New approach to the synthesis of phosphorodichloridites, phosphorochloridites, and trialkyl phosphites

Article abstract of DOI:10.1080/10426500902719222

Different trivalent organophosphorus esters such as phosphorodichloridites, phosphorochloridites, and mixed trialkyl phosphites have been easily synthesized in good yields using a HCl-catalyzed reaction of the corresponding chlorophosphine and alkoxytrimethylsilane by mutual exchange of the alkoxy and chlorine ligand p^IIICl/ROSiR′₃; exchange reaction). Chemoselectivity of the exchange reaction with primary and secondary alkoxytrimethylsilanes, as well as with alkoxytrimethylsilanes and thioalkoxytrimethylsilanes, respectively, has also been examined. It has been also found that the substitution reaction of chlorophosphines with secondary amine occurs more rapidly than the exchange reaction with ROSiR′ ₃.

Full text of DOI:10.1080/10426500902719222

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Phosphorus, Sulfur, and Silicon
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New Approach to the Synthesis
of Phosphorodichloridites,
Phosphorochloridites, and
Trialkyl Phosphites
Piotr Majewski a
a Institute of Organic Chemistry, Technical
University, Łódź, Poland
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Phosphorodichloridites, Phosphorochloridites, and Trialkyl Phosphites, Phosphorus,
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Phosphorus, Sulfur, and Silicon, 184:942–955, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500902719222
New Approach to the Synthesis of
Phosphorodichloridites, Phosphorochloridites,
and Trialkyl Phosphites
Piotr Majewski
Institute of Organic Chemistry, Technical University, Lꢀ o´dz´, Poland
Different trivalent organophosphorus esters such as phosphorodichloridites, phos-
phorochloridites, and mixed trialkyl phosphites have been easily synthesized in
good yields using a HCl-catalyzed reaction of the corresponding chlorophos-
phine and alkoxytrimethylsilane by mutual exchange of the alkoxy and chlo-
rine ligand (PIIICl/ROSiRꢀ3 ; exchange reaction). Chemoselectivity of the exchange
reaction with primary and secondary alkoxytrimethylsilanes, as well as with
alkoxytrimethylsilanes and thioalkoxytrimethylsilanes, respectively, has also been
examined. It has been also found that the substitution reaction of chlorophos-
phines with secondary amine occurs more rapidly than the exchange reaction with
ROSiRꢀ .
3
Keywords Mixed trialkyl phosphites; phosphorochloridites; phosphorodichloridites
INTRODUCTION
Trivalent organophosphorus esters, including phosphorodichloridites,
phosphorochloridites, and trialkyl phosphates, are usually formed
in the reactions of organophosphorus chlorides with the equimolar
amount of the appropriate alcohol in the presence of a tertiary amine.1
Another methodology consists in the exchange reaction of the chlorine
atom of a chlorophosphine with alkoxy groups of alkoxytrimethylsi-
lanes (PIIICl/ROSiRꢀ3). However the latter route has not been widely
used for synthesis.2
It is also known that the exchange reaction (PIIICl/R1OSiR3) is some-
times more useful than the substitution reaction (PIIICl/R1OH/HNR32).
For example, O-alkyl 2-chloro-cycloalkylphosphorochloridites cannot
Received 19 December 2007; accepted 29 February 2008.
Dedicated to Professor Marian Mikolꢀajczyk from the CBMiM PAN in Lꢀ o´dz´, Poland,
on the occasion of his 70th birthday.
Address correspondence to Piotr Majewski, Institute of Organic Chemistry, Technical
˙
University, Zeromskiego 116, 90-924 Lꢀ o´dz´, Poland. E-mail: piotr.majewski@p.lodz.pl
942

