs that
3
1
and also the difference in
J
PH4 SSCs. The H CSs of PH, can be used due to its low population and the signal overlap-
and aryl protons and P CSs are diastereomer dependent ping with the main product.
in these products as well. Thus, it is likely that NMR para- To develop a well-argued relationship between the NMR
meters, being related to local magnetic environments, could parameters and the fine isomeric structure, DFT calculations
be used in fine structural analysis. of the NMR parameters were carried out for these structural
3
1
H
4
In general, three chiral centers (at P, C and C ) may gene- hypotheses. It is well demonstrated that modern GIAO CS cal-
4
4′
1
3
15
1
rate four diastereomers: Δ
and Δ /Λ
P
R
c
R
c
/Λ
P
S
c
S
c
, Λ
P
R
c
R
c
‡/Δ
P
S
c
S
c
, Δ
R
P c
S
c
/
culations on C, N and H nuclei achieved experimental
Λ
P
S
R
c c
P
S
c
R
c
P
R
c
S
c
. However, when both aryls in chiral accuracy and can be used as an additional tool for chemical
structure elucidation. There are a number of examples of appli-
cation of such calculations on these nuclei to obtain fine infor-
mation on the isomeric, tautomeric and conformational
‡
The isomer III might be produced from isomer Δ
P
R
c
R
c
(Λ
P
S
c
S
c
) by the Berry
(Δ ).
3
9–53,57–60
pseudorotation process, so its configuration was assigned as Λ
P
R
c
R
c
P
S
c
S
c
structure.
At the same time the examples of
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Fig. 2 Energy minimized structures of the main isomers of the title spirophosphorane 4.
application of these approaches on phosphorus are rather product to the II-nd isomer and the least populated product to
5
4–56
sparse.
We used a combination (PBE1PBE/6-311G(2d,2p)//PBE1PBE/
6
the III-rd isomer.
3
The
4
JHP between P and H is also very stereospecific
3
1
-31+G(d)) that proved to be reliable and effective for P NMR (Table 1). First, the calculations predict SSCs to have large
CS calculations. First, the geometry optimization in the absolute values and be essentially different, at least, for the I-st
frames of the DFT (PBE1PBE/6-31+G(d)) method predicts that and III-rd isomers. For the II-nd isomers there are two
these three main isomers are close in energy (Table 1). different values for each half but these SSC are close to the
Additional calculations with the inclusion of solvent effects corresponding SSCs of the I-st and III-rd isomers, respectively.
(in the frames of the PCM model, Table S1†) do not In spite of the fact that theory slightly underestimates these
change notably the energy distribution. In general, these SSCs, the calculated values and tendencies are in good agree-
results are in qualitative agreement with experimental findings ment with the experimentally observed data (Table 1). Thus,
that all three isomers are present in the reaction mixture after the comparison of the experimental versus calculated data also
some time.
The results of the CS and SSC calculations (GIAO PBE1PBE/ conclusion.
-311G(2d,2p)) for optimized structures are also in agreement These conclusions were supported by solid-state data in
allows the assignment that is in accordance with the above
6
with preliminary conclusions (some essential data are sum- some cases. Namely, good crystals suitable for X-ray analysis
marized in Table 1). According to the calculations, the PH, were grown for the second isomer of racemic 4, which is crys-
3
1
4
H and NH protons and P CSs should be notably different, tallized as a conglomerate, and for the major product of
particularly, for the I-st and the III-rd isomers. Namely, for the racemic 5. The results of X-ray single crystal diffraction turned
I-isomer the PH proton should resonate at a higher field than out to be in full agreement with the NMR data. In crystals the
4
for the III-isomer, while for the H and the NH protons the major product of 5 is realized in the I form (see Fig. 3) with
3
1
reverse should be observed. Likewise the P resonance signal both aryls directed opposite to the P–H bond. In general, the
of the I-isomer should be at a lower field than in the solid-state geometry is close to the DFT optimized one.
III-isomer. For the II-isomer, intermediate values are expected
It is interesting that the crystallized product of 4
(Table 1). Thus, according to the CS data the major (“a”) corresponded to the asymmetrical II-form that is also in agree-
product should be assigned to the I-isomer for all title com- ment with the conclusion based on the NMR data. Thus for
pounds. The second non-symmetrical product corresponds to the title chiral pentacoordinate spirophosphoranes there are
the II-diastereomer while the minor product may be assigned several NMR parameters that can be used to establish the iso-
to the III-isomer.
meric structure. These relationships are summarized in Fig. 4.
Some SSCs also demonstrate spectacular distinctions for
three isomers (Table 1) that correlate well with experimental
data. As can be seen the JHP constants are characteristic
Correlation of NMR parameters with the isomeric structure for
other chiral pentacoordinate spirophosphoranes
1
of these isomers and can be used to assign the isomeric struc- The interplay of the NMR experiment and theory can be safely
ture. The smallest values (715.4 Hz) are predicted for the I-st used to determine the isomeric structure of chiral pentacoordi-
isomers while for the III-rd forms these values are notably nate spirophosphoranes with six-membered heterocycles. To
larger (762.7 Hz). For the II-isomers the PH direct SSCs are this end it is of interest to see if this approach could also be
expected to have intermediate values (742.6 Hz). The calcu- applied to determine the isomeric structure of other similar
lations slightly underestimate (by ca. 1.1) the experimental chiral pentacoordinate spirophosphoranes, e.g. with five-mem-
data although the correlation is quite good. Thus, the com- bered heterocycles. For example, there are experimental data
parison of the calculated versus experimental SSCs allows the for a series of chiral pentacoordinate spirophosphoranes
33–37
assignment of the major product to the I-st isomer, the second obtained from α-amino carbonic acids (Scheme 2).
These
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Fig. 3 Molecular geometry of diastereomers 4b (left) and 5a (right) as determined from X-ray single crystal diffraction.
SSCs (2.4 Hz) in the “III” forms that were not seen in the
“I” isomers presumably due to their small values.
