COMMUNICATION
Synthesis and reactivity of O-acyl selenophosphates{
Janusz Rachon,* Grzegorz Cholewinski and Dariusz Witt
Received (in Cambridge, UK) 17th February 2005, Accepted 21st March 2005
First published as an Advance Article on the web 12th April 2005
DOI: 10.1039/b502473k
anhydrides containing electron-withdrawing (2d) and electron-
The synthesis of several new O-acyl selenophosphates were
investigated. The stability and reactivity of the products were
studied and related to their structure.
donating (2c) groups attached to their carboxyl functionalities
could not be isomerised to a corresponding 3 derivative, whereas
this was seen for compounds 2a and 2e. This observation excludes
the possibility that the isomerisation takes place via an ionic
mechanism.
O-acyl dithiophosphates are unstable and isomerise to O-thioacyl
monothiophosphates and S-acyl monothiophosphates. Treatment
of the above mixture with dithiophosphoric acid gives exclusively
S-acyl dithiophosphates. These compounds have proved to be
efficient, chemoselective thioacylating agents.1 So far however, the
mechanism of the isomerisation has remained undetermined.
Organoselenium compounds play an important role in biologi-
cal processes2,3 and their synthesis has been intensively studied.4
The synthesis of the selenium analogues of mixed anhydrides,
followed by an investigation of their thermodynamic stability and
reactivity, may lead to new and interesting reagents.
When a mixture of anhydrides 2h and 2o were stirred together at
room temperature overnight, acyl group exchange was observed
that lead to the formation of all possible anhydrides (2g, 2h, 2o and
2p). Moreover, there was no isomerisation of these anhydrides
either in the mixture or separately (Table 1, entries 7, 8, 15, and
16). When a mixture of 2b and 2k was stirred overnight, acyl
exchange again occurred and anhydrides 2a, 2b, 2k, and 2l were
formed. In this case however, isomerisation was observed in the
mixture and derivatives 3a, 3b, 3k and 3l were formed
respectively—similar to the behaviour of the separate anhydrides
(Table 1, entries 1, 2, 11, and 12). As can be seen, the rapid acyl
group exchange of type 2 compounds is responsible for the
formation of crossover products 3a and 3l. The most interesting
behaviour of all was observed for two mixtures; one of 2b and 2o,
and the other of 2k and 2p. Upon acyl group exchange, all possible
anhydrides were observed. However in these mixtures, only 3b plus
3a and 3k plus 3l were formed respectively. We can therefore
conclude (i) acyl group exchange is more rapid than isomerisation
and (ii) isomerisation of one type 2 anhydride cannot initiate the
isomerisation of another (i.e. there is no entrainment effect).
In the next stage of the study we took further steps to verify our
proposed isomerisation mechanism. Our working hypothesis
assumed O–C(O) bond homolysis and formation of monoseleno-
phosphoric and carbonyl radicals. Further recombination via
selenium could thus afford the isomeric derivatives 3.
To the best of our knowledge, O-acyl selenophosphates 2 have
not been the subject of systematic studies. Nonetheless, the
reaction of monoselenophosphoric acid salts 1 with acyl chlorides
has been reported to yield O-acyl derivatives 2 exclusively,5 even
though monoselenophosphoric acid salts 1 are ambidentate
nucleophiles.
We have synthesized a wide range of mixed anhydrides: O-acyl
monoselenophosphates, monoselenophosphonates and monosele-
nophosphinites 2, and also investigated their thermodynamic
stability and reactivity (Scheme 1).
The results of our experiments are presented in Table 1.
Syntheses of type 2 compounds were complete after 15 min at
room temperature in THF solvent. Subsequently, we observed that
some mixed anhydrides of type 2 isomerised to their Se-acyl
1
derivatives 3. The diagnostic 31P NMR coupling constant JP–Se
was useful for monitoring the isomerisation process.6 The yield of
isomerised product depended on the substituents at the P and Cacyl
atoms (see Table 1). Cyclic derivatives 2a–b, 2e–f (entries 1, 2, 5
and 6) displayed higher degrees of isomerisation than acyclic
derivatives 2k–n (entries 11–14). Higher yields of Se-acyl
derivatives 3 were observed for alkyl carboxylic acid mixed
anhydrides 2b, 2f and 2l (entries 2, 6, 12) than for aryl carboxylic
acid mixed anhydrides 2a, 2e and 2k (entries 1, 5, 11). The
We therefore performed the reactions of monoselenophosphoric
acid salt 1a with various chloroformates (Scheme 2 and Table 2,
R3 5 alkoxy or aryloxy). 31P NMR analysis of the crude reaction
mixtures indicated that Se-alkoxycarbonyl-monoselenophosphates
5
were the major products together with traces of
O-alkoxycarbonyl-monoselenophosphates 4. This means that
isomerisation is very rapid and occurs upon formation of the type
4 compound.
Surprisingly, in the reaction of salt 1a with benzyl chlorofor-
mate, the Se-benzyl ester 6a was obtained, probably via
decarboxylation of 4a or 5a. 5a was also detected and isolated
from the reaction mixture (Table 2). The formation of 6a in the
mixture supports the hypothesis of O–C(O) bond homolysis. The
benzyloxycarbonyl and monoselenophosphoric radicals can react
together to give compound 5a, or undergo decarboxylation to give
a benzyl radical. This radical may then react with 4 or a
monoselenophosphoric radical to afford 6a. Decarboxylation of
the benzyloxycarbonyl radical is very rapid,7 meaning the
Scheme 1 The synthesis of mixed anhydrides of types 2 and 3.
{ Electronic Supplementary Information (ESI) available: Experimental
conditions and characterisation of all presented compounds. See http://
*rachon@chem.pg.gda.pl
2692 | Chem. Commun., 2005, 2692–2694
This journal is ß The Royal Society of Chemistry 2005
Rachon, Janusz
