University of California

California Institute of Technology

Princeton University

Firmenich Sa

David W C MacMillan

Kateri A Ahrendt

Alan B Northrup

Zhiwei Zuo

Julie Quintaine

Teresa Beeson

Vy M Dong

Tehshik Yoon

Nick A Paras

Methods described herein enable the production of numerous molecular species through decarboxylative cross-coupling via use of photoredox and transition metal catalysts. For example, methods described herein enable the production of numerous molecular species through decarboxylative cross-coupling via use of photoredox and transition metal catalysts. A method described herein, in some embodiments, comprises providing a reaction mixture including a photoredox catalyst, a transition metal catalyst, a coupling partner and a substrate having a carboxyl group. The reaction mixture is irradiated with a radiation source resulting in cross-coupling of the substrate and coupling partner via a mechanism including decarboxylation, wherein the coupling partner is selected from the group consisting of a substituted aromatic compound and a substituted aliphatic compound.

Decarboxylative cross-coupling and applications thereof

The alpha alkylation of an aldehyde with a polycyclic olefin followed by a ring opening step is presented in order to provide a compound of formula (I) in the form of any one of its stereoisomers or a mixture thereof and where in R represents a hydrogen atom or Clinear alkyl group; R, R, R, and Rrepresent, when taken separately, independently of each other, a hydrogen atom or a Clinear alkyl group or a Clinear or branched alkyl group; or Rand R, when taken together, represent a Clinear, branched or cyclic alkanediyl group and n is 1 or 2 is presented. 

Alpha alkylation of aldehyde with a polycyclic olefin

Methods described herein enable the production of numerous molecular species through decarboxylative cross-coupling via use of photoredox and transition metal catalysts. A method described herein, in some embodiments, comprises providing a reaction mixture including a photoredox catalyst, a transition metal catalyst, a coupling partner and a substrate having a carboxyl group. The reaction mixture is irradiated with a radiation source resulting in cross-coupling of the substrate and coupling partner via a mechanism including decarboxylation, wherein the coupling partner is selected from the group consisting of a substituted aromatic compound and a substituted aliphatic compound.

Nonmetallic organic catalysts are provided that facilitate the enantioselective reaction of &#x3b1;,&#x3b2;-unsaturated ketones. The catalysts are chiral imidazolidinone compounds having the structure of formula (IIA) or (IIB) or are acid addition salts thereof, wherein, in one preferred embodiment, Ris C-Calkyl, Ris phenyl or 2-methylfuryl, Rand Rare hydrogen, and Ris phenyl optionally substituted with 1 or 2 substituents selected from the group consisting of halo, hydroxyl, and C-Calkyl. The chiral imidazolidinones are useful in catalyzing a wide variety of reactions, including cycloaddition reactions, Friedel-Crafts alkylation reactions, and Michael additions.

Enantioselective transformation of &#x3b1;,&#x3b2;-unsaturated ketones using chiral organic catalysts

Nonmetallic, chiral organic catalysts are used to catalyze an enantioselective aldol coupling reaction between aldehyde substrates. The reaction may be carried out with a single enolizable aldehyde, resulting in dimerization to give a &#x3b2;-hydroxy aldehyde, or trimerization to give a dihydroxy tetrahydropyran. The reaction may also conducted with an enolizable aldehyde and a second aldehyde, which may or may not be enolizable, so that the coupling is a cross-aldol reaction in which the &#x3b1;-carbon of the enolizable aldehyde adds to the carbonyl carbon of the second aldehyde in an enantioselective fashion. Reaction systems composed of at least one enolizable aldehyde, an optional additional aldehyde, and the nonmetallic chiral organic catalyst are also provided, as are methods of implementing the enantioselective aldol reaction in the synthesis of sugars.

