Synthesis and chemical properties of benzo[e]-1,2-oxaphosphorinine derivatives - Analogues of coumarins

Article abstract of DOI:10.1080/10426500701764957

The 4-aryl(alkyl)benzo[e]-1,2-oxaphosphorine derivatives (phosphacoumarins) were obtained by the reaction of 2,2,2-trihalogenobenzo[d]-1,3,2- dioxaphospholes with terminal acetylenes. The reactions of phosphacoumarins with halogens and Grignard reagents w

Full text of DOI:10.1080/10426500701764957

Phosphorus, Sulfur, and Silicon, 183:566–570, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500701764957
Synthesis and Chemical Properties of
Benzo[e ]-1,2-Oxaphosphorinine
Derivatives—Analogues of Coumarins
E. N. Varaksina, D. A. Tatarinov, K. Yu. Cherkin,
A. V. Nemtarev, V. F. Mironov, and A. I. Konovalov
A. E. Arbuzov Institute of Organic and Physical Chemistry, Russian
Academy of Sciences, Russia
The 4-aryl(alkyl)benzo[e]-1,2-oxaphosphorine derivatives (phosphacoumarins)
were obtained by the reaction of 2,2,2-trihalogenobenzo[d]-1,3,2-dioxaphospholes
with terminal acetylenes. The reactions of phosphacoumarins with halogens and
Grignard reagents were investigated.
Keywords 2,2,2-trihalogenobenzo-1,3,2-dioxaphosphole; acetylene; alkenylphosphine
oxide; Grignard reagent; phosphacoumarin; phosphorinine
INTRODUCTION
We have earlier shown that the interaction of 2,2,2-trihalogenobenzo[d]-
1,3,2-dioxaphospholes with arylacetylenes unexpectedly gives the 4-
aryl-2,6-dihalogenobenzo[e]-1,2-oxaphoshorinines,1 which are the P-
analogues of natural coumarins.2 It was found that some highly se-
lective transformations, such as P C bond and phosphoryl group for-
mation, unusually easy ipso-substitution of the phenylene oxygen, and
at last, chlorination of the phosphole’s benzene fragment takes place
under mild conditions. In this connection, the mentioned above reac-
tion is of considerable interest not only for the synthetic utilization in
the phosphorus chemistry, but also as a versatile approach to the rare
P-heterocyclic systems, which are P-analogues of the biologically active
compounds (coumarins).
We have also shown that the 5-chloro- and 5-bromo-3 5,6-dibromo-,4
and 5-methyl-2,2,2-trihalogenobenzo[d]-1,3,2-dioxaphospholes5 easily
The work was supported by Russian Foundation for Basic Research (grant 07-
03-00180a), Russian Federation Program for Young Scientist Support (grant MK-
1434.2006.3) and Russian Science Support Foundation.
Address correspondence to E. N. Varaksina, A. E. Arbuzov Institute of Organic and
Physical Chemistry, Russian Academy of Sciences, Russia. E-mail: minorov@iopc.knc.ru
566

