An unusual cascade reaction of 4,5-dihydro-4,4-bis(trifluoromethyl)-2-phenyl-6,7-(4-chlorobenzo)[e]-1,3,2-dioxaphosphepin-5-one with chloral

Article abstract of DOI:10.1016/j.mencom.2010.01.017

The reaction of 4,5-dihydro-4,4-bis(trifluoromethyl)-2-phenyl-6,7-(4-chlorobenzo)[e]-1,3,2-dioxaphosphepin-5-one with chloral (1:2) proceeds with evolving hexafluoroacetone and gives spiro{2-oxo-4-trichloromethyl-4,5-dihydro-2-phenyl-6,7-(4-chlorobenzo)[f]-1,3,2-dioxaphosphepine-5,2'-(3'-trichloromethyl)oxirane} with a high stereoselectivity. Configuration of the four chiral centres (P²_SC⁴_SC⁵_SC^3'_S /P²_RC⁴_RC⁵_RC^3'_R) was determined by a single crystal X-ray diffraction.

Full text of DOI:10.1016/j.mencom.2010.01.017

Mendeleev
Communications
Mendeleev Commun., 2010, 20, 44–46
An unusual cascade reaction of 4,5-dihydro-
4,4-bis(trifluoromethyl)-2-phenyl-6,7-(4-chlorobenzo)[e]-
1,3,2-dioxaphosphepin-5-one with chloral
Vladimir F. Mironov,*a,b Yuliya Yu. Borisova,a Liliya M. Burnaeva,a Dmitry B. Krivolapov,b
Igor A. Litvinov,b Vladislav V. Zverev,b Rashid Z. Musinb and Irina V. Konovalovaa
a A. M. Butlerov Chemical Institute, Kazan State University, 420008 Kazan, Russian Federation.
Fax: +7 843 231 5416; e-mail: liliya.burnaeva@ksu.ru
b A. E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Centre of the Russian Academy
of Sciences, 420088 Kazan, Russian Federation. Fax: +7 843 273 1872; e-mail: mironov@iopc.kcn.ru
DOI: 10.1016/j.mencom.2010.01.017
The reaction of 4,5-dihydro-4,4-bis(trifluoromethyl)-2-phenyl-6,7-(4-chlorobenzo)[e]-1,3,2-dioxaphosphepin-5-one with chloral
(1:2) proceeds with evolving hexafluoroacetone and gives spiro{2-oxo-4-trichloromethyl-4,5-dihydro-2-phenyl-6,7-(4-chloro-
benzo)[f]-1,3,2-dioxaphosphepine-5,2'-(3'-trichloromethyl)oxirane} with a high stereoselectivity. Configuration of the four chiral
centres (PS2CS4C5SC3S' /P2RC4RCR5C3R' ) was determined by a single crystal X-ray diffraction.
The reactions of PIII derivatives with carbonyl compounds are
important for the synthesis of compounds bearing pentacoordi-
nated phosphorus, which are the intermediates in the nucleophilic
displacement reaction at tetracoordinated phosphorus species.1–6
Ph
O
P
O
Cl
Recently,7,8 we found that the reaction of λ3σ3-1,3,2-dioxa-
benzophospholes having a γ- or δ-carbonyl group to the phos-
phorus atom in exocyclic substituent leads to the formation of
‘carcass’ phosphoranes. In spite of the formation of a few chiral
centres, the process has a high regio- and stereoselectivity. The
reaction was also applied to the PIII derivatives bearing γ-endo-
cyclic carbonyl group relative to the phosphorus atom, such as
4,5-dihydro-4,4-bis(trifluoromethyl)-2-phenyl-6,7-benzo[e]- and
4,5-dihydro-4,4-bis(trifluoromethyl)-2-phenyl-6,7-(4-chlorobenzo)-
[e]-1,3,2-dioxaphosphepin-5-ones 1a,b. The 5-carbaphosphatrane
derivatives with pentacoordinated phosphorus atom, containing
three oxygen atoms in equatorial sets and two less apicophilic
carbon ones in apical sets were unexpectedly obtained in the
reaction of compounds 1a,b with hexafluoroacetone.9
In this work, we attempted to use chloral as another reactive
compound for the synthesis of 5-carbaphosphatranes. However,
the interaction of chloral with dioxaphosphepine 1b is more
complex and proceeds by two main directions. The first direc-
tion leads to the formation of the unusual derivative with tetra-
coordinated phosphorus atom – spiro{2-oxo-4-trichloromethyl-
4,5-dihydro-2-phenyl-6,7-(4-chlorobenzo)[f]-1,3,2-dioxaphos-
phepine-5,2'-(3'-trichloromethyl)oxirane} 2. The evolving of
hexafluoroacetone, detected owing to the characteristic odour,
took place in the course of the reaction. The content of com-
pound 2 in the reaction mixture is about 70%.† The second
direction involves the formation of 5-carbaphosphatrane deriva-
tive 3 as a minor compound.