Direct, enantioselective aldol coupling of aldehydes using chiral organic catalysts

Nonmetallic, chiral organic catalysts are used to catalyze enantioselective fluorination of enolizable aldehydes. Reaction systems composed of an enolizable aldehyde, an electrophilic fluorination reagent, and a nonmetallic chiral catalyst in the form of an imidazolidinone salt are also provided.

Enantioselective alpha-fluorination of aldehydes using chiral organic catalysts

Nonmetallic, chiral organic catalysts are used to catalyze the 1,4-addition of an aromatic nucleophile to an &#x3b1;,&#x3b2;-unsaturated aldehyde. The aromatic nucleophile may be an N,N-disubstituted aniline compound, or an analog thereof. The reaction is efficient and enantioselective, and proceeds with a variety of substituted and unsubstituted aromatic nucleophiles and aldehydes. The invention also provides a method for the deamination of aromatic N,N-disubstituted amines such as those resulting from the 1,4-addition of an aromatic nucleophile to an &#x3b1;,&#x3b2;-unsaturated aldehyde.

Enantioselective 1,4-addition of aromatic nucleophiles to &#x3b1;,&#x3b2;-unsaturated aldehydes using chiral organic catalysts

Enantioselective transformation of &agr;,&bgr;-unsaturated aldehydes using chiral organic catalysts

A novel tandem acyl-Claisen rearrangement reaction is provided. An allylic reactant such as an allylic amine or an allylic thioether, having at least two functional groups that enable the reactant to undergo at least two successive Claisen rearrangement reactions, is reacted with an acid chloride in the presence of a Lewis acid catalyst composition composed of a Lewis acid and a second catalyst component selected from the group consisting of tertiary amines and non-nitrogenous bases. The stereochemistry of the reaction product is readily controlled by the positioning and size of substituents on the allylic reactant. The reaction may be carried out on a solid support, i.e., on the surface of a substrate suitable for conducting solid phase chemical reactions.

Tandem acyl-Claisen rearrangement in the preparation of chiral products

Acid addition salts of imidazolidinones are provided as catalysts for transforming a functional group within a first reactant by reaction with a second reactant. Exemplary first reactants are &agr;,&bgr;-unsaturated carbonyl compounds such as &agr;,&bgr;-unsaturated ketones and &agr;,&bgr;-unsaturated aldehydes. Chiral imidazolidinone salts can be used to catalyze enantioselective reactions, such that a chiral product is obtained from a chiral or achiral starting material in enantiomerically pure form.

Chiral imidazolidinone-based catalyst composition and reaction system

Catalytic processes employing chiral imidazolidinone-based catalyst composition

A method is provided for catalytically transforming a functional group within a first reactant by reaction with a second reactant in the presence of a nonmetallic, organic catalyst composition composed of a heteroatom-containing activator and an acid, or a salt of a heteroatom-containing activator and an acid. Exemplary first reactants are &agr;,&bgr;-unsaturated carbonyl compounds such as &agr;,&bgr;-unsaturated ketones and &agr;,&bgr;-unsaturated aldehydes. The heteroatom of the activator is a Group 15 or Group 16 element such as nitrogen, oxygen, sulfur or phosphorus, and exemplary heteroatom-containing activators are amines. Chiral heteroatom-containing activators can be used to catalyze enantioselective reactions, such that a chiral product is obtained from a chiral or achiral starting material in enantiomerically pure form.

Chemical transformation of substrates using nonmetallic, organic catalyst compositions

A novel Claisen rearrangement reaction is provided. An allylic reactant such as an allylic amine, an allylic ether or an allylic thioether is reacted with an acid chloride in the presence of a Lewis acid catalyst composition composed of a Lewis acid and a base selected from the group consisting of tertiary amines and non-nitrogenous bases. The stereochemistry of the reaction product is readily controlled by the positioning and size of substituents on the allylic reactant. The reaction may be carried out on a solid support, i.e., on the surface of a substrate suitable for conducting solid phase chemical reactions.

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Princeton, NJ, United States of America

David W C MacMillan