Triaminophosphine ligands for carbon-nitrogen and carbon-carbon bond formation
View Patent ↗Methods and compounds are provided for the formation of carbon-nitrogen or carbon-carbon bonds comprising reacting an amine or an aryl boronic acid with an aryl halide in the presence of a palladium catalyst, a base, and a compound of formula II:
1. A compound of formula I:
wherein
each X is independently (CH 2 ) n and each n is independently 1-3;
Y is a single bond, O, (C 1 -C 8 )alkylene, (C 5 -C 12 )arylene, carbonyl, oxycarbonyl, carbonyloxy, NR a , or S(O) m ;
each R 1 is independently H, (C 1 -C 8 )alkyl, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, (C 1 -C 8 )perfluoroalkyl, (C 5 -C 12 )aryl, (C 5 -C 2 )heteroaryl, (C 5 -C 12 )heterocyclyl, Si((C 1 -C 6 )alkyl) 3 , Si((C 1 -C 6 )alkoxy) 3 , Si((C 5 -C 12 )aryl) 3 , or Si((C 5 -C 12 )aryloxy) 3 ;
R 2 is H, OR a , (C 1 -C 8 )alkyl, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, (C 1 -C 8 )perfluoroalkyl, (C 5 -C 12 )aryl, (C 5 -C 12 )heteroaryl, (C 5 -C 12 )heterocyclyl, Si((C 1 -C 6 )alkyl) 3 , Si((C 1 -C 6 )alkoxy) 3 , Si((C 5 -C 12 )aryl) 3 , Si((C 5 -C 12 )aryloxy) 3 , NHR a , N(R a ) 2 , halo, nitro, cyano, S(O) m OR a , SO 3 H, or P(O) 2 OR a ;
R a is H, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkylcarbonyl, (C 5 -C 12 )aryl, or (C 5 -C 12 )aryloxy;
m is 0-2;
any alkyl is optionally substituted with one to three halo, hydroxyl, nitro, cyano, (C 5 -C 12 )aryl, (C 1 -C 6 )alkoxy, trifluoromethyl, oxo, thioxo, or NR b R c , groups, wherein R b and R c are each independently hydrogen, (C 1 -C 6 )alkyl, or C(═O)OR d wherein R d is hydrogen or (C 1 -C 6 )alkyl;
any alkyl is optionally interrupted with one to three oxy, thio, amino, sulfinyl, or sulfonyl groups;
any alkyl is optionally partially unsaturated;
any aryl is optionally substituted with one or more halo, hydroxyl, nitro, cyano, (C 1 -C 6 )alkoxy, trifluoromethyl, oxo, NR b R c , or C(O)OR d groups;
provided that when R 1 is methyl, —Y—R 2 is not hydrogen or (C 1 -C 6 )alkyl; and
provided that when R 1 is hydrogen, —Y—R 2 is not hydrogen.
2. The compound of claim 1 wherein each X is —CH 2 — and each R 1 is (C 1 -C 8 )alkyl.
3. The compound of claim 1 wherein each R 1 is isobutyl.
4. The compound of claim 1 wherein Y is a single bond and R 2 is methyl.
5. The compound of claim 1 wherein the compound of formula I is
6. The compound of claim 1 wherein each X is —CH 2 —.
7. The compound of claim 1 wherein each X is —(CH 2 ) 2 —.
8. The compound of claim 1 wherein each X is —(CH 2 ) 3 —.
9. The compound of claim 1 wherein at least one R 1 is (C 1 -C 4 )alkyl.
10. The compound of claim 1 wherein at least one R 1 is isobutyl.
11. The compound of claim 1 wherein each X is —CH 2 — and each R 1 is (C 1 -C 4 )alkyl.
12. The compound of claim 1 wherein Y is a single bond.
13. The compound of claim 1 wherein R 2 is (C 1 -C 8 )alkyl.
14. The compound of claim 1 wherein the compound of formula I is a compound of the formula:
15. The compound of claim 14 wherein R 2 is H, OR a , (C 1 -C 8 )alkyl, (C 3 -C 8 )cycloalkyl, (C 5 -C 12 )aryl, (C 5 -C 12 )heteroaryl, NHR a , N(R a ) 2 , halo, nitro, cyano, or SO 3 H.
16. The compound of claim 1 wherein the compound of formula I is a compound of the formula shown:
(C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, (C 1 -C 8 )perfluoroalkyl, (C 5 -C 12 )aryl, (C 5 -C 12 )heteroaryl, (C 5 -C 12 )heterocyclyl, Si((C 1 -C 6 )alkyl) 3 , Si((C 1 -C 6 )alkoxy) 3 , Si((C 5 -C 12 )aryl) 3 , or Si((C 5 -C 12 )aryloxy) 3 ;
Z is methyl or hydrogen.
17. The compound of claim 1 wherein the compound of formula I is a compound of the formula:
, wherein R 2 is OR a , (C 1 -C 8 )alkyl, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, (C 1 -C 8 )perfluoroalkyl, (C 5 -C 12 )aryl, (C 5 -C 12 )heteroaryl, (C 5 -C 12 )heterocyclyl, Si((C 1 -C 6 )alkyl) 3 , Si((C 1 -C 6 )alkoxy) 3 , Si((C 5 -C 12 )aryl) 3 , Si((C 5 -C 12 )aryloxy) 3 , NHR a , N(R a ) 2 , halo, nitro, cyano, S(O) m OR a , SO 3 H, or P(O) 2 OR a .
18. The compound of claim 14 wherein R 2 is OR a , (C 1 -C 8 )alkyl, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, (C 1 -C 8 )perfluoroalkyl, (C 5 -C 12 )aryl, (C 5 -C 12 )heteroaryl, (C 5 -C 12 )heterocyclyl, NHR a , N(R a ) 2 , halo, nitro, cyano, S(O) m OR a , SO 3 H.