SODIUM HYPOPHOSPHITE 1
Me Me
Sodium Hypophosphite
N N
N N
NaH2PO2, Raney Ni
(2)
NaH2PO2
Et py, H2O, AcOH Et
CN CHO
64%
CO2-t-Bu CO2-t-Bu
[7681-53-0] H2NaO2P (MW 87.98)
(4)(5)
InChI = 1/Na.H3O2P/c;1-3-2/h;3H2,(H,1,2)/q+1;/p-1/
fNa.H2O2P/qm;-1
InChIKey = SIGUVTURIMRFDD-NFDKWQDSCG
Hydrophosphorylation of Alkenes. Terminal alkenes (6),
when treated with sodium hypophosphite in the presence of
(source of hydrogen in heterogeneous catalytic transfer reduc-
Azobisisobutyronitrile, yield phosphonous acids (7) (eq 3).11
tions;1 10 synthesis of phosphonous acids via hydrophospho-
rylation of terminal alkenes11)
Physical Data: decomposes upon strong heating with release of
O
NaH2PO2, AIBN
phosphine, which is highly flammable in air.
P
R OH (3)
R
Solubility: sol water, alcohol; insol ether.
H2SO4, EtOH H
Form Supplied in: monohydrate, white solid.
(6)(7)
Handling, Storage, and Precautions: explodes when triturated
with chlorates or other oxidizing agents.
1. Boyer, S. K.; Bach, J.; McKenna, J.; Jagdmann, E. Jr., J. Org. Chem.
Functional Group Reductions. Sodium hypophosphite is
1985, 50, 3408.
a very effective and mild hydrogen-transfer reagent capable of
2. (a) Johnstone, R. A.; Wilby, A. H., Tetrahedron 1981, 37, 3667.
reducing a wide range of functional groups when utilized with
(b) Brienne, M.-J.; Varech, D.; Leclercq, M.; Jacques, J.; Radembino,
the appropriate catalyst. The reductions of aldehydes to alcohols,1 N.; Dessalles, M.-C.; Mahuzier, G.; Gueyouche, C.; Bories, C.; Loiseau,
P.; Gayval, P., J. Med. Chem. 1987, 30, 2232.
alkynes to alkenes,2 azides to amines,1 benzoquinones to dihydro-
3. Entwistle, I. D.; Johnstone, R. A. W.; Telford, R. P., J. Chem. Res. (S)
benzoquinones,3 epoxides to alcohols,1 alkyl or aryl halides to
1977, 117.
alkanes or arenes,1,4 ketones to alcohols,1 nitriles to aldehydes,5
4. Sauer, G.; Heindl, J.; Wachtel, H., Tetrahedron Lett. 1988, 29, 6425.
nitroalkenes to oximes,6 nitroarenes to aryl amines,7 N-oxides to
5. (a) Backeberg, O. G.; Staskun, B., J. Chem. Soc. 1962, 3961.
amines,1 alkenes to alkanes,8 oximes to ketones,1,9 and phenols to
(b) Compagnone, R. S.; Rapoport, H., J. Org. Chem. 1986, 51, 1713.
arenes,10 as well as the hydrogenolysis of benzylic ethers,1 have
6. (a) Davey, D. D.; Lumma, W. C., Jr., J. Org. Chem. 1989, 54, 3211.
all been effected. Reactions have been carried out in solvent sys-
(b) Varma, R. S.; Varma, M.; Kabalka, G. W., Synth. Commun. 1986, 16,
tems ranging from aqueous to anhydrous organic solvents, typ-
91.
ć%
ically at elevated temperatures (50 75 C), with excess sodium
7. (a) Entwistle, I. D.; Jackson, A. E.; Johnstone, R. A. W.; Telford, R. P., J.
hypophosphite and most often Palladium on Carbon as the cata-
Chem. Soc., Perkin Trans. 1 1977, 443. (b) Best, W. M.; Wege, D., Aust.
lyst. Reaction workup generally involves filtration of the catalyst,
J. Chem. 1986, 39, 647. (c) Entwistle, I. D., Tetrahedron Lett. 1979, 555.
extraction if appropriate, and removal of solvent.
8. Sala, R.; Doria, G.; Passcarotti, C., Tetrahedron Lett. 1984, 4565.
Studies on polyfunctional molecules have shown the reduction
9. Monti, D.; Gramatica, P.; Speranza, G.; Taglapietra, S.; Manitto, P.,
to be tunable; while treatment of cinnamonitrile (1) with sodium
Synth. Commun. 1986, 16, 803.
hypophosphite and 5% Pd/C yields 87% of dihydrocinnamoni-
10. (a) Entwistle, I. D.; Hussey, B. J.; Johnstone, R. A. W., Tetrahedron Lett.
trile (2),1 reduction with sodium hypophosphite and Raney Nickel
1980, 21, 4747. (b) Brigas, A. F.; Johnstone, R. A. W., Tetrahedron Lett.
gives only cinnamaldehyde (3)5 (eq 1). A more profound demon- 1990, 31, 5789.
stration of selectivity is seen in the conversion of (4) to(5) (eq 2),
11. (a) Karanewsky, D. S.; Badia, M. C.; Cushman, D. W.; DeForrest, J.
intermediates in the synthesis of (+)-pilocarpine.5b M.; Dejenka, T.; Loots, M. J.; Perri, M. J.; Petrillo, E. W., Jr.; Powell,
J. R., J. Med. Chem. 1988, 31, 204. (b) Nifant ev, E. E., Magdeeva, R.
CN
K.; Shchepet eva, N. P., J. Gen. Chem. USSR (Engl. Transl.) 1980, 50,
NaH2PO2 Ph NaH2PO2
1416. (c) Nifante ev, É. E.; Korateev, M. P., J. Gen. Chem. USSR (Engl.
Raney Ni 5% Pd/C
(1)
(1)
Transl.) 1967, 37, 1293.
CHO CN
Ph Ph
Jeffrey O. Saunders
(3) (2)
Vertex Pharmaceuticals, Cambridge, MA, USA
Avoid Skin Contact with All Reagents