Synthesis of Phosphorodichloridites
943
be obtained from the reaction of 2-chloro-cycloalkylphosphorochlo-
ridites and an alcohol in the presence of a tertiary amine; the ex-
change reaction between 2-chlorocycloalkylphosphorochloridite and
the respective alkoxysilane affords good yields, however.3 More-
over the monomethoxylation at the PIII atom of (dichlorophosphinyl)
methylamine is possible only via the exchange reaction.4
However, in some cases, the exchange reaction with alkoxytrimethyl-
silanes requires very harsh conditions. It has been found that the re-
placement of all chlorine atoms in PCl3 by the exchange reaction is
rather difficult. For example, treatment of phosphorus trichloride with
an excess of butoxytrimethylsilane easily affords the phosphorochlo-
ridite via the formation of the corresponding phosphorodichloridite,5
but the efficient replacement of the last chlorine atom is difficult, and
the reaction must be performed at high temperatures and in the pres-
ence of [PyH]Cl as a catalyst.6,7 Attempts to accelerate the exchange
reaction between phosphorus trichloride and alkoxysilanes in the pres-
ence of ZnCl2 as catalyst have failed.8
The aim of our work was to elaborate mild conditions for the ex-
change reaction and thus to find a convenient approach to differ-
ent functional trivalent organophosphorus esters including phospho-
rodichloridites, phosphorochloridites, and mixed trialkylphosphites.
We also examined the chemoselectivity of the exchange reaction of
the P-chlorine ligand with alkoxy groups of primary and secondary
alkoxytrimethylsilanes as well as with alkoxy and thioalkoxy groups
of alkoxytrimethylsilanes and thioalkoxytrimethylsilanes, respectively.
We have also compared the reactivity of the PIIICl moiety in the ex-
change reaction with ROSiRꢀ3 and in the substitution reaction with
a secondary amine in order to predict whether the exchange reac-
tions with suitable alkoxytrimethylsilanes bearing amine functionality
might occur.
RESULTS AND DISCUSSION
Hydrogen Chloride as a Catalyst for the Exchange Reaction
(PIIICl/ROSiRꢀ3)
In our preliminary experiments, we have found that treatment of PCl3
with (CH3)3SiOC2H5 under dry argon atmosphere at room temperature
affords diethylphosphorodichloridite in satisfactory yield (80–85 mol %
after 48 h, 31P NMR analysis of the crude reaction mixture). However,
when the reaction was carried out in the presence of argon, which was
not additionally dried, the product was formed almost quantitatively.

944
P. Majewski
SCHEME 1
This observation suggests that the exchange reaction (Scheme 1) is
facilitated by the presence of catalytic amounts of HCl derived from
the reaction of PCl3 with traces of water. This methodology seems to be
especially useful in the preparation of different trivalent phosphorus
esters.
Synthesis of Dichlorides 3
In order to test the synthetic applicability of the exchange reaction,
a number of simple trimethylsilylated alcohols containing different
functionalities have been used, including methoxytrimethylsilane (1a),
ethoxytrimethylsilane (1b), trimethyl (propoxy)silane (1c), trimethyl
(buthoxy)silane (1d), benzyloxytrimethylsilane (1e), 3-(trimethyl-
siloxy)propane-nitrile
(1f),
trimethyl(2,2,2-trichloroethoxy)silane
(1g), decyloxytrimethylsilane (1h), ethyl (RS)-2-(tri-methylsililoxy)
propionoate (1i), N-palmitoyletanolamine trimethylsilyl ether (1j),
and N-boc-etanolamine trimethylsilylether (1k).
These compounds have been treated with PCl3 in methylene chlo-
ride solution under mild conditions (see the Experimental section) to
achieve monomethoxylation at the PIII atom. The exchange reaction
effectively led to the corresponding phosphorodichloridites 3 according
to Scheme 2a.
SCHEME 2a
The yields and physical constants of the products are presented in
Table I.

