Chiral single phosphorus ligand PC-Phos based on xanthene framework, preparation method of full structure of ligand and application

A technology of xanthene and pc-phos is applied in the field of novel chiral monophosphine ligands and their preparation, which can solve the problems of high toxicity of reagents, lengthy synthesis routes, expensive raw materials and the like

Active Publication Date: 2017-12-01
EAST CHINA NORMAL UNIV
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  • Application Information

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Problems solved by technology

Based on the above, the present invention overcomes the disadvantages of expensive raw materials, tedious synthetic routes, high toxicity of reagents, difficult synthesis of enantiomers and low yield when synthesizing phosphine-containing chiral ligands in the prior art. , providing a class of classic achiral bisphosphine ligands similar to XantPhos, based on the modification of the xanthene skeleton, which is convenient for the efficient synthesis of a new type of C-central chiral monophosphine ligand

Method used

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  • Chiral single phosphorus ligand PC-Phos based on xanthene framework, preparation method of full structure of ligand and application
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  • Chiral single phosphorus ligand PC-Phos based on xanthene framework, preparation method of full structure of ligand and application

Examples

Experimental program
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Effect test

Embodiment 11a

[0120] Example 1 1a(S,R s ) synthesis (reference scheme 1)

[0121] Step 1: In a 250mL dry single-necked bottle, add under nitrogen atmosphere (20mmol,

[0122] 9.24g) and 60mL THF, stirred at -78°C for 10 minutes, added dropwise n-BuLi (1.0eq., 12.5mL, 1.6M), continued to stir for 1.5 hours, added dropwise ClPPh 2 (1.0eq., 3.57mL), stirred for another 1 hour, added dropwise n-BuLi (2.0eq., 25mL, 1.6M), stirred for another 1.5 hours, added dropwise DMF (15eq., 20mL), and slowly rose to room temperature Continue to stir for 1 hour, separate the layers, extract the aqueous layer three times with ethyl acetate, combine the organic phases, wash with water and saturated sodium chloride respectively, dry over anhydrous sodium sulfate, filter, spin dry, and purify by column chromatography to obtain The yield was 65%. 1 H NMR (400MHz, CDCl 3 ):δ10.17(s,1H),7.68-7.60(m,2H),7.45(d,J=7.6Hz,1H),7.38-7.30(m,10H),7.11(t,J=9.0Hz, 1H), 7.05(t, J=7.6Hz, 1H), 1.65(s, 6H); 31 P NMR (1...

Embodiment 2

[0127] Example 2 The synthesis (reference scheme one)

[0128] Concrete operation with reference to embodiment 1, raw material used is The yield was 99%. 1 H NMR (500MHz, CDCl 3 )δ7.50-7.26(m,13H),7.21(d,J=6.5Hz,1H),7.12(t,J=8.0Hz,1H),7.02(t,J=7.5Hz,1H),6.70- 6.55(m,3H),6.05(br,1H),1.69(s,3H),1.63(s,3H),1.29(s,9H); 13 C NMR (125MHz, CDCl 3 )δ158.50, 152.38 (J c,p =17Hz), 147.70, 137.09 (J c,p =11Hz), 136.35, 134.03, 133.95, 133.74 (J c,p =19Hz), 133.32, 132.22, 130.57, 130.00 (J c,p =2Hz), 129.06, 128.60, 128.53, 126.97, 125.19, 123.55, 123.24, 113.44, 56.21, 34.43, 32.35, 22.99; 31 P NMR (202MHz, CDCl 3 )δ-17.81; HRMS (ESI) calculated for [C 32 h 33 NO 2 PS][M+H] + :526.1964; found: 526.1959.

Embodiment 31b

[0129] Example 3 1b(R,R s ) synthesis (reference scheme 1)

[0130] Referring to Example 1 for the specific operation, the metal reagent used is 4-methoxyphenyllithium, and the yield is 83%. 1 H NMR (500MHz, CDCl 3 )δ7.49-7.34(m,10H),7.34-7.25(m,4H),7.22-7.11(m,4H),7.11-6.99(m,2H),6.65(s,1H),6.23(br, 1H), 1.69(s,3H), 1.61(s,3H), 1.28(s,9H), 1.21(s,9H).; 13 CNMR (125MHz, CDCl 3 )δ152.51(J c,p =17Hz), 152.45, 149.64, 148.00, 139.06, 137.0 (J c,p =12Hz), 136.7(J c,p =11Hz), 134.3(J c,p =21Hz), 133.6(J c,p =20Hz), 132.15, 130.57, 130.1 (J c,p =10Hz), 128.76, 128.51 (J c,p =13Hz), 128.51, 128.41, 127.22, 126.71, 125.15, 124.74, 123.2 (J c,p =65Hz), 56.12, 34.50, 34.37, 32.48, 31.36, 22.81; 31 P NMR (202MHz, CDCl 3 )δ-17.95; HRMS (ESI) calculated for [C 42 h 47 NO 2 PS][M+H] + :660.3060,found:660.3054.

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Abstract

The invention discloses a novel single phosphorus ligand PC-Phos of a xanthene framework. The ligand is a compound as shown in a formula (1) or an enantiomer, racemate or diastereoisomer of the compound as shown in the specification. The invention further discloses a preparation method of the ligand. A formula 2 and a formula 4 as shown in the specification serve as raw materials, and substitution reaction, addition reaction, condensation reaction and reduction reaction are performed to prepare the ligand. Alternatively, a formula 6 and the formula 4 as shown in the specification serve as raw materials, are subjected to condensation reaction and subjected to addition reaction with a formula as shown in the specification to prepare the ligand. Chiral sulfonamide 4 with two structures and different types of metallic reagents are subjected to addition reaction, and optical voidness of four full structures 1 (S, Rs), 1 (R, Rs), 1 (S, Ss) and 1 (R, Ss) of the chiral single phosphorus ligand can be obtained. The invention further discloses an application of the ligand to asymmetric cyclization reaction in catalytic allene amine molecules. The ligand has quite high reaction activity, stereo-selectivity and wide application values.

Description

technical field [0001] The invention relates to a novel chiral monophosphine ligand and its preparation method and application, in particular to a class of novel chiral monophosphine ligand PC-Phos based on xanthene skeleton modification and its preparation method and application, belonging to the technical field of organic chemistry . Background technique [0002] Chirality is one of the basic properties of nature. For example, proteins, the basic substances of life, are almost all composed of L-type amino acids, the ribose configurations in DNA and RNA are all D-type, and the helices of DNA and proteins also show specific characteristics. Chirality. It is well known that (R)-thalidomide can be used as a tranquilizer to reduce the reaction of human pregnancy, while (S)-thalidomide has teratogenic effect, so the use of racemic thalidomide has caused a lot of human tragedies of fetal malformation. It can be seen that the synthesis of optically pure molecules is not only a c...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07F9/655B01J31/24C07D471/04
CPCB01J31/2404B01J2531/18C07D471/04C07F9/65522
Inventor 张俊良张培超王以栋王磊
Owner EAST CHINA NORMAL UNIV
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