Conformational analysis of six-membered ring dioxaphosphinanes. Part 1: Anancomeric thiophosphates

Article abstract of DOI:10.1016/j.tet.2004.09.025

A study of the conformation of a series of anancomeric axial and equatorial 2-aryloxy-2-thio-1,3,2λ⁵-dioxaphosphinanes 2-12 in solution and solid state is reported. In accord to the stereoelectronic theory, aryl thiophosphates substituted with

Full text of DOI:10.1016/j.tet.2004.09.025

Tetrahedron 60 (2004) 10927–10941
Conformational analysis of six-membered ring
dioxaphosphinanes. Part 1: Anancomeric thiophosphates
†
Javier Hernandez, Rafael Ramos, Noe Sastre, Rocıo Meza, Herbert Hommer, Magali Salas
‡
§
¶
´
´
and Barbara Gordillo
´
*
´ ´ ´
Departamento de Quımica, Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional, Apartado Postal 14-740,
Mexico, D F., Mexico
Received 27 March 2004; revised 2 September 2004; accepted 9 September 2004
Available online 1 October 2004
Abstract—A study of the conformation of a series of anancomeric axial and equatorial 2-aryloxy-2-thio-1,3,2l5-dioxaphosphinanes 2–12 in
solution and solid state is reported. In accord to the stereoelectronic theory, aryl thiophosphates substituted with electron-withdrawing (EW)
groups will tend to occupy axial positions in chair ring conformations due to the stabilizing endo-anomeric (npO–s*P–X) hyperconjugative
interaction. The antiperiplanar orientation of the orbitals involved in the stereoelectronic interaction is a requirement that is fulfiled in the
axial series of compounds when the ring adopts a chair conformation. Therefore, in the equatorial series of thiophosphates, the axial seeking
characteristics of aryloxy-EW groups might render the molecule with distortion of the chair conformation. An opposite trend is anticipated
for the less axial seeking aryl thiophosphates substituted with electron releasing (ER) groups. A detailed analysis of the 3JHH, 3JPH and 3JCP
coupling constants allowed us to conclude that there is no contribution of high energy twist-boat conformations in the equatorial
thiophosphates substituted with aryl-EW groups in solution. In consequence, single chair conformations were found in solid state for aryl
thiophosphates in both configurations. X-ray geometrical analysis of bond distances and bond angles supports clearly the participation
of hyperconjugative endo-anomeric (npO–s*P–OAr) effect in the stabilization of axial series of compounds and the participation of
endo-anomeric (npO–sP*]S) effect in the stabilization of the equatorial thiophosphates in chair conformations.
q 2004 Published by Elsevier Ltd.
˚
is due to the longer P–O (1.58 A) endo-cyclic bond
1. Introduction
˚
distances as compared to C–O in 1,3-dioxanes (1.42 A) or
6
˚
Six-membered ring thiophosphates are interesting systems
from the conformational point of view since there are
several electronic effects, as the endo- and exo-anomeric
effects, that can play an important role in the conformational
preferences of the substituents on phosphorus.1–3 Steric
effects in thiophosphates are not very important as in the
monosubstituted cyclohexanes4 or as in the closest hetero-
cyclic system, the 2-substituted-1,3-dioxanes.5 The
decreased 1,3-syn axial steric hindrance of the substituent
with the 4,6-hydrogens of the 1,3,2-dioxaphosphinane ring
C–C in cyclohexane (1.54 A), as well as the propensity of
the endo-cyclic oxygens to adopt sp2 hybridization instead
of sp3 that renders the ring with more flexibility than the
corresponding 1,3-dioxane or cyclohexane.7 As observed
in the pentacoordinative chemistry of phosphorus com-
pounds,8 electronegative substituents in phosphates and
thiophosphates will tend to adopt axial orientations, and
electron-donating substituents, equatorial ones (Scheme 1).9
Keywords: Dioxaphosphinanes; Thiophosphates; Conformation; NMR;
LFER correlations; X-ray crystal structures.
* Corresponding author. Tel.: C525 5061 3729; fax: C525 5747 7113;
e-mail: ggordill@cinvestav.mx
†
´ ´
Present address: Centro de Investigacion en Alimentacion y Desarrollo A.
C. Hermosillo Sonora, Mexico.
´ ´
Present address: Unidad de Servicios de Apoyo en Resolucion Analıtica
‡
§
Universidad Veracruzana, Xalapa Veracruz, Mexico.
´ ´
Present address: Departamento Ciencias Basicas Ingenierıa y Tecnologıa
´
´
Universidad Autonoma de Tlaxcala, Tlaxcala, Mexico.
¶ Present address: Degussa Construction Polymers GmbH, D-83308
Trostberg, Germany.
Scheme 1.
0040–4020/$ - see front matter q 2004 Published by Elsevier Ltd.
doi:10.1016/j.tet.2004.09.025

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J. Hernandez et al. / Tetrahedron 60 (2004) 10927–10941
10928
exo-anomeric (npY–s*P–O endo-cyclic) hyperconjugative inter-
action will promote that an electron releasing substituent,
such as an amine, tend to occupy the equatorial position in a
dioxaphosphinane ring (Scheme 2b).7 The equatorial isomer
might also be favored by the npO–s*P]S endo-hyperconju-
gative intraction.11
From experimental point of view, van Nuffel et al.12 have
proved the participation of stereoelectronic interactions in
the axial conformational preference of several phosphates
and their thio derivatives, through the shortening of the
endo-cyclic P–O bond and the lengthening of the P–X bond
that is based on the resonance hybrids shown in Scheme 2. It
is worth of mention that since the interconversion barrier of
chair-to-twist or chair-to-boat conformations in 1,3,2-
dioxaphosphinanes is very low (0.5–3.5 kcal/mol),1 the
stabilizing endo- or exo-anomeric interactions and/or the
steric hindrance when the substituents are bulky, can force
the molecule to adopt a twist-boat conformation in
preference to the chair (Scheme 3).7
Scheme 2.
These preferences rely on stereoelectronic grounds, the
endo-anomeric (npO–s*P–X) effect favoring the axial con-
former when the X-substituent is electronegative (such as
halogen, OR, etc.), because the acceptor s* antibonding
orbital of an electronegative substituent is lower-lying than
the antibonding orbital of an electron-releasing substituent,
therefore giving rise to a more stabilizing 2 electrons/2
orbitals interaction (Scheme 2a).3,10 On the contrary, the
Reported in this work is the conformational analysis in
solution and solid state of a series of axial and equatorial
anancomeric aryl thiophosphates substituted with electron-
withdrawing (EW) and electron-releasing (ER) groups
1
(2–12), (Scheme 4). Spectroscopic data, as H, 13C and
31P NMR are correlated with Hammett constants (sp),13
within the context of LFER theory.14 We analyzed
thoroughly the X-ray geometrical parameters of two axial
and two equatorial compounds substituted with EW or ER
groups to account for the participation of the endo-anomeric
(npO–s*P–OAr) and (npO–sP*]S) stabilizing interactions.
Scheme 3.
2. Results
The synthesis of both series of aryl thiophosphates 2–12-ax
and 2–12-eq was accomplished through the stereoselective
formation of the phosphite intermediates from the phospho-
chloridite and aryl alcohols as shown in Scheme 5. Due to
the epimerization of the equatorial phosphite intermediate
in the presence of an excess of phenol,15 in route A, the
p-X-substituted phenol was slowly added to the phosphoro-
chloridite (1). On the contrary, in route B the thermo-
dynamically more stable axial phosphite was obtained by
addition of 1 to the corresponding p-X-substituted phenol.
Scheme 4.
Scheme 5.

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J. Hernandez et al. / Tetrahedron 60 (2004) 10927–10941
10929
Table 1. Selected 1H and 31P NMR chemical shifts (in ppm) for axial aryl thiophosphates 2–12 in CDCl3
Chemical shifts (d)
1H
31P
Compound
H4,6a
H5a
H5e
H7,8
2-ax (XZNO2)
3-ax (XZCN)
4-ax (XZCHO)
5-ax (XZBr)
6-ax (XZCl)
7-ax (XZNHCOCH3)
8-ax (XZH)
9-ax (XZC6H5)
10-ax (XZCH3)
11-ax (XZOCH3)
12-ax (XZNH2)
4.76
4.73
4.75
4.75
4.75
4.77
4.79
4.81
4.77
1.86
1.85
1.83
1.82
1.83
1.86
1.82
1.83
1.82
1.90
1.87
1.85
1.87
1.90
1.88
1.88
1.88
1.84
1.42
1.43
1.42
1.42
1.45
1.44
1.43
1.44
1.41
54.3
54.5
55.1
55.5
55.6
55.9
55.8
55.8
56.2
56.7
56.8
4.77
a
1.81
a
1.86
a
1.42
a
a Undetermined (mixed with the equatorial epimer).
Table 2. Selected 1H and 31P NMR chemical shifts (in ppm) for equatorial aryl thiophosphates 2–12 in CDCl3
Chemical shifts (d)
1H
31P
Compound
H4,6a
H5a
H5e
H7,8
2-eq (XZNO2)
3-eq (XZCN)
4-eq (XZCHO)
5-eq (XZBr)
6-eq (XZCl)
7-eq (XZNHCOCH3)
8-eq (XZH)
9-eq (XZC6H5)
10-eq (XZCH3)
11-eq (XZOCH3)
12-eq (XZNH2)
4.85
4.84
4.79
4.76
4.83
4.80
4.83
4.78
4.80
4.73
4.52
1.77
1.79
1.54
1.64
1.71
1.75
1.70
1.67
1.59
1.63
1.68
1.90
1.87
1.69
1.77
1.87
1.85
1.89
1.77
1.72
1.75
1.82
1.41
1.41
1.34
1.32
1.39
1.38
1.39
1.34
1.34
1.31
1.38
59.2
59.3
59.5
60.0
60.1
60.4
60.4
60.4
60.9
61.0
61.3
1
Table 3. H NMR backbone coupling constants (in Hz) for axial aryl thiophosphates 2–12. First-order analysis in CDCl3 at 27 8C
Compound/coupling
constant
3JH4,6aH5a
3JH4,6aH5e
3JH4,6aH7,8
2JH5aH5e
3JH4,6aP
4JH5aP
4JH5eP
4JH7,8P
2-ax (XZNO2)
3-ax (XZCN)
4-ax (XZCHO)
5-ax (XZBr)
6-ax (XZCl)
7-ax (XZNHCOCH3)
8-ax (XZH)
9-ax (XZC6H5)
10-ax (XZCH3)
11-ax (XZOCH3)
12-ax (XZNH2)
11.3
10.5
8.0
10.8
11.1
12.9
10.8
9.9
3.0
2.5
2.7
2.8
3.0
2.9
2.8
2.9
3.0
6.2
6.4
6.2
6.2
6.6
6.2
6.6
6.2
6.2
14.6
14.8
13.0
14.8
14.1
13.0
14.4
13.8
14.5
2.6
1.2
1.2
1.2
1.1
1.3
1.3
1.2
1.2
1.0
1.5
2.6
1.3
1.5
2.7
1.3
1.8
2.6
2.9
2.7
2.3
2.5
2.2
2.2
2.1
2.3
2.6
2.2
2.2
a
1.0
1.1
1.0
1.1
1.0
1.1
10.7
10.8
3.3
b
6.2
b
14.5
b
1.2
b
1.0
b
3.0
b
2.2
b
b
a The signal was not observed.
b Undetermined (mixed with its equatorial epimer).
The thermal equilibration of equatorial phosphites to the
axial epimers was achieved by heating them in toluene
(route C). The equatorial phosphite intermediates substi-
tuted with EW groups tend to epimerize to the axial ones in
shorter heating times than those substituted with ER groups.
The equatorial or axial phosphites were reacted stereo-
specifically with sulfur to produce the thiophosphates 2–12-
eq or 2–12-ax under the conditions shown in Scheme 5. We
observed that equatorial aryl thiophosphates were obtained
in a cleaner manner, without their configurational isomers, if
the reaction was maintained under vigorously toluene
reflux, particularly in the case of aryl-EW thiophosphates.
series of thiophosphates (2–12) was assessed by analysis of
their spectral NMR characteristics. The chemical shifts (d)
of 1H are reported in Tables 1 and 2. The correct assignment
of the signals and the backbone coupling constants in the 1H
NMR (Tables 3 and 4) were obtained through the first-order
analysis of the spectra, along with homo and heteronuclear
decoupling experiments. The complete assignment of 13C
signals (Tables 5 and 6), was achieved by means of 1H, 13
C
correlated 2D NMR spectra, as well as inverse 1H-detected
HMQC and HMBC experiments. Two-dimensional tech-
niques were particularly useful for the assignment of 13C
NMR signals of the configurational p-phenyl thiophos-
phates (9-ax and 9-eq). The participation of the stereoelec-
tronic interactions was analyzed in the solid state through
The conformational analysis of the axial and equatorial