These differences are reproduced by theory. According to
our calculations performed for the simplest compounds from
this series with i-Pr (7) or Bz (8) groups at chiral carbons
(
Table 2), indeed, the “I” isomer has to resonate at a higher
3
1
field in the P NMR spectra than the “III” form.
The calculated SSCs are also qualitatively consistent with
the experimental values, although some underestimation is
also seen. First, a larger one bond SSC is predicted for the
“
III” isomers (Table 2) than for the “I” form. According to the
3
calculations, the JPH SSCs should be notably smaller than for
Fig. 4 Schematic representation of three isomers of 4–6 and the main the title compounds. Moreover, for the “III”-isomers one
relationships between the NMR parameters and isomeric structure.
may expect a long range four bond SSC between HP and H
4
Magnetically equivalent fragments are colored identically.
(
2.0 versus 0.5 Hz) larger than for the “I” isomer. Thus, several
NMR parameters can also be used to determine the relative
configuration at chiral carbons in these pentacoordinate
spirophosphoranes.
Discussion
Let us consider why some relationships are different in these
two series of spirophosphoranes. There are two essential NMR
Scheme 2
features that distinguish 5-membered spirophosphoranes from
3
6
-membered compounds: (a)
J
PH – small absolute value for
compounds were extensively analyzed by CD and X-ray single
diffraction. When enantiomerically pure reagents were being
used, the reactions produced only two diastereomers.
3
1
31
the 5-cycle and large for the 6-cycle; (b) δ P > δ P for
I
III
3
1
31
6-membered and δ
I
P < δ PIII for 5-membered.
To reveal key factors that determine these differences we
A brief survey of available NMR data demonstrates that
there are also some specific features of experimental CSs and
SSCs characteristic of two diastereomers although somewhat
distinct from those observed for the title compounds. First, for
analyzed the influence of substituents at carbon chiral centers
and the nature of the fused aromatic fragments theoretically.
To simplify the task and to exclude the specific influence of
fused aromatic fragments, the models with the benzo frag-
ment instead of the naphthyl group were analyzed (Fig. 5a
and b, Table 3). According to these calculations, the relation-
ships between the NMR parameters and isomeric structure are
expected to be essentially similar to the title compounds.
Thus, there is no specific effect of the naphthyl moiety on the
NMR parameters’ distribution in these isomers.
3
1
five-membered spirophosphoranes the reverse P CS distri-
bution is observed, i.e. the “I” isomers resonate at a higher
field than “III” isomers (some data are included in Table 2).§
1
Second, the JPH values are smaller for the “I” isomers than for
3
the “III”-forms. As to the JPH constants they are notably
4
smaller (<13 Hz). Third, there are substantial long range J
H
̲
The next step to simplify the model is to check whether
there is a specific influence of substituents at chiral carbons
(e.g. steric interactions). For this purpose we analyzed models
1
§
Unfortunately, H CS’s data cannot be analyzed in this case as different sol-
vents were used in experiments for different diastereomers.
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a
Table 2 Some experimental and calculated NMR parameters for compounds 7 and 8
b
δ31
1
3
4
Comp.
R at C
i-Pr
4
Isomer
ΔE
P
δH
6
δH
4
δH
5
J
PH
J
PH4
J
H6H4
c
37
d
7
I
Exp (a)
.19
−65.0
−65.6
−63.7
−62.1
7.18
7.82
7.43
7.79
3.71
3.73
3.80
3.70
5.76
2.82
3.47
2.84
798.5
697.2
824.4
724.0
13.0
8.8
n/d
5.9
n/d
0.5
2.4
2.0
0
3
7
III
Exp (b)
0
3
6
8
Bz
I
Exp (a)
0
−63.0
−68.5
−60.0
−64.5
7.09
7.95
5.64
6.62
n/d
4.16
n/d
n/d
3.02
n/d
804.9
710.3
810.2
733.6
n/d
10.8
n/d
9.4
n/d
0.4
2.4
2.1
3
6
III
Exp (b)
3.58
3.81
2.67
a
Chemical shifts in ppm, spin–spin couplings in Hz. Relative energy, in kcal mol−1
b
c
d
.
Experimental data. No data.
Fig. 5 Step-by-step simplification of the title pentacoordinate spirophosphoranes.
a
Table 3 Calculated NMR parameters for models 9–12
b
δ31
1
3
Comp.
R at C
Ph
4
Isomer
ΔE
P
δH
6
δH
4
δH
5
J
PH
J
PH4
9
I
III
0
−72.7
−80.6
7.41
7.90
5.11
4.87
3.56
3.24
717.5
770.5
35.4
20.8
0.92
1
0
1
2
Me
t-Bu
Ph
I
III
0
1.02
−72.8
−78.5
7.19
7.62
4.04
3.84
3.41
2.78
707.9
762.2
34.5
25.3
1
I
III
0
0.84
−73.5
−76.7
7.11
7.67
3.77
3.44
3.30
2.74
687.4
771.5
30.1
21.1
1
I
III
0
0.30
−93.8
−88.1
7.71
7.30
4.86
5.28
3.45
2.60
729.1
826.4
21.2
0.6
a
Chemical shifts in ppm, spin–spin couplings in Hz. Relative energy, in kcal mol−1
b
.
with small (Me, 10) and large (t-Bu, 11) alkyl groups, as well as
In order to reveal the impact of the fused aromatic unit on
aromatic (Ph, 9) fragments at chiral centers (Fig. 5c and d). NMR parameters, the benzo fragment was replaced by a
According to calculations (Table 3), the main tendencies are double bond (12, Fig. 4e) in the next step. In this case the
3
1
also the same as for the title compounds. That is there is no reverse distribution of P CSs for the two main isomers and
3
specific influence of the R at the chiral carbon atoms on the notably smaller JPH SSCs are expected. This is very similar to
3
1
3
δ P and J difference in the main isomers.
the trends found in 5-membered compounds.
