Yale University

University of California

Other

University of Illinois

Basf Se Corporation

Basf Corporation

John F Hartwig

Patrick Fier

Motoi Kawatsura

Blake C Hamann

Douglas S Clark

Hiroyuki Morimoto

Jay D Keasling

Martin Ernst

Thomas Carl Semple

Christoph Kiener

Jing Huang

Aindrila Mukhopadhyay

Stephan Zuend

Sheila I Hauck

Chutian Shu

Oliver Loeber

Huiyuan Chen

Bo Su

Quinetta Shelby

Kevin H Shaughnessy

Luis M Alcazar-Roman

Janis Louie

Michael S Driver

Grace Mann

Zhennan Liu

Noriyasu Kataoka

Pawel Dydio

Hanna M Key

Ala Bunescu

Fernando Garcia Lopez

Toshimichi Ohmura

Qilong Shen

Zhijian Liu

Wojciech Chaładaj

Shaozhong Ge

Tyler Wilson

Chen Cheng

The present invention provides for a genetically modified host cell capable of producing an unnatural compound, such as terpenoid, comprising a P450 enzyme comprising an artificial cofactor, and the host cell is capable of uptaking the artificial cofactor by comprising a heterologous heme transport transmembrane protein, or homologue thereof.

Host cells and methods useful for producing unnatural terpenoids using a novel artificial metalloenzyme

The present invention is drawn to artificial metalloenzymes for use in cyclopropanation reactions, amination and C&#x2014;H insertion.

Artificial metalloenzymes containing noble metal-porphyrins

A process for the preparation of amino alcohols includes condensing a compound of Formula (II), a stereoisomer, a tautomer, or a salt thereof with a compound of Formula (IIIa) or Formula (IIIb), a stereoisomer, a tautomer, or a salt thereof to form a condensation product; hydroxylating or acyloxylating the condensation product in the presence of an oxidant to obtain a hydroxylation or acyloxylation product; and subjecting the hydroxylation or acyloxylation product to one or more subsequent reactions comprising a hydrolysis reaction, alcohol deprotection, an amino lysis reaction, or a combination of two or more thereof to obtain an amino alcohol of Formula (I). 

Process for preparation of amino alcohols

Reaction mixtures for silvlating arene substrates and methods of using such reaction mixtures to silyiate the arene substrates are provided. Exemplary reaction mixtures include the arene substrate, a liganded metal catalyst, a hydrogen acceptor and an organic solvent. The reaction conditions allow for diverse substituents on the arene substrate.

Intermolecular C-H silylation of unactivated arenes

A composition, consisting essentially of copper, a fluoroalkyl group, and a ligand comprising at least one group-V donor. The molar ratio of copper to the fluoroalkyl group is approximately 1.

One-component reagent for the fluoroalkylation reaction

The present invention provides compositions and methods for the selective C&#x2014;H fluorination of nitrogen-containing heteroarenes with AgF, which has previously been considered too reactive for practical, selective C&#x2014;H fluorination. Fluorinated heteroarenes are prevalent in numerous pharmaceuticals, agrochemicals and materials. However, the reactions used to introduce fluorine into these molecules require pre-functionalized substrates or the use of Fgas. The present invention provides a mild and general method for the C&#x2014;H fluorination of nitrogen-containing heteroarene compounds to 2-fluoro-heteroarenes with commercially available AgF. In various embodiments, these reactions occur at ambient temperature within one hour and occur with exclusive selectivity for fluorination at the 2-position. Exemplary reaction conditions are effective for fluorinating diazine heteroarenes to form a single fluorinated isomer.

C-H fluorination of heterocycles with silver (II) fluoride

The coupling of aryl, heteroaryl, and vinyl halides with &#x3b1;,&#x3b1;-difluoroketones or silyl ethers or siylenol ethers of &#x3b1;,&#x3b1;-difluoroketones and &#x3b1;,&#x3b1;-difluoroamides and esters are described. Further derivatization of the coupling products (such as ketone cleavage and Baeyer-Villiger oxidation) is also described.

