Jianrong (Steve) Zhou

Intermolecular, Catalytic Asymmetric Hydroamination of Bicyclic Alkenes and Dienes in High Yield and Enantioselectivity

A set of catalytic, intermolecular hydroaminations of strained bicyclic olefins and dienes are reported that occur in both high yield and high enantioselectivity. These reactions occur with a catalyst generated from [Ir(cyclooctene)Cl]2, sterically hindered and electron-rich derivatives of the Segphos and BIPHEP family of ligands, and a soluble base. This system catalyzes the addition of various anilines to norbornene, norbornadiene, and other bicyclic olefins. The products from addition of p-anisidine can be transformed to BOC-protected norbornylamine and to substituted cyclopentanes in nearly enantiopure form. Mechanistic studies show that addition of aniline-d2 occurs in a syn fashion and suggest that the catalytic cycle comprises oxidative addition of aniline to form a bis-anilide hydride complex, followed by migratory insertion of olefin and reductive elimination of product in a series of steps involving iridium complexes containing ancillary bisphosphine and arylamide ligands.

Iridium-Catalyzed Intermolecular Hydroamination of Unactivated Aliphatic Alkenes with Amides and Sulfonamides

The intermolecular addition of N-H bonds to unactivated alkenes remains a challenging, but desirable, strategy for the synthesis of N-alkylamines. We report the intermolecular amination of unactivated α-olefins and bicycloalkenes with arylamides and sulfonamides to generate synthetically useful protected amine products in high yield. Mechanistic studies on this rare catalytic reaction revealed a resting state that is the product of N-H bond oxidative addition and coordination of the amide. Rapid, reversible dissociation of the amide precedes reaction with the alkene, but an intramolecular, kinetically significant rearrangement of the species occurs before this reaction with alkene.

Asymmetric Intermolecular Heck Reaction of Aryl Halides

The asymmetric intermolecular Heck reaction has been limited to aryl and vinyl triflates. Herein, we extend the reaction to aryl and vinyl bromides. Various cyclic olefins coupled with high enantioselectivity. Only bisphosphine oxides on a spiro backbone formed highly stereoselective Pd catalysts. The use of alcoholic solvents and alkylammonium salts were essential to promote halide dissociation from neutral arylpalladium complexes.

Iridium‐Catalyzed H/D Exchange at Vinyl Groups without Olefin Isomerization

Exchange of a hydrogen atom with a deuterium atom (H/D exchange) was one of the first catalytic C H activation processes reported to occur by organometallic intermediates. This process has experienced a renaissance recently because of the value of deuterated and tritiated compounds in the study of reaction mechanisms and biological processes. In general, deuterium or tritium can be introduced during a synthesis with a deuterated or tritiated reagent, or after the synthesis is complete by H/D or H/T exchange. If regioand stereoselective H/D or H/Texchange could be developed, the latter approach would be simpler to conduct and more cost effective than the introduction of the label during synthesis. Moreover, it would avoid the handling of tritiated synthetic intermediates. H/D exchange of aromatic hydrogen atoms is well known and has been conducted with a variety of catalysts, including acid, base, and metal complexes. H/D exchange of nonactivated, aliphatic C H bonds has also been conducted with transition-metal catalysts, including [Cp*Ir(PMe3)], [6,7] [Cp*Ir(carbene)], and [(Tp)Ir] complexes. H/D exchanges catalyzed by the recently developed systems afford a high degree of isotope incorporation, and some have been conducted with D2O as the deuterium source. [10] In contrast to H/D exchange at aryl and alkyl groups, H/D exchange at vinyl groups has not been studied extensively. Most existing examples of H/D exchange at vinyl groups have been conducted with cyclic or isolated olefins, such as cyclopentene, styrene, and tert-butylethylene, presumably to avoid complications from olefin isomerization. A more general, selective H/D exchange of alkene hydrogen atoms has been limited because alkene isomerization often occurs under conditions that lead to C H activation. For example, H/ D exchange of 1-pentene and 1-hexene has caused isomerization to the more stable internal isomers at elevated temperature, at room temperature, and under photochemical conditions. We report a catalytic system that overcomes this limitation. We show that H/D exchange catalyzed by an iridium complex containing an aliphatic pincer ligand occurs at the vinylic positions without olefin isomerization. This selectivity, along with high functional group compatibility, is demonstrated by H/D exchange between C6D6 and a series of olefins containing various functional groups, as well as natural products and natural product analogues. The discovery of this H/D exchange chemistry resulted from studies with the amidoiridium hydride complex [(dtbpp)Ir(H)(NH2)] (1) (dtbpp = 1,5-bis(di-tert-butylphosphino)pentan-3-yl) [Eq. (1)], that we had previously shown to form by oxidative addition of ammonia. The reaction of pentene in C6D6 in the presence of catalytic amounts of 1 led to rapid H/D exchange of the olefinic hydrogen atoms with the C6D6 solvent. No isomerization of the olefin was observed, and less than 1% deuterium was incorporated into the alkyl chain, including the allylic positions.