PH
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Fig. 6 Some geometrical parameters and calculated 3D structures for different 5- and 6-membered pentacoordinate spirophosphoranes.
Thus, in both series the nature of the substituent at the
This study shows that the interplay of NMR experiments
chiral center is not principal. The nature of the fused aro- and DFT calculations of NMR parameters is a powerful and
matic fragment is also not crucial. But NMR parameters are reliable method for determining the relative configurations of
considerably different for compounds with the aromatic the pentacoordinate P–H-spirophosphoranes in solution.
system and those without the aromatic system. In this case,
it is the geometry of the heterocycle which plays the crucial
role: while in 6-membered spirophosphoranes with the fused Experimental section
aromatic system the heterocycle adopts boat conformation,
in 5- and 6-membered compounds without the aromatic
fragment the heterocycle is essentially flat (or envelope)
NMR spectroscopy
All NMR experiments were performed with 600, 500 and
1
400 MHz (600.1, 500.1 and 400.1 MHz for H NMR; 150.9,
(
4 4
Fig. 6). Therefore, in the first case the H –C –N–P dihedral
1
3
3
125.8 and 100.6 MHz for
C NMR; 242.9, 202.5 and
angle is about 156° and results in a large JPH value, in the
3
1
15
1
62.0 MHz for P NMR, 60.81 MHz for N NMR, 376.5 for
latter cases these angles are ca. 126° and 107°, thus small
1
9
3
F respectively) spectrometers equipped with a 5 mm dia-
J
PH should be observed. The same difference in the confor-
3
1
meter probehead and a pulsed gradient unit capable of produ-
mation leads to a different distribution of P CSs in the two
cing magnetic field pulse gradients in the z-direction of 53.5
main isomers.
G cm− . For H– C correlations the HSQC experiment is opti-
1
1
13
1
13
mized for J = 145 Hz. For H– C long range correlations the
1
31
HMBC experiment is optimized for J = 8 Hz. For H– P long
range correlations the HMBC experiment is optimized for J =
Conclusions
1
15
The major product of the Betti based derivatives corresponds 8 Hz. For H– N correlations the HSQC experiment is opti-
to the isomers with both substituents at chiral carbons being mized for J = 90 Hz. For H– N long range correlations the
opposite to the P–H proton. The next populated product HMBC experiment is optimized for J = 6 Hz. For F– H long
corresponds to the isomer with different chiralities at carbons. range correlations the HETCOR experiment is optimized for J =
The least populated isomer is one with both substituents 3 Hz. DOSY experiments were performed with ledbpgp2s,
1
15
1
9
1
being at the same side of the heterocycle as the P–H bond.
For such pentacoordinate chiral spirophosphoranes NOE experiments were performed with 1D DPFGNOE tech-
bearing two six-membered rings at the phosphorus atom the niques. CSs (δ in ppm) were referenced to the solvent CDCl
using a stimulated echo sequence and two spoil gradients.
3
1
13
distinct NMR features, which allow establishing the isomeric (δ = 7.27 ppm for H and 77.0 ppm for C NMR) and to
3
1
structure, can be formulated as follows: the Δ
P
R
c
S
c
/Λ
P
R
c
S
c
external H
3 4
PO (0.0 ppm) for P NMR spectra, to external
1
13
15
isomer has two nonequivalent sets of signals in H ( C) NMR; CH CN (235.5 ppm) for N NMR spectra, to external C F
3
6 6
3
1
19
the Δ R R /Λ S S isomer resonances at a lower field in
P
(−164.9 ppm) for F NMR spectra.
P
c
c
P c c
1
NMR, the PH proton resonances at a higher field,
JPH is
3
Calculations
smaller, JPH is larger than similar parameters for the Δ
Λ R R isomer.
P c c
S S /
The quantum chemical calculations were performed using the
For similar spirophosphoranes bearing two five-membered Gaussian 03 software package. Full geometry optimizations
rings at the phosphorus atom the NMR indicators are slightly have been carried out within the framework of the DFT
P
c c
6
1
3
1
different, in full agreement with the theory.
(PBE1PBE) method using 6-31+G(d) basis sets. P CSs were
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5
6
+
−
calculated at the PBE1PBE/6-311G(2d,2p) level of theory.
8.79 (3 H, br, NH
3
). IR (KBr): ν = 1503 (COO ), 1582, 1598
3
1
−
−1
+
P CSs were referred to H PO calculated at the same level (CvCnaphth), 1664 (COO ), 3066, 3254 cm (NH ); elemental
3
4
3
5
6 1
of theory. The linear scaling procedure was applied.
were referred to TMS.
H CSs analysis calcd (%) for C19
H
15BrF
3
NO
3
: C51.60, H3.42, Br 18.07,
N 3.17; found: C 51.78, H 3.57, Br 17.89, N 3.35.
-(α-Aminobenzyl)-6-bromo-2-naphthol (3). Yield: 95.9%;
m.p. 137–138 °C. δ (500.1 MHz; CDCl ; TMS) 6.13 (1 H, s,
1
Synthesis of 1-(α-aminobenzyl)-2-naphthols (1–3)
H
3
Compounds 1–3 were synthesized in several steps. First, PhCHN), 7.19–7.89 (10 H, m, Ph). IR (KBr): ν = 1589, 1613
the corresponding 1,3-diaryl-2,3-dihydro-1H-naphth[1,2-e][1,3] (CvCnaphth), 3292, 3362 cm− (NH ); elemental analysis calcd (%)
1
2
6
2–64
oxazines were obtained.
trifluoroacetic acid in the presence of water. The free bases C62.04, H4.47, Br 24.16, N4.35.
were isolated by treating the resulting trifluoroacetates with (Δ R R /Λ S S )-6a-Hydro-5,14-diphenyldinaphtho[2,1-b,2,1-h]-
which were then hydrolyzed by for C17H14BrNO: C62.21, H4.30, Br 24.35, N 4.27; found:
6
5
P
c
c
P c c
6
6
sodium carbonate.