Synthesis of Phosphorodichloridites
945
TABLE I Dichlorophosphoridites ROPCl2 3
Lit. or Mol.
Yielda,b
[%]
31P-NMR
[δ, ppm]
Formulag
3
R
Bp. [◦C]/Torr
(Mol. Weight)
a
b
c
d
e
f
CH3
C2H5
n-C3H7
n-C4H9
C6H5CH2
NCC2H4
Cl3CCH2
CH3(CH2)8CH2
70
85
69
79
71
72
75
65
40/85
181.5
177.9
178.6
178.5
177.8
179.6
178.6
175.5
[21]
[22]
[23]
[24]
[9,25]
36–40/65
65–68/65
63–64/50
80–83/3
78–80/5
47–49.5/2
132–135/6
[25]
[26]
g
h
C10H21Cl2OP
(259.16)
[27]
C18H36Cl2NO2P
(384.36)
C7H14Cl2NO3P
(262.07)
i
j
C2H5OC(O)CHCH3
c
c
d
d
178.5
177.8e
179.8
180.0f
C15H31C(O)NHCH2CH2
k
(CH3)3COC(O)NHCH2CH2
c
d
aYield of distilled products.
bReaction time: a–d 24 h, e–i 1 week, f–h, j two weeks, k 1 h; the reaction is carried
out in the presence of stoichiometric amount of pyridine.
cCrude oil contains 96–98 mol % of product.
dReaction mixture was filtered, then evaporated and kept 15 min under vacuum
(40 ◦C / 2 Torr).
eTwo rotamers.
f Product is unstable at room temperature forming during one week cyclic
chlorophosphoroamidite, (3l), (31P NMR, δ = 153.9 ppm, ref. [10]).
gSatisfactory microanalyses obtained: C 0.35, H 0.25, P 0.30. All new
compounds shown IR (film) absorption bands characteristic for a POC moiety: broad
bands between 1170–1105 cm−1, ref. [28].
As shown in Table I, the simple dichloridites (b–d), as well as those
containing the most commonly used protecting groups (methyl, 2,2,2-
trichloroethyl, 2-cyanoethyl and benzyl9), are formed in good yields (a,
e–g).
It is also worth noting that mild conditions of the exchange pro-
cedure allow obtaining dichlorides, which contain carboester and car-
boamide functional groups, in excellent yields (i–k). However, dichlo-
ridites 3j,k appear to be unstable, and cyclic chlorophosphoroamidites
have been formed. It has been found that the phosphorodichloridite
3k, formed as a primary product of the exchange reaction, gave quan-
titatively the cyclic chlorophosphoroamidite 3l10 after 7 days (31P
NMR) (Scheme 2b). The dichloridite 3j was found to be stable at room
temperature.

946
P. Majewski
SCHEME 2b
Synthesis of Mixed Alkyl Chloridites 4, Mixed Trialkyl
Phosphites 5, and Their Derivatives 6
The successful application of the exchange method to the synthe-
sis of phosphorodichloridites encouraged us to attempt the prepara-
tion of mixed dialkylphosphorochloridites 4 and mixed trialkylphos-
phites 5. These compounds have been obtained according to Scheme 3.
Dichloridites 3h,i, as well as 2-chloro-(1,3,2)dioxaphospholane (7a) and
the trimethylsilylated alcohols 1e, i–k, have been used to produce
the mixed chloridites 4a,b and the mixed trialkylphosphites 5a,b. 2-
Chlorobenzo(1,3,2)dioxophosphinin-4-one (7b) was also used as a phos-
phitylating agent giving the trialkylphosphites 6a,b in the reaction
with 1j and 1k.
SCHEME 3
Yields, physical constants, and some spectroscopic data of 4, 5, and
6 are shown in Table II.

947

948
P. Majewski
All compounds 4–6 are unstable at higher temperatures and could
not be distilled even at low pressure, with exception of 5a, which was
obtained in 89% yield by vacuum distillation.
The mixed chloridites 4a,b, the mixed trialkyl phosphite 5b, and the
analogs 6a,b containing rather large alkyl substituents were obtained
as oils in high yields (more than 95%, see Table II). Their stability at
room temperature is presumably connected with the low ability of the
two different bulky alkoxy substituents to undergo mutual exchange
between two molecules of the mixed chloridites or mixed trialkylphos-
phites, respectively.
Chemoselectivity
Careful attention has been paid to investigate the chemoselectivity of
the exchange reaction (PIIICl/ROSiRꢀ3) of the P-chlorine ligand with:
a) Alkoxy groups of primary and secondary alkoxytrimethylsilanes
b) Alkoxy groups and thioalkoxy groups of alkoxytrimethylsilanes and
thioalkoxy-trimethylsilanes. Chemoselectivity was studied by ex-
amining two model reactions:
a) 2-chlorobenzo-(1,3,2)-dioxaphosphinin-4-one (7b) with tris-O, O, O-
trimethylsilyl-glycerol (1m), Scheme 4 (a)
b) 2-chlorobenzo-(1,3,2)-dioxaphosphinin-4-one (7b) with tris-S, O, O-
trimethylsilylthio-glycerol (1n), Scheme 4 (b)
SCHEME 4
The results are given in Table III. In each case, two trivalent
organophosphorus esters 8c,d and 8e,f were formed in almost quan-
titative yields. The structures of 8c,d and 8e,f and their molar ratios
have been determined from spectral data (1H, 31P NMR, Experimental
section, see also hydrolyses of the esters). It was found that in the first
model reaction (Scheme 4a), the ester 8c possessing phosphitylated

