Iridium Catalyst for Chiral Amine Synthesis～ Eﬃcient synthesis of chiral amines by reduc ve amina on ～ver.2

Asymmetric synthesis of optically active amine compounds
eg. Synthesis of optically active amine compounds combination with chiral auxiliary

J. Org. Chem. 2022, 87, 8458–463.

Chiral amines are useful compounds used in a wide range of applications such as synthetic intermediates forpharmaceuticals, agrochemicals, and functionalized materials.
We have newly developed asymmetric iridium catalysts for reductive amination of ketones under mild conditions.
With the aid of chiral amino alcohols as chiral auxiliary, these catalysts realize practical preparation of various optically active amines which can not be synthesized efficiently by conventional method. Please use them for yourproduct development and research.

High reactivity

High catalytic activity

Reductive amination proceeds at a substrate-to-catalyst molar ratio(S/C) of >5,000.

High stereoselectivity
Asymmetric catalyst＋

Combination with easily-available amino alcohols

Chiral auxiliaries

as chiral auxiliaries leads high stereoselectivity.

Simple operation
No need ofNo need of H2 and pressure vessel on

special equipment

both reductive amination and auxiliary cleavage.

Short reaction process
Mild reaction condition

No need of isolation of imine.
Enable one-pot synthesis till auxiliary cleavage.
From room temperature to 60 ℃

Example
Synthesis of optically active 2-aminotetralins(S)‐Ir‐PSA36

Chiral auxiliary

RS/C

Isolated yield(％)

ee (％)

H

5,0008082

6‐F

5,0007782

6‐Cl

1,0008684

6‐Br

1,0008684

6‐CN

1,0009381

be efficiently obtained from β-tetralones substituted

6‐OMe

5,0009486with electron-withdrawing (cyano, halogen) or electron

7‐OMe

5,0009184

8‐OMe

5,0008787

Chiral 2-aminotetralins with high optical purity can-donating (methoxy) groups. The effect of substitution
position was almost not observed.

Scale up synthesis for application of pharmaceutical intermediate.

In the scale-up synthesis of (S)-2-amino-5-methoxytetralin, the important intermediate of Rotigotine, the reductive amination of 5-methoxy-2-tetralone was completed even at S/C = 10,000.
Since the selectivity of this reaction was high enough, the optical purity was easily increased to 99% de by recrystallization. Following cleavage of the auxiliary group afforded 99%
ee of 2-amino-5-methoxytetralin hydrochloride in 72% total yield. In addition, the metal component could be almost completely removed by the recrystallization and the residual Ir in theproduct was less than 1 ppm.

OFC-12 (202107)

Synthesis of optically active acyclic β-arylamines

Various chiral acyclic -arylamines are also efficiently obtained in the reaction. In the caseof ketones having -arylacetone scaffolds, the combination of Ir-PSA18 and phenylglycinol performs well. The reaction proceeds efficiently even in the presence of nitro groups, phenolichydroxyl groups or sulfonamides. In addition, this method can be applied to substrates withheterocycle such as pyridine or thiophene.

Combination of catalyst and chiral auxiliary group

The combination of the catalyst andthe chiral auxiliary group is very important in our catalyst system. Pleaseconsider the appropriate combinationaccording to the substrate structure.
If the product is an enantiomer ofthe desired compound, it can be synthesized by setting both of the catalyst and chiral auxiliary group theopposite senses.

Contract synthesis / Contract development
We can find a suitable catalyst for your preferred substrate. We will also search for appropriate chiral auxiliary groups and reaction conditions. We are also available for custom synthesis,
so please contact us.

OFC-12 (202107)

Product List
ProductProduct No.

Package

07060-68

100 mg07071-68

100 mg07658-68

100 mg07035-68

100 mg44078-525g

44078-32

25 g42247-2A

5g

42247-3A

25 g

30757-1A

1g

30757-2A

25 g

18382-1A

5g

18382-2A

25 g

01769-555g01770-555g

Chloro[(S)-N-{pyridin-2-yl(2,4,6-trimethylphenyl)methyl}methanesulfonamidato](pentamethylcyclopentadienyl)iridium(III)

Abbreviation: (S)-Ir-PSA18
CAS RN® : Chloro[(R)-N-{pyridin-2-yl(2,4,6-trimethylphenyl)methyl}methanesulfonamidato](pentamethylcyclopentadienyl)iridium(III)

Abbreviation: (R)-Ir-PSA18
CAS RN® : -Cl Ir
N
N Ms
Mes

Chloro[(S)-N-(1-(4-methoxy-3,5-dimethylpyridin-2-yl)-1-phenylethyl)
methanesulfonamidato](pentamethylcyclopentadienyl)iridium(III)

Abbreviation: (S)-Ir-PSA３６
CAS RN® : Chloro[(R)-N-(1-(4-methoxy-3,5-dimethylpyridin-2-yl)-1-phenylethyl)
methanesulfonamidato](pentamethylcyclopentadienyl)iridium(III)

Abbreviation: (R)-Ir-PSA３６
CAS RN® : L-Valinol [(S)-(-)-2-Amino-3-methyl-1-butanol ]CAS RN® : 2026-48-4

D-Valinol [(R)-(-)-2-Amino-3-methyl-1-butanol ]CAS RN® : 4276-09-9(S)-(+)-2-Phenylglycinol

CAS RN® : 20989-17-7(R)-(-)-2-Phenylglycinol [D(-)-α-Phenylglycinol]

CAS RN® : 56613-80-0(S)-2-Amino-5-methoxytetralin (S)-mandelate

CAS RN® : 439133-67-2(S)-2-Amino-5-methoxytetralin hydrochloride

CAS RN® : 58349-17-0

OFC-12 (202305)