1,7,5,11,6-dioxadiazaphosphaspiro[5.5]undecadiene-7a,16a (4a).
0.54 g, 51.6%, method A); (0.28 g, 26.5%, method B);
m.p. 180–182 °C. δH (600.1 MHz; CDCl ; TMS) 7.86 (2 H, d,
(
Synthesis of P–H-spirophosphoranes (4–6)
3
3
3
Spirophosphoranes (4–6) were synthesized by the reaction of
the Betti bases and hexaethyltriamidophosphite: (1) without d, JHH 8.8, H
the addition of the catalyst (method A, only 4) resulting in the 7.37 (2 H, dd,
predominant formation of the (Δ
the addition of diethylamine hydrochloride (5 mol%) as the
catalyst (method B), which allows obtaining (Δ R R /Δ S S )-
JHH 8.7, H10, H10′), 7.83 (2 H, d, JHH 8.7, H12, H12′), 7.74 (2 H,
3
3
3
8
, H8′), 7.49 (2 H, dd, JHH 8.7, JHH 7.5, H13, H13′),
3
3
J
HH
4
8.7, JHH 7.5, H , H11′), 7.32 (4 H, dd,
11
3
3
P
R
c
R
c
/Δ
P
S
c
S
c
)-isomer; (2) with
JHH 8.7, JHH 7.3, JHH 1.8, H16, H16′, H20, H20′), 7.19 (6 H, m,
17–H19, H17′–H19′), 7.08 (1 H, d, JPH 788.5, H ), 7.07 (2 H, d,
JHH 8.8, H , H ), 5.95 (2 H, dd, J 34.1, J 6.9, H , H ),
7 7′ PH HH
1
H
6
3
3
3
P
c
c
P
c
c
4
4′
2
3
and (Δ
: 1 by influencing the rate of P–Z bond cleavage (Z = O, N).
Method A: 1-(α-Aminobenzyl)-2-naphthol (1) (4 mmol) 130.4 (s, C , C ), 129.4 (s, C , C ), 128.9 (s, C , C ), 128.5
P
R
c
S
c
/Δ
P
S
c
R
c
≡Δ
P
S
c
R
c
/Δ
P
R
c
S
c
)-isomers in a ratio close to 4.18 (2 H, dd,
J
PH 14.2,
J
HH 6.9, H
5 C
, H5′). δ (150.9 MHz;
6
7
2
1
3 2
CDCl ; TMS) 150.7 (d, JPC 6.0, C , C2′), 143.3 (s, C15, C15′),
1
4
14′
9
9′
8
8′
was dissolved in dry benzene (12 mL) under heating. Then (s, C12, C12′), 128.1 (s, C17, C17′, C19, C19′), 126.7–126.5 (br, C13
,
3
the solution of hexaethyltriamidophosphite (2 mmol) in dry
C
13′, C16, C16′, C18, C18′, C20, C20′), 124.8 (d, JPC 8.5, C
3
, C3′),
3
benzene (3 mL) was added and the reaction mixture was kept 123.5 (s, C , C ), 121.6 (s, C , C ), 121.2 (d, J 2.1, C7,
1
1
11′
10
10′
PC
at reflux under argon for 8 hours. After that the solvent was
C
7′), 53.6 (s, C
removed and the residue was analyzed by H and P NMR (s, P ). δ (60.8 MHz; CDCl
spectroscopy for the diastereomers’ (4a and 4b) ratio determi- IR (KBr): ν = 1193 (POC), 1586, 1620 (CvCnaphth), 2354
4
, C4′). δ
P
(242.9 MHz; CDCl
3 3 5
; NH ) 60.4 (d, JPN 45.0, N , N5′).
3
; H
3
PO
4
) −75.4
1
31
1
6
N
(PH), 3414 cm− (NH); elemental analysis calcd (%) for
P: C 77.55, H 5.17, N 5.32, P 5.88; found: C77.35,
H 5.01, N 5.49, P 6.02.
(Δ /Λ )-6a-Hydro-5,14-diphenyldinaphtho[2,1-b,2,1-h]-
1
nation ((Δ
P c c P c c P c c P c c P c c
R R /Λ S S ) : (Δ R S /Λ S R ) = 65 : 35). Pure (Δ R R /
Λ
P
S
c
S
c
)-P–H-phosphorane (4a) was obtained by recrystallization
34 27 2 2
C H N O
from benzene.
Method B: 1-(α-Aminobenzyl)-2-naphthols (1–3) (4 mmol)
P
R
c
S
c
P c c
S R
were dissolved in dry benzene (12 mL) under heating. Then 1,7,5,11,6-dioxadiazaphosphaspiro[5.5]undecadiene-7a,16a (4b).
dry diethylamine hydrochloride (0.1 mmol, 5 mol%) was (0.3 g, 28.4%, method B); m.p. 149–150 °C. δH (600.1 MHz;
3
3
added followed by the addition of hexaethyltriamidophosphite CDCl
solution (2 mmol) in dry benzene (3 mL). The resulting reac- 10′), 7.84 (1 H, d, JHH 8.5, H
tion mixture was kept at reflux under argon for 5 hours. After 7.79 (1 H, d, J
3
; TMS) 7.88 (1 H, d, JHH 8.2, H10), 7.85 (1 H, d, JHH 8.4,
3
3
H
8
), 7.83 (1 H, d, JHH 8.2, H13),
3
3
8.7, H ), 7.78 (1 H, d, J
8.4, H13′), 7.52
HH
8′
HH
3
3
that the solvent was removed and the residue was analyzed by (1 H, t, JHH 7.5, H12), 7.48 (1 H, t, JHH 7.5, H12′), 7.45 (2 H, d,
1
31
3
3
3
3
3
H and P NMR spectroscopy for the diastereomers’ (a and b)
J
HH 8.0, H16′, H20′), 7.41 (1 H, t, JHH 7.5, H11), 7.38 (1 H, t,
JHH 7.5, H11′), 7.34 (1 H, d,
1
ratio determination ((Δ R R /Λ S S ) : (Δ R S /Λ S R ) = 1 : 1.1
J
823.5, H ), 7.29 (2 H, t,
P
c
c
P
c
c
P
c
c
P
c
c
PH 6
3
for 4, 1 : 1 for 5, 1 : 0.9 for 6). Pure (Δ
/Λ
R
P c
R
c
/Λ
P
S
c
S
c
)-4a–6a and
J
J
HH 7.5, H17′, H19′), 7.22 (2 H, d, JHH 7.5, H18′), 7.19 (1 H, d,
3
3
(
Δ
P
R
c
S
c
P
S
c
c
R )-4b–6b diastereomers of P–H-phosphoranes
HH 8.5, H
7
), 7.16 (1 H, d, JHH 8.7, H7′), 7.02 (2 H, d, JHH 7.3,
3
3
were obtained by fractional crystallization from benzene.