Synthesis of Phosphorodichloridites
949
TABLE III Reaction of 2-Chlorobenzo(1,3,2)dioxaphosphinin-4-one
(7b) with Tris-O,O,O-trimethylsilylglycerol (1m) and
Tris-S,O,O-trimethylsilylthioglycerol (1n)
Starting Silylated
Alcohol
Productsa XY =
- o-OC6H4C(O)O-
31P-NMR δ(ppm) Isomers ratio
(CH3)3SiOCH2
CH[OSi(CH3)3]
CH2OSi(CH3)3
1m
(CH3)SiOCH2
CH[OSi(CH2)3] CH2OP(XY)
8c
(CH3)3SiOCH2
CH(OPXY)CH2OSi(CH3)3
8d
(CH3)3SiSCH2
CH[OSi(CH3)3] CH2OP(XY)
8e
125.5
125.6
124.9
125.4
8c:8d
(5:1)b
(CH3)3SiSCH2
CH[OSi(CH3)3]
CH2OSi(CH3)3
1n
8e:8f
(5:1)b
(CH3)3SiSCH2CH(OPXY)
CH2OSi(CH3)3
8f
aCrude oil contains 96–98 mol % of product; the isomer mixture has not been
subjected to elemental microanalysis; reaction time in each case 24 h at –65◦C and
then 4 h at 20◦C.
bThe ratio of the isomers has been confirmed chemically. The exchange products
were hydrolyzed to HOCH2CH(OH)CH2OP(O)H(OH) (9c) and
(HOCH2)2CHOP(O)H(OH) (9d), as well as HSCH2CH(OH)CH2OP(O)H(OH) (9e) and
HSCH2CH[OP(O)H(OH)]CH2OH (9f), respectively, and their molar ratio has been
determined by 1H and 31P NMR spectroscopy. The ratio was 5:1 in each case (see the
Experimental section). There is no evidence for the formation of thiophosphitylated
esters.
hydroxy group at a primary carbon atom was the major product. Mo-
lar ratio of 8c:8d was 5:1. In the second reaction (Scheme 4b), two
esters possessing phosphitylated hydroxy group at primary (8e) and
secondary (8f) carbon atoms were also formed in molar ratio 8e:8f =
5:1. In the latter case, S-phosphitylatet ester has not been found among
the reaction products (see the Experimental section). On the basis of
our results, it can be concluded that the exchange rate of chlorine atom
of chlorophosphine by alkoxy and thioalkoxy group is as follows:
RIOSi(CH3)3 > RIIOSi(CH3)3 ꢁRSSi(CH3)3
RI − primary alkyl group, RII − secondary alkyl group
It might be expected that the higher reactivity of alkoxy groups
containing a primary carbon atom in the exchange reaction is due to
the different steric requirements of the alkoxy ligands. However, the
higher reactivity of the alkoxy group compared to that of the tioalkoxy