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J. Hernandez et al. / Tetrahedron 60 (2004) 10927–10941
10930
Table 4. 1H NMR backbone coupling constants (in Hz) for equatorial aryl thiophosphates 2–12. First-order analysis in CDCl3 at 27 8C
Compound/coupling
constant
3JH4,6aH5a
3JH4,6aH5e
3JH4,6aH7,8
2JH5aH5e
3JH4,6aP
4JH5aP
4JH5eP
4JH7,8P
2-eq (XZNO2)
3-eq (XZCN)
4-eq (XZCHO)
5-eq (XZBr)
6-eq (XZCl)
7-eq (XZNHCOCH3)
8-eq (XZH)
9-eq (XZC6H5)
10-eq (XZCH3)
11-eq (XZOCH3)
12-eq (XZNH2)
10.5
11.2
10.4
10.6
11.2
10.8
10.9
9.9
2.6
2.7
2.7
2.8
3.0
2.3
2.6
2.9
2.6
2.6
2.6
6.3
6.6
6.3
5.9
6.6
6.2
6.3
6.2
6.6
6.3
6.6
14.6
14.5
14.5
14.5
14.0
14.1
14.5
14.2
14.5
14.5
14.5
1.2
3.3
2.8
2.6
2.5
2.6
2.3
3.0
2.6
2.6
3.3
1.0
a
2.8
3.6
2.3
2.3
2.3
2.3
2.3
2.3
2.6
2.6
2.6
2.2
2.0
2.3
2.0
2.0
2.4
2.3
2.0
2.6
2.0
2.0
1.8
a
a
a
a
a
11.2
10.9
11.2
2.3
a
a
a The signal was not observed.
Table 5. Selected 13C NMR signal assignments in axial aryl thiophosphates 2–12a
Compound
C4,6
C5
C7,8
Ci
Co
2-ax (XZNO2)
3-ax (XZCN)
4-ax (XZCHO)
5-ax (XZBr)
6-ax (XZCl)
7-ax (XZNHCOCH3)
8-ax (XZH)
9-ax (XZC6H5)
10-ax (XZCH3)
11-ax (XZOCH3)
12-ax (XZNH2)
77.7 (9.1)
77.1 (9.3)
76.7 (8.9)
77.2 (8.9)
76.7 (10.4)
76.8 (9.5)
76.2 (8.8)
77.1 (8.9)
76.9 (8.9)
76.9 (8.9)
76.2 (9.3)
40.6 (4.9)
40.3 (5.2)
40.2 (5.6)
40.8 (4.8)
40.6 (4.9)
42.7 (5.0)
39.9 (4.4)
40.7 (4.7)
40.7 (4.6)
40.7 (4.8)
40.5 (4.7)
22.4 (9.6)
22.3 (9.9)
22.1 (10.0)
22.4 (9.6)
22.6 (9.5)
22.5 (9.8)
21.9 (9.9)
22.5 (9.6)
22.4 (9.9)
22.4 (9.5)
22.3 (9.8)
156.2 (6.1)
154.3 (6.2)
155.4 (5.5)
150.6 (6.4)
149.5 (6.3)
147.5 (6.2)
150.5 (7.0)
150.8 (6.5)
148.8 (6.2)
144.9 (7.2)
143.8 (7.8)
121.3 (5.4)
121.3 (5.2)
120.7 (5.5)
122.6 (4.9)
121.7 (5.2)
121.9 (5.0)
119.8 (5.5)
121.0 (5.0)
120.4 (4.8)
121.7 (4.8)
121.1 (5.2)
a Chemical shifts (d) in ppm from TMS in CDCl3. In parentheses JCP in Hz.
Table 6. Selected 13C NMR signal assignments in equatorial aryl thiophosphates 2–12a
Compound
C4,6
C5
C7,8
Ci
Co
2-eq (XZNO2)
3-eq (XZCN)
4-eq (XZCHO)
5-eq (XZBr)
6-eq (XZCl)
7-eq (XZNHCOCH3)
8-eq (XZH)
9-eq (XZC6H5)
10-eq (XZCH3)
11-eq (XZOCH3)
12-eq (XZNH2)
76.1 (5.5)
76.0 (5.5)
75.9 (5.4)
75.6 (5.5)
76.1 (5.7)
75.8 (5.5)
75.4 (5.5)
75.5 (5.5)
75.3 (5.5)
75.6 (5.5)
75.8 (5.5)
40.8 (5.5)
40.9 (6.6)
40.8 (5.8)
40.9 (5.5)
41.3 (5.1)
41.1 (5.5)
41.0 (4.4)
41.0 (5.5)
41.0 (5.5)
40.9 (5.6)
40.8 (5.5)
22.1 (8.9)
22.1 (8.9)
22.1 (10.0)
22.0 (10.0)
22.5 (9.5)
22.4 (9.5)
22.1 (10.0)
22.1 (10.0)
22.1 (10.0)
22.0 (10.0)
21.9 (9.9)
155.0 (7.7)
152.6 (6.6)
155.0 (6.0)
149.5 (8.9)
149.4 (8.0)
149.6 (8.1)
150.3 (7.7)
149.9 (7.7)
148.3 (7.7)
144.0 (7.7)
142.6 (8.8)
122.1 (4.4)
122.4 (4.4)
122.0 (4.4)
123.1 (4.5)
123.1 (5.0)
121.7 (4.6)
121.1 (4.4)
121.5 (5.5)
121.0 (5.5)
122.0 (4.4)
121.8 (4.4)
a Chemical shifts (d) in ppm from TMS in CDCl3. In parentheses JCP in Hz.
the X-ray diffraction analysis of four thiophosphates, two of
the axial series [2-ax (XZNO2), and 10-ax (XZCH3)] and
two of the equatorial [2-eq (XZNO2) and 11-eq (XZ
OCH3)]. These molecules are examples of aryl thiophos-
phates with EW or ER groups in both configurations.
equatorial series appear at around 4.85 ppm. 13C NMR
chemical shifts of carbons in the heterocycle are scarcely
sensitive to configuration, however a slight downfield shift
(1.3 ppm in average) is observed for C4,6 for the axial
compounds, thus not giving evidence of a g-gauche effect
(see discussion below). The coupling constants 2JCP of C4,6
for the axial thiophosphates are 3–5 Hz larger than the
equatorial ones (Tables 5 and 6). The conformational
analysis of the complete series of thiophosphates was
performed with the coupling constants JHH, JHP and JCP
(Tables 3–6). Heteronuclear 1H{31P}decoupling experi-
ments led to simplification of the signals, therefore vicinal
3JHP were easily obtained by direct comparison with the
1H NMR signals of the undecoupled spectra. For com-
pounds (2–11)-ax the irradiation at 1.41–1.45 ppm (CH3’s
at C4, C6) led to decoupling of the methine (H4,6a) multiplet
to an apparent doublet of double doublet (ddd) with
3. Discussion
3
3
3
3.1. NMR analysis
As observed in Tables 1 and 2, in the axial series of
thiophosphates (2–12), the proton H5a is slightly upfield
shifted (ca. 0.05 ppm) than the H5e, this trend is also
observed for the equatorial epimers (2–12). The chemical
shift of protons H4,6a for the axial thiophosphates is at
around 4.75 ppm meanwhile the same protons in the