H , H ), 6.99 (1 H, d, J
H17, H19), 5.87 (1 H, dd, JPH 26.3, JHH 6.7, H4′), 5.81 (1 H,
7.3, H ), 6.93 (1 H, t, J
7.3,
1
6
20
HH
3
18
3
HH
Physical data
3
3
2
3
4
dd, JPH 33.1, JHH 7.1, H ), 4.00 (1 H, dd, JPH 13.8, JHH 6.7,
2
3
1
2·CF
-[Amino-(4-fluorophenyl)methyl]-2-naphthol trifluoroacetate H ), 3.80 (1 H, dd,
J
16.2, JHH 7.1, H ). δ (150.9 MHz;
PC 5.9, C
5
′
PH
5
C
2
2
(
3
COOH). Yield: 82.2%; m.p. 150–151 °C. δ
H
(400.1 MHz; CDCl
3
; TMS) 151.7 (d,
J
2
), 151.6 (d, JPC 10.7, C2′),
6 9
DMSO-d ; TMS) 6.30 (1 H, s, PhCHN), 7.19–8.06 (10 H, m, Ph), 144.7 (s, C15′), 143.9 (s, C15), 131.5 (s, C , C9′), 129.9 (s, C13),
+
−
8
(
.80 (3 H, br, NH ). IR (KBr): ν = 1516 (COO ), 1586, 1601 129.2 (s, C19′), 129.7 (s, C13′), 128.6 (s, C ), 127.8 (s, C18′), 127.4
3 19
−
−1
+
CvCnaphth), 1665 (COO ), 3066, 3288 cm (NH
analysis calcd (%) for C19 NO
found: C 59.68, H 3.77, N 3.55.
-(α-Aminobenzyl)-6-bromo-2-naphthol trifluoroacetate −76.7 (s, P
3
); elemental (s, C12, C12′), 127.3 (br, C18, C20′), 126.9 (s, C20), 124.3 (s, C11),
H
15
F
4
3
: C59.85, H3.96, N 3.67; 124.2 (s, C11′), 122.4 (s, C
8
), 122.3 (s, C8′), 122.1 (s, C7′), 121.0
(s, C ), 54.7 (s, C ), 53.8 (s, C ). δ (242.9 MHz; CDCl ; H PO )
7
4′
4
P
3
3
4
1
1
6
). δ
N
(60.8 MHz; CDCl
3 3 5
; NH ) 61.9 (d, JPN 30.0, N ),
1
(
3·CF
3
COOH). Yield: 84.0%; m.p. 162–164 °C. δ (400.1 MHz; 59.9 (d, JPN 38.0, N5′). IR (KBr): ν = 1194 (POC), 1589, 1623
H
DMSO-d ; TMS) 6.29 (1 H, s, PhCHN), 7.30–8.16 (10 H, m, Ph), (CvCnaphth), 2358 (PH), 3416 cm− (NH); elemental analysis
1
6
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calcd (%) for C34
found: C77.38, H4.98, N 5.42, P 6.05.
/Λ )-6a-Hydro-5,14-diphenyldinaphtho[2,1-b,2,1-h]-
H
27
N
2
O
2
P: C 77.55, H 5.17, N 5.32, P 5.88;
δ
P
(242.9 MHz; CDCl
3
; H
3
PO
4
6 N
) −76.6 (s, P ). δ (60.8 MHz;
1
1
CDCl ; NH ) 62.4 (d, JPN 30.0, N ), 60.2 (d, JPN 45.0, N5′).
δ
3
3
5
(Δ S S
P c c
R R
P c c
F
(376.5 MHz; CDCl
3
; C
6
F
6
) −115.8 (s, F18′), −116.6 (s, F18).
1
,7,5,11,6-dioxadiazaphosphaspiro[5.5]undecadiene-7a,16a (4c). IR (KBr): ν = 1191 (POC), 1586, 1624 (CvCnaphth), 2358
M.p. 180–182 °C. δ (600.1 MHz; CDCl ; TMS) 7.54 (1 H, d, (PH), 3422 cm− (NH); elemental analysis calcd (%) for
1
H
3
1
3
J
PH 848.6, H
6
), 7.14 (2 H, d,
PH 25.6, JHH 6.1, H
J
HH 8.6, H
), 3.58 (2 H, dd, JPH 17.3, JHH 5.6, H
7
), 5.74 (2 H, dd,
34 25 2 2 2
C H F N O P: C 72.59, H 4.48, N 4.98, P 5.51; found:
). C 72.74, H 4.59, N 4.83, P 5.41.
3
3
2
3
J
4
5
δP (242.9 MHz; CDCl ; H PO ) −80.7 (s, P ). δ (60.8 MHz;
(Δ S S /Λ R R )-6a-Hydro-5,14-di(p-fluorophenyl)dinaphtho
3
1
3
4
6
N
P
c
c
P c c
CDCl
could not be isolated.
