Phosphorus compounds and methods thereof
The disclosure concerns phosphorus compounds of formula (I), (II) and (III) and methods of synthesising these compounds. The phosphorus compound can be a cyclic phosphorus compound. The method comprises reacting a compound having two Michael acceptor groups with a hypophosphite ester, acid, salt or solvate thereof and an optional organosilicon compound. The diene can be a cyclodiene.
1 . A method of synthesising a phosphorus compound of Formula (I), a salt, solvate or isomer thereof:
wherein Y is selected from an optionally substituted C 1-10 alkylene, optionally substituted C 1-10 alkenylene, optionally substituted silylene, optionally substituted aminoylene, acylene, thioacylene, sulfinylene, sulfonylene, —P(O)(OZ)— or —P + (R 9 R 10 )—;
Z is selected from H, optionally substituted alkyl or a metal cation;
R 1 , R 2 , R 7 and R 8 are independently selected from oxo, halo, optionally substituted alkyl; optionally substituted alkenyl; optionally substituted haloalkyl; optionally substituted alkynyl; optionally substituted oxyalkyl; optionally substituted amino, optionally substituted thio, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocyclyl, optionally substituted heteroaryl, and optionally substituted aryl;
wherein R 1 and R 5 can be linked to form an optionally substituted cycloalkyl;
R 3 , R 4 , R 5 , and R 6 are independently selected from H, oxo, halo, optionally substituted alkyl;
optionally substituted alkenyl; optionally substituted haloalkyl; optionally substituted alkynyl;
optionally substituted oxyalkyl; optionally substituted amino, optionally substituted thio, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocyclyl, optionally substituted heteroaryl, and optionally substituted aryl;
R 9 and R 10 are independently selected from H, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloyl, optionally substituted aryl, optionally substituted heteroaryl;
the method comprising:
a) reacting a compound of Formula (A) with a hypophosphite ester, acid, salt or solvate thereof and an optional organosilicon compound, the compound of Formula (A) is
wherein Y is selected from an optionally substituted C 1-10 alkylene, optionally substituted C 1-10 alkenylene, optionally substituted silylene, optionally substituted amino, acylene, thioacylene, sulfinylene, sulfonylene, —P(O)(OZ)— or —P + (R 13 R 14 )—;
wherein R 1 , R 2 , R 7 and R 8 are independently selected from oxo, halo, optionally substituted alkyl;
optionally substituted alkenyl; optionally substituted haloalkyl; optionally substituted alkynyl;
optionally substituted oxyalkyl; optionally substituted amino, optionally substituted thio, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocyclyl, optionally substituted heteroaryl, and optionally substituted aryl;
wherein R 1 and R 8 can be linked to form an optionally substituted cyclo moiety;
R 3 and R 5 are independently selected from H, oxo, halo, optionally substituted alkyl; optionally substituted alkenyl; optionally substituted haloalkyl; optionally substituted alkynyl; optionally substituted oxyalkyl; optionally substituted amino, optionally substituted thio, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocyclyl, optionally substituted heteroaryl, and optionally substituted aryl; and
wherein R 13 and R 14 are independently selected from H, optionally substituted C 1 -C 10 alkyl, optionally substituted C 3 -C 10 cycloalkyl, optionally substituted C 3 -C 10 heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl.
2 . The method according to claim 1 , wherein the hypophosphite ester, acid, salt or solvate thereof is selected from hypophosphorous acid (H 3 PO 2 ), ammonium hypophosphite (NH 4 H 2 PO 2 ) and sodium hypophosphite (NaPO 2 H 2 ), potassium hypophosphite, calcium bis (hypophosphite), copper hypophosphite, nickel (II) bis (hypophosphite), magnesium hypophosphite, anilinium hypophosphite, methyl hypophosphite, ethyl hypophosphite, or a combination thereof.
3 . The method according to claim 1 , wherein the organosilicon compound is selected from bis(trimethylsilyl)amine (HMDS), N,N-Bis (trimethylsilyl)methylamine, bis(dimethylamino)dimethylsilane, N,O-bis(trimethylsilyl)acetamide (BSA), N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA), N,N-dimethyltrimethylsilylamine, hexamethyldisiloxane, N,N-diethyltrimethylsilylamine 1-(trimethylsilyl) pyrrolidine trimethylsilyl chloride (TMSCl), trimethylsilyl bromide (TMSBr), chlorotriethylsilane, and a combination thereof.
4 . The method according to claim 1 , wherein a molar ratio of hypophosphite ester, acid, salt or solvate thereof to the organosilicon compound is about 1:10 to about 1:1.
5 . The method according to claim 1 , wherein the step of reacting a compound of Formula (A) with the hypophosphite ester, acid, salt or solvate thereof and the organosilicon compound further comprises a base.
6 . The method according to claim 5 , wherein the base is selected from triethylamine, diethylamine, Hünigs base, pyrrolidine, pyridine, lutidine, piperidine 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,4-diazabicyclo[2.2.2]octane (DABCO), sodium hydroxide, potassium hydroxide, ammonium hydroxide, sodium carbonate, sodium hydrogen carbonate, barium hydroxide, calcium carbonate, caesium carbonate, or a combination thereof.
7 . The method according to claim 1 , wherein the step of reacting a compound of Formula (A) with the hypophosphite ester, acid, salt or solvate thereof and the organosilicon compound further comprises a solvent, wherein the solvent is selected from tetrahydrofuran (THF), toluene, xylenes, methylene chloride, dichloroethane, tetrachloroethane, ethers, dimethylacetamide (DMA), or a combination thereof.
8 . The method according to claim 1 , the method further comprises a step of treating a product of step (a) with an acid.
9 . The method according to claim 1 , wherein the compound of Formula (A) is reacted with the hypophosphite ester, acid, salt or solvate thereof and the organosilicon compound at a temperature of about 70° C. to about 150° C.
10 . The method according to claim 1 , the method further comprises a step (b) after (a) of modifying the compound of formula (I) at the Y moiety.
11 . The method according to claim 1 , the method further comprises a step (b) after (a) of modifying the compound of formula (I) with a protecting group compound.
12 . The method according to claim 11 , wherein the protecting group compound is selected from ethylene glycol, methanol, ethanol, propylene glycol, 2,2-dimethyl-1,3-propanediol (neopentylglycol), dimethyl hydrazine, 1,2-ethanedithiol and 1,3-propanedithiol.
13 . The method according to claim 1 , the method further comprises a step of reducing the compound of formula (I).
14 . The method according to claim 1 , the method further comprises a step reducing the phosphorus compound of Formula (I) in order to form a phosphorus compound of Formula (II):
wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 and Y are as disclosed herein.
15 . The method according to claim 1 , the method further comprises of functionalising the compound of Formula (II) in order to form a phosphorus compound of Formula (III):
wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 and Y are as disclosed herein;
R 15 is selected from halo, oxo, optionally substituted amino, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl.
16 . The method according to claim 15 , wherein the optional substituent at R 15 comprises another compound of Formula (III).
17 . The method according to claim 15 , wherein the optional substituent at R 15 is selected from:
wherein represents a bond to R 15 of compound of Formula (III).