950
P. Majewski
group in the exchange reaction should depend on different nature and
reactivity of the C-O-Si and C-S-Si bonds in these reagents.
Comparison of PCl Reactivity Towards Trimethylsilyl Alcohols
(Exchange Reaction, PIIICl/ROSiRꢀ3) and Towards Secondary
Amines (Substitution Reaction, PIIICl/HNR2)
The rate of exchange reaction between the PCl group and silyloxy moi-
ety of alkoxytrimethylsilanes and the rate of the substitution reac-
tion of PCl moiety by secondary amines have been investigated using
model reaction between PCl3 and O-tri-methylsilyl-(-)-ephedryne (1l)
in the presence of pyridine (Scheme 5). The course of this reaction has
been monitored by 1H, 13C, and 31P NMR spectroscopy. It has been
found that the primary product of this reaction—the enantiomeric
phosphoroamidodichloridite 10—was transformed into the optically
pure cyclic chlorophosphoroamidite, (2R,4S,5R)-2-chloro-3,4-dimethyl-
5-phenyl-(1,3,2)oxazaphospholidine (11),11a,b during 24 h at room tem-
perature. The assignment of trans configuration between the chlorine
atom and the substituents of the oxazaphospholidine ring in 11 is based
3
on the value of JPH between the phosphorus atom and the hydrogen
atom connected to the benzyl carbon atom.11c
SCHEME 5
Our results show that the substitution of chlorophosphine by the
secondary amine proceeds faster than the exchange reaction between
the PCl moiety and alkoxytrimethylsilane. Of course the final prod-
ucts are the result of the internal exchange reaction of the PIIICl and
ROSi(CH3)3 moieties of 10.
CONCLUSION
Phosphorodichloridites, mixed phosphorochloridites, and mixed phos-
phites are easily prepared by HCl-catalyzed exchange reaction of the
chlorine atoms of the corresponding chlorophosphine and alkoxy lig-
ands of an alkoxytrimethylsilane (PIIICl/ROSiR3ꢀ ).

Synthesis of Phosphorodichloridites
951
The exchange reaction is chemoselective, and in the case of pri-
mary and secondary alkoxytrimethylsilanes, the former are more reac-
tive. The exchange reaction is also chemoselective with alkoxy and
thioalkoxy ligands. The alkoxy ligands are more reactive than the
thioalkoxy ones.
It was also established that the substitution of the PCl moiety by a
secondary amine proceeds faster then the exchange reaction between
the PCl moiety and an alkoxy ligand of alkoxytrimethylsilane.
EXPERIMENTAL
All reactions were carried out in atmosphere of argon not additionally
dried. IR spectra were recorded using a Specord 71 IR C Zeiss spec-
trophotometer.
NMR spectra were obtained with a 250 Bruker Avance Spectrom-
eter. Chemical shifts are reported as δ values using TMS as internal
standard or 85% H3PO4 as an external standard. Solvents were ob-
tained from commercial suppliers and used after typical purification
and drying using molecular sieves.
All alcohols and thiols were obtained commercially with the ex-
ception of N-palmytoil etanolamine, which was prepared according
to the literature procedure.12 Commercially unavailable trimethylsi-
lyl derivatives of alcohols, 1, were obtained by the reaction of the
alcohols (thiols) with trimethylchlorosilane/triethylamine or pyridine
in ether: 3-(trimethylsilyloxy)propenenitryle (1f),13 trimethyl(2,2,2-
trichloroethoxy)silane (1g),14 decyloxytrimethylsilane (1h) [15], ethyl
(R, S)-2-(trimethylsilyloxy)propionate (1i) [16], N-palmitoylethanola-
mine trimethylsilyl ether (1j),17 N-boc-etanolamine trimethylsilyl
ether (1k), trimethylsilyl-(-)ephedrin (1l),18 tris-O, O, O-trimethylsilyl
glycerol (1m),19,20 and tris-S, O, O-trimethylsilyl thioglycerol (1n).
1
3
1j: H NMR (CDCl3): δ = 0.12 [s, 9H, (CH3)3Si], 0.87 (t, JHH = 6.5
Hz, 3H, CH3), 1.20–1.32 [m, 24H, (CH2)12], 1.60[m, 3JHH = 6.5 Hz, 2H,
3
3
CH2CH2C(O)], 2.16 [t, JHH = 6.5 Hz, 2H, CH2C(O)], 3.70 (m, JHH
=
5.2 Hz, 2H, CH2N), 3.63 (t, 3JHH = 5.2 Hz, 2H, CH2O), 5.8 (1H, bs, NH).
1k: 1H NMR (CDCl3): δ = 0,03 [s, 9H, (CH3)3Si], 1.37 [s, 9H,
(CH3)3C], 3.21 (m, 2H, CH2N), 3.92 (m, 2H, CH2O), 4.70 (m, 1H, NH),
7.00-8.23 (4H, arom-H).
1n: 1H NMR (CDCl3): δ = 0.21 [s, 9H, (CH3)3Si], 0.31 [s, 9H,
3
(CH3)3Si], 0.36 [s, 9H, (CH3)3Si], 2.72, 2.89 (2H, AB system, JAB
=
3
12.5 Hz, JHH = 6.0 Hz, CH2S), 3.73, 3.81 (2H, AB system, JAB = 10.2
3
3
3
Hz, JHH = 5.5 Hz, JHH = 4.7 Hz, CH2O), 3.90 – 4.01 (m, JHH = 6.0
Hz, 3JHH = 5.5 Hz, 3JHH = 4.7 Hz, 1H, CH).