Δ R R /Λ S S )-6a-Hydro-5,14-di(p-fluorophenyl)dinaphtho (1 H, d, J 849.0, H ), 5.70 (2 H, dd, J 25.0, J
3 3 5
; NH ) 64.0 (d, JPN 38.0, N , N5′). Individual substance [2,1-b,2,1-h]-1,7,5,11,6-dioxadiazaphosphaspiro[5.5]undecadiene-
7a,16a (5c). M.p. 171–173 °C. δ
H
(600.1 MHz; CDCl
3
; TMS) 7.52
1
3
3
(
6.8, H4,
P
c
c
P
c
c
PH
6
PH
HH
2
3
[
7
2,1-b,2,1-h]-1,7,5,11,6-dioxadiazaphosphaspiro[5.5]undecadiene-
a,16a (5a). (0.34 g, 30.1%, method B); m.p. 171–173 °C. CDCl
H
4′), 3.56 (2 H, dd, JPH 17.6, JHH 5.7, H
; H PO ) −80.5 (s, P ). δ (60.8 MHz; CDCl
8.3, H , H10′), (d, JPN 45.0, N , N ). δ (376.5 MHz; CDCl ; C F ) −115.5
5
, H5′). δ
P
(242.9 MHz;
3
3
4
6
N
3 3
; NH ) 64.2
3
1
δH (600.1 MHz; CDCl ; TMS) 7.84 (2 H, d, J
7
7
H11′), 7.26 (4 H, dd, J 8.6, J 5.7, H , H , H16′, H20′), 7.09 naphtho[2,1-b,2,1-h]-1,7,5,11,6-dioxadiazaphosphaspiro[5.5]
(
3
HH
10
5
5′
F
3
6 6
3
3
.81 (2 H, d, JHH 8.3, H13, H13′), 7.76 (2 H, d, JHH 8.7, H
.51 (2 H, t, JHH 8.3, H12, H12′), 7.39 (2 H, t, JHH 8.3, H11 (Δ /Λ )-6a-Hydro-2,11-dibromo-5,14-diphenyldi-
8
, H8′), (s, F18, F18′). Individual substance could not be isolated.
3
3
,
P
R
c
R
c
P c c
S S
3
4
HH
FH
16
20
1
3
1 H, d, JPH 792.1, H
6
), 7.08 (2 H, d, JHH 8.7, H
4 H, t, JHH 8.7, H17, H19, H17′, H19′), 5.91 (2 H, dd, JPH 34.1, m.p. 189–192 °C. δ
JHH 6.9, H , H ), 4.17 (2 H, dd, J 14.2, J
7
, H7′), 6.88 undecadiene-7a,16a (6a). (0.45 g, 32.8%, method B);
3
3
(
H 3
(600.1 MHz; CDCl ; TMS) 7.98 (2 H, br,
3
2
3
3
6.9, H , H ). H , H10′), 7.71 (2 H, d, JHH 9.1, H , H13′), 7.65 (2 H, d,
5 5′ 10 13
4
4′
PH
HH
1
3
3
δ
C
(150.9 MHz; CDCl
3
; TMS) 161.9 (d,
J
CF 245.3, C18, C18′),
J
8
HH 8.7, H , H8′), 7.55 (2 H, t, JHH 9.1, H12, H12′), 7.27 (4 H,
2
4
1
50.8 (d, JPC 5.8, C
2
, C2′), 139.4 (d, JCF 2.0, C15, C15′), 130.5 (s, br, H16, H20, H16′, H20′), 7.19 (6 H, m, H17, H18, H19, H17′, H18′
,
1
3
C , C ), 129.7 (s, C , C ), 129.4 (s, C , C ), 128.8 (s, C , C13′), H19′), 7.08 (1 H, d, J 790.4, H ), 7.09 (2 H, d, J 8.7, H7,
HH
1
4
14′
9
9′
8
8′
13
PH
6
3
3
1
28.5–128.3 (br, C16, C16′, C20, C20′), 126.9 (s, C12, C12′), 124.7
H
7′), 5.89 (2 H, dd, JPH 34.1, JHH 6.7, H
4
, H4′), 4.17 (2 H, dd,
(150.9 MHz; CDCl ; TMS) 151.7
3
2
3
(d,
J
PC 8.2, C
3
, C3′), 123.8 (s, C11, C11′), 121.5 (s, C10, C10′),
J
PH 14.0, JHH 6.7, H
5
, H5′). δ
C
3
2
1
21.4 (s, C , C ), 115.1 (d, J 20.0, C , C , C , C19′), 53.2 (s, C , C ), 143.5 (s, C , C ), 131.1 (s, C , C14′), 131.0 (s, C10,
7
7′
CF
17
17′
19
2
2′
15
15′
14
(
(
(
s, C
4
, C4′). δ
P
(242.9 MHz; CDCl
3
; H
3
PO
4
) −75.2 (s, P
6
). δ
N
C
10′), 130.5 (s, C12, C12′), 129.4 (s, C
9
, C9′), 128.9 (s, C17, C19
,
,
1
60.8 MHz; CDCl
3
; NH ) 61.0 (d,
3
JPN 58.0, N , N5′). δ
5
F
C17′, C19′), 128.7 (s, C , C8′), 127.1–126.9 (br, C16, C18, C20, C16′
8
3
376.5 MHz; CDCl ; C F ) −116.0 (s, F , F ). IR (KBr): ν = C18′, C20′), 125.4 (d, J 8.6, C , C ), 124.0 (s, C , C13′), 123.0
3
6
6
18
18′
PC
3
3′
13
1
(
195 (POC), 1588, 1623 (CvCnaphth), 2364 (PH), 3420 cm−1 (s, C
7
, C7′), 117.9 (s, C11, C11′), 52.2 (s, C
; H PO ) −76.4 (s, P ). δ (60.8 MHz; CDCl
C 72.59, H 4.48, N 4.98, P 5.51; found: C 72.66, H 4.31, N 4.87, (d, JPN 35.0, N , N ). IR (KBr): ν = 1199 (POC), 1587, 1619
4
, C4′). δ
P
(242.9 MHz;
NH); elemental analysis calcd (%) for
C
34
H
25
F
2
N
2
O
2
P: CDCl
3
3
4
6
N
3
; NH ) 60.4
3
1
5
5′
(CvCnaphth), 2353 (PH), 3419 cm− (NH); elemental analysis
)-6a-Hydro-5,14-di(p-fluorophenyl)dinaphtho calcd (%) for C34 25Br P: C 59.67, H 3.68, Br 23.35,
2,1-b,2,1-h]-1,7,5,11,6-dioxadiazaphosphaspiro[5.5]undecadiene- N 4.09, P 4.53; found: C 59.86, H 3.49, Br 23.54, N 3.89, P 4.48.
