The present application describes process for preparing an ortho-allylated hydroxy aryl compounds such as compounds of Formula (I) by reacting an allylic alcohol with a hydroxy aryl compound in the presence of aluminum compound selected from alumina and aluminum alkoxides and in a non-protic solvent wherein at least one carbon atom ortho to the hydroxy group in the hydroxy aryl compound is unsubstituted. The present application also includes compounds of Formula (I).

##STR00001##

The present application describes process for preparing an ortho-allylated hydroxy aryl compounds such as compounds of Formula (I) by reacting an allylic alcohol with a hydroxy aryl compound in the presence of aluminum compound selected from alumina and aluminum alkoxides and in a non-protic solvent wherein at least one carbon atom ortho to the hydroxy group in the hydroxy aryl compound is unsubstituted. The present application also includes compounds of Formula (I).

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The present disclosure provides certain processes of making 3-fluoro-5-(((1S,2aR)-1,3,3,4,4-pentafluoro-2a-hydroxy-2,2a,3,4-tetrahydro-1H-cyclopenta[cd]inden-7-yl)oxy)-benzonitrile (Compound 1) and certain polymorphs thereof. Also provided are pharmaceutical compositions comprising a crystalline polymorph form of Compound 1 and processes for preparing such polymorph forms.

The present disclosure provides certain processes of making 3-fluoro-5-(((1S,2aR)-1,3,3,4,4-pentafluoro-2a-hydroxy-2,2a,3,4-tetrahydro-1H-cyclopenta[cd]inden-7-yl)oxy)-benzonitrile (Compound 1) and certain polymorphs thereof. Also provided are pharmaceutical compositions comprising a crystalline polymorph form of Compound 1 and processes for preparing such polymorph forms.

A process for synthesizing an azo compound by oxidation of a hydrogen compound in the presence of a catalyst and a compound of formula (I) is described in which R.sub.1, R.sub.2 and R.sub.3
(R.sub.1)(R.sub.2)C(PO.sub.3(R.sub.3).sub.2).sub.2  (I)
are as defined. The use of a compound of formula (I) as complexing agent for a catalyst is also described.

A process for synthesizing an azo compound by oxidation of a hydrogen compound in the presence of a catalyst and a compound of formula (I) is described in which R.sub.1, R.sub.2 and R.sub.3
(R.sub.1)(R.sub.2)C(PO.sub.3(R.sub.3).sub.2).sub.2  (I)
are as defined. The use of a compound of formula (I) as complexing agent for a catalyst is also described.

A process for synthesizing an azo compound by oxidation of a hydrogen compound in the presence of a catalyst and a compound of formula (I) is described in which R.sub.1, R.sub.2 and R.sub.3
(R.sub.1)(R.sub.2)C(PO.sub.3(R.sub.3).sub.2).sub.2  (I)
are as defined. The use of a compound of formula (I) as complexing agent for a catalyst is also described.

Disclosed is a method of synthesizing a (1R,2R)-nitroalcohol compound of formula (I), as shown in the following reaction scheme, including: subjecting a compound of formula (II) and a compound of formula (III) to a condensation reaction in an organic solvent in the presence of a copper complex generated in situ from a chiral (1S,2R)-amino alcohol ligand and a cupric salt to produce the (1R,2R)-nitroalcohol compound of formula (I), where R.sup.1 and R.sup.2 are defined in the same manner as that in the specification. The method involves mild reaction conditions, excellent diastereoselectivity and high chemical yield, and thus it is suitable for industrial applications. ##STR00001##

Disclosed is a method of synthesizing a (1R,2R)-nitroalcohol compound of formula (I), as shown in the following reaction scheme, including: subjecting a compound of formula (II) and a compound of formula (III) to a condensation reaction in an organic solvent in the presence of a copper complex generated in situ from a chiral (1S,2R)-amino alcohol ligand and a cupric salt to produce the (1R,2R)-nitroalcohol compound of formula (I), where R.sup.1 and R.sup.2 are defined in the same manner as that in the specification. The method involves mild reaction conditions, excellent diastereoselectivity and high chemical yield, and thus it is suitable for industrial applications. ##STR00001##

The present invention discloses a method for directly constructing highly optically active tetrasubstituted allenic acid compounds, i.e., a one-step process for directly constructing highly optically active axially chiral tetrasubstituted allenic acid compounds by using tertiary propargyl alcohol, carbon monoxide and water as reactants in an organic solvent in the presence of palladium catalyst, chiral diphosphine ligand, monophosphine ligand and organic phosphoric acid. The method of the present invention has the following advantages: operations are simple, raw materials and reagents are readily available, the reaction conditions are mild, the substrate has high universality, the functional group has good compatibility, and the reaction has high enantioselectivity (90%˜>99% ee). The highly optically active allenic acid compounds obtained by the present invention can be used as an important intermediate to construct γ-butyrolactone compounds containing tetrasubstituted chiral quaternary carbon centers, tetrasubstituted allenic alcohol and other compounds.