Synthesis and Chemical Properties of Benzo[E]-1,2-Oxaphosphorinine Derivatives567
react with arylacetylenes with the formation of the substituted
benzo[e]-1,2-oxaphoshorinine derivatives with a high regioseletivity of
all the processes mentioned above.
To determine the synthetic scope of the reaction the other types
of acetylenes—sterically hindered naphthylacetylene, ordinary alky-
lacetylenes such as hex-1-yne were involved in the reaction with 2,2,2-
trichlorophosphole 1.
It was found, that the phosphole 1 easily reacts with naphthy-
lacetylene in methylene chloride used as a solvent. According to 13C
NMR spectrum only two phosphorus containing compounds in the ra-
tio 2:3 are formed, which are the diastereoisomers. This phenomena
is caused by the fact that molecule of 2,6-dichloro-4-naphthylbenzo[e]-
1,2-oxaphoshorinine 2 has asymmetric phosphorus atom and exhibits
the athropoisomerism due to a hindered rotation around the C4–C9
bond. The diastereoisomerism disappears after hydrolysis of compound
2 (phosphorus atom in compound 3 is non-chiral) (Scheme 1).
SCHEME 1
The reaction of hex-1-yne with 1 leads to the formation of two
benzo[e]-1,2-oxaphosphorinines 4, 5 in the 9 : 1 ratio (Scheme 2). The
minor product contains a chlorine atom in ortho-position to endocyclic
oxygen atom. Corresponding hydroxy-derivatives 6 and 7 were isolated
by the fractional crystallization.
SCHEME 2
So,
the
reaction
of
the
2,2,2-trihalogenobenzo[d]-1,2,3-
dioxaphospholes with various acetylenes is a selective and versatile
approach to the rare benzo[e]-1,2-oxaphoshorinines with the alkyl,
aryl, naphtyl substituents in the heterocyclic fragment.

568
E. N. Varaksina et al.
The influence of the phosphorus nature of the phosphole on the course
of the reaction was also investigated. The reaction of the hexacoor-
dinated species 8 with phenylacetylene or hexyne mainly yields the
para-chlorinated to endocyclic oxygen phosphorinines 9, which were
converted into the stable compounds 10 (Scheme 3).
SCHEME 3
The anionic tetrachlorophenylendioxaphosphate 11, which was also
obtained from phosphole 1, selectively forms with acetylenes isomers
12 meta-chlorinated to the endocyclic oxygen in the same conditions.
The phosphonic acids 13 were isolated after hydrolysis of compounds
12 (Scheme 4).
SCHEME 4
The reactions of phosphonium salts 14 unexpectedly leads only to
the formation of cis- and trans- isomers 15 and 16, which are obtained
as the products of a classical electrophilic addition, both in the reaction
with phenylacetylene and hex-1-yne (Scheme 5).
The chemical properties of phosphorinines were investigated for the
first time. The reactions with halogenating agents—phosphorus pen-
tachloride, chlorine, and bromine—were carried out. It turned out, that
the reaction of phosphorinine 9a with phosphorus pentachloride is of
multistage character. At the initial stage, the chlorination of phospho-
ryl group with the formation of phosphorane 17 was observed by the
31P NMR (Scheme 6). An excess of phosphorus pentachloride easily
converts compound 17 into phosphonium derivative 18.

Synthesis and Chemical Properties of Benzo[E]-1,2-Oxaphosphorinine Derivatives569
SCHEME 5
SCHEME 6
The reaction of compound 9a with an excess of chlorine in of methy-
lene chloride gives the addition product 19 as a mixture of two di-
astereoisomers (Scheme 7). The structure of the compound was un-
ambiguously determined by 13C, 13C-1H NMR. The hydrogen chloride
can be eliminated by the prolonged heating, hydrolysis, and aminoly-
sis. The resulting 3-chlorosubstituted phosphorinines 21 and 22 were
obtained and characterized by the NMR.
SCHEME 7
3-Bromosubstituted phosphorinine 23 was obtained by the reaction
of phosphorinine 9a with bromine. In this case, the intermediate ad-
dition product, like compound 19 was not detected by the 31P NMR
(Scheme 8).

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E. N. Varaksina et al.
SCHEME 8
The resulting benzo[e]-1,2-oxaphoshorinine can be selectively halo-
genated, that will allow to use them for the further modification in the
palladium-catalyzed cross-coupling reactions.
SCHEME 9
It was recently found, that the reaction of chlorophosphorinine 9a
with equimolar amount of phenylmagnesium chloride leads to the
mixture of phenyl-substituted phosphorinine 27 and acyclic derivative
26. When an excess of the Grignar reagents is used the alkenylphosphi-
neoxides can be obtained with the quantitative yield. The compounds
like phosphineoxides 25 and 26 are very perspective as the complexing
and extracting reagents (Scheme 9).
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