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J. Hernandez et al. / Tetrahedron 60 (2004) 10927–10941
10931
3
3JHHZ9.9–11.3 Hz (anti), JHHZ2.5–3.3 Hz (gauche) and
hybridization,22 and it has been observed frequently that
these two factors cannot be separated for to understand the
behavior.23 Thus as expected, an EW group in aryl
phosphazanes24 provoke dishielding of the phosphorus
nucleus resulting in a downfield shift of 31P NMR signal.
Nevertheless, the opposite behavior is observed for
cinnamyl phosphonates25 and aryl phosphates.9a The
fundamental difference between these three types of
organophosphorus compounds is that in phosphonates or
phosphates the aromatic ring is in a group linked to
phosphorus through a single bond; however, in aryl
phosphazenes the aromatic ring is in a group linked to
phosphorus through a double bond. From this observation it
is evident that the transfer of charge density from the
aromatic ring to phosphorus or vice versa follows a different
mechanism when the transmission is through a s or through
a p bond.26 In this work we found that the 31P NMR signals
of arylthiophosphates are reversibly correlated with sp
being the correlation factor RZ0.979 for the axial series
of thiophosphates and RZ0.982 for the equatorial. From
the slope of the lines mZK1.871 for the axial series and
mZK1.631 for the equatorial it can be deduced that the
phosphorus of the axial isomers is more sensitive to charge
polarization of the aromatic ring than the phosphorus of
the equatorial ones. The reversible correlation may be
explained by a change in bond distances and bond angles
involving a-bonded atoms to phosphorus and the changes in
torsion angles with b-atoms as proposed by Gorenstein for
phosphates.27 We will discuss this point in the structural
3JHPZ1.2–2.6 Hz, these coupling constants are consistent
with a chair conformation.2,16 A similar experiment was
performed for the compounds (2–12)-eq, irradiation at 1.31–
1.41 ppm led to a double of triplets (dt) for the methine
(H4a) with JHH3Z9.9–11.2 Hz (anti), JHHZ2.6–3.0 Hz
(gauche) and JHPZ2.3–3.6 Hz, here also values of
coupling constants suggest that in solution the series of
equatorial thiophosphates are in chair conformation. On the
3
3
3
3
other hand, the JC5P and JC7,8P coupling constants
obtained from the 13C NMR spectra of compounds (2–12)
are in the range of 4.4–5.7 and 8.9–10.0 Hz, respectively,
for both, axial and equatorial, series of thiophosphates
(Tables 5 and 6) suggesting also a chair conformation for the
six-membered ring in solution.2,17 The fact that the JCP is
3
not showing dependence on configuration, support the
argument given by Quin18 and Nifantiev19 on the uses of
3JCP as the most useful C–P coupling constant to analyze the
conformation of dioxaphosphinanes (note that in an ideal
chair conformation the dioxaphosphinane dihedral angles
uC5–C4–O3–P and uC5–C6–O1–P are 608 meanwhile uC8–C6–O1–P
and uC7–C4–O3–P are 1808).
3.2. Electronic effects
In phosphorus compounds with aromatic rings, it has been
demonstrated that EW or ER groups in the para position of
the ring, causes polarization of charge density inducing
changes in chemical shifts and coupling constants on the
phosphorus and linked atoms.20 Depending upon the
aromatic organophosphorus compound, the so-called sub-
stituent-induced chemical shifts (SCS) exhibits in 31P NMR
one of the two possible tendencies, one that correlates 31P
chemical shifts directly with Hammett (sp) constants and
the other that correlates them reversibly.21 The factors
that determine the tendency are the electronegativity of the
a-atoms directly linked to phosphorus and the phosphorus
analysis below. On the other hand, neither the 1H nor the 13
C
chemical shifts of the dioxaphosphinane ring correlate well
with the Hammett (sp) constants. However, a good normal
correlation of 13C chemical shifts of the Cipso with sp was
found (RZ0.926 for the axial and RZ0.911 for the
equatorial), Cipso of NO2 substituted arylthiophosphate
being downfield shifted from Cipso of OCH3 aryl thiophos-
phate, as shown in Tables 5 and 6.
Figure 1. ORTEP drawing of ax-2-p-nitrophenoxy-2-thio-cis-4,6-dimethyl-1,3,2l5-dioxaphosphinane (2-ax), molecule A and B.

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J. Hernandez et al. / Tetrahedron 60 (2004) 10927–10941
10932
Figure 2. ORTEP drawing of eq-2-p-nitrophenoxy-2-thio-cis-4,6-dimethyl-1,3,2l5-dioxaphosphinane (2-eq).
Based on the grounds of the stereoelectronic theory, EW
groups will show more propensity to occupy axial
orientations than ER groups (Scheme 2), therefore a detailed
comparison of the structural parameters of the two axial
2-ax (XZNO2), and 10-ax (XZCH3) and the two equatorial
2-eq (XZNO2) and 11-eq (XZOCH3) thiophosphates not
only led us to account for the participation of stereoelec-
tronic interactions in the conformation adopted for the
molecules but also for the reversible correlation found in the
chemical shift of the signals of 31P NMR with sp. We also
analyzed the steric compression of the aryloxy group in
the axial thiophosphates and the flexibility of the 1,3,2-
dioxaphosphinane ring for to relieve the intramolecular van
der Waals repulsive compression of the nonbonded
substituents through compromise between the intraannular
torsional strain and the Baeyer strain, as proposed for highly
hindered thiophosphoramidates.7
the compounds; the sum of the four angles at the phosphorus
goes from 436.04 to 439.718 (see Table 11). However, it is
notable that equatorial thiophosphates are closer than the
axial to the expected ideal tetrahedral angle (4368). The
dioxaphosphinane ring lacks of perpendicular symmetry,
the oxygens are almost flat edges [the internal COP angles
are of around 1198 for 2-ax, 2-eq and 10-ax and around 1168
for 11-eq] and the phosphorus is a puckery end [the OPO
angles are of around 1068 for 2-ax, 2-eq and 10-ax and 1048
for 11-eq]. There is ring flattening in the OPO region for
both the axial and equatorial thiophosphates [torsion angles:
3.3. Structural analysis
The ORTEP drawings obtained from the X-ray analysis of
2-ax, 2-eq, 10-ax and 11-eq are shown in Figures 1–4. Data
collection and refinement parameters, bond distances, bond
angles, and torsion angles are provided in Tables 7–10.
Thiophosphates 2-ax, 2-eq and 11-eq crystallized in the
monoclinic space group P21/n, P21/c and P21/a correspond-
ingly, whereas 10-ax crystallized in the orthorhombic P
space group P21 n b. In the case of compound 2-ax, two
molecules were found in the asymmetric unit. Molecules A
and B are not in equivalent positions, and it is interesting to
note that the change of torsion angle P2–O10–C11–C12 by
748 brings with it a change in bond angle C4–O3–P2 (from
1208 in molecule A to 1178 in molecule B) that speaks about
the high flexibility of the dioxaphosphinane ring in the OPO
region ascribed to the propensity of the endo-cyclic oxygens
to change from sp3 to sp2 hybridization.7
3.4. Torsion and bond angles
Figure 3. ORTEP drawing of ax-2-p-methylphenoxy-2-thio-cis-4,6-
dimethyl-1,3,2l5-dioxaphosphinane (10-ax).
The geometry at the phosphorus center is tetrahedral for all

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J. Hernandez et al. / Tetrahedron 60 (2004) 10927–10941
10933
Figure 4. ORTEP drawing of eq-2-p-methoxyphenoxy-2-thio-cis-4,6-dimethyl-1,3,2l5-dioxaphosphinane (11-eq).
(uPOCC5) are in the range of 44.6–55.88; and the internal
(uOPOC) are in the range of 33.1–52.78] being the flattening
less severe for 11-eq than all others. The OPO ring flattening
has also been found in analog phosphates.9a
47.58) leading to considerable Pitzer strain. As a conse-
quence, there is not a very good agreement between the
values of cos u and Kcos q/(1Ccos q) for this molecule
(0.68 vs 0.65) as for the others, indicating that the
compromise between bond angles and torsion angles
imposed by the constraint of the dioxaphosphinane ring
which leads to the minimum strain in 2-eq, is not perfect.
We have observed that for thiophosphoramidates in
conformations other than chair, the compromise between
cos u and Kcos q/(1Ccos q) is not fulfilled either.7 Our
interpretation of this result is that due to the axial seeking
characteristics of the p-NO2-phenoxy substituent, the
molecule will tend to deform out of an ideal chair that
otherwise in the case of 2-eq obligates the aryloxy group to
The Baeyer and Pitzer strain4,29 are summarized in Table 11
for compounds 2-ax, 2-eq, 10-ax and 11-eq [calculated as
the average of the internal bond angles (q), and torsion
angles (u) of the dioxaphosphinane ring, respectively].
Taking into consideration that the bond angle in a molecule
free of Baeyer strain (propane) is 112.48, the molecule with
the highest Baeyer strain is 2-eq (113.18). Contrary to what
is expected, the intraannular torsion angles also decrease for
2-eq more than for any other compound (51.7–54.38 vs
Table 7. X-ray crystal data for compounds 2, 10-ax and 11-eqa
2-ax
2-eq
10-ax
11-eq
Formula
Fw
C11H14NO5PS
303.26
C11H14NO5PS
303.28
C12H17O3PS
272.29
C12H17O4PS
288.30
Crystal system
Crystal size (mm)
Space group
Radiation
Monoclinic
0.12!0.18!0.24
P21/n
Mo Ka
0.71073
8.04550(10)
26.9886(4)
13.06750(10)
90.00
95.805(6)
90.00
2822.88(6)
8
4.36–49.94
1.427
0.357
Monoclinic
0.54!0.45!0.39
P21/c
Orthorombic P
0.50!0.50!0.30
P21 n b
Monoclinic
0.33!0.30!0.18
P21/a
Mo Ka
Mo Ka
Mo Ka
˚
Wavelength (A)
˚
0.71073
6.856(1)
22.911(1)
9.128(1)
90.00
91.3(11)
90.00
1433.3(10)
4
11–12
0.71073
9.7597(10)
11.257(2)
12.9736(10)
90.00
90.00
90.00
1425.4(4)
4
0.71073
7.9454(10)
20.1215(10)
9.4777(10)
90.00
104.407(10)
90.00
1467.6(7)
4
11–12
a (A)
˚
b (A)
˚
c (A)
a (deg)
b (deg)
g (deg)
3
˚
V (A )
Z
2qmax (deg)
4.80–53.94
1.269
0.333
rcalc (mg mK3
)
1.41
0.351
1.30
0.333
Absorption coefficient
(mmK1
)
No. of reflections collected
No. of independent
reflections
5315
4947
3475
3122
1645
1645
2101
1792
No. of observed reflections
R1 [FO4s(F)]
wR2
2142
2348
1298
1285
0.0380
0.1002
0.1587
0.1377
0.963
0.037
0.047
0.057
0.048
1.028
0.0004
0.0338
0.0961
0.0500
0.1060
1.034
0.0327
0.0395
0.0549
0.0423
1.111
R1 (all data)
wR2
GOF on F2
Max. shift for final cycle of
least-squares
D/s
0.000
0.000
0.0002
0.000
0.223
0.000
0.33
0.001
0.344
0.000
0.17
Max. peak in final differ-
3
ence syntheses (e/A )
˚
a Standard deviations are in parentheses.