The stereoselectivity of the formation of product 2 is very high.
In spite of three additional asymmetric centres, only one diastereo-
isomer was formed and isolated in view of crystals suitable for
X-ray diffraction (as a solvate with one CH2Cl2 molecule).‡ The
molecular geometry of compound 2 is shown in Figure 1. The
phosphorus atom has a distorted tetrahedral configuration, a
seven-membered heterocycle has a distorted boat conformation
and includes the planar four-atoms fragment C(5)C(5a)C(9a)O(1),
the atoms P(2), O(3) and C(4) being situated on one side and at
CF3
CF3
O
1b
CCl3CHO
– (CF3)2C=O
12
11
13
O
O
10
1
O
9
O
*
P
P 2
CCl3
8
9a
O
3 O
*
Cl
O
4
5
7
5a
Cl
16
6
*
CCl3
F3C
CF3
O
*
18
CCl3
17
2
3
Scheme 1
various distances of the latter. Phenyl and trichloromethyl sub-
stituents, as well as oxirane carbon atom [C(11)], are in pseudo-
equatorial sets, the phosphoryl oxygen and the oxirane cycle
†
Solvents and commercial reagents were purified by conventional methods
before use. All experiments were performed under an atmosphere of dry
argon. Melting points are uncorrected. Measurements involved a Boetius
melting point apparatus. NMR experiments were performed in CDCl3
at 20 °C with Varian Unity-300 (31P, 31P-{1H} at 121.42 MHz; 19F at
282.4 MHz) and Bruker Avance-600 spectrometers with a 5 mm diameter
inverse probe head with Z-active shielded gradients working at 600 MHz
for 1H and 150.864 MHz for 13C. The dH and dP values were determined
relative to internal (HMDS) or external (H3PO4) standard. The dF values
were determined relative to internal standard (C6F6) and then re-calculated
relative to CFCl3. The dC values were determined relative to the deuterated
solvent signal. IR spectra were recorded on a Specord M-80 instrument
in Nujol. EI mass spectra were obtained with a TRACE MS Finnigan
MAT instrument; the ionization energy was 70 eV and the ion source
temperature was 200 °C. The samples were introduced into the ion
source via a direct inlet system. The evaporating ampoule was heated
from 35 to 150 °C at a rate of 35 K min–1. The mass spectrometric data
were processed using the Xcalibur system program.
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© 2010 Mendeleev Communications. All rights reserved.

Mendeleev Commun., 2010, 20, 44–46
oxygen are in pseudoaxial sets. The trichloromethyl substituent
and the C(4)–C(5) bond are situated in trans-configuration.
