phosphonate and a-hydroxyphosphonate moieties have been
described as phosphate mimics with stable C–P linkages, some
of them exhibiting important biological properties.23 Aldehyde
19 was easily obtained from commercially available 1,2:3,4-di-O-
isopropylidene-a-D-galactopyranose 18 by oxidation mediated
by Dess–Martin periodinane (Scheme 2).24
In conclusion, we have developed an environmentally friendly
and high-yielding procedure for the nucleophilic addition of
phosphines and dialkyl phosphites on a series of electrophiles,
using inexpensive CaO under mild and solventless conditions.
The reactions proceed following a general trend by which
simple and a,b-unsaturated carbonyls give exclusively the 1,2-
addition reaction. Conversely, methyl acrylate and vinyl sulfone
regioselectively lead to the 1,4-addition process. This green
procedure was also successfully applied to sugar aldehydes to
afford carbohydrate-derived a-hydroxyphosphonates.
Experimental
General method for the addition of diphenylphosphine and
diethyl phosphite to unsaturated derivatives
Calcium oxide (1.0 mmol) was added to a mixture of
1–8,19 (1.0 mmol) and diphenyl phosphine or diethyl phosphite
(1.0 mmol). The corresponding mixture was stirred at rt for
3–72 h, EtOAc (or EtOH for 8) was added, and the suspension
was filtered through a Celite pad. The filtrate was concentrated
to dryness and purified by column chromatography to give
compounds 9–17,20 in 49–91% yields.
Scheme 2 Addition of diethyl phosphite to carbohydrate-derived
aldehyde 19.
Treatment of 19 with diethyl phosphite in the presence of
CaO (1.0 equiv.) led to the formation of 6-C-phosphonate
20, obtained as a non-resolved mixture of diastereoisomers
in a 4.5 : 1 ratio, as deduced from 1H-NMR spectrum. The
Acknowledgements
o
pyranose ring of both isomers adopts the S2 conformation,25
Financial support from the University of Camerino, MIUR,
the Integrated Action HI-2006-0131, the Direccio´n General de
Investigacio´n of Spain, and the Junta de Andaluc´ıa (Grants
CTQ2008-02813 and FQM 134) is gratefully acknowledged.
E.M.-C. thanks MICINN for a grant.
as deduced from the vicinal coupling constants. Assignment
of the configuration at C-6 was carried out by studying the
conformational preference around the C5–C6 bond (Fig. 1).
Notes and references
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Fig. 1 Conformational preference for hydroxyphosphonate 20.
3
The high values of the coupling constants JC4,P (8.8 Hz)
and 3JP,OH (24 Hz) for the minor diastereoisomer, together with
3
the low value for J5,6 (4.8 Hz) is in agreement with the 6S
configuration and a preferred gg conformation26 around the
C5–C6 bond, stabilized by an O6–H ◊ ◊ ◊ O4 hydrogen bond. For
the major 5R configuration, equilibrium between the gg and tg
staggered conformations can be deduced.
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