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J. Hernandez et al. / Tetrahedron 60 (2004) 10927–10941
10934
a
˚
Table 8. Selected bond lengths (A) for 2, 10-ax and 11-eq
2-ax molecule A
2-ax molecule B
2-eq
10-ax
11-eq
O1–P2
O3–P2
O10–P2
S9–P2
O1–C6
O3–C4
C4–C5
C5–C6
C6–C8
C4–C7
C11–O10
1.559(3)
1.562(3)
1.605(3)
1.8952(15)
1.476(6)
1.481(4)
1.515(5)
1.509(6)
1.505(5)
1.506(6)
1.403(4)
1.560(2)
1.574(3)
1.604(3)
1.8946(16)
1.478(4)
1.470(5)
1.515(5)
1.512(5)
1.505(5)
1.513(5)
1.395(4)
1.5732(12)
1.5691(13)
1.5889(14)
1.9093(7)
1.466(2)
1.469(2)
1.504(3)
1.497(3)
1.502(3)
1.498(3)
1.403(2)
1.565(3)
1.568(2)
1.601(3)
1.9009(13)
1.500(5)
1.508(6)
1.493(7)
1.519(7)
1.487(7)
1.511(7)
1.407(4)
1.572(2)
1.567(2)
1.578(2)
1.9091(10)
1.472(3)
1.470(4)
1.494(4)
1.504(4)
1.498(4)
1.509(5)
1.406(3)
a Standard deviations in parentheses.
Table 9. Selected bond angles (q) in deg for 2, 10-ax and 11-eqa
2-ax molecule A
2-ax molecule B
2-eq
10-ax
11-eq
O1–P2–O3
O1–P2–O10
O1–C6–C5
O3–C4–C5
O3–P2–O10
O1–P2–S9
106.49(14)
98.72(15)
107.5(3)
105.92(14)
99.94(14)
108.6(3)
105.72(7)
103.39(7)
109.71(14)
108.20(14)
102.39(7)
116.24(6)
116.23(6)
120.33(11)
122.57(11)
112.27(14)
121.4(1)
105.78(14)
105.33(15)
106.9(3)
104.06(11)
102.53(11)
109.0(2)
109.7(3)
109.0(3)
110.0(3)
109.2(2)
105.24(14)
114.64(12)
112.68(12)
120.2(2)
118.2(2)
112.7(3)
126.5(2)
116.9(3)
121.3(4)
117.58(11)
104.81(14)
114.83(11)
113.82(12)
117.0(2)
119.3(2)
113.5(3)
124.2(2)
115.9(3)
121.9(3)
116.01(11)
100.33(15)
113.65(11)
114.77(12)
120.6(3)
118.0(3)
111.8(4)
122.2(2)
121.8(3)
117.0(3)
115.58(11)
98.50(11)
115.76(8)
116.90(9)
116.48(18)
116.49(16)
114.7(2)
124.34(17)
118.3(3)
120.2(3)
O3–P2–S9
C4–O3–P2
C6–O1–P2
C6–C5–C4
P2–O10–C11
O10–C11–C12
O10–C11–C16
S9–P2–O10
120.10(16)
117.67(16)
111.24(5)
116.61(9)
a Standard deviations in parentheses.
Table 10. Selected torsion angles (u) in deg. for 2, 10-ax and 11-eqa,b
2-ax molecule A
2-ax molecule B
2-eq
10-ax
11-eq
S9–P2–O3–C4
O10–P2–O3–C4
O1–P2–O3–C4
O1–C6–C5–C4
S9–P2–O1–C6
O10–P2–O1–C6
O3–P2–O1–C6
P2–O3–C4–C5
P2–O3–C4–C7
P2–O1–C6–C8
P2–O1–C6–C5
C11–O10–P2–O1
C11–O10–P2–O3
C11–O10–P2–S9
C12–C11–O10–P2
C16–C11–O10–P2
O3–C4–C5–C6
O10–P2–O3–C4
O1–P2–O3–C4
P2–O1–C6–C5
K165.36
65.30
K38.85
61.66
169.23
K64.92
43.90
K174.17
58.07
K47.07
56.05
172.06
K63.10
45.56
93.03
K145.52
K37.58
57.24
K97.54
140.29
33.06
50.56
177.98
K169.53
K44.60
K61.19
48.53
K165.97
69.46
K39.85
61.99
170.43
K62.08
43.62
76.35
K157.93
K52.66
54.84
K77.19
154.73
52.50
55.77
179.03
K178.82
K55.20
98.19
K155.26
K29.35
112.70
K72.75
K55.09
K157.93
K52.66
K55.20
47.03
55.30
49.23
170.86
K179.80
K56.48
K179.36
70.80
K55.59
K124.54
58.92
K57.14
65.30
K38.85
K56.48
179.08
K173.55
K51.43
K176.28
74.18
K52.24
132.16
K50.53
K58.85
58.07
171.63
179.79
K56.37
K82.74
167.59
43.57
173.35
80.42
59.32
K102.95
K61.68
K145.52
K37.58
K44.60
K123.37
K58.90
69.46
K39.85
K56.37
K47.07
K51.43
a Standard deviations in parentheses.
b Right-hand rule.28
be in the equatorial position. This argument might be
supported by the fact that the aryloxy group in 2-eq has
torsion angles [uO10PO1C6Z140.38 and uO10PO3C4Z145.58]
that are almost 408 away from the 1808 (expected for the
group in equatorial orientation) and pointing towards a
pseudo-axial position.
3.5. Stereoelectronic interactions
Several years ago, Gorenstein30 coined the term ‘gauche
NMR effect’ to support the observation that in molecules
with gauche segments all the atoms that conform the
segment tend to be shielded, therefore upfield shifted. In

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J. Hernandez et al. / Tetrahedron 60 (2004) 10927–10941
10935
Table 11. Structural properties of 2, 10-ax and 11-eq
11-eq
2-eq
10-ax
2-ax
Molecule A
Molecule B
Geometry at
phosphorusa
Baeyer strainb
Pitzer strainc
cos u
437.56
436.04
438.40
439.71
438.63
111.66
54.34
0.58
113.13
47.46
0.68
112.18
51.66
0.62
112.47
50.84
0.63
112.22
52.38
0.61
Kcos q/(1Ccos q)
0.58
0.65
0.61
0.62
0.61
a Calculated as the sum of the bond angles (O1P2O3), [OP2O10(mean)], [OP2S9(mean)] and (S9P2O10) in deg.
b Calculated as the average value of the bond angles (O1P2O3), (O1C6C5), (O3C4C5), (C4O3P2), (C6C5C4), and (C6O1P2) in deg.
c Calculated as the average absolute value of the torsion angles (O1P2O3C4), (O1C6C5C4), (O3P2O1C6), (O3C4C5C6), (P2O3C4C5), and (P2O1C6C5) in
deg.
cyclic six-membered ring dioxaphosphinanes the 31P NMR
signal of axial substituted compounds is normally upfield
shifted from the equatorial,2 thus demonstrating the
participation of a gauche NMR effect. The ground, in
which this gauche NMR effect relies is the decrease in the
intraannular OPO bond of the dioxaphosphinanes, and it
was nicely demonstrated by Gorenstein27 that at least in
phosphates there is a correlation between the OPO bond
angle and the 31P NMR chemical shift. We thought of the
possibility to explain the observed reversibility of 31P NMR
shifts with sp or substituent-induced chemical shifts (SCS)
with the changes in OPO bond angles, however unfortu-
nately we found the opposite, that means that the
compounds of the same series of thiophosphates, axial or
equatorial, with smaller intraannular OPO bond are down-
field shifted than those with larger OPO bond angles. For
example, the OPO angle for 2-ax is 106.28 and for 10-ax is
105.788 and their 31P NMR are shifted to 54.3 and 56.2 ppm,
respectively; by the same taken, the OPO bond angle for
2-eq is 105.728 and for 11-eq is 104.068 and their 31P NMR
signals are shifted to 59.2 and 61.0 ppm, respectively. The
other factor that can be disregarded from our data is that
the shielding of the 31P NMR signal is due to a dp–pp
interaction involving the aryloxy group31,32 because in such
case, we would expect that an ER group as p-OCH3 would
enhance the orbital overlap causing an upfield shift of the
signal and an EW group as p-NO2 a downfield shift.
Alternatively the reversibility found in SCS may be
explained by an effect of a compensation of charge density
to the 31P nucleus given by the assistance of the free electron
pairs of the endo-cyclic oxygens of the dioxaphosphinane
ring, when an EW group is substituted in the para position
of the phenyl ring of the aromatic thiophosphate, as shown
in Scheme 6 (structure A). This hypothesis is supported by
the fact that analog phosphinanes33 where compensation of
charge density on phosphorus by endo-cyclic a-atoms is not
possible, show a normal SCS trend (Scheme 6, structures B
and C).
It is worthwhile to note that the transfer of charge density by
endo-cyclic oxygens to phosphorus give rise to the known
attractive endo-anomeric npO–s*P–OAr hyperconjugative
interaction for axial thiophosphates that stabilize the chair
conformation with the aryl-EW group more than with the
aryl-ER. On the other hand, the attractive endo-anomeric
npO–s*P]S hyperconjugative interaction for equatorial
thiophosphates stabilizes the P]S group in the axial
position of a chair conformation more than P]O in analog
equatorial phosphates.34 Indeed, by doing an individual
examination of the bond lengths (Table 8), we observed that
the data indicate clearly that both endo-hyperconjugative
interactions do participate in the stabilization of these
anancomeric thiophosphates (see Scheme 2). In particular,
for 2-ax we found that endo-cyclic O1–P2 or O3–P2 bonds
˚
are shorter [1.560 A (mean between molecule A and B) and
˚
1.568 A (mean between molecule A and B), respectively]
˚
than the exo-cyclic O10–P [1.605 A (mean between
molecule A and B)]. For 10-ax we also found evidence of
the npO–s*P–OAr endo-hyperconjugative interaction since
˚
the O1–P2 or O3–P2 bonds (1.565 and 1.568 A, respec-
˚
tively) are shorter than O10–P2 (1.601 A). The fact that the
shortening of the endo-cyclic O–P bonds in 2-ax (XZNO2)
˚
is more pronounced than in 10-ax (XZMe) [1.564 A
˚
(mean) for 2-ax vs 1.567 A (mean) for 10-ax] and the
lengthening of the O10–P2 bond is also more important for
˚
˚
2-ax than for 10-ax [1.605 A for 2-ax vs 1.601 A for 10-ax]
is in agreement with the increase in the axial seeking
characteristics of aryloxy substituted with EW as compared
with ER groups. On the other hand, for the equatorial
thiophosphates 2-eq (XZNO2) and 11-eq (XZOCH3) the
anomeric npO–s*P]S endo-hyperconjugative interaction is
supported by the shortening of the endo-cyclic O1–P2 or
Scheme 6.