Ph
O
O
P
CCl3CHO
O
1
CCl3
CF3
CF3
C(13)
C(12)
Cl
11
C(14)
C(15)
Cl(1)
C
O
4
Cl(2)
C(4)
C(10)
O(3)
O(2)
C(16)
H(4)
Ph
O
Cl(3)
Ph
O
O
P(2)
O
P
P
O
O(1)
C(9a)
O
Cl
C(9)
CCl3
C(5a)
CCl3
C(5)
Cl
CF3
O
O(5)
CF3
C(8)
Cl(7)
C(6)
O
F3C CF3
C(7)
H(17)
C(17)
5
6
C(18)
Cl(4)
Cl(6)
Ph
Cl(5)
O
P
O
– (CF3)2C=O
(CF3)2C=O
O
CF3
CF3
Figure 1 Molecular geometry of compound 2 in a crystal (a solvate with
disordered CH2Cl2 molecule, the solvent is omitted for clarity). Selected
bond lengths (Å) and bond angles (°): P(2)–O(2) 1.465(4), P(2)–O(3)
1.591(4), P(2)–O(1) 1.594(4), P(2)–C(10) 1.777(7), O(3)–C(4) 1.433(7),
C(4)–C(5) 1.555(8), C(5)–C(5a) 1.503(8), C(5)–C(17) 1.482(8), O(5)–C(5)
1.430(7), O(5)–C(17) 1.431(8), O(2)–P(2)–O(3) 116.2(3), O(2)–P(2)–O(1)
109.9(3), O(3)–P(2)–O(1) 103.8(2), O(2)–P(2)–C(10) 115.8(3), O(1)–P(2)–
C(10) 107.4(3), O(5)–C(5)–C(17) 58.8(4), O(5)–C(5)–C(5a) 116.8(5),
C(17)–C(5)–C(5a) 123.1(5), O(5)–C(5)–C(4) 114.0(5), O(5)–C(17)–C(5)
58.8(4), O(5)–C(17)–C(18) 116.2(5).
Cl
O
CCl3
O
7
Ph
Ph
O
O
P
P
CCl3CHO
O
O
CCl3
– CCl3CHO
Cl
Cl
CCl3
CCl3
O
O
The reaction of compound 1b with chloral. The mixture of phosphonite
1b9 (7 mmol, 2.85 g), chloral (16 mmol, 2.52 g) and CH2Cl2 (20 ml) was
kept during two months in an argon atmosphere (20 °C). Methylene chloride
and chloral excesses were removed in a vacuum; the residue was dissolved
in the CH2Cl2–pentane mixture (5:1) and was kept for six days. The
precipitate was filtered off, washed with CH2Cl2–pentane mixture (5:1)
and dried in a vacuum (0.1 Torr). Compound 2, colourless crystals,
mp 221–222 °C (decomp.), yield 58%. IR (Nujol, n/cm–1): 3005, 2948,
1901, 1740, 1592, 1481, 1440, 1414, 1305, 1272, 1205, 1132, 1114,
1070, 1013, 997, 927, 902, 887, 830, 803, 758, 745, 728, 703, 687, 670,
632, 623, 614, 603. 31P-{1H} NMR ([2H6]DMSO) dP: 14.8. 1H NMR
8
9
Ph
Ph
O
O
O
P
P
O
O
Cl
CCl3
CCl3
O
Cl
O
CCl3
O
CCl3
10
11
3
([2H6]DMSO): 5.71 (s, H18), 5.84 (s, H4, JPH 3.0 Hz), 7.07 (d, H9,
3JHH 8.9 Hz), 7.50 (dd, H8, JHH 8.9 Hz, JHH 2.6 Hz), 7.58 (d, H6,
4JHH 2.6 Hz), 7.61 (m, H12, H14), 7.73 (m, H11, H15, H13). 13C NMR
([2H6]DMSO) (a multiplicity of the signal in 13C-{1H} spectrum is given
3
4
2
Scheme 2
1
2
in parentheses): 81.45 [ddd (d), C4, JHC4 164.7 Hz, JPOC4 6.6 Hz,
The mechanism of the cascade formation of spirane 2 is
rather complex and unclear. Nevertheless, we may propose the
following reaction scheme, which can be conditionally divided
into two parts (Scheme 2). The first part is an unusual reaction
3JHC17 1.6 Hz], 63.91 [m (s), C5, 2JHCC5 2.0–2.3 Hz, 2JHCC5 2.0–2.3 Hz,
