N-Heterocyclic Phosphines

A method of making a vinylphosphonate having a structure represented by a formula:

• wherein Q is selected from O, S, and NR26;
• wherein R26, when present, is selected from hydrogen and C1-C8 alkyl;
• wherein each of XA and XB is independently selected from NR1, O, and S;
• wherein each occurrence of R1, when present, is independently selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-C10 aryl, —(C1-C3 alkyl)(C6-C10 aryl), and 4-10 membered heteroaryl, and wherein each occurrence of R1, when present, is independently substituted with 0, 1, 2, 3, or 4 independently selected R5 groups;
• wherein each of RX and RY is independently selected from hydrogen, C6-C10 aryl, and 4-10 membered heteroaryl, or wherein each of RX and RY are optionally covalently bonded together and, together with the intermediate carbon atoms, comprise a 5- to 7-membered cycloalkyl or 5- to 7-membered aryl;
• wherein RA is an electron withdrawing group;
• wherein RB is selected from hydrogen, C1-C6 alkyl, C2-C6 alkylene, C3-C10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-C10 aryl, —(C1-C3 alkyl)(C6-C10 aryl), and 4-10 membered heteroaryl, and wherein RB is substituted with 0, 1, 2, 3, or 4 independently selected R6 groups;
• and
• wherein each of RC and RD is independently selected from hydrogen, C1-C6 alkyl, C3-C10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-C10 aryl, and 4-10 membered heteroaryl, and wherein each of RC and RD is independently substituted with 0, 1, 2, 3, or 4 independently selected R6 groups, or wherein each of RC and RD are optionally covalently bonded together and, together with the intermediate carbon atoms, comprise a 3- to 10-membered cycloalkyl;
• wherein each occurrence of R5, when present, is independently selected from halogen, —NO2, —CN, —OH, —SH, —NH2, C1-C3 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C3 haloalkyl, C1-C3 cyanoalkyl, C1-C3 hydroxyalkyl, C1-C3 haloalkoxy, C1-C3 alkoxy, C1-C3 thioalkyl, C1-C3 alkyl(C1-C3 alkoxy), C1-C3 alkylamino, (C1-C3)(C1-C3) dialkylamino, C3-C7 cycloalkyl, C6-C10 aryl, —(C═O)(C1-C3 alkyl), —(S═O)(C1-C3 alkyl), —SO2(C1-C3 alkyl), —CO2R11, —(C═O)NR12aR12b, —SO2NR12aR12b, —O(C═O)NR12aR12b, —NHSO2NR12aR12b, and —NH(C═O)NR12aR12b;
• wherein each occurrence of R11, when present, is independently selected from hydrogen and C1-C4 alkyl;
• wherein each occurrence of R12a and R12b, when present, is independently selected from hydrogen and C1-C3 alkyl;
• and
• wherein each occurrence of R6, when present, is independently selected from halogen, —NO2, —CO2(C1-C3 alkyl), C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 alkoxycarbonyl, C3-C7 cycloalkyl, and phenyl,
• or a derivative thereof,
• the method comprising the step of reacting an allene having a structure represented by a formula:
• or a derivative thereof, with a compound having a structure represented by a formula:
• wherein n is selected from 0 and 1;
• wherein p is selected from 0, 1, 2, 3, 4, and 5;
• wherein Y is selected from 0 and S;
• wherein R26, when present, is selected from hydrogen and C1-C8 alkyl;
• wherein Z is selected from C═O, C═S, S═O, and SO2;
• wherein each of RX and RY is independently selected from hydrogen, C6-C10 aryl, and 4-10 membered heteroaryl, or wherein each of RX and RY are optionally covalently bonded together and, together with the intermediate carbon atoms, comprise a 5- to 7-membered cycloalkyl or 5- to 6-membered aryl;
• wherein R2 is selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-C10 aryl, —(C1-C3 alkyl)(C6-C10 aryl), and 4-10 membered heteroaryl, and wherein R2 is substituted with 0, 1, 2, 3, or 4 independently selected R5 groups;
• wherein each of R3a and R3b, when present, is independently selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-C10 aryl, —(C1-C3 alkyl)(C6-C10 aryl), and 4-10 membered heteroaryl, and wherein each of R3a and R3b is independently substituted with 0, 1, 2, 3, or 4 independently selected R5 groups;
• and
• wherein R4 is selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-C10 aryl, and 4-10 membered heteroaryl, and —(C1-C3 alkyl)(C6-C10 aryl), and wherein R4 is substituted with 0, 1, 2, 3, or 4 independently selected R5 groups,
• or a derivative thereof.