´
J. Hernandez et al. / Tetrahedron 60 (2004) 10927–10941
10936
˚
˚
O3–P2 bonds [1.572 A (mean) for 2-eq and 1.570 A (mean)
for 11-eq], although somewhat less than in the axial
isomers, and slight lengthening of the P]S bonds
performed microanalyses of configurational isomers 3–9.
Microanalyses of configurational isomers 2, 10, 11 and
12-eq were recorded in Thermo Finnigan Flash 1112
analyzer.
˚
˚
(1.909 A for 2-eq or 11-eq vs 1.895 and 1.901 A for 2-ax
and 10-ax, respectively). It is clear that this stereoelectronic
mechanism of stabilization of the equatorial thiophosphates
is less important than the axial one, because in the equilibria
of mobile aryl thiophosphates the axial conformer always
predominates over the equatorial.1,2 This might be a result
of the bonding electron repulsion caused by the lone pairs on
sulfur when it is in the axial position.11
n-Hexane was used for recrystallization of all samples,
affording crystals suitable for X-ray diffraction analysis.
Crystallographic work was performed in an Enraf-Nonius
CAD-4 diffractometer. Data collection: CAD-4 Software.35
Cell refinement: CAD-4 Software. Data reduction for the
axial structures 2-ax and 10-ax: WINGX,36 solved by direct
methods SHELXS9737 and refined with SHELXL97.38 Data
reduction for the equatorial structures 2-eq and 11-eq:
CRYSTALS,39 solved and refined with CRYSTALS.39
Molecular graphics: CAMERON40 and dihedral angles:
PLATON.41 Crystallographic data for structures have been
deposited at Cambridge Crystallographic Data Center and
the deposition numbers are: CCDC 234720 for 2-ax, CCDC
234719 for 10-ax, CCDC 235613 for 2-eq, and CCDC
235614 for 11-eq.
4. Conclusions
The conformational analysis of a series of axial and
equatorial anancomeric p-X-aryloxy thiophosphates is
analyzed in terms of the electronic characteristics of the
3
3
3
p-substituent. The coupling constants JHH, JHP and JCP
and X-ray structures suggest that in solution and solid state,
the 1,3,2-dioxaphosphinane ring is in a chair conformation
regardless of configuration. We observed that there is a
reverse substituent-induced chemical shifts on the 31P NMR
signals being the effect more pronounced for axial than for
equatorial thiophosphates. These results could be explained
by the compensation of charge density on phosphorus by the
lone pairs on endo-cyclic oxygens of the dioxaphosphinane
ring for thiophosphates substituted with aryl EW groups.
5.1. General procedure for the preparation of
intermediates arylphosphites
Route A. In a three-necked 250 mL flask, fitted with a
stirbar, and rubber septa, were placed 3.64 mmol of p-X-
phenol, and 45 mL of dry toluene. The solution was stirred
at room temperature until the p-X-phenol was solubilized
(in the case of some p-X-phenols as p-acetamido, and
p-amino, 10 mL of acetonitrile was added in order to
solubilize them), then 3.64 mmol of the phosphorochloridite
1, followed by 3.64 mmol of triethylamine were added at
once, via syringe, resulting in precipitation of triethylam-
monium chloride. The suspension was stirred for 5 min and
the solid was filtered off through a filter tipped cannula. The
solid was washed two times with 15 mL of dry toluene
collecting the filtrate in a round-bottomed flask. The solvent
was then removed under vacuum without heating to avoid
epimerization of the equatorial phosphites to the axial ones.
In all cases, products were yellowish oils.
The structural analysis performed by X-ray on four
thiophosphates, two axial and two equatorial, led to the
conclusion that in all cases, the dioxaphosphinane ring is
flatten in the OPO region and is lacking of perpendicular
symmetry being the endo-cyclic oxygens flat regions of the
ring and the phosphorus atom a puckery end. A thoroughful
analysis of bond distances allowed to support the partici-
pation of the anomeric npO–s*P–OAr endo-hyperconjugative
interaction for to stabilization of axial thiophosphates and
the anomeric npO–s*P]S endo-hyperconjugative interaction
for to stabilization equatorial thiophosphates, both in chair
conformations.
Route B. In a three-necked 250 mL flask, fitted with
dropping funnel, a stirbar, and rubber septa, were placed
3.64 mmol of p-X-phenol, 3.64 mmol of triethylamine, and
45 mL of dry ethyl ether. The mixture was stirred at room
temperature for 30 min and 3.64 mmol of the phosphoro-
chloridite 1 was added dropwise via syringe maintaining the
stirring for additional 30 min. The solid in the resulting
suspension was filtered off through a filter tipped cannula
and the filtrate added to a lateral outlet round-bottomed flask
equipped with a stirbar, rubber septa and reflux condenser.
The solution was heated under reflux for 2 h and after
cooling, the solvent was removed in a rotary evaporator. In
all cases, products were yellowish oils.
5. Experimental
Melting points are uncorrected. Nuclear magnetic resonance
spectra were recorded on Jeol Eclipse 270 and Bruker
Avance 300 spectrometers in CDCl3 (d 7.26, H; d 77.0,
1
13C), 1H at 270.2 and 300.1 MHz, 13C at 67.8 and
75.5 MHz, and 31P at 109.3 and 121.5 MHz, respectively.
Phosphorus NMR spectra are reported in ppm downfield
(C) from 85% H3PO4 used as external standard. Mass
spectra (EI) were measured on a Hewlett Packard 5989A
spectrometer using electron impact (EI) at 70 eV. The
reactions were performed under an atmosphere of nitrogen
in oven-dried glassware. Solvents and solutions were
transferred by syringe-septum and cannula techniques.
Toluene was of reagent grade and was dried and distilled
immediately before use from sodium/benzophenone.
Triethylamine was dried and distilled from LiAlH4.
Products were purified by flash column chromatography
on silica gel 230–400 mesh. Yields are given for isolated
products. Galbraith Laboratories, Inc., Knoxville, TN
Route C. In a round-bottomed 250 mL flask, fitted with
reflux condenser, a stirbar, and rubber septa, were placed
3.64 mmol of the equatorial phosphites (obtained from route
A) and 45 mL of dry toluene. The solution was stirred under
reflux for 12–48 h until the epimerization to the axial
isomers was complete. The epimerization process was
followed by 31P NMR (equatorial phosphites are downfield
shifted than axial phosphites by around 5 ppm, see

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J. Hernandez et al. / Tetrahedron 60 (2004) 10927–10941
10937
Scheme 5). Phosphites substituted with electron releasing
groups (ERG) took longer for to epimerize than those
substituted with electron-withdrawing groups (EWG). After
cooling, the solvent was removed under vacuum in a rotary
evaporator.
(MCK234), 41 (MCK262). Anal. Calcd for
C11H14O5PNS: C, 43.57; H, 4.65. Found: C, 43.80; H, 4.51.
5.2.4. ax-2-p-Cyanophenoxy-2-thio-cis-4,6-dimethyl-1,3,
2l5-dioxaphosphinane (3-ax). According to the general
procedure described above, 1.0 g (3.98 mmol) of axial
p-cyanophenyl phosphite (route B), was treated with
elemental sulfur. Flash chromatography (hexanes/ethyl
acetate 85:15) gave 1.04 g of the product as pale yellow
crystals (93% yield) of mp 110–111 8C. 1H NMR d 1.43 (d,
JZ2.5 Hz, 6H), 1.85 (m, JZ14.8, 10.5, 1.5 Hz, 1H), 1.87
(m, JZ14.8, 2.5, 1.3 Hz, 1H), 4.73 (m, JZ10.5, 6.4, 2.5,
1.2 Hz, 2H), 7.30 (dd, 3JZ9.1 Hz, 4JHPZ1.3 Hz, 2H), 7.65
(d, 3JZ9.1 Hz, 2H); 13C NMR d 22.3 (d), 40.3 (d), 77.1 (d),
108.8 (s, CN), 118.3 (s, Cp), 121.3 (d, Co), 134.1 (s, Cm),
154.3 (d, Ci); 31P NMR d 54.5. Mass spectrum (m/z) 283
(MC), 242 (MCK41), 216 (MCK67), 197 (MCK86), 165
(MCK118), 149 (MCK134), 119 (MCK164), 90 (MCK
193), 69 (MCK234), 41 (MCK242). Anal. Calcd for
C12H14O3PNS: C, 50.88; H, 4.98. Found: C, 50.91; H, 5.16.
5.2. General procedure for the preparation of aryl
thiophosphates 2–12
In a round-bottomed 100 mL flask, fitted with a reflux
condenser, a stirbar, and rubber septa, were placed
2.21 mmol of elemental sulfur. A solution of 2.21 mmol
of equatorial phosphite (obtained from route A) or axial
phosphite (obtained from route B or C) in 60 mL of dry
toluene was added to the flask and the resulting suspension
was stirred under reflux for 24 h. After cooling, the
suspension was concentrated under vacuum and the residue
washed with an aqueous solution of 10% sodium bicarbon-
ate. The product was extracted with methylene chloride and
the organic layer dried over sodium sulfate. The solvent was
removed in a rotary evaporator and the crude product was
purified by flash chromatography using hexane/ethyl acetate
as eluent.
5.2.5. eq-2-p-Cyanophenoxy-2-thio-cis-4,6-dimethyl-1,3,
2l5-dioxaphosphinane (3-eq). According to the general
procedure described above, 1.5 g (5.97 mmol) of equatorial
p-cyanophenyl phosphite (route A), was treated with
elemental sulfur. Flash chromatography (hexanes/ethyl
acetate 80:20) gave 1.52 g of the product as pale yellow
crystals (90% yield) of mp 106–107 8C. 1H NMR d 1.41 (d,
JZ2.0 Hz, 6H), 1.79 (m, JZ14.5, 11.2 Hz, 1H), 1.87 (m,
JZ14.5, 2.7, 3.6 Hz, 1H), 4.84 (m, JZ11.2, 6.6, 2.7, 3.3 Hz,
5.2.1. ax-2-Chloro-cis-4,6-dimethyl-1,3,2-l3-dioxaphos-
phinane (1). This compound was obtained from a mixture
of meso- and rac-pentanediols and phosphorus trichloride
by the stereoselective approach reported by us.42
2H), 8.26 (d, 3JZ8.6 Hz, 2H), 8.57 (d, 3JZ8.9 Hz, 2H); 13
C
5.2.2. ax-2-p-Nitrophenoxy-2-thio-cis-4,6-dimethyl-1,3,
2l5-dioxaphosphinane (2-ax). According to the general
procedure described above, 1.0 g (3.69 mmol) of axial
p-nitrophenyl phosphite (route B), was treated with
elemental sulfur. Flash chromatography (hexanes/ethyl
acetate 75:25) gave 1.0 g of yellow crystals (90% yield)
of mp 111–112 8C. 1H NMR d 1.42 (d, JZ2.3 Hz, 6H), 1.86
(m, JZ14.6, 11.3, 1.0 Hz, 1H), 1.90 (m, JZ14.6, 3.0,
2.6 Hz, 1H), 4.76 (m, JZ11.3, 6.2, 3.0, 2.6 Hz, 2H), 7.36
NMR d 22.1 (d), 40.9 (d), 76.0 (d), 109.4 (s, CN), 118.1 (s,
Cp), 122.4 (s, Co), 133.8 (s, Cm), 152.6 (d, Ci); 31P NMR d
59.3. Mass spectrum (m/z) 283 (MC), 242 (MCK41), 216
(MCK67), 197 (MCK86), 165 (MCK118), 149 (MCK
134), 119 (MCK164), 90 (MCK193), 69 (MCK234), 41
(MCK242). Anal. Calcd for C12H14O3PNS: C, 50.88; H,
4.98. Found: C, 51.02; H, 5.21.
3
4
3
(dd, JZ8.9 Hz, JHPZ1.2 Hz, 2H), 8.24 (d, JZ8.9 Hz,
2H); 13C NMR d 22.4 (d), 40.6 (d), 77.7 (d), 121.3 (d, Co),
126.0 (s, Cm), 145.1 (s, Cp), 156.2 (d, Ci); 31P NMR d 54.3.
Mass spectrum (m/z) 303 (MC), 262 (MCK41), 236
(MCK67), 218 (MCK85), 171 (MCK132), 149 (MCK
154), 123 (MCK180), 97 (MCK206), 69 (MCK234), 41
(MCK262). Anal. Calcd for C11H14O5PNS: C, 43.57; H,
4.65. Found: C, 43.67; H, 4.85.
5.2.6. ax-2-p-Formylphenoxy-2-thio-cis-4,6-dimethyl-
1,3,2l5-dioxaphosphinane (4-ax). According to the gen-
eral procedure described above, 1.0 g (3.94 mmol) of axial
p-formylphenyl phosphite (route B), was treated with
elemental sulfur. Flash chromatography (hexanes/ethyl
acetate 60:40) gave 1.01 g of the product as oil (90%
1
yield). H NMR d 1.42 (d, JZ2.2 Hz, 6H), 1.83 (m, JZ
13.0, 8.0 Hz, 1H), 1.85 (m, JZ13.0, 2.7, 1.5 Hz, 1H), 4.75
3
(m, JZ8.0, 6.2, 2.7, 1.2 Hz, 2H), 7.35 (dd, JZ8.6 Hz,
4JHPZ1.5 Hz, 2H), 7.87 (d, 3JZ8.6 Hz, 2H), 9.94 (s, CHO);
13C NMR d 22.1 (d), 40.2 (d), 76.7 (d), 120.7 (d, Co), 131.7
(d, Cm), 133.3 (s, Cp), 155.4 (d, Ci), 190.8 (s, CHO); 31P
NMR d 55.1. Mass spectrum (m/z) 286 (MC), 245 (MCK
41), 219 (MCK67), 199 (MCK87), 167 (MCK119), 149
(MCK137), 138 (MCK148), 121 (MCK165), 97 (MCK
189), 69 (MCK217), 41 (MCK245). Anal. Calcd for
C12H15O4PS: C, 50.35; H, 5.28. Found: C, 50.46; H, 5.40.
5.2.3. eq-2-p-Nitrophenoxy-2-thio-cis-4,6-dimethyl-1,3,
2l5-dioxaphosphinane (2-eq). According to the general
procedure described above, 1.5 g (5.54 mmol) of equatorial
p-nitrophenyl phosphite (route A), was treated with
elemental sulfur. Flash chromatography (hexanes/ethyl
acetate 75:25) gave 1.52 g of pale yellow crystals (91%
1
yield) of mp 90–91 8C. H NMR d 1.41(d, JZ2.2 Hz, 6H),
1.77 (m, JZ14.6, 10.5, 1.0 Hz, 1H), 1.90 (m, JZ14.6, 2.6,
2.8 Hz, 1H), 4.85 (m, JZ10.5, 6.3, 2.6, 1.2 Hz, 2H), 7.35
3
4
3
(dd, JZ9.2 Hz, JHPZ1.6 Hz, 2H), 8.23 (d, JZ8.9 Hz,
2H); 13C NMR d 22.1 (d), 40.8 (d), 76.1 (d), 122.1 (d, Co),
125.4 (s, Cm), 145.1 (s, Cp), 155.0 (d, Ci); 31P NMR d 59.2.
Mass spectrum (m/z) 303 (MC), 262 (MCK41), 236
(MCK67), 218 (MCK85), 205 (MCK98), 171 (MCK
132), 149 (MCK154), 123 (MCK180), 97 (MCK206), 69
5.2.7. eq-2-p-Formylphenoxy-2-thio-cis-4,6-dimethyl-1,
3,2l5-dioxaphosphinane (4-eq). According to the general
procedure described above, 1.0 g (3.94 mmol) of equatorial
p-formylphenyl phosphite (route A), was treated with
elemental sulfur. Flash chromatography (hexanes/ethyl
acetate 60:40) gave 1.02 g of brown crystals (91% yield)

