Phosphine ligands for catalytic reactions

A method of preparing a compound comprising:

• metalation of a biaryl halide to form a biaryl lithium species;
• reacting a chlorophosphate with said biaryl lithium species to form a biaryl phosphonate;
• reduction of said biaryl phosphonate to form primary phosphine;
• and
• reacting said primary phosphine with a divinylketone;
• wherein said compound has a structure corresponding to formula (I),
• or a salt thereof,
• wherein
• Ar1 and Ar2 are each independently aryl or heteroaryl, and wherein Ar1 and Ar2 are each independently optionally substituted with one or more R1 and R2, respectively;
• R1 and R2 are independently selected at each occurrence from the group consisting of hydrogen;
• amino;
• hydroxyl;
• cyano;
• halo;
• alkyl;
• alkenyl;
• alkynyl;
• haloalkyl;
• haloalkoxy;
• oxoalkyl;
• alkoxy;
• aryloxy;
• heteroaryloxy;
• arylamino;
• heteroarylamino;
• alkylamino;
• dialkylamino;
• cycloalkyl optionally substituted with alkyl, alkenyl, alkynyl, alkoxy, cyano, halo, haloalkyl or haloalkoxy;
• cycloalkyloxy optionally substituted with alkyl, alkenyl, alkynyl, alkoxy, cyano, halo, haloalkyl or haloalkoxy;
• 5- or 6-membered heteroaryl optionally substituted with alkyl, alkenyl, alkynyl, alkoxy, cyano, halo, haloalkyl or haloalkoxy;
• phenyl optionally substituted with alkyl, alkenyl, alkynyl, alkoxy, cyano, halo, haloalkyl or haloalkoxy;
• hydroxyalkyl;
• hydroxyalkoxy;
• alkoxyalkyl;
• aminoalkyl;
• N-alkylaminoalkyl;
• N,N-dialkylaminoalkyl;
• N,N,N-trialkylammoniumalkyl;
• L1-C(O)—OR1′, L1-P(O)—(OR1′)2, or L1-S(O)2—OR1′, wherein L1 is a bond or alkylene, and R1′ is selected from the group consisting of hydrogen, alkyl and hydroxyalkyl;
• L2-O—C(O)—R2′, wherein L2 is a bond or alkylene, and R2 is alkyl or hydroxyalkyl;
• L3-C(O)—NR3′R4′, wherein L3 is a bond or alkylene, and R3′ and R4′ are each independently selected from the group consisting of hydrogen, alkyl, and hydroxyalkyl;
• L4-NR5′C(O)—R6′, wherein L4 is a bond or alkylene, R5′ is hydrogen or alkyl, and R6′ is alkyl or hydroxyalkyl;
• sulfamoyl;
• N-(alkyl)sulfamoyl;
• N,N-(dialkyl)sulfamoyl;
• sulfonamide;
• sulfate;
• alkylthio;
• thioalkyl;
• and a ring containing an alkylene or —O—(CH2)m—O— formed by the joining together of any two R1 or any two R2 or an R1 and an R2, wherein m is 1, 2, 3 or 4;
• X is a 6-membered cyclic phosphine of formula (Ia):
• wherein ring A includes three carbon ring atoms in addition to the phosphorus and 2 carbon ring atoms of formula (Ia);
• wherein the ring atoms of ring A are each independently optionally substituted with one or more substituents selected from the group consisting of alkenyl;
• alkoxy;
• alkoxyalkyl;
• alkyl;
• alkylamino;
• alkylthio;
• alkynyl;
• aminoalkyl;
• N-alkylaminoalkyl;
• N,N-dialkylaminoalkyl;
• N,N,N-trialkylammoniumalkyl;
• arylalkyl optionally substituted with alkyl, alkenyl, alkynyl, alkoxy, cyano, halo, haloalkyl or haloalkoxy;
• cycloalkyl optionally substituted with alkyl, alkenyl, alkynyl, alkoxy, cyano, halo, haloalkyl or haloalkoxy;
