710
Short Papers
SYNTHESIS
A Convenient Synthesis of 4-Halo-3-(hydroxymethyl)-2,5-dihydro-1,2-oxaphospholes
Valery K. Brel
Institute of Physiologically Active Compounds of Russian Academy of Science, Chernogolovka, Moscow region, 142432, Russia
E-mail: brel@ipac1.sherna.msk.su
Received 5 September 1997; revised 29 October 1997
Dedicated to Professor Ron Caple on the occasion of his 60th birthday
Abstract: Several 5-alkyl-2-ethoxy-4-halo-3-(hydroxymethyl)-5-
methyl-2-oxo-2,5-dihydro-1,2-oxaphospholes 5a–f were synthe-
sized by a simple and efficient four-step procedure starting from
propargyl alcohol.
Key words: propargyl alcohol, phosphorylated allenes, phospho-
nic heterocycles
The unusual system comprising of interlinked unsaturated
centers, differing in properties and reactivity, in mole-
cules of phosphorylated allenes as well as the ready avail-
ability of these compounds and the wide variety of
chemical reactions based on them have long attracted the
attention of chemists.1,2 Phosphorylated allenes have
been widely used as building blocks in organic chemis-
try.3 It is known that these compounds react with halo-
gens,4 protic acids,5 sulfenyl chlorides,6 selenenyl
chlorides,7 potassium dichloroiodate (KICl2)8 and N,N-di-
ethylbenzeneselenenylamide (in the presence of pyridine/
SO3)9 with the formation of unsaturated heterocyclic
compounds10 due to the participation of the phosphoryl
oxygen atom as an internal nucleophile in the final step of
the addition (Scheme 1).
Scheme 2
Scheme 1
Phosphorylated allenes 4a–c were prepared directly from
alcohols 3a–c in 64–86% yield by Horner–Mark [2,3]sig-
matropic rearrangement of the unstable phosphites gener-
ated in situ by reaction with diethyl chlorophosphite in the
presence of triethylamine in diethyl ether at –40°C and
then kept at 20°C. Compounds 4a–c were stable enough
to be handled at ambient temperature. The reactions of al-
lenes 4a–c with bromine and chlorine were carried out in
carbon tetrachloride at low temperature (–25 or –20°C).
The hydroxy group was deprotected by stirring the meth-
anol solution of the reaction mixture in the presence of
HCl, at room temperature. Analytically pure 2,5-dihydro-
1,2-oxaphospholes 5a,c,d,f were isolated as colorless or
pale yellow oils by column chromatography on silica gel.
Products 5b and 5e were isolated as colorless crystals.
2,5-Dihydro-1,2-oxaphospholes 5b,c,e,f are a mixture of
In continuation of earlier work on the synthesis of 1,2-,
1,3-alkadienes,11 and in connection with our ongoing in-
terest in developing new synthetic strategies for the con-
struction of phosphonic heterocycles,12 we present herein
a convenient synthesis of new 2,5-dihydro-1,2-oxaphos-
pholes. Our aim was to synthesize 4-halo-3-(hydroxy-
methyl)-2,5-dihydro-1,2-oxaphospholes, new phosphonic
heterocycles with hydroxymethyl groups.
2,5-Dihydro-1,2-oxaphospholes bearing a hydroxymethyl
group at C-3 position 5a–f were synthesized by the fol-
lowing sequence (Scheme 2). Propargyl alcohol was pro-
tected by reaction with ethyl vinyl ether to afford the ether
2 in nearly quantitative yield. This compound could be
isolated in 85% yield by distillation over anhydrous potas-
sium carbonate. The alkynols 3a–c were prepared in 68–
72% yield. The corresponding magnesium derivative re-
acted at 0–15 °C with carbonyl compounds to afford the
corresponding products 3a–c without any deprotection of
the primary alcohol.
E- and Z-isomers in ~1:1 ratio as indicated by 1H and 31
P
NMR.
Compounds 5a–f were identified by IR,1H and 31P spec-
tral data (Table 1). In IR spectra all compounds 5a–f show
the double bond, P=O and OH groups absorption at 1626–
1632 cm–1, 1250–1258 cm–1 and 367l–3593 cm–1 respec-
Brel, Valery K.
