Graphene adsorption multi-component chiral catalyst and application thereof in asymmetric hydrogenation

Abstract

The invention discloses a graphene adsorption multi-component chiral catalyst and application thereof in asymmetric hydrogenation, and belongs to the field of organic chemistry. A hybrid material multi-component chiral catalyst 2a @ graphene adsorbed on graphene is prepared by using an in-situ immobilization strategy, and when the catalyst is applied to hydrogenation of a dehydroamino acid derivative, a good asymmetric induction effect is shown, and the conversion rate reaches 99% or above and the highest ee is 96%. And after the reaction is finished, recycling can be realized through simple filtration. The graphene adsorption multi-component chiral catalyst provides a good reference for developing other heterogeneous hybrid chiral catalysts based on non-covalent interaction asymmetric reaction.

Description

technical field

[0001] The invention relates to a graphene adsorption multi-component chiral catalyst and its application in asymmetric hydrogenation, belonging to the field of asymmetric synthesis in organic chemistry. Background technique

[0002] Multicomponent chiral catalysts (MCCs) contain mixtures of several chemical entities (e.g., ligands, metals, and other functional moieties) that facilitate various regio- and stereoselectivities by exploiting the synergy between each active site reaction, thereby mimicking an enzyme. The immobilization method of MCC system is not well studied.

[0003] In traditional immobilization methods (see figure 1 a), Random anchoring of ligands on the irregular surface of a solid support (eg, polystyrene resin) via covalent bonds, followed by the introduction of active metals. This process may prevent the formation of MCCs with the desired structure due to the constraints imposed by the distance between each immobilized component (such ...

Examples

Embodiment 1

[0028] Example 1 Synthesis of hybrid material 2a adsorbed on graphene

[0029] Preparation of Compound S3

[0030] 224mg 1-pyrenebutanoic acid S1 (0.78mmol), 300mg R-[1,1'-naphthalene]-2,2'-dimethoxy-6-butanol S2 (0.78mmol), 320mg DCC and 8mL di Chloromethane was mixed, then 190 mg DMAP (1.55 mmol) was added and stirred overnight at room temperature. The reaction mixture was quenched with celite, stirred for 1 h, filtered and concentrated in vacuo to obtain a light yellow oily crude product, which was purified by silica gel column chromatography (ethyl acetate / petroleum ether=1:10) to obtain 480 mg of S3 with a yield of 94%. Pale yellow solid. mp:72℃; [ɑ]=+30.6°(20℃, c=0.01g / ml, DCM). 1 H NMR (400MHz, CDCl 3 )δ8.32(d,J=9.1Hz,1H),8.19-8.14(m,2H),8.13-8.06(m,2H),8.07-7.95(m,4H),7.94-7.82(m,3H) ,7.65(s, 1H),7.49-7.41(m,2H),7.38-7.31(m,1H),7.25-7.22(m,1H),7.19-- 7.15(m,1H),7.08(s,2H ),4.23-4.14(m,2H),3.77(s,6H),3.40(t,J=7.4Hz,2H),2.76(t,J=7.4Hz,2H),2.49-2.45(m,2H) ,2.25-2.2...

Embodiment 2

[0046] Example 2 Hybrid material 2a hydrogenation catalytic reaction adsorbed on graphene

[0047] The hybrid material 2a@graphene adsorbed on graphene catalyzes the asymmetric hydrogenation of dehydroamino acids 6a-h, and the results are as follows:

[0048]

[0049] The specific operation is as follows: under argon protection, mix [Rh (COD) 2 ] BF 4 (2.0 mg, 0.005 mmol) and ligand 2 (7.0 mg, 0.01 mmol) were prepared in situ to obtain catalyst 2a. Graphene (20mg) was added in the above solution and stirred for 30 minutes to obtain the hybrid material 2a@graphene adsorbed on the graphene. The hybrid material 2a@graphene (0.01mmol, 10mM, based on (Monophos) 2 / Rh unit), substrate 6 (1 mmol, 1.0 M) in anhydrous ethyl acetate (5.0 mL). The test tube was placed in a stainless steel autoclave and sealed, replaced with hydrogen 3 times, the final hydrogen pressure was adjusted to 20 atm and stirring was started. At the end of the reaction (1.5 h), hydrogen was released and t...

Embodiment 3

[0058] Example 3 2a@graphene reuse

[0059] 2a@graphene adsorbed on graphene is filtered at the end of the reaction in Example 2, and continues to be used in the asymmetric hydrogenation of phenyl β-dehydroamino acid ester 6a, using the same reaction conditions as in Example 2, the number of cycles and conversion rate are the same as those for Mapping selectivity relationship ( Figure 5 ).

