Zhejiang University

Hangzhou Liucha Pharmaceutical Ltd.

Xufeng Lin

Lei Wang

Qiaoxia Zhou

Shirui Chang

Weiye Sun

Linxi Yao

Haorui Gu

Huanyu Shan

Chaoyang Hong

Chenglong Wu

Provided herein is 3,3,3′,3′-tetramethyl-1,1′-spirobiindane-7,7′-diol, which is a compound represented by formula I, or an enantiomer or a raceme thereof. The is prepared with a 3,3,3′,3′-tetramethyl-1,1′-spirobiindane-7,7′-diol 3,3,3′,3′-tetramethyl-1,1′-spirobiindane-7,7′-dicarbaldehyde derivative as a starting material through a Baeyer-Villiger oxidation rearrangement reaction and an alkaline hydrolysis reaction. The 3,3,3′,3′-tetramethyl-1,1′-spirobiindane-7,7′-diol comprises two gem-dimethyl groups and is a key intermediate for preparing corresponding 3,3,3′,3′-tetramethyl-1,1′-spirobiindane-based monophosphine ligands, such as phosphonite ligands, phosphite ligands, phosphoramidite ester ligands, phosphoric acid and phsophonamidate. The 3,3,3′,3′-tetramethyl-1,1′-spirobiindane-7,7′-diol skeleton provided herein could be used in chemical industry and has economic practicality and industrial application prospects.

3,3,3',3′-tetramethyl-1,1′-spirobiindane-7,7′-diol

Disclosed are 7,7′-dihalo-3,3,3′,3′-tetramethyl-1,1′-spirobiindane and a preparation method thereof. The 7,7′-dihalo-3,3,3′,3′-tetramethyl-1,1′-spirobiindane is a compound represented by formula I, or an enantiomer, a raceme or a diastereomer thereof. The compound of formula I could be prepared by using a racemic or optically active 3,3,3′,3′-tetramethyl-1,1′-spirobiindane-6,6′-diol as a raw material through a series of reactions. The 7,7′-dihalo-3,3,3′,3′-tetramethyl-1,1′-spirobiindane is a key intermediate for preparing 3,3,3′,3′-tetramethyl-1,1′-spirobiindane-based phosphine ligand compounds represented by formula II or III.

7,7′-dihalo-3,3,3′,3′-tetramethyl-1,1′-spirobiindane and preparation method thereof

The present application discloses a 3,3,3',3&#x2032;-tetramethyl-1,1&#x2032;-spirobiindane-based phosphine ligand, an intermediate, a preparation method and uses thereof. The compound of phosphine ligand is a compound having a structure represented by formula I or formula II, or an enantiomer, a raceme, or diastereomer thereof. The phosphine ligand can be prepared via a preparation scheme in which the cheap and easily available 6,6&#x2032;-dihydroxyl-3,3,3&#x2032;,3&#x2032;-tetramethyl-1,1&#x2032;-spirobiindane is used as a raw material and the compound represented by formula III serves as the key intermediate. The new phosphine ligand developed by the present application can be used in catalytic organic reaction, in particular as a chiral phosphine ligand that is widely used in many asymmetric catalytic reactions including asymmetric hydrogenation and asymmetric allyl alkylation, and thus it has economic practicability and industrial application prospect. 

Compound of 3,3,3',3&#x2032;-tetramethyl-1,1&#x2032;-spirobiindane-based phosphine ligand, and preparation method thereof

Provided are a 3,3,3',3&#x2032;-tetramethyl-1,1&#x2032;-spirobiindane-based monophosphine ligand and intermediates thereof, and preparation methods and uses of the same. The monophosphine ligand is a compound represented by formula I or formula I&#x2032;, or an enantiomer, a raceme or a diastereoisomer thereof, including phosphonite ligands, phosphite ligands, phosphoramidite ester ligands, phosphoric acid and phosphonic amide. The monophosphine ligand is prepared with a known 3,3,3&#x2032;,3&#x2032;-tetramethyl-1,1&#x2032;-spirobiindane-7,7&#x2032;-diol derivative as a raw material through a scheme in which the compound presented by formula II acts as an intermediate. The present disclosure provides a novel monophosphine ligand, which can be used as a ligand in a metal-catalysed organic reactions or in directly catalyzing an organic reaction, especially as a chiral monophosphine ligand widely used in many chiral catalytic reactions such as asymmetric addition, asymmetric hydrogenation, asymmetric coupling, and asymmetric allyl alkylation, having economic practicality and industrial application prospects. 

3,3,3',3'-tetramethyl-1,1'-spirobiindane-based monophosphine ligand, intermediates thereof, preparation method and use of the same

Provided are a compound of 3,3,3',3&#x2032;-tetramethyl-1,1&#x2032;-spirobiindane-based bisoxazoline ligand, an intermediate, a preparation method and uses thereof. The compound of bisoxazoline ligand is a compound having a structure represented by formula I, or an enantiomer, a raceme, or diastereomer thereof. The bisoxazoline ligand can be prepared via a preparation scheme in which the cheap and easily available 6,6&#x2032;-dihydroxyl-3,3,3&#x2032;,3&#x2032;-tetramethyl-1,1&#x2032;-spirobiindane is used as a starting raw material and the compound represented by formula II serves as the key intermediate through a series of reactions. The new bisoxazoline ligand developed by the present application can be used in catalytic organic reaction, in particular as a chiral bisoxazoline ligand that is widely used in many asymmetric catalytic reactions of metal catalysis, and thus it has economic practicability and industrial application prospect. 

Compound of 3,3,3',3&#x2032;-tetramethyl-1,1&#x2032;-spirobiindane-based bisoxazoline ligand, intermediate thereof, preparation method thereof and use thereof

The invention discloses a tetramethyl-7,7'-spirobiindane-based phosphinooxazoline ligand compound and its preparation method and use. The phosphinooxazoline ligand compound is a compound having a structure shown in general formula I or an enantiomer, a raceme or a diastereoisomer thereof. The phosphinooxazoline ligand obtained through a series of reaction steps using cheap and easily available 3,3,3&#x2032;,3&#x2032;-tetramethyl-1,1&#x2032;-spirobiindane-6,6&#x2032;-diol as a starting material. The novel phosphinooxazoline ligand developed in the invention can be used to organic catalytic reactions, especially as a chiral phosphinooxazoline ligand widely used in metal-asymmetric catalytic reactions, having economical practicality and industrial application prospects. 

3,3,3',3&#x2032;-tetramethyl-1,1&#x2032;-spirobiindane-based phosphinooxazoline ligand compound, preparation method and uses of the same

A plug for use in a passage or conduit of a human body is provided. The plug includes a plug body with a first end and a second end. The plug body has a protrusion on an exterior wall. The plug also includes an attaching member at the first end to attach the plug to the passage or conduit. The plug further includes an axial retention tube within the plug body. The plug further includes a reservoir. The reservoir connects to the retention tube at a third end thereof. The reservoir and the retention tube are configured to regulate the flow of fluid in the passage or conduit.

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Hangzhou, China

Xufeng Lin