952
P. Majewski
1m: 1H NMR (C6D6): δ = 0.19 [s, 18H, (CH3)3Si], 0.27 [s, 9H,
(CH3)3Si], 3.71, 3.79 (AB system, JAB = 10.2 Hz, 3JHH = 5.7 Hz, 3JHH
=
4.8 Hz, 4H, CH2O), 3.93 (m, 3JHH = 5.7 Hz, 3JHH = 4.8 Hz, 1H, CHO).
Dichlorophosphoridites ROPCl2 (3), Chlorophosphoridites
(R1O)(R2O)PCl (4), and Trialkylphosphites (R1O)(R2O)(R3O)P (5),
as Well as Their Analogs (6): General Procedure
The trivalent phosphorus compound containing a P-Cl bond (0.01 mol)
in methylene chloride (15 mL) was treated with the equimolar amount
of alkoxytrimethylsilane under argon at –65◦C. The tube was sealed
and kept at –65◦C for 3 h and then at room temperature for the
time indicated in Tables I and II. After evaporation of the solvent and
trimethylchlorosilane, the crude product was distilled under reduced
pressure or kept under vacuum (45 ◦C, 0.5 h, 0.01 Torr). The results in-
cluding yields, some physical and spectral properties are summarized
in Tables I and II.
1
3h: H NMR (CDCl3): δ = 0.90 (t, JHH = 6.5 Hz, 3H, CH3), 1.29 [m,
14H, (CH2)7], 1.72 (q, JHH = 6.5Hz, 2H, CH2CH2O), 4.25 (m, 3JHH = 6.5
Hz, 3JPH = 7.7 Hz, 2H, CH2O).
1
3
3i: H NMR (CDCl3): δ = 1.25 (t, JHH = 7.0 Hz, 3H, CH3), 1.55 (m,
3JHH = 7.0 Hz, 4JPH = 0.5 Hz, 3H, CH3CH), 4.19 (q, 3JHH = 7.0 Hz, 2H,
CH2O), 5.10 (m, 3JPH = 13.5 Hz, 3JHH = 7.0 Hz, 1H, CHOP).
3j: 1H NMR (CDCl3): δ = 0.92 (t, JHH = 6.7 Hz, 3H, CH3), 1.30
3
[m, 24H, (CH2)12], 1.70 (m, 2H, CH2), 1.85 (m, 2H, CH2), 3.51 (m, 2H,
CH2N), 4.14 (m, 2H, CH2OP), 5.31 (m, 1H, NH).
1
3k: H NMR (CDCl3): δ = 1.45 (s, 9H, CH3), 1.59 (s, 1H, NH), 3.40
3
3
3
(t, JHH = 5.0 Hz, 2H, CH2N), 4.25 (dt, JHH = 5.0 Hz, JPH = 8.3 Hz,
2H, CH2OP), 5.1 (m, 1H, NH).
4a: 1H NMR (CDCl3): δ = 0.81 (t, 3JHH = 6.5 Hz, 3H, CH3), 1.20 [m,
3
14H, (CH2)7], 1.68 (q, JHH = 6.5 Hz, 2H, CH2CH2O), 3.94 (m, JHH
=
6.5 Hz, 3JHH = 7.5 Hz, 2H, CH2O), 4.98 (d, 3JPH = 7.5 Hz, 2H, CH2Ar),
7.27–7.30 (5H, arom-H).
4b: 1H NMR (CDCl3): δ = 1.26 (t, 3JHH = 7.0 Hz, 3H, CH2CH3), 1.28
(d, 3JHH = 7.0 Hz, 3H, CHCH3), 4.19 (q, 3JHH = 7.0 Hz, 2H, CH2OC=O),
4.91 (q, 3JHH = 7.0 Hz, 1H, CHOP), 7.35–7.38 (5H, arom-H).
5a: 1H NMR (CDCl3): δ = 0.81 (t, 3JHH = 6.5 Hz, 3H, CH3), 1.20 [m,
14H, (CH2)7], 1.68 (q, 3JHH = 6.5 Hz, 2H, CH2CH2O), 4.07 (q, 3JHH = 6.5
Hz, 3JPH = 6.5 Hz, 4H, CH2CH2O), 4.81 (d, 3JPH = 7.5 Hz, 4H, CH2Ph),
7.29–7.30 (10H, arom-H).
6a: 1H NMR (CDCl3): δ = 1.38 [s, 9H, (CH3)3C], 3.21 (m, 2H, CH2N),
3.92 (m, 2H, CH2O), 4.70 (m, 1H, NH), 7.00–8.23 (4H, arom-H).

