Processes for the preparation of biphenyl compounds
The invention concerns processes for the synthesis of a compound of the formula: wherein: R 1 and R 2 are each, independently, C 1 -C 12 alkyl, CO 2 R 3 , OR 4 , R 5 (OR 6 ), or C 6 -C 18 aryl; R 3 -R 6 are each, independently, C 1 -C 12 alkyl or C 6 -C 12 aryl; and n and m are each, independently, O or an integer from 1-5; said process comprising:—contacting a compound of the formula H0-R 7 -0H with BH 3 and a compound of the formula in the presence of a nickel-containing catalyst to produce a first product, where R 7 is a C 2 -C 12 hydrocarbon group and X is a halogen, OMs or OTs;—contacting the first product in situ with a compound of the formula: in the presence of a nickel-containing catalyst to produce a compound of formula I, where Z is a halogen.
1. A process for the synthesis of a compound of the formula:
wherein:
R 1 and R 2 are each, independently, C 1 -C 12 alkyl, CO 2 R 3 , OR 4 , R 5 (OR 6 ), or C 6 -C 18 aryl;
R 3 -R 6 are each, independently, C 1 -C 12 alkyl or C 6 -C 12 aryl; and
n and m are each, independently, 0 or an integer from 1-5;
said process comprising:
reacting a compound of the formula HO—R 7 —OH with BH 3 and a compound of the formula
in the presence of a nickel-containing catalyst to produce a first product, where R 7 is a C 2 -C 12 hydrocarbon group and X is a halogen, OTs, or OMs;
contacting the first product with a compound of the formula:
in the presence of a nickel-containing catalyst to produce a compound of formula I, where Z is a halogen and where the nickel-containing catalyst is independently selected from NiCl 2 (dppp), NiCl 2 (dppe), NiCl 2 (PPh 3 ) 2 and Ni(COD) 2 .
2. A process for the synthesis of a compound of the formula:
wherein:
R 1 and R 2 are each independently, C 1 -C 12 alkyl, CO 2 R 3 , OR 4 , R 5 (OR 6 ), or C 6 -C 18 aryl;
R 3 -R 6 are each independently, C 1 -C 12 alkyl or C 6 -C 12 aryl; and
n and m are each, independently, 0 or an integer from 1-5; said process comprising:
reacting a compound of the formula HO—R 7 —OH with BH 3 to produce an intermediate compound prior to contacting said intermediate compound with a compound of the formula:
in the presence of a nickel-containing catalyst to produce a first product, where R 7 is a C 2 -C 12 hydrocarbon group and X is a halogen, OTs, or OMs;
contacting the first product with a compound of the formula:
in the presence of a nickel-containing catalyst to produce a compound of formula I, where Z is a halogen and where the nickel-containing catalyst is independently selected from NiCl 2 (dppp), NiCl 2 (dppe), NiCl 2 (PPh 3 ) 2 and Ni(COD) 2 .
3. The process of claim 1 , wherein the nickel-containing catalyst is NiCl 2 (dppp).
4. The process of claim 1 , wherein said compound of formula I is prepared in the presence of toluene solvent.
5. The process of claim 1 , wherein n and m are each, independently, 1 or 2.
6. The process of claim 1 , wherein at least one of R 1 and R 2 is CO 2 R 3 where R 3 is methyl or ethyl.
7. The process of claim 1 , wherein;
R 1 and R 2 are each, independently, C 1 -C 4 alkyl, CO 2 R 3 , OR 4 , or C 6 -C 18 aryl; and
R 3 -R 6 are each, independently, C 1 -C 4 alkyl or C 6 -C 12 aryl.
8. The process of claim 1 , wherein X is Br.
9. The process of claim 1 , wherein said first product is of the formula
10. The process of claim 1 , wherein said reacting and contacting steps are performed seriatim.
11. The process of claim 10 , wherein said reacting and contacting steps are performed seriatim in a single reaction vessel.