Copper catalyzed halogenaton and reaction products

A method to induce a 1,3-halogen a migration comprising contacting a compound of Formula (I):

• wherein
• X is Cl, Br, or I;
• R1 is H, alkyl, aryl, heteroaryl, or cycloalkyl;
• R2 is H, halo, alkyl, alkoxy, aryl, or heteroaryl;
• and
• n is 0, 1, 2, 3, or 4;
• with a hydroborane in the presence of an effective amount of copper(I), a base, and an electron-rich bidentate phosphine ligand, to provide a compound of Formula (II):
• wherein each Rx is independently a boron ligand or both Rx groups together form a bidentate boron ligand.

A method to enantioselectively induce a 1,3-halogen a migration comprising contacting a compound of Formula (I):

• wherein
• X is Cl, Br, or I;
• R1 is H, alkyl, aryl, heteroaryl, or cycloalkyl;
• R2 is H, halo, alkyl, alkoxy, aryl, or heteroaryl;
• and
• n is 0, 1, 2, 3, or 4;
• with a hydroborane in the presence of an effective amount of copper(I), a base, and a chiral electron-rich bidentate phosphine ligand, to provide an enantioenriched compound of Formula (II):
• wherein each Rx is independently a boron ligand or both Rx groups together form a bidentate boron ligand.

A method for preparing a chiral ligand comprising contacting a compound of Formula (I):

• wherein
• X is Cl, Br, or I;
• R1 is H, alkyl, aryl, heteroaryl, or cycloalkyl;
• R2 is H, halo, alkyl, alkoxy, aryl, or heteroaryl;
• and
• n is 0, 1, 2, 3, or 4;
• with a hydroborane in the presence of an effective amount of copper(I), a base, and an electron-rich bidentate phosphine ligand, to provide a compound of Formula (II):
• wherein each Rx is independently a boron ligand or both Rx groups together form a bidentate boron ligand;
• contacting the compound of Formula (II) with an excess of ammonia or an ammonia equivalent;
• and converting the boronate to a diphenylphospine moiety to provide a chiral ligand of Formula (II-A):
• wherein Y is amino and Rx is phenyl.

A method for preparing a chiral ligand comprising contacting a compound of Formula (III):

• wherein
• X is Cl, Br, or I;
• R2 is H, halo, alkyl, alkoxy, aryl, or heteroaryl;
• and
• n is 0, 1, 2, or 3;
• with a hydroborane in the presence of an effective amount of copper(I), a base, and an electron-rich bidentate phosphine ligand, to provide a compound of Formula (IV):
• wherein each Rx is independently a boron ligand or both Rx groups together form a bidentate boron ligand;
• contacting the compound of Formula (IV) with an excess of ammonia or an ammonia equivalent;
• and converting the boronate to a diphenylphospine moiety.

A method for preparing a chiral ligand comprising contacting a compound of Formula (V):

• wherein
• X is Cl, Br, or I;
• R2 is H, halo, alkyl, alkoxy, aryl, or heteroaryl;
• and
• n is 0, 1, 2, or 3;
• with a hydroborane in the presence of an effective amount of copper(I), a base, and an electron-rich bidentate phosphine ligand, to provide a compound of Formula (VI):
• wherein each Rx is independently a boron ligand or both Rx groups together form a bidentate boron ligand;
• contacting the compound of Formula (VI) with a compound of Formula (VIa):
• in the presence of an alkyl lithium agent to form a coupled product, oxidizing the coupled product to provide a phosphine, oxidizing the phosphine compound, to provide a phosphine oxide compound, cyclizing the phosphine oxide compound at the bromide and boronate moieties, dimerizing the resulting product in the presence of a strong base, and reducing the phosphine oxide moieties to phosphines, to provide a binapine chiral ligand.

A method for preparing a chiral ligand comprising contacting a compound of Formula (I):

• wherein
• X is Cl, Br, or I;
• R1 is H, alkyl, aryl, heteroaryl, or cycloalkyl;
• R2 is H, halo, alkyl, alkoxy, aryl, or heteroaryl;
• and
• n is 0, 1, 2, or 3;
• with a hydroborane in the presence of an effective amount of copper(I), a base, and an electron-rich bidentate phosphine ligand, to provide a compound of Formula (II):
• wherein each Rx is independently a boron ligand or both Rx groups together form a bidentate boron ligand;
• contacting the compound of Formula (II) with an excess of tert-butylphosphine oxide in the presence of a strong base to displace the benzylic halide with the tert-butylphosphine oxide, carrying out a hydroformylation reaction in the presence of a Rhodium catalyst followed by cyclization, forming a dimer of the resulting product, and reducing the phosphine oxide moieties to provide a DuanPhos derivative chiral ligand of Formula (VII):