Iridium-Catalyzed, Intermolecular Hydroamination of Unactivated Alkenes with Indoles

The addition of an N-H bond to an olefin is the most direct route for the synthesis of alkylamines. Currently, intermolecular hydroamination is limited to reactions of a narrow range of reagents containing N-H bonds or activated alkenes, and all the examples of additions to unactivated alkenes require large excesses of alkene. We report intermolecular hydroamination reactions of indoles with unactivated olefins. The reactions occur with as few as 1.5 equiv of olefin to form N-alkylindoles exclusively and in good yield. Characterizations of the catalyst resting state, kinetic data, labeling studies, and computational data imply that the addition occurs by olefin insertion into the Ir-N bond of an N-indolyl complex and that this insertion reaction is faster than insertion of olefin into the Ir-C bond of the isomeric C-2-indolyl complex.

An Enantioselective, Intermolecular α-Arylation of Ester Enolates To Form Tertiary Stereocenters

In transition-metal catalyzed, asymmetric α-arylation of carbonyl compounds, formation of tertiary centers with high enantioselectivity is a longstanding problem, due to easy enolization of the monoarylation products. Herein, we report such examples using a palladium catalyst supported by a new, (R)-H(8)-BINOL-derived monophosphine. Silyl ketene acetals, together with a weakly basic activator, were used as equivalents of ester anions, and they reacted smoothly with aryl triflates in excellent enantiomeric excess (ee). The usefulness of the reaction was demonstrated in a gram-scale synthesis of (S)-Naproxen in 92% ee.

An enantioselective allylation reaction of aldehydes in an aqueous medium

Abstract An enantioselective allylation reaction of aldehydes with enantioselectivities up to 92% has been achieved in an aqueous medium, by using ( S,S )-2,6-bis(4-isopropyl-2-oxazolin-2-yl)pyridine as the chiral source.

A catalytic enantioselective allylation reaction of aldehydes in an aqueous medium

Abstract A modified Yamamoto–Yanagisawas catalyst ( S )-Tol-BINAP·AgNO 3 was successfully applied to a catalytic enantioselective allylation reaction of aldehydes in an aqueous system. The reactions with aromatic aldehydes afforded the desired products in high yields with good stereoselectivities.

An enantioselective indium-mediated allylation reaction of aldehydes and ketones in dichloromethane

Abstract An enantioselective indium-mediated addition reaction of allylic bromides to carbonyl compounds was achieved in dichloromethane in the presence of (−)-cinchonidine. The desired products were obtained in moderate to excellent yields and with up to 75% enantioselectivity.

Asymmetric Conjugate Addition of Organoboron Reagents to Common Enones Using Copper Catalysts

Copper complexes of phosphoramidites efficiently catalyzed asymmetric addition of arylboron reagents to acyclic enones. Importantly, rare 1,4-insertion of arylcopper(I) was identified which led directly to O-bound copper enolates. The new mechanism is fundamentally different from classical oxidative addition/reductive elimination of organocopper(I) on enones.