[0060] The results show that under the action of the same catalyst, the hydrogenation reaction has nearly quantitative conversion and stable enantioselectivity (96-92% ee), and has been recycled at least 13 times. However, after the catalyst was cycled 7 times, it was necessary to extend the reaction time from 1.5 hours to 10 hours to ensure complete conversion of the substrate, indicating that the hybrid material 2a@graphene adsorbed by the catalyst on graphene was reactive during the continuous hydrogenation process. Gradually decreases.

technical field

[0001] The invention relates to a graphene adsorption multi-component chiral catalyst and its application in asymmetric hydrogenation, belonging to the field of asymmetric synthesis in organic chemistry. Background technique

[0002] Multicomponent chiral catalysts (MCCs) contain mixtures of several chemical entities (e.g., ligands, metals, and other functional moieties) that facilitate various regio- and stereoselectivities by exploiting the synergy between each active site reaction, thereby mimicking an enzyme. The immobilization method of MCC system is not well studied.

[0003] In traditional immobilization methods (see figure 1 a), Random anchoring of ligands on the irregular surface of a solid support (eg, polystyrene resin) via covalent bonds, followed by the introduction of active metals. This process may prevent the formation of MCCs with the desired structure due to the constraints imposed by the distance between each immobilized component (such ...

Examples

Embodiment 1

[0028] Example 1 Synthesis of hybrid material 2a adsorbed on graphene

[0029] Preparation of Compound S3

[0030] 224mg 1-pyrenebutanoic acid S1 (0.78mmol), 300mg R-[1,1'-naphthalene]-2,2'-dimethoxy-6-butanol S2 (0.78mmol), 320mg DCC and 8mL di Chloromethane was mixed, then 190 mg DMAP (1.55 mmol) was added and stirred overnight at room temperature. The reaction mixture was quenched with celite, stirred for 1 h, filtered and concentrated in vacuo to obtain a light yellow oily crude product, which was purified by silica gel column chromatography (ethyl acetate / petroleum ether=1:10) to obtain 480 mg of S3 with a yield of 94%. Pale yellow solid. mp:72℃; [ɑ]=+30.6°(20℃, c=0.01g / ml, DCM). 1 H NMR (400MHz, CDCl 3 )δ8.32(d,J=9.1Hz,1H),8.19-8.14(m,2H),8.13-8.06(m,2H),8.07-7.95(m,4H),7.94-7.82(m,3H) ,7.65(s, 1H),7.49-7.41(m,2H),7.38-7.31(m,1H),7.25-7.22(m,1H),7.19-- 7.15(m,1H),7.08(s,2H ),4.23-4.14(m,2H),3.77(s,6H),3.40(t,J=7.4Hz,2H),2.76(t,J=7.4Hz,2H),2.49-2.45(m,2H) ,2.25-2.2...

Embodiment 2

[0046] Example 2 Hybrid material 2a hydrogenation catalytic reaction adsorbed on graphene

[0047] The hybrid material 2a@graphene adsorbed on graphene catalyzes the asymmetric hydrogenation of dehydroamino acids 6a-h, and the results are as follows:

[0048]

[0049] The specific operation is as follows: under argon protection, mix [Rh (COD) 2 ] BF 4 (2.0 mg, 0.005 mmol) and ligand 2 (7.0 mg, 0.01 mmol) were prepared in situ to obtain catalyst 2a. Graphene (20mg) was added in the above solution and stirred for 30 minutes to obtain the hybrid material 2a@graphene adsorbed on the graphene. The hybrid material 2a@graphene (0.01mmol, 10mM, based on (Monophos) 2 / Rh unit), substrate 6 (1 mmol, 1.0 M) in anhydrous ethyl acetate (5.0 mL). The test tube was placed in a stainless steel autoclave and sealed, replaced with hydrogen 3 times, the final hydrogen pressure was adjusted to 20 atm and stirring was started. At the end of the reaction (1.5 h), hydrogen was released and t...

Embodiment 3

[0058] Example 3 2a@graphene reuse

[0059] 2a@graphene adsorbed on graphene is filtered at the end of the reaction in Example 2, and continues to be used in the asymmetric hydrogenation of phenyl β-dehydroamino acid ester 6a, using the same reaction conditions as in Example 2, the number of cycles and conversion rate are the same as those for Mapping selectivity relationship ( Figure 5 ).

[0060] The results show that under the action of the same catalyst, the hydrogenation reaction has nearly quantitative conversion and stable enantioselectivity (96-92% ee), and has been recycled at least 13 times. However, after the catalyst was cycled 7 times, it was necessary to extend the reaction time from 1.5 hours to 10 hours to ensure complete conversion of the substrate, indicating that the hybrid material 2a@graphene adsorbed by the catalyst on graphene was reactive during the continuous hydrogenation process. Gradually decreases.

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