A method of making a compound having a structure represented by a formula:

• wherein n is selected from 0 and 1;
• wherein p is selected from 0, 1, 2, 3, 4, and 5;
• wherein each of XA and XB is independently selected from NR1, O, and S;
• wherein each occurrence of R1, when present, is independently selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-C10 aryl, —(C1-C3 alkyl)(C6-C10 aryl), and 4-10 membered heteroaryl, and wherein each occurrence of R1, when present, is independently substituted with 0, 1, 2, 3, or 4 independently selected R5 groups;
• wherein Y is selected from O, S, and NR26;
• wherein R26, when present, is selected from hydrogen and C1-C8 alkyl;
• wherein Z is selected from C═O, C═S, S═O, and SO2;
• wherein each of RX and RY is independently selected from hydrogen, C6-C10 aryl, and 4-10 membered heteroaryl, or wherein each of RX and RY are optionally covalently bonded together and, together with the intermediate carbon atoms, comprise a 5- to 7-membered cycloalkyl or 5- to 6-membered aryl;
• wherein R2 is selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-C10 aryl, —(C1-C3 alkyl)(C6-C10 aryl), and 4-10 membered heteroaryl, and wherein R2 is substituted with 0, 1, 2, 3, or 4 independently selected R5 groups;
• wherein each of R3a and R3b, when present, is independently selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-C10 aryl, —(C1-C3 alkyl)(C6-C10 aryl), and 4-10 membered heteroaryl, and wherein each of R3a and R3b is independently substituted with 0, 1, 2, 3, or 4 independently selected R5 groups;
• wherein R4 is selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-C10 aryl, and 4-10 membered heteroaryl, and —(C1-C3 alkyl)(C6-C10 aryl), and wherein R4 is substituted with 0, 1, 2, 3, or 4 independently selected R5 groups;
• wherein each occurrence of R5, when present, is independently selected from halogen, —NO2, —CN, —OH, —SH, —NH2, C1-C3 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C3 haloalkyl, C1-C3 cyanoalkyl, C1-C3 hydroxyalkyl, C1-C3 haloalkoxy, C1-C3 alkoxy, C1-C3 thioalkyl, C1-C3 alkyl(C1-C3 alkoxy), C1-C3 alkylamino, (C1-C3)(C1-C3) dialkylamino, C3-C7 cycloalkyl, C6-C10 aryl, —(C═O)(C1-C3 alkyl), —(S═O)(C1-C3 alkyl), —SO2(C1-C3 alkyl), —CO2R11, —(C═O)NR12aR12b, —SO2NR12aR12b, —O(C═O)NR12aR12b, —NHSO2NR12aR12b, and —NH(C═O)NR12aR12b;
• wherein each occurrence of R11, when present, is independently selected from hydrogen and C1-C4 alkyl;
• and
• wherein each occurrence of R12a and R12b, when present, is independently selected from hydrogen and C1-C3 alkyl,
• or a derivative thereof, the method comprising:
• a) providing a first compound having a structure represented by a formula:
• wherein X1 is halogen, or a derivative thereof;
• and
• b) reacting with a second compound having a structure represented by a formula:
• or a derivative thereof,
• in the presence of a base.

A compound having a structure represented by a formula:

• wherein Q is selected from O, S, and NR26;
• wherein R26, when present, is selected from hydrogen and C1-C8 alkyl;
• wherein each of XA and XB is independently selected from NR1, O, and S;
• wherein each occurrence of R1, when present, is independently selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-C10 aryl, —(C1-C3 alkyl)(C6-C10 aryl), and 4-10 membered heteroaryl, and wherein each occurrence of R1, when present, is independently substituted with 0, 1, 2, 3, or 4 independently selected R5 groups;
• wherein each of RX and RY is independently selected from hydrogen, C6-C10 aryl, and 4-10 membered heteroaryl, or wherein each of RX and RY are optionally covalently bonded together and, together with the intermediate carbon atoms, comprise a 5- to 7-membered cycloalkyl or 5- to 7-membered aryl;
• wherein RA is an electron withdrawing group;
• wherein RB is selected from hydrogen, C1-C6 alkyl, C2-C6 alkylene, C3-C10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-C10 aryl, —(C1-C3 alkyl)(C6-C10 aryl), and 4-10 membered heteroaryl, and wherein RB is substituted with 0, 1, 2, 3, or 4 independently selected R6 groups;
• and
• wherein each of RC and RD is independently selected from hydrogen, C1-C6 alkyl, C3-C10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-C10 aryl, and 4-10 membered heteroaryl, and wherein each of RC and RD is independently substituted with 0, 1, 2, 3, or 4 independently selected R6 groups, or wherein each of RC and RD are optionally covalently bonded together and, together with the intermediate carbon atoms, comprise a 3- to 10-membered cycloalkyl;
• wherein each occurrence of R5, when present, is independently selected from halogen, —NO2, —CN, —OH, —SH, —NH2, C1-C3 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C3 haloalkyl, C1-C3 cyanoalkyl, C1-C3 hydroxyalkyl, C1-C3 haloalkoxy, C1-C3 alkoxy, C1-C3 thioalkyl, C1-C3 alkyl(C1-C3 alkoxy), C1-C3 alkylamino, (C1-C3)(C1-C3) dialkylamino, C3-C7 cycloalkyl, C6-C10 aryl, —(C═O)(C1-C3 alkyl), —(S═O)(C1-C3 alkyl), —SO2(C1-C3 alkyl), —CO2R11, —(C═O)NR12aR12b, —SO2NR12aR12b, —O(C═O)NR12aR12b, —NHSO2NR12aR12b, and —NH(C═O)NR12aR12b;
• wherein each occurrence of R11, when present, is independently selected from hydrogen and C1-C4 alkyl;
• wherein each occurrence of R12a and R12b, when present, is independently selected from hydrogen and C1-C3 alkyl;
• and
• wherein each occurrence of R6, when present, is independently selected from halogen, —NO2, —CO2(C1-C3 alkyl), C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 alkoxycarbonyl, C3-C7 cycloalkyl, and phenyl,
• or a derivative thereof.