Synthesis of Phosphorodichloridites
953
1
3
6b: H NMR (CDCl3): δ = 0.94 (t, JHH = 6.7 Hz, 3H, CH3), 1.32
3
[m, 24H, (CH2)12], 1.64 [m, JHH = 6.7 Hz, 2H, CH2CH2C(O)], 2.14 [t,
3JHH = 6.7 Hz, 2H, CH2C(O)], 3.44–3.55 (m, 2H, CH2N), 4.08 (m, 2H,
CH2O), 6.0 (br s, 1H, NH), 7.00–8.23 (4H, arom-H).
Reaction of 2-Chlorobenzo(1,3,2)dioxaphosphinin-4-one (7b)
With Tris-O,O,O-trimethylsilylglycerol (1m) and
Tri s - S,O,O-trimethylsilylthioglycerol (1n)
The reaction was carried out as described above in the general proce-
dure. The reaction time in each case was 25 h at –65◦C and then 4 h at
20◦C. The crude product obtained after filtration and evaporation of the
solvent and trimethylchlorosilane has been kept under vacuum (45 ◦C,
0.5 h, 0.01 Torr). The results are summarized in Table III.
1
Isomers 8c and 8d: H NMR (CDCl3): δ = 0.12, 0.13, 0.30 [s, 9H,
(CH3)3Si], 3.75–4.07 (m, 5H, CH2CHCH2), 6.95–8.07 (4H, arom-H). 31
P
NMR (CDCl3): δ = 125.5 (8c), 125.6 (8d), 8c:8d = 5:1.
Hydrolysis of 8c and 8d gave 3-hydroxyphosphinyloxypropane-1,2-
diol (9c) and 2-hydroxyphosphinyloxypropane-1,3-diol (9d).29
Isomers 9c and 9d: 1H NMR (D2O): δ = 3.50–4.05 (m, 5H, CH2-CH-
CH2 of 9a and 9b), 6.60 (d, 1JPH = 643 Hz, 1H, 9a), 6.73 (d, 1JPH = 640
Hz, 1H, 9b). 31P NMR (D2O): δ = 66.4 (9b), 67.6 (9a), 9a:9b = 5:1.
1
Isomers 8e and 8f: H NMR (CDCl3): δ = 0.21, 0.32, 0.41, [s, 9H,
(CH3)3)Si], 2.40–2.75 (m, 2H, CH2S), 3.55–4.09 (m, 3H, CH-CH2), 7.00–
7.45 (4H, arom-H); 31P NMR (CDCl3): δ = 124.9 (8e), 125.4 (8d), 8e:8d
= 5:1.
Hydrolysis of isomers 8e and 8f gave 3-hydroxyphosphinyloxy-2-
hydroxy-1-thiol (9e) and 2-hydroxyphosphinyloxy-3-hydroxypropane-
1-thiol (9f).
1
Isomers 9e and 9f: H NMR (D2O): δ = 2.30–2.65 (m, 2H, CH2S of
9e and 9f), 3.61–4.15 (m, 3H, CH-CH2 of 9e and 9f), 6.65 (d, 1JPH = 6.6
Hz, 14H, 9e), 6.78 (d, JPH = 6.6 Hz, 1H, 9f). 31P NMR (D2O): δ = 6.9
(9f), 8.0 (9e), 9e:9f = 5:1.
Reaction of Trimethylsilyl-(-)-ephedrine with PCl3
in the Presence of Pyridine
To a cooled (–65◦C) chloroform-d solution (0.6 mL) of trimethylsilyl-
(-)-ephedryne (1l) (0.19 g, 0.8 mmol) and pyridine (0.06 g, 0.8 mmol)
in a NMR tube, was added in atmosphere of argon phosphorus trichlo-
ride (0.11 g, 0.8 mmol), and the mixture was kept at –65◦C for 2 h.
Then the mixture was allowed to warm up to 20◦C and was kept at

