Unsymmetrically substituted phospholane catalysts
View Patent ↗The present invention is based on new ligand systems of the general formula (I). These ligand systems can be used advantageously in transition metal-catalyzed asymmetric syntheses. Likewise encompassed are the transition metal complexes thus prepared, a process for preparing the ligands and the use of the complexes in asymmetric synthesis.
1. A ligand system having the structure of general formula (I)
wherein
* represents stereocenter;
R 3 and R 4 are each independently selected from the group consisting of (C 1 -C 8 )-alkyl, (C 1 -C 8 )-alkoxy, HO—(C 1 -C 8 )-alkyl, (C 2 -C 8 )-alkoxyalkyl, (C 6 -C 18 )-aryl, (C 7 -C 19 )-aralkyl, (C 3 -C 18 )-heteroaryl, (C 4 -C 19 )-heteroaralkyl, (C 1 -C 8 )-alkyl-(C 6 -C 18 )-aryl, (C 1 -C 8 )-alkyl-(C 3 -C 18 )-heteroaryl, (C 3 -C 8 )-cycloalkyl, (C 1 -C 8 )-alkyl-(C 3 -C 8 )-cycloalkyl, and (C 3 -C 8 )-cycloalkyl-(C 1 -C 8 )-alkyl;
R 7 and R 8 are each independently H, R 3 , or
R 3 and R 7 and/or R 7 and R 8 and/or R 8 and R 4 are joined to one another via a (C 3 -C 5 )-alkylene bridge;
R 1 and R 2 are each independently (C 1 -C 8 )-alkyl, (C 6 -C 18 )-aryl, (C 7 -C 19 )-aralkyl, (C 3 -C 18 )-heteroaryl, (C 4 -C 19 )-heteroaralkyl, (C 1 -C 8 )-alkyl-(C 6 -C 18 )-aryl, (C 1 -C 8 )-alkyl-(C 3 -C 18 )-heteroaryl, (C 3 -C 8 )-cycloalkyl, (C 1 -C 8 )-alkyl-(C 3 -C 8 )-cycloalkyl, (C 3 -C 8 )-cycloalkyl-(C 1 -C 8 )-alkyl, (C 1 -C 8 )-alkyl-O, (C 6 -C 18 )-aryl-O, (C 7 -C 19 )-aralkyl-O, (C 3 -C 8 )-cycloalkyl-O, (C 1 -C 8 )-alkyl-NH, (C 6 -C 18 )-aryl-NH, (C 7 -C 19 )-aralkyl-NH, (C 3 -C 8 )-cycloalkyl-NH, ((C 1 -C 8 )-alkyl) 2 N, ((C 6 -C 18 )-aryl) 2 N, ((C 7 -C 19 )-aralkyl) 2 N, or ((C 3 -C 8 )-cycloalkyl) 2 N; and
A is a ring system having the following structure:
wherein
Q is O, NH, NH—NH, NR—NR, NOR, NR, S, CH 2 or C═C(R) 2 ;
R is H, (C 1 -C 8 )-alkyl, (C 6 -C 18 )-aryl, (C 7 -C 19 )-aralkyl, (C 1 -C 8 )-alkyl-(C 6 -C 18 )-aryl, (C 3 -C 8 )-cycloalkyl, (C 1 -C 8 )-alkyl-(C 3 -C 8 )-cycloalkyl, or (C 3 -C 8 )-cycloalkyl-(C 1 -C 8 )-alkyl;
R′ is R or R′″; and
R′″ is one or more electron-withdrawing groups selected from the group consisting of flourine, chlorine, CF 3 CO, CF 3 SO 2 , CF 3 , and CnF 2n+1 .
2. The ligand system according to claim 1 ,
wherein
the formula (I) compound has an enantiomeric enrichment of >90%.
3. A complex, comprising:
a ligand according to claim 1 ; and
at least one transition metal.