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J. Hernandez et al. / Tetrahedron 60 (2004) 10927–10941
10938
1
of mp 55–57 8C. H NMR d 1.34 (d, JZ2.3 Hz, 6H), 1.54
(m, JZ14.5, 10.4, 1.8 Hz, 1H), 1.69 (m, JZ14.5, 2.7,
2.3 Hz, 1H), 4.79 (m, JZ10.4, 6.3, 2.7, 2.8 Hz, 2H), 7.30
(m, 2H), 7.80 (m, 2H), 9.91 (s, CHO); 13C NMR d 22.1 (d),
40.8 (d), 75.9 (d), 122.0 (d, Co), 131.4 (d, Cm), 133.6 (s, Cp),
155.0 (d, Ci), 190.8 (s, CHO); 31P NMR d 59.5. Mass
spectrum (m/z) 286 (MC), 219 (MCK67), 199 (MCK87),
169 (MCK117), 149 (MCK137), 138 (MCK148), 122
(MCK164), 85 (MCK201), 69 (MCK217), 41 (MCK
245). Anal. Calcd for C12H15O4PS: C, 50.35; H, 5.28.
Found: C, 50.35; H, 5.41.
Calcd for C11H14O3PSCl: C, 45.14; H, 4.82. Found: C,
45.27; H, 5.04.
5.2.11. eq-2-p-Chlorophenoxy-2-thio-cis-4,6-dimethyl-1,
3,2l5-dioxaphosphinane (6-eq). According to the general
procedure described above, 2.8 g (10.73 mmol) of equa-
torial p-chlorophenyl phosphite (route A), was treated with
elemental sulfur. Flash chromatography (hexanes/ethyl
acetate 90:10) gave 1.54 g of white crystals (50% yield)
1
of mp 59–60 8C. H NMR d 1.39 (d, JZ2.0 Hz, 6H), 1.71
(m, JZ14.0, 11.2 Hz, 1H), 1.87 (m, JZ14.0, 3.0, 2.3 Hz,
3
1H), 4.83 (m, JZ11.2, 6.6, 3.0, 2.5 Hz, 2H), 7.16 (d, JZ
8.6 Hz, 2H), 7.38 (d, 3JZ8.6 Hz, 2H); 13C NMR d 22.5 (d),
41.3 (d), 76.1 (d), 122.9 (d, Cp), 123.1 (d, Co), 130.1 (d, Cm),
149.4 (d, Ci); 31P NMR d 60.1. Mass spectrum (m/z) 292
(MC), 224 (MCK68), 149 (MCK143), 128 (MCK164),
99 (MCK193), 69 (MCK154), 41 (MCK251). Anal.
Calcd for C11H14O3PSCl: C, 45.14; H, 4.82. Found: C,
45.17; H, 4.98.
5.2.8. ax-2-p-Bromophenoxy-2-thio-cis-4,6-dimethyl-1,
3,2l5-dioxaphosphinane (5-ax). According to the general
procedure described above, 1.0 g (3.27 mmol) of axial
p-bromophenyl phosphite (route B), was treated with
elemental sulfur. Flash chromatography (hexanes/ethyl
acetate 85:15) gave 1.03 g of white crystals (93% yield)
of mp 132–133 8C. 1H NMR d 1.42 (d, JZ2.2 Hz, 6H), 1.82
(m, JZ14.8, 10.8, 1.0 Hz, 1H), 1.87 (m, JZ14.8, 2.8,
2.7 Hz, 1H), 4.75 (m, JZ10.8, 6.2, 2.8, 1.2 Hz, 2H), 7.19
5.2.12. ax-2-p-Acetamidophenoxy-2-thio-cis-4,6-di-
methyl-1,3,2l5-dioxaphosphinane (7-ax). According to
the general procedure described above, 3.0 g (10.73 mmol)
of axial p-acetamidophenyl phosphite (route A-to-C), was
treated with elemental sulfur. Flash chromatography
(hexanes/ethyl acetate 85:15) gave 0.75 g of white crystals
3
4
3
(dd, JZ8.9 Hz, JHPZ1.4 Hz, 2H), 7.49 (d, JZ8.9 Hz,
2H); 13C NMR d 22.4 (d), 40.8 (d), 77.2 (d), 118.3 (s, Cp),
122.6 (d, Co), 133.1 (s, Cm), 150.6 (d, Ci); 31P NMR d 55.5
(56.0). Mass spectrum (m/z) 338 (MCC1), 296 (MCK41),
270 (MCK67), 188 (MCK149), 172 (MCK165), 149
(MCK188), 69 (MCK268), 41 (MCK296). Anal. Calcd
for C11H14O3PSBr: C, 39.19; H, 4.19. Found: C, 39.17; H,
4.16.
1
(22% yield) of mp 188–190 8C. H NMR d 1.44 (d, JZ
2.3 Hz, 6H), 1.86 (m, JZ13.0, 12.9, 1.0 Hz, 1H), 1.88 (m,
JZ13.0, 2.9, 1.8 Hz, 1H), 2.79 (s, 3H), 4.77 (m, JZ12.9,
6.2, 2.9, 1.3 Hz, 2H), 7.12 (d, 3JZ8.9 Hz, 2H), 7.49 (d, 3JZ
8.9 Hz, 2H), 8.56 (s, 1H); 13C NMR d 22.5 (d), 24.7 (s), 42.7
(d), 76.8 (d), 121.9 (d, Co), 122.6 (s, Cp), 135.1 (s, Cm),
147.5 (d, Ci), 168.4 (s); 31P NMR d 55.9. Mass spectrum
(m/z) 315 (MC), 273 (MCK42), 205 (MCK110), 187
(MCK128), 125 (MCK190), 108 (MCK207), 69 (MCK
246), 43 (MCK272). Anal. Calcd for C13H18O4PNS: C,
49.52; H, 5.75. Found: C, 49.64; H, 5.79.
5.2.9. eq-2-p-Bromophenoxy-2-thio-cis-4,6-dimethyl-1,
3,2l5-dioxaphosphinane (5-eq). According to the general
procedure described above, 1.5 g (4.91 mmol) of equatorial
p-bromophenyl phosphite (route A), was treated with
elemental sulfur. Flash chromatography (hexanes/ethyl
acetate 80:20) gave 1.54 g of white crystals (90% yield)
1
of mp 64–65 8C. H NMR d 1.32 (d, JZ2.0 Hz, 6H), 1.64
(m, JZ14.5, 10.6 Hz, 1H), 1.77 (m, JZ14.5, 2.8, 2.3 Hz,
5.2.13. eq-2-p-Acetamidophenoxy-2-thio-cis-4,6-dimethyl-
1,3,2l5-dioxaphosphinane (7-eq). According to the general
procedure described above, 3.0 g (10.73 mmol) of equa-
torial p-acetamidophenyl phosphite (route A), was treated
with elemental sulfur. Flash chromatography (hexanes/ethyl
acetate 70:30) gave 1.54 g of pale yellow crystals (90%
1H), 4.76 (m, JZ10.9, 6.3, 2.6, 2.3 Hz, 2H), 7.01 (dd, 3JZ
4
3
8.6 Hz, JHPZ1.3 Hz, 2H), 7.38 (d, JZ8.6 Hz, 2H); 13C
NMR d 22.0 (d), 40.9 (d), 75.6 (d), 118.6 (s, Cp), 123.1 (d,
Co), 132.5 (s, Cm), 149.5 (d, Ci); 31P NMR d 60.0. Mass
spectrum (m/z) 338 (MCC1), 305 (MCK32), 252 (MCK
85), 190 (MCK147), 172 (MCK165), 149 (MCK188),
101 (MCK236), 69 (MCK268), 41 (MCK296). Anal.
Calcd for C11H14O3PSBr: C, 39.19; H, 4.19. Found: C,
39.21; H, 4.28.
1
yield) of mp 102–104 8C. H NMR d 1.38 (d, JZ2.4 Hz,
6H), 1.75 (m, JZ14.1, 10.8 Hz, 1H), 1.85 (m, JZ14.1, 2.3,
2.3 Hz, 1H), 2.14 (s, 3H), 4.80 (m, JZ10.8, 6.2, 2.3, 2.6 Hz,
2H), 7.10 (dd, 3JZ8.6 Hz, 4JHPZ1.3 Hz, 2H), 7.46 (d, 3JZ
8.6 Hz, 2H), 7.64 (s, 1H); 13C NMR d 22.4 (d), 24.7 (s), 41.1
(d), 75.8 (d), 121.0 (s, Cp), 121.7 (d, Co), 135.5 (s, Cm),
149.6 (d, Ci), 168.6 (s); 31P NMR d 60.4. Mass spectrum
(m/z) 315 (MC), 273 (MCK42), 229 (MCK86), 205
(MCK110), 187 (MCK128), 125 (MCK190), 108 (MCK
207), 69 (MCK246), 43 (MCK272). Anal. Calcd for
C13H18O4PNS: C, 49.52; H, 5.75. Found: C, 49.64; H, 5.92.
5.2.10. ax-2-p-Chlorophenoxy-2-thio-cis-4,6-dimethyl-
1,3,2l5-dioxaphosphinane (6-ax). According to the gen-
eral procedure described above, 2.8 g (10.73 mmol) of axial
p-chlorophenyl phosphite (route A-to-C), was treated with
elemental sulfur. Flash chromatography (hexanes/ethyl
acetate 85:15) gave 0.72 g of white crystals (23% yield)
of mp 126–128 8C. 1H NMR d 1.45 (d, JZ2.1 Hz, 6H), 1.83
(m, JZ14.1, 11.1, 1.1 Hz, 1H), 1.90 (m, JZ14.1, 3.0,
1.3 Hz, 1H), 4.75 (m, JZ11.1, 6.6, 3.0, 1.1 Hz, 2H), 7.12 (d,
3JZ8.8 Hz, 2H), 7.30 (d, 3JZ8.8 Hz, 2H); 13C NMR d 22.6
(d), 40.6 (d), 76.7 (d), 121.7 (d, Co), 129.8 (s, Cp), 130.5 (s,
Cm), 149.5 (d, Ci); 31P NMR d 55.6. Mass spectrum (m/z)
292 (MC), 224 (MCK68), 149 (MCK143), 128 (MCK
164), 99 (MCK193), 69 (MCK154), 41 (MCK251). Anal.
5.2.14. ax-2-Phenoxy-2-thio-cis-4,6-dimethyl-1,3,2l5-
dioxaphosphinane (8-ax).15 According to the general
procedure described above, 1.0 g (4.42 mmol) of axial
phenyl phosphite (route B), was treated with elemental
sulfur. Flash chromatography (hexanes/ethyl acetate 95:5)
gave 1.05 g of white crystals (92% yield) of mp 120–122 8C.
1H NMR d 1.43 (d, JZ2.6 Hz, 6H), 1.82 (m, JZ13.8, 9.9,