954
P. Majewski
that temperature for 24 h. During that period, the reaction mixture
was analyzed qualitatively and quantitatively by means of 1H and 31
P
NMR spectroscopy at definite time intervals. The mixture consists of
phosphoroamidodichloridite (10) and oxazaphospholidine (11). The mo-
lar ratio 10:11 changes with time as follows: 15:85 at 1 h, 35:65 at 5
h, 68:32 at 10 h, and 85:15 at 18 h. After 24 h, only compound 11 was
observed. After evaporation of the solvent, hexane (2 mL) was added to
the residue, and the mixture was filtered. The filtrate was evaporated
to give analytically pure 11 as oil. Yield 99.5%.
When a similar experiment was interrupted at the point when the
temperature of the reaction mixture had reached 20◦C, it was possible
in an analogous manner to isolate the phosphoroamidodichloridite 10
contaminated with the oxazaphospholidine 11 (7 mol %). Yield 98.2%.
1
3
10: H NMR (CDCl3): δ = 0.00 [s, 9H, (CH3)Si], 1.26 (m, JHH = 7.5
Hz, 4JPH = 2.5 Hz, 3H, CHCH3), 2.70 (d, 3JPH = 5.0 Hz, 3H, NCH3), 3.70
3
3
3
(m, JPH = 16.2 Hz, JPH = 7.5 Hz, JHH = 5.0 Hz, 1H, CHN), 4.60 (d,
3JHH = 5.0 Hz, 1H, CHO), 7.20–7.41 (5H, arom-H). 13C NMR (CDCl3):
δ = –0.33 [s, Si(CH3)3], 14.2 (d, 3JPC = 9.9 Hz, CHCH3), 29.2 (d, 2JPC
=
1.7 Hz, NCH3), 63.5 (d, 2JPC = 38.6 Hz, NCH3), 77.0 (d, 3JPC = 5.7 Hz,
CHOSiMe3), 126.4, 127.4, 127.8, 127.9 (s, arom-C). 31P NMR (CDCl3):
δ = 162.7.
11: 1H NMR (CDCl3): δ = 0.68 (d, 3JHH = 6.5 Hz, 3H, CHCH3), 2.66
(dd, 3JPH = 16.0 Hz, 4JHH = 2.7 Hz, 3H, NCH3), 3.62 (m, 3JHH = 6.5 Hz,
3JHH = 8.0 Hz, JPH = 7.0 Hz, 1H, CHCH3), 5.78 (dd, JHH = 8.0 Hz,
3
3
3JPH = 1.0 Hz, 1H, CHO), 7.19–7.32 (5H, arom-H). 13C NMR (CDCl3):
3
2
δ = 14.0 (d, JPC = 5.3 Hz, CHCH3), 28.5 (d, JPC = 14.0 Hz, NCH3),
57.5 (d, 2JPC = 6.7 Hz, NCH3), 87.3 (d, JPC = 9.1, CHO), 126.5, 127.0,
2
127.8, 127.9 (s, arom-C). 31P NMR (CDCl3): δ = 171.6.
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