a,16a (5b). (0.28 g, 24.8%, method B); m.p. 141–143 °C. (Δ /Λ )-6a-Hydro-2,11-dibromo-5,14-diphenyldi-
; TMS) 7.89 (1 H, d, JHH 8.0, H10′), 7.85 naphtho[2,1-b,2,1-h]-1,7,5,11,6-dioxadiazaphosphaspiro[5.5]
1
P 5.32.
(
Δ
P
R
c
S
c
/Λ
P
S
c
R
c
H
2 2 2
N O
[
7
P
R
c
S
c
P c c
S R
3
H 3
δ (600.1 MHz; CDCl
3
3
(
1 H, d, J 8.0, H ), 7.84 (1 H, d, J 8.8, H ), 7.80 (1 H, d, undecadiene-7a,16a (6b). (0.3 g, 21.8%, method B);
HH 10 HH 8′
3
3
3
JHH 7.7, H
8
), 7.78 (1 H, d, JHH 8.1, H13′), 7.73 (1 H, d, JHH 8.5, m.p. 156–158 °C. δ
H
(600.1 MHz; CDCl
3
; TMS) 8.02 (1 H, d,
3
3
4
3
3
4
H
7
13), 7.54 (1 H, t, JHH 7.2, H12′), 7.48 (1 H, t, JHH 7.5, H12),
.43 (1 H, t, J
J
HH 1.7, H10′), 7.99 (1 H, d,
J
HH 1.9, H10), 7.73 (1 H, d,
9.1, H , H13′), 7.63 (1 H, d,
3
3
7.5, H11′), 7.39 (3 H, m, H , H16′, H20′), 7.32
JHH 8.7, H ), 7.67 (2 H, d, J
J
HH
11
8′
HH
8
1
3
3
4
(
1 H, d, JPH 824.0, H
6
), 7.18 (1 H, d, JHH 8.9, H7′), 7.16 (1 H, d,
HH 9.1, H13), 7.56 (1 H, dd, JHH 9.1, JHH 1.7, H12′), 7.52 (1 H,
3
3
3
4
1
JHH 9.2, H
7
), 6.95 (2 H, dd, JHH 9.2, H17′, H19′), 6.91 (2 H, dd, dd, JHH 9.1, JHH 1.9, H12), 7.33 (1 H, d, JPH 828.0, H
6
), 7.28
3
4
3
JHH 8.8, J 5.4, H , H ), 6.58 (1 H, dd, J
.82 (1 H, dd, JPH 27.7, JHH 6.8, H4′), 5.76 (1 H, dd, JPH 33.6,
8.8, H , H ), (4 H, m, H16′, H17′, H19′, H20′), 7.23 (1 H, m, H18′), 7.19 (1 H, d,
FH
16
20
3
HH
17
19
2
2
3
3
5
J
HH 8.7, H7′), 7.16 (1 H, d, JHH 9.1, H
7
), 7.01 (1 H, m, H18),
3
3
3
2
J
HH 7.6, H
4
), 3.95 (1 H, dd, JPH 14.0, JHH 6.8, H5′), 3.77 (1 H, 6.96 (4 H, br, H16, H17, H19, H20), 5.78 (1 H, dd,
J
PH 27.5,
2
3
3
2
3
dd, J 16.8, J 7.2, H ). δ (150.9 MHz; CDCl ; TMS) 162.0
(
C
JHH 6.9, H ), 5.74 (1 H, dd, J 33.7, J 7.3, H ), 3.95 (1 H,
PH
HH
5
C
1
3
4′
PH
HH
4
1
2
3
3
2
3
d, JCF 247.3, C18′), 161.6 (d, JCF 244.8, C18′), 151.1 (d, JPC 9.9, dd, JPH 13.8, JHH 6.5, H5′), 3.77 (1 H, dd, JPH 16.3, JHH 7.3,
2
3
2
2′), 151.0 (d,
J
PC 14.8, C
2
), 139.8 (d,
J
PC 3.0, C15′), 139.1
5 C 3
H ). δ (150.9 MHz; CDCl ; TMS) 151.8 (d, JPC 16.2, C2′), 151.7
3
4
2
(d, J 3.4, C ), 130.7 (s, C ), 130.6 (s, C ), 129.8 (d, J 10.0, (d, J 20.3, C ), 144.0 (s, C ), 143.4 (s, C ), 131.3 (s, C ),
PC 15 14′ 14 PC PC 2 15′ 15 9′
4
C
8
), 129.4 (d, JPC 23.6, C8′), 128.9 (s, C10′), 128.8 (s, C10), 128.3 131.2 (s, C10′), 131.1 (s, C10), 130.9 (s, C
9
), 130.5 (s, C12′), 130.4
3
3
(
(
(
d,
J
FC 8.5, C16′, C20′), 128.0 (d,
JFC 8.2, C16, C20), 127.1 (s, C12), 129.8 (s, C14′), 129.7 (s, C14), 129.1 (br, C8′, C17′, C19′),
3
s, C12′), 126.9 (s, C ), 124.8 (d, J 9.1, C ), 123.9 (s, C11′), 123.7 128.7 (s, C ), 128.5 (s, C , C ), 127.8 (s, C ), 127.2 (s, C ),
12
PC
3′
8
17
19
18′
18
3
3
s, C11), 122.9 (d, JPC 10.9, C
21.4 (d, JPC 2.7, C
3
), 121.6 (s, C13′), 121.5 (s, C13), 127.0 (s, C16′, C20′), 126.6 (s, C16, C20), 125.2 (d, JPC 7.7, C3′),
), 120.4 (d, JPC 1.3, C7′), 115.4 (d, JFC 21.5, 124.0 (s, C13′), 123.9 (s, C13), 123.5 (d,
3
3
2
3
1
7
2
J
PC 10.6, C
3
), 123.4
3
C17′, C19′), 114.7 (d, J 21.3, C , C ), 53.3 (s, C ), 52.6 (s, C ). (d, J 2.7, C ), 123.0 (br, C ), 117.9 (s, C11′), 117.7 (s, C11),
PC
17
19
4′
4
PC
7
7′
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Dalton Trans.