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J. Hernandez et al. / Tetrahedron 60 (2004) 10927–10941
10939
1.0 Hz, 1H), 1.88 (m, JZ14.4, 2.8, 2.6 Hz, 1H), 4.79 (m,
(m, JZ14.5, 3.0, 2.7 Hz, 1H), 2.32 (s, CH3), 4.77 (m, JZ
3 4
3
JZ10.8, 6.6, 2.8, 1.3 Hz, 2H), 7.19 (m, 3H), 7.35 (m, JZ
10.7, 6.2, 3.0, 1.2 Hz, 2H), 7.06 (dd, JZ8.5 Hz, JHPZ
8.9 Hz, 2H); 13C NMR d 21.9 (d), 39.9 (d), 76.2 (d), 119.8
(d, Co), 125.5 (s, Cp), 129.5 (s, Cm), 150.5 (d, Ci); 31P NMR
d 55.8.
1.5 Hz, 2H), 7.17 (d, JZ8.5 Hz, 2H); 13C NMR d 20.9 (s,
CH3), 22.4 (d), 40.7 (d), 76.9 (d), 120.4 (s, Cp), 130.6 (d,
Co), 135.3 (s, Cm), 148.8 (d, Ci); 31P NMR d 56.2. Mass
spectrum (m/z) 272 (MC), 204 (MCK68), 186 (MCK86),
149 (MCK123), 124 (MCK148), 108 (MCK164), 91
(MCK181), 69 (MCK203), 43 (MCK229), 41 (MCK
231). Anal. Calcd for C12H17O3PS: C, 52.93; H, 6.29.
Found: C, 53.03; H, 6.40.
3
5.2.15. eq-2-Phenoxy-2-thio-cis-4,6-dimethyl-1,3,2l5-
dioxaphosphinane (8-eq).15 According to the general
procedure described above, 3.0 g (13.27 mmol) of equa-
torial phenyl phosphite (route A), was treated with
elemental sulfur. Flash chromatography (hexanes/ethyl
acetate 98:2) gave 3.18 g of white crystals (93% yield) of
mp 55–56 8C. 1H NMR d 1.39 (d, JZ2.3 Hz, 6H), 1.70 (m,
JZ14.5, 10.9 Hz, 1H), 1.89 (m, JZ14.5, 2.6, 2.3 Hz, 1H),
4.83 (m, JZ10.9, 6.3, 2.6, 2.3 Hz, 2H), 7.20 (m, 3H), 7.35
(m, 2H); 13C NMR d 22.1 (d), 41.0 (d), 75.4 (d), 121.1 (d,
Co), 125.5 (s, Cp), 129.5 (s, Cm), 150.3 (d, Ci); 31P NMR d
60.4.
5.2.19. eq-2-p-Methylphenoxy-2-thio-cis-4,6-dimethyl-
1,3,2l5-dioxaphosphinane (10-eq). According to the gen-
eral procedure described above, 3.5 g (14.58 mmol) of
equatorial p-methylphenyl phosphite (route A), was treated
with elemental sulfur. Flash chromatography (hexanes/ethyl
acetate 80:20) gave 3.6 g of white crystals (91% yield) of
mp 82–83 8C. 1H NMR d 1.34 (d, JZ2.6 Hz, 6H), 1.59 (m,
JZ14.5, 11.2, 2.3 Hz, 1H), 1.72 (m, JZ14.5, 2.6, 2.6 Hz,
1H), 2.27 (s, CH3), 4.80 (m, JZ10.9, 6.3, 2.6, 2.6 Hz, 2H),
5.2.16. ax-2-p-Phenylphenoxy-2-thio-cis-4,6-dimethyl-
1,3,2l5-dioxaphosphinane (9-ax). According to the gen-
eral procedure described above, 3.5 g (11.59 mmol) of
axial p-phenylphenyl phosphite (route B, or the sequence
A-to-C), was treated with elemental sulfur. Flash chroma-
tography (hexanes/ethyl acetate 98:2) gave 3.48 g of white
powder (90% yield) of mp 145–146 8C. 1H NMR d 1.44 (d,
JZ2.2 Hz, 6H), 1.83 (m, JZ13.8, 9.9, 1.0 Hz, 1H), 1.88 (m,
JZ13.8, 2.9, 2.9 Hz, 1H), 4.81 (m, JZ9.9, 6.2, 2.9, 1.2 Hz,
2H), 7.27 (m, 2H), 7.35 (m, 1H), 7.44 (m, 2H), 7.59 (m, 4H);
13C NMR d 22.5 (d), 40.7 (d), 77.1 (d), 121.0 (d, Co), 127.4
4
7.03 (dd, 3JZ8.6 Hz, JHPZ2.0 Hz, 2H), 7.08 (d, 3JZ
8.6 Hz, 2H); 13C NMR d 20.8 (s, CH3), 22.1 (d), 41.0 (d),
75.3 (d), 121.0 (d, Co), 129.9 (d, Co), 135.1 (s, Cm), 148.3 (d,
Ci); 31P NMR d 60.9. Mass spectrum (m/z) 272 (MC), 204
(MCK68), 186 (MCK86), 149 (MCK123), 124 (MCK
148), 108 (MCK164), 91 (MCK181), 69 (MCK203), 43
(MCK229), 41 (MCK231). Anal. Calcd for C12H17O3PS:
C, 52.93; H, 6.29. Found: C, 52.73; H, 6.41.
5.2.20. ax-2-p-Methoxyphenoxy-2-thio-cis-4,6-dimethyl-
1,3,2l5-dioxaphosphinane (11-ax). According to the gen-
eral procedure described above, 3.0 g (11.71 mmol) of axial
p-methoxyphenyl phosphite (route B, or the sequence A-to-
C), was treated with elemental sulfur. Flash chromatog-
raphy (hexanes/ethyl acetate 85:15) gave 2.93 g of white
powder (92% yield) of mp 94–96 8C. 1H NMR d 1.42 (d, JZ
2.2 Hz, 6H), 1.81 (m, JZ14.5, 10.8, 1.0 Hz, 1H), 1.86 (m,
JZ14.5, 3.3, 3.0 Hz, 1H), 3.78 (s, OCH3), 4.77 (m, JZ10.8,
0
0
0
(s, Cm), 127.8 (s, Cp ), 128.7 (s, Co ), 129.2 (s, Cm ), 138.5
(s, Cp), 140.5 (s, Ci ), 150.8 (d, Ci); 31P NMR d 55.8. Mass
0
spectrum (m/z) 334 (MC), 266 (MCK68), 186 (MCK148),
170 (MCK164), 141 (MCK193), 91 (MCK243), 69
(MCK265), 28 (MCK306). Anal. Calcd for
C17H19O3PS: C, 61.07; H, 5.73. Found: C, 61.05; H, 5.44.
5.2.17. eq-2-p-Phenylphenoxy-2-thio-cis-4,6-dimethyl-
1,3,2l5-dioxaphosphinane (9-eq). According to the general
procedure described above, 2.5 g (8.27 mmol) of equatorial
p-phenylphenyl phosphite (route A), was treated with
elemental sulfur. Flash chromatography (hexanes/ethyl
acetate 98:2) gave 2.51 g of white powder (91% yield) of
3
4
6.2, 3.3, 1.2 Hz, 2H), 6.78 (dd, JZ8.8 Hz, JHPZ1.5 Hz,
2H), 6.87 (d, 3JZ8.8 Hz, 2H); 13C NMR d 22.4 (d), 40.7 (d),
56.0 (s, OCH3), 76.9 (d), 115.0 (s, Cm), 121.7 (d, Co), 144.9
(d, Ci), 157.29 (d, Cp); 31P NMR d 56.7. Mass spectrum
(m/z) 288 (MC), 220 (MCK68), 202 (MCK86), 140
(MCK148), 124 (MCK164), 95 (MCK193), 69 (MCK
219), 41 (MCK247). Anal. Calcd for C12H17O4PS: C,
49.99; H, 5.94. Found: C, 50.06; H, 6.11.
1
mp 165–166 8C. H NMR d 1.34 (d, JZ2.0 Hz, 6H), 1.67
(m, JZ14.2, 9.9 Hz, 1H), 1.77 (m, JZ14.2, 2.9, 2.3 Hz,
1H), 4.78 (m, JZ9.9, 6.2, 2.9, 3.0 Hz, 2H), 7.19 (m, 2H),
7.28 (m, 1H), 7.36 (m, 2H), 7.48 (m, 4H); 13C NMR d 22.1
0
(d), 41.0 (d), 75.5 (d), 121.5 (d, Co), 127.0 (s, Cm ), 127.3 (s,
5.2.21. eq-2-p-Methoxyphenoxy-2-thio-cis-4,6-dimethyl-
1,3,2l5-dioxaphosphinane (11-eq). According to the gen-
eral procedure described above, 2.5 g (9.76 mmol) of
equatorial p-methoxyphenyl phosphite (route A), was
treated with elemental sulfur. Flash chromatography
(hexanes/ethyl acetate 80:20) gave 1.54 g of white crystals
(90% yield) of mp 93–94 8C. 1H NMR d 1.31 (d, JZ2.0 Hz,
6H), 1.63 (m, JZ14.5, 10.9 Hz, 1H), 1.75 (m, JZ14.5, 2.6,
2.6 Hz, 1H), 3.71 (s, OCH3), 4.73 (m, JZ10.9, 6.3, 2.6,
2.6 Hz, 2H), 6.77 (dd, 3JZ8.9 Hz, 4JHPZ1.6 Hz, 2H), 7.04
(d, 3JZ8.9 Hz, 2H); 13C NMR d 22.0 (d), 40.9 (d), 55.6 (s,
OCH3), 75.6 (d), 114.3 (s, Cm), 122.0 (d, Co), 144.0 (d, Ci),
156.9 (d, Cp); 31P NMR d 61.0. Mass spectrum (m/z) 288
(MC), 220 (MCK68), 202 (MCK86), 170 (MCK118),
140 (MCK148), 124 (MCK164), 119 (MCK169), 95
(MCK193), 69 (MCK219), 41 (MCK247). Anal. Calcd
0
0
Cp ), 128.2 (s, Co ), 128.8 (s, Cm), 138.6 (d, Cp), 140.2 (s,
0
Ci ), 149.9 (d, Ci); 31P NMR d 60.4. Mass spectrum (m/z)
334 (MC), 266 (MCK68), 186 (MCK148), 170 (MCK
164), 141 (MCK193), 115 (MCK219), 85 (MCK249), 69
(MCK265), 41 (MCK293). Anal. Calcd for C17H19O3PS:
C, 61.07; H, 5.73. Found: C, 61.28; H, 6.00.
5.2.18. ax-2-p-Methylphenoxy-2-thio-cis-4,6-dimethyl-
1,3,2l5-dioxaphosphinane (10-ax). According to the
general procedure described above, 1.5 g (6.25 mmol) of
axial p-methylphenyl phosphite (route B, or the sequence
A-to-C), was treated with elemental sulfur. Flash chroma-
tography (hexanes/ethyl acetate 80:20) gave 1.03 g of white
crystals (89% yield) of mp 138–139 8C. 1H NMR d 1.41 (d,
JZ2.2 Hz, 6H), 1.82 (m, JZ14.5, 10.7, 1.1 Hz, 1H), 1.84