• dialkylamino;
• halo;
• haloalkyl;
• fluoroalkyl;
• heteroaryl optionally substituted with alkyl, alkenyl, alkynyl, alkoxy, cyano, halo, haloalkyl or haloalkoxy;
• heterocycloalkyl optionally substituted with alkyl, alkenyl, alkynyl, alkoxy, cyano, halo, haloalkyl or haloalkoxy;
• hydroxy;
• hydroxyalkyl;
• oxo;
• an exocyclic double bond optionally substituted with alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocyclyl, or heteroaryl;
• a 3- to 7-membered spiro ring containing zero, one, or two heteroatoms;
• phenyl optionally substituted with alkyl, alkenyl, alkynyl, alkoxy, cyano, halo, haloalkyl or haloalkoxy;
• L1-C(O)—OR1′, L1-P(O)—(OR1′)2, or L1S(O)2—OR′, wherein L1 is a bond or alkylene, and R1′ is selected from the group consisting of hydrogen, alkyl or hydroxyalkyl;
• L2-O—C(O)—R2′, wherein L2 is a bond or alkylene, and R2′ is alkyl or hydroxyalkyl;
• L3-C(O)—NR3′R4′, wherein L3 is a bond or alkylene, and R3′ and R4′ are each independently selected from the group consisting of hydrogen, alkyl, and hydroxyalkyl;
• L4-NR5′C(O)—R6′, wherein L4 is a bond or alkylene, R5′ is hydrogen or alkyl, and R6′ is alkyl or hydroxyalkyl;
• and L7-NR8′—S(O)2—R9′, wherein L7 is a bond or alkylene, R8′ is hydrogen or alkyl, and R9′ is alkyl or hydroxyalkyl;
• as to R10, R11, R12, and R13,
• i. R10 or R11 together with R12 or R13 form a ring;
• or
• ii. R10 and R11 together with the carbon atom to which they are attached form a spirocyclic ring and/or R12 and R13 together with the carbon atom to which they are attached form a spirocyclic ring;
• or
• iii. one or more of R10, R11, R12 and R13 form a ring together with a ring substituent of ring A;
• or
• iv. R10, R11, R12, and R13 do not form a ring, wherein R10, R11, R12 and R13 are each independently selected from the group consisting of hydrogen;
• alkyl;
• alkenyl;
• haloalkyl;
• alkynyl;
• oxoalkyl;
• cycloalkyl optionally substituted with alkyl, alkenyl, alkynyl, alkoxy, cyano, halo, haloalkyl or haloalkoxy;
• heterocyclyl optionally substituted with alkyl, alkenyl, alkynyl, alkoxy, cyano, halo, haloalkyl or haloalkoxy;
• heteroaryl optionally substituted with alkyl, alkenyl, alkynyl, alkoxy, cyano, halo, haloalkyl or haloalkoxy;
• phenyl optionally substituted with alkyl, alkenyl, alkynyl, alkoxy, cyano, halo, haloalkyl or haloalkoxy;
• hydroxyalkyl;
• alkoxyalkyl;
• aminoalkyl;
• N-alkylaminoalkyl;
• N,N-dialkylaminoalkyl;
• N,N,N-trialkylammoniumalkyl;
• thioalkyl;
• L13-C(O)—OR14′, L13-P(O)—(OR14′)2, or L13-S(O)2—OR14′, wherein L13 is a bond or alkylene, and R14′ is selected from the group consisting of hydrogen, alkyl and hydroxyalkyl;
• L15-O—C(O)—R16′, wherein L15 is alkylene and R16′ is alkyl or hydroxyalkyl;
• L17-C(O)—NR18′R19′, wherein L17 is a bond or alkylene, and R18′ and R19′ are each independently selected from the group consisting of hydrogen, alkyl, and hydroxyalkyl;
• and L20-NR21′C(O)—R22′, wherein L20 is alkylene, R21′ is hydrogen or alkyl, and R22′ is alkyl or hydroxyalkyl.