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5
4.5 (s, C4′), 53.6 (s, C
4 P 3 3 4
). δ (242.94 MHz; CDCl ; H PO ) −77.7
Notes and references
1
(s, P ). δ (60.8 MHz; CDCl ; NH ) 61.9 (d, JPN 30.0, N5),
6
N
1
3
3
5
9.9 (d, JPN 40.0, N5′). IR (KBr): ν = 1191 (POC), 1586, 1617
1 K. M. Pietrusiewicz and M. Zabłocka, Chem. Rev., 1994, 94,
1375.
−
1
(CvCnaphth), 2370 (PH), 3422 cm (NH); elemental analysis
calcd (%) for C H Br N O P: C 59.67, H 3.68, Br 23.35,
2 R. Noyori, in Asymmetric Catalysis in Organic Synthesis, John
Wiley & Sons, New York, 1994.
3 L. D. Quin, in A Guide to Organophosphorus Chemistry,
Wiley-Interscience, New York, 2000.
4 I. Ojima, in Catalytic Asymmetric Synthesis, Wiley-VCH,
New York, 2000.
5 J. Drabowicz, P. Łyźuwa, J. Omelańczuk, K. M. Pietrusiewicz
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3
4
25
2 2 2
N 4.09, P 4.53; found: C 59.75, H 3.57, Br 23.12, N 4.27, P 4.65.
/Λ )-6a-Hydro-2,11-dibromo-5,14-diphenyldi-
naphtho[2,1-b,2,1-h]-1,7,5,11,6-dioxadiazaphosphaspiro[5.5]
undecadiene-7a,16a (6c). M.p. 189–192 °C. δ (600.1 MHz;
), 5.71 (2 H, dd,
(
Δ
P
S
c
S
c
P
R
c
R
c
H
1
3 6
CDCl ; TMS) 7.54 (1 H, d, JPH 852.3, H
3
3
2
3
JPH 25.1, J
6.9, H , H ), 3.58 (2 H, dd, J 18.1, J 5.1,
HH
HH
4
4′
PH
H
5
, H5′). δ
P
(242.9 MHz; CDCl
3
; H
3
PO
4
6
) −81.4 (s, P ).
Individual substance could not be isolated.
7
F. H. Westheimer, Acc. Chem. Res., 1968, 1, 70.
X-ray structure determination
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Soc., 1984, 106, 4916.
Data sets for single crystals of 4b and 5a were collected on
Bruker AXS Kappa APEX and Smart Apex diffractometers
respectively with graphite-monochromated Mo Kα radiation
9
J. R. Knowles, Annu. Rev. Biochem., 1980, 49, 877.
1
1
1
1
1
1
1
0 P. J. J. M. van Ool and H. M. Buck, Recl. Trav. Chim. Pays-
Bas, 1984, 103, 119.
(
λ = 0.71073 Å) using complete sphere mode. Programs used:
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6
8
69
data collection APEX2, data reduction ‘SAINT’ absorption
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70
71
2
structure refinement by full-matrix least-squares against F
7
1
using SHELXL-97 , hydrogen atoms calculated and refined as
riding atoms, except the hydrogens attached to phosphorus
and nitrogen atoms which were located from a difference
Fourier map and refined isotropically. The crystals contain
solvent channels, modeled by disordered ethanol and acetone
molecules. Crystals 5b contain a solvate benzene molecule,
which is disordered and was refined with geometry and
vibrational parameter constraints.
2004, 29, 495.
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Crystal data for 4b
130, 3952.
3
Formula C34
H
27
N
2
O
2
P, crystal size 0.39 × 0.39 × 0.15 mm , M = 17 W. W. Cleland and A. C. Hengge, Chem. Rev., 2006, 106,
5
1
26.54, orthorhombic, space group P2 2 2 , a = 8.6029(2), b =
3252.
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1
1 1
3
c
−
3
−1
g cm , μ = 0.138 mm , T = 150(2) K, θ range = 1.67 to 31.17°, 19 M. Eder, M. Stolz, T. Wallimann and U. Schlattner, J. Biol.
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meters, R
−
1
= 0.0406, wR
2
= 0.0941 [I > 2σ(I)]; flack parameter
4429.
0.03(2), maximal residual electron density: 0.400/−0.229 e Å−3
.
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Formula C37H F N O P, crystal size 0.24 × 0.17 × 0.12 mm ,
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3
Engl., 1997, 36, 432.
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3
8
.799(5), c = 17.269(9) Å, β = 95.512(7)°, V = 5878(6) Å , Z = 8, 24 Y. Takagi, M. Warashina, W. J. Stec, K. Yoshinari and
= 1.360 g cm− , μ = 0.144 mm , T = 293(2) K, θ range = 2.11
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CCDC 1542633 and 1542634 contain the supplementary 29 L. W. Tremblay, G. F. Zhang, J. Y. Dai, D. Dunaway-Mariano
3
−1
K. Taira, Nucleic Acids Res., 2001, 29, 1815.
ρ
c
(
1
2
−3
K. N. Allen, Science, 2003, 299, 2067.
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