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J. Hernandez et al. / Tetrahedron 60 (2004) 10927–10941
10940
In Phosphorus Chemistry Developments in American Science;
Walsh, E. N., Griffith, E. J., Parry, R. W., Quin, L. D., Eds.;
ACS Symposium Series, 486; American Chemical Society:
Washington, DC, 1992; Chapter 11.
for C12H17O4PS: C, 49.99; H, 5.94. Found: C, 49.81; H,
6.29.
5.2.22. ax-2-p-Aminophenoxy-2-thio-cis-4,6-dimethyl-
1,3,2l5-dioxaphosphinane (12-ax). A mixture of 1.3 g
(11.86 mmol) of p-aminophenyl phosphites (ax/eq 7:93)
was obtained through route B. The mixture was maintained
at room temperature because heating led to decomposition
of the intermediate phosphites. The mixture of phosphites
was treated with elemental sulfur according to the general
procedure described above. Flash chromatography (hex-
anes/ethyl acetate 35:65) was unsuccessful to purify the
axial isomer, therefore it was analyzed as a mixture. 13C
NMR d 22.3 (d), 40.5 (d), 76.2 (d), 116.5 (s, Cm), 121.1 (d,
Co), 144.8 (d, Ci), 143.8 (s, Cp); 31P NMR d 56.8.
9. (a) Eliel, E. L.; Gordillo, B.; White, P. S.; Harris, D. L.
Heteroat. Chem. 1997, 8, 509. (b) McEwen, W. E. Top.
Phosphorus Chem. 1965, 2, 1.
10. Tatcher, G. R. J.; Kluger, R. In Advances in Physical Organic
Chemistry; Bethell, D., Ed.; Academic: New York, 1989; Vol.
25, p 99.
11. Verkade, J. G. Phosphorus Sulfur 1976, 2, 251.
12. Van Nuffel, P.; Van Alsenoy, C.; Lenstra, A. T. H.; Geise, H. J.
J. Mol. Struct. 1984, 125, 1.
13. Hansch, C.; Leo, A.; Taft, R. W. Chem. Rev. 1991, 91, 165.
14. Carey, F. A.; Sundberg, R. J. Advanced Organic Chemistry.
Part A: Structure and Mechanisms, 3rd ed.; Plenum: New
York, 1990; Chapter 4.
5.2.23. eq-2-p-Aminophenoxy-2-thio-cis-4,6-dimethyl-
1,3,2l5-dioxaphosphinane (12-eq). According to the gen-
eral procedure described above, 4.0 g (23.73 mmol) of
equatorial p-aminophenyl phosphite (route A), was treated
with elemental sulfur. Flash chromatography (hexanes/ethyl
acetate 35:65) gave 1.5 g of brown crystals (23% yield) of
mp 93–94 8C. 1H NMR d 1.38 (d, JZ2.0 Hz, 6H), 1.68 (m,
JZ14.5, 11.2 Hz, 1H), 1.82 (m, JZ14.5, 2.6, 2.6 Hz, 1H),
3.25 (br, NH2), 4.52 (m, JZ11.2, 6.6, 2.6, 3.3 Hz, 2H), 6.64
(m, 2H), 6.98 (m, 2H); 13C NMR d 21.9 (d), 40.8 (d), 75.8
(d), 115.4 (s, Cm), 121.8 (d, Co), 142.6 (d, Ci), 142.6 (s, Cp);
31P NMR d 61.3. Mass spectrum (m/z) 274 (MCC1), 205
(MCK68), 187 (MCK86), 125 (MCK148), 109 (MCK
164), 94 (MCK179), 69 (MCK204), 41 (MCK232). Anal.
Calcd for C11H16O3PNS: C, 48.35; H, 5.90. Found: C,
48.52; H, 6.04.
´
15. Gordillo, B.; Gardun˜o, C.; Guadarrama, G.; Hernandez, J.
J. Org. Chem. 1995, 60, 5180.
16. The value of 3JHaHaZ8 Hz for compounds 4-ax (XZCHO) is
3
somewhat small, however values of JHaHeZ2.8 Hz and
3JHPZ1.2 Hz discard population of a twist conformer.
17. Quin, L. D. The Heterocyclic Chemistry of Phosphorus;
Wiley: New York, 1981; Chapter 6.
18. Quin, L. D. Stereospecificity in 31P-Element Couplings:
Phosphorus–Carbon Coupling. In Phosphorus-31 NMR Spec-
troscopy in Stereochemical Analysis: Organic Compounds and
Metal Complexes; Quin, L. D., Verkade, J. G., Eds.; VCH:
Deerfield Beach, FL, 1987; p 391.
19. Nifantiev, E. E.; Sorokina, S. F.; Borisenko, A. A. J. Gen.
Chem. 1984, 55, 1481.
20. Pomerantz, M.; Chou, W.-N.; Witczak, M. K.; Smith, C. G.
J. Org. Chem. 1987, 52, 159.
21. Gorenstein, D. G. In Phosphorus-31 NMR; Principles and
Applications; Gorenstein, D. G., Ed.; Academic: New York,
1984; Chapter 1.
Acknowledgements
22. Cremlyn, R. J.; Woods, M. J. Chem. Eng. Data 1981, 26, 231.
23. (a) Letcher, J. H.; Van Wazer, J. R. J. Chem. Phys. 1966, 44,
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Chem. 1967, 5.
´
We thank CONACyT (Mexico) for financial support (Grant
32221-E). We are grateful to Geiser Cuellar for the
elemental analysis of some of the compounds.
24. Pomerantz, M.; Marynick, D. S.; Rajeshwar, K.; Chou, W.-N.;
Throckmorton, L.; Tsai, E. W.; Chen, P. C. Y.; Cain, T. J. Org.
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