CC4
3JHC6CC5 4.3–4.5 Hz], 123.61 [br. m (br. s), C5a], 131.67 [dd (s), C6,
1JHC6 170.0 Hz, JHC8CC6 6.1 Hz], 129.34 [ddd (s), C7, JHC9CC7 11.0 Hz,
3
3
2JHCC7 3.6 Hz, JHCC7 3.2 Hz], 130.81 [dd (s), C8, JHC8 170.1 Hz,
2
1
3JHC6CC8 5.1 Hz], 121.90 [dd (d), C9, JHC9 167.8 Hz, JPOCC9 5.5 Hz],
148.24 [dddd (d), C9a, 3JHC6CC9a 9.5 Hz, 3JHC8CC9a 9.5 Hz, 2JPOC9a 9.4 Hz,
2JHC9C9a 4.2 Hz], 125.02 [dt (d), C10, 1JHC10 195.7 Hz, 3JHC12,14CC10 7.6 Hz],
130.99 [dddd (d), C11, 1JHC11 165.0 Hz, 2JPCC11 10.5 Hz, 3JHC13CC11 7.4 Hz,
1
3
‡
X-ray diffraction data for 2: C17H10Cl7O4P·CH2Cl2, M = 642.30, mono-
clinic, space group P21/n, a = 11.804(3), b = 11.430(5) and c = 18.364(5) Å,
b = 95.59(3)°, V = 2465.9(14) Å3, Z = 4, dcalc = 1.73 g cm–3. Cell param-
eters and intensities of 4947 independent reflections (3247 with I ³ 2s)
were measured on an Enraf-Nonius CAD-4 diffractometer in the w-scan
mode, q £ 74.00°, using CuKα radiation with graphite monochromator.
The intensity falling was not observed at three control measurements. An
empirical absorption correction based on y-scans was applied [m(CuKα) =
= 10.2 cm–1]. The structure was solved by direct method using the SIR
program13 and refined by the full matrix least-squares using SHELX-9714
program package. All non-hydrogen atoms were refined anisotropically.
The hydrogen atoms were calculated and refined as riding atoms. The
final divergence factors are R = 0.079, Rw = 0.194 based on 3247 reflections
with F2 ³ 2s2. All calculations were performed on PC using WinGX15
program. Cell parameters, data collection and data reduction were performed
on Alpha Station 200 computer using MoLEN.16 In the methylene chloride
molecule Cl4A (Cl4B) and H atoms are disordered in a crystal and were
refined with occupancy of 0.701(8) [0.299(8)]. Figures were made using
the program PLATON.17
3JHC15
7.4 Hz], 129.21 [ddd (d), C12, 1JHC12 167.4 Hz, 3JPCCC12 16.0 Hz,
8.3 Hz], 134.03 [br. dt (d), C13, 1JHC13 163.9 Hz, 3JHC11CC13 7.0 Hz,
CC11
3JHC14
CC12
4JPCCCC13 2.1 Hz], 96.32 [d (d), C16, 3JPOCC16 13.8 Hz], 69.83 [dd (s), C17,
1JHC17 193.2 Hz, JHC4CC17 4.4 Hz], 93.56 [d (s), C18, JHC17 10.8 Hz].
3
2
C18
MS, m/z (%): 554 (0.63) [M] (calc. for C17H1035Cl7O4P, 554), 519 (2.0)
+
·
[M – Cl]+, 483 (3.3) [M – HCl – Cl]+, 437 (0.82) [M – CCl3]+, 389
(37.7) [C15H935Cl3O4P]+, 366 (48.2) [C16H935Cl2O4P]+, 294 (100.0)
[C14H1235ClO3P]+. Found (%): C, 33.43; H, 1.97; Cl, 49.57; P, 4.32. Calc.
for C17H10Cl7O4P·CH2Cl2 (%): C, 33.62; H, 1.87; Cl, 49.73; P, 4.82.