Metal-catalyzed coupling of aryl and vinyl halides with alpha, alpha-difluorocarbonyl compounds

Selectively fluorinated molecules are important as materials, pharmaceuticals, and agrochemicals, but their synthesis by simple, mild, laboratory methods is challenging. We report a straightforward method for the cross-coupling of a difluoromethyl group with readily available reagents to form difluoromethylarenes. The reaction of electron-neutral, electron rich, and sterically hindered aryl and vinyl iodides with the combination of CuI, CsF and TMSCFH leads to the formation of difluoromethylarenes in high yield with good functional group compatibility. This transformation is surprising, in part, because of the prior observation of the instability of CuCFH.

Difluoromethylation of aryl and vinyl iodides

The invention provides compositions and methods of using the compositions in fluorinating aryl precursors containing a leaving group replaceable by fluoride ion. The compositions include a metal ion source, a fluoride ion source, and a compound, which is an aryl precursor of the aryl fluoride, and which has a leaving group replaceable by the fluoride. Exemplary methods of the invention make use of such compositions and methods to prepare an aryl fluoride compound. In an exemplary embodiment, the fluoride ion source is a source ofF.

Fluorination of aryl compounds

A method of forming a fluorinated molecular entity includes reacting in a reaction mixture an aromatic halide, copper, a fluoroalkyl group, and a ligand. The aromatic halide includes an aromatic group and a halogen substituent bonded to the aromatic group. The ligand includes at least one group-V donor selected from phosphorus and an amine. The overall molar ratio of copper to aromatic halide in the reaction mixture is from 0.2 to 3. The method further includes forming a fluoroalkylarene including the aromatic group and the fluoroalkyl group bonded to the aromatic group. A composition, which may be used in the method, consists essentially of copper, the fluoroalkyl group, and the ligand, where the molar ratio of copper to the fluoroalkyl group is approximately 1.

Fluoroalkylation methods and reagents

A method includes reacting an amino group, a composition including rhodium and an organic ligand, and a substrate having structural formula (I) in a reaction mixture. Ris an organic group including a spcarbon atom bonded to C. Ris selected from the group consisting of hydrogen, methyl, and an organic group including a spcarbon atom bonded to C. Rand Rindependently are selected from the group consisting of hydrogen, methyl, and an organic group including a spcarbon atom bonded to C. The method further includes forming a hydroaminated product in the reaction mixture.

Hydroamination of alkenes

A catalytic process for the synthesis of aromatic primary amines, reagent compositions for effecting the process, and transition metal complexes useful in the process, are provided.

Process for the synthesis of arylamines from the reaction of an aromatic compound with ammonia or a metal amide

The present invention is directed to a catalyst composition, comprising: (1) a catalyst precursor having the general structure MSXwherein M is a transition metal selected from the group consisting of iridium, molybdenum, and tungsten; S is a coordinating ligand; X is a counterion; and n is an integer from 0 to 5; and (2) a phosphoramidite ligand having the structure wherein O&#x2014;C&#x2014;O is an aliphatic or aromatic diolate and wherein R, R, Rand Rare selected from the group consisting of substituted or unsubstituted aryl groups, substituted or unsubstituted heteroaryl groups, substituted or unsubstituted aliphatic groups, and combinations thereof, with the proviso that at least one of R, R, R, or Rmust be a substituted or unsubstituted aryl or heteroaryl group. The present invention is also directed to activated catalysts made from the above catalyst composition, as well as methods of allylic amination and etherification using the above catalysts.

Enantioselective amination and etherification

Catalyst for aromatic C&mdash;O, C&mdash;N, and C&mdash;C bond formation

A process for the catalytic coupling of aliphatic or alkyl branched alicyclic hydrocarbons with a functionalizing reagent under thermal conditions to selectively functionalize the hydrocarbon at its primary C&mdash;H site.

Selective, catalytic, thermal functionalization of primary C-H hydrocarbon bonds

Growing community of inventors

Berkeley, CA, United States of America

John F Hartwig