4. The complex according to claim 3 wherein the at least one transition metal is rhodium or ruthenium.
5. A process for preparing the ligand according to claim 1 , comprising:
reacting a compound of general formula (II) or (II′)
with a compound of general formula (III)
thereby forming a P-A bond; and
wherein the compound of general formula (II) is reacted, subsequently replacing a remaining —X with a phosphine group having the structure PR 1 R 2 ;
wherein A is a ring system having the following structure:
wherein
Q is O, NH, NH—NH, NR—NR, NOR, NR, S, CH 2 or C═C(R) 21 ;
R is H, (C 1 -C 8 )-alkyl, (C 6 -C 18 )-aryl, (C 7 -C 19 )-aralkyl, (C 1 -C 8 )-alkyl-(C 6 -C 18 )-aryl, (C 3 -C 8 )-cycloalkyl, (C 1 -C 8 )-alkyl-(C 3 -C 8 )-cycloalkyl, or (C 3 -C 8 )-cycloalkyl-(C 1 -C 8 )-alkyl;
R″ is R or R′″; and
R′″ is one or more electron-withdrawing groups selected from the group consisting of fluorine, chlorine, CF 3 CO, CF 3 SO 2 , CF 3 , and CnF 2n+1
X is a nucleophilic leaving group; and
R 1 and R 2 are each independently (C 1 -C 8 )-alkyl, (C 6 -C 18 )-aryl, (C 7 -C 19 )-aralkyl, (C 3 -C 18 )-heteroaryl, (C 4 -C 19 )-heteroaralkyl, (C 1 -C 8 )-alkyl-(C 6 -C 18 )-aryl, (C 1 -C 8 )-alkyl-(C 3 -C 18 )-heteroaryl, (C 3 -C 8 )-cycloalkyl, (C 1 -C 8 )-alkyl-(C 3 -C 8 )-cycloalkyl, (C 3 -C 8 )-cycloalkyl-(C 1 -C 8 )-alkyl, (C 1 -C 8 )-alkyl-O, (C 6 -C 18 )-aryl-O, (C 7 -C 19 )-aralkyl-O, (C 3 -C 8 )-cycloalkyl-O, (C 1 -C 8 )-alkyl-NH, (C 6 -C 18 )-aryl-NH, (C 7 -C 19 )-aralkyl-NH, (C 3 -C 8 )-cycloalkyl-NH, ((C 1 -C 8 )-alkyl) 2 N, ((C 6 -C 18 )-aryl) 2 N, ((C 7 -C 19 )-aralkyl) 2 N, ((C 3 -C 8 )-cycloalkyl) 2 N,
R 3 , R 4 , R 3 and R 4 are each independently selected from the group consisting of (C 1 -C 8 )-alkyl, (C 1 -C 8 )-alkoxy, HO—(C 1 -C 8 )-alkyl, (C 2 -C 8 )-alkoxyalkyl, (C 6 -C 18 )-aryl, (C 7 -C 19 )-aralkyl, (C 3 -C 18 )-heteroaryl, (C 4 -C 19 )-heteroaralkyl, (C 1 -C 8 )-alkyl-(C 6 -C 18 )-aryl, (C 1 -C 8 )-alkyl-(C 3 -C 18 )-heteroaryl, (C 3 -C 8 )-cycloalkyl, (C 1 -C 8 )-alkyl-(C 3 -C 8 )-cycloalkyl, (C 3 -C 8 )-cycloalkyl-(C 1 -C 8 )-alkyl, R 7 and R 8 are each independently H, R 3 , or R 3 and R 7 and/or R 7 and R 8 and/or R 8 and R 4 are joined to one another via a (C 3 -C 5 )-alkylene bridge; and
M is a metal selected from the group consisting of Li, Na, K, Mg, and Ca, or is an organosilyl group.
6. A process for an asymmetric hydrogenation or hydroformylation of a substrate, comprising:
catalyzing the asymmetric reaction with a catalyst comprising the complex according to claim 4 .
7. A process for asymmetric hydrogenation or hydroformylation, comprising:
catalyzing the asymmetric reaction with a catalyst comprising the complex according to claim 4 .
8. The process according to claim 7 ,
wherein
an E/Z mixture of prochiral N-acylated β-aminoacrylic acid or derivatives thereof is hydrogenated.
9. The process according to claim 6 ,
wherein the asymmetric reaction is a hydrogenation, and comprises
hydrogenation with hydrogen gas or transfer hydrogenation.
10. The process according to claim 9 ,
wherein the asymmetric reaction comprises hydrogen gas, and
a hydrogen pressure is from 0.1 to 100 bar.
11. The process according to claim 9 ,
wherein a temperature of the asymmetric hydrogenation is from −20° C. to 100° C.
12. The process according to claim 6 ,
wherein a substrate/catalyst ratio is from 50 000:1 to 10:1.
13. The process according to claim 6 ,
wherein the asymmetric reaction catalysis is in a membrane reactor.