Compound 3 was obtained by removing the solvent from filtrate (after
filtration of compound 2) and crystallization of a residue under a layer of
pentane. Yield 17%, colourless crystals, mp 118–119 °C (decomp.). IR
(Nujol, n/cm–1): 1614, 1592, 1476, 1462, 1441, 1355, 1323, 1293, 1223,
1168, 1127, 1109, 1069, 1041, 1018, 1003, 973, 935, 893, 867, 853, 839,
825, 794, 774, 764, 746, 728, 693, 645, 630. 31P-{1H} NMR (CDCl3) dP:
4
6.0 (s). 19F NMR (CDCl3) dF: –72.8 (q, CF3, JFF 10.7 Hz), –73.9 (q,
CCDC 748834 contains the supplementary crystallographic data for this
paper. These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
For details, see ‘Notice to Authors’, Mendeleev Commun., Issue 1, 2010.
CF3, 4JFF 10.7 Hz). MS, m/z: 562 [M]+ (calc. for C17H935Cl4F6O4P, 562).
·
Found (%): C, 36.09; H, 2.01; P, 5.61. Calc. for C17H9Cl4F6O4P (%):
C, 36.17; H, 1.60; P, 5.50.
– 45 –

Mendeleev Commun., 2010, 20, 44–46
Table 1 Selected bond lengths and bond angles of intermediate 4 in twist-
boat conformation.
Bond
d/Å
Angle
j/°
1–2
1–3
1–4
1–5
1–6
1.720
1.667
1.713
1.802
1.819
2–1–3
2–1–4
2–1–5
2–1–6
3–1–4
3–1–5
3–1–6
97.2
5
159.7
110.7
94.7
90.6
107.7
115.4
4
1
6
2
3
are –1532.01034, –2239.54278 and –3771.54913, respectively;
that is, the formation of intermediate 4 demands very slight
expenditure of energy (2.6 kcal mol–1).
Figure 2 Calculated geometry of pentacoordinated phosphorus interme-
diate 4.
This work was supported by the Russian Foundation for
Basic Research (grant no. 07-03-00180).
of replacement of a hexafluoroacetone fragment by chloral,
which leads to the formation of dioxaphosphepine 8 via a range
of intermediates 4–7. The first stage of this process is likely
the symmetry-allowed [1 + 2]-cycloaddition or the cheletropic
reaction, which yields spirophosphorane 4, bearing a three-
membered cycle. The recent quantum-chemical calculations for
the related reaction of chloral with 2-methoxy-5,6-benzo[d]-
1,3,2-dioxaphosphorin-4-one give a relatively stable intermediate
spirophosphorane structurally similar to the intermediate 4.10
The structure of 5 may be a transition state in passing to bipolar
intermediate 6, which converts further to bipolar species 7. This
bipolar ion is an unstable intermediate of the reversible reaction
of PIII derivative 8 with hexafluoroacetone. Chloral and hexafluoro-
acetone have a closely related reactivity, but a quite different
volatility, that leads to the fast removal of hexafluoroacetone
from the reaction sphere.
The second part of the reaction scheme, starting from the
interaction of chloral with intermediate phosphepine 8, is analo-
gous to the first one in some general features. It involves a
cascade formation of intermediates 9–11. Distinct from bipolar
ion 6, the intermediate 11 turns into epoxide 2 as a result of the
alkoxide anion intramolecular attack on the carbon atom bound
to trichloromethyl group with simultaneous P=O bond formation.
We made an attempt to study the mechanism of the reaction
by the quantum chemical calculations. First, the structures of
compound 1b and intermediate 4 were investigated by the
density functional theory (DFT) method with the PBE func-
tional and Triple z basis, using the Priroda program.11,12 A few
conformations of seven-membered heterocycle of compound
1b, namely, boat and twist-boat ones were optimized, in which
a phenyl substituent is located in the equatorial and axial sets.
Among them a twist-boat form with an equatorial orientation of
phenyl substituent is most favourable. The selected bond lengths
and bond angles of intermediate 4 in twist-boat conformation
are given in Table 1, and the molecular geometry is shown in
Figure 2. The configuration of the phosphorus atom in spiro-
phosphorane 4 is more likely a distorted square pyramid rather
than a trigonal bipyramid. The full energies of chloral, compound
1b and intermediate 4, calculated by DFT/PBE/TZ2P method
Online Supplementary Materials
Supplementary data associated with this article can be found
in the online version at doi:10.1016/j.mencom.2010.01.017.
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