An unprecedented direct C–H bond functionalization of unprotected phenols with α-aryl α-diazoacetates and diazooxindoles was developed. A tris(2,4-di-tert-butylphenyl) phosphite derived gold complex promoted the highly chemoselective and site-selective C–H bond functionalization of phenols and N-acylanilines with gold-carbene generated from the decomposition of diazo compounds, furnishing the corresponding products in moderate to excellent yields at rt. The salient features of this reaction include readily available starting materials, unprecedented C–H functionalization rather than X–H insertion, good substrate scope, mild conditions, high efficiency, and ease in further transformation. To the best of our knowledge, this is the first example of C–H functionalization of unprotected phenols with diazo compounds.

Highly Site-Selective Direct C–H Bond Functionalization of Phenols with α-Aryl-α-diazoacetates and Diazooxindoles via Gold Catalysis

Catalytic asymmetric synthesis of spirooxindoles: recent developments

ConspectusCatalytic asymmetric cycloadditions and cascade cyclizations are a major focus for the enantioselective construction of chiral carbo- and heterocycles. A number of chiral Lewis acids and organocatalysts have been designed for such reactions. The development of broadly applicable catalysts bearing novel chiral backbones to meet the demands of various applications is an ongoing challenge. Approximately 10 years ago, we introduced a group of conformationally flexible C2-symmetric N,N′-dioxide amide compounds, which represent a new class of privileged ligands. The coordination of the four oxygens of a chiral N,N′-dioxide around a central metal generates an octahedral tricyclometalated Lewis acid catalyst that can carry out various enantioselective reactions. In this Account, we summarize our recent studies on asymmetric cycloadditions between various dienophiles and dienes, dipoles and dipolarophiles, and cascade cyclizations catalyzed by chiral N,N′-dioxide–metal complexes. In principle, these uniq...

Asymmetric Cycloaddition and Cyclization Reactions Catalyzed by Chiral N,N′-Dioxide–Metal Complexes

The catalytic enantioselective assembly of spirocyclic molecules featuring a spiro quaternary carbon stereocenter is currently of great interest because such privileged 3D structures are widely present in natural products that exhibit a broad spectrum of biological and pharmacological activities. This review summarizes the advances based on six major synthetic strategies and showcases the reaction mechanisms in detail. The advantages and limitations of each synthetic strategy are presented, and the remaining synthetic opportunities are outlined.

Catalytic Enantioselective Construction of Spiro Quaternary Carbon Stereocenters

The metal-catalyzed asymmetric conjugate addition (ACA) reaction has emerged as a general and powerful approach for the construction of optically active compounds and is among the most significant and useful reactions in synthetic organic chemistry In recent years, great progress has been made in this area with the use of various chiral metal complexes based on different chiral ligands This review provides comprehensive and critical information on the enantioselective 1,4-conjugate addition of nonorganometallic (soft) nucleophiles and their importance in synthetic applications The literature is covered from the last 10 years, and a number of examples from before 2007 are included as background information The review is divided into multiple parts according to the type of nucleophile involved in the reaction (such as C-, B-, O-, N-, S-, P-, and Si-centered nucleophiles) and metal catalyst systems used

Recent Advances in Metal-Catalyzed Asymmetric 1,4-Conjugate Addition (ACA) of Nonorganometallic Nucleophiles.

Efficient enantioselective NH insertion reactions of secondary and primary anilines were catalyzed by palladium(0) in combination with chiral guanidine derivatives. A broad range of substituted anilines were tolerated, and the corresponding products were obtained in high yield (up to 99 %) with good enantioselectivity (up to 94 % ee) under mild reaction conditions. The NH insertion mechanism was examined by the study of kinetic isotope effects, control experiments, HRMS, and spectroscopic analysis.

Asymmetric N ? H Insertion of Secondary and Primary Anilines under the Catalysis of Palladium and Chiral Guanidine Derivatives

Highly diastereo- and enantioselective synthesis of spirooxindole-cyclohexaneamides through N,N′-dioxide/Ni(II)-catalyzed Diels–Alder reactions

A highly enantioselective tandem Michael/ring-closure reaction of α,β-unsaturated pyrazoleamides and amidomalonates has been accomplished in the presence of a chiral N,N'-dioxide-Yb(OTf)3 complex (Tf: trifluoromethanesulfonyl) to give various substituted chiral glutarimides with high yields and diastereo- and enantioselectivities. Moreover, this methodology could be used for gram-scale manipulation and was successfully applied to the synthesis of (-)-paroxetine. Further nonlinear and HRMS studies revealed that the real catalytically active species was a monomeric L-PMe2 -Yb3+ complex. A plausible transition state was proposed to explain the origin of the asymmetric induction.

Catalytic Michael/Ring‐Closure Reaction of α,β‐Unsaturated Pyrazoleamides with Amidomalonates: Asymmetric Synthesis of (−)‐Paroxetine

N,N′-Dioxide/nickel(II) complexes have been developed to catalyze the inverse-electron-demand hetero-Diels–Alder reaction of β,γ-unsaturated α-ketoesters with acyclic enecarbamates. After detailed screening of the reaction parameters, mild optimized reaction conditions were established, affording 3,4-dihydro-2H-pyranamines in up to 99 % yield, 99 % ee and more than 95:5 d.r. The catalytic system was also efficient for β-substituted acyclic enecarbamates, affording more challenging 2,3,4-trisubstituted 3,4-dihydro-2H-pyranamine with three contiguous stereogenic centers in excellent yields, diastereoselectivities, and enantioselectivities. The reaction could be scaled up to a gram scale with no deterioration of either enantioselectivity or yield. Based on these experiments and on previous reports, a possible transition state was proposed.

Yuhang Zhou

Papers

Asymmetric N ? H Insertion of Secondary and Primary Anilines under the Catalysis of Palladium and Chiral Guanidine Derivatives

Highly diastereo- and enantioselective synthesis of spirooxindole-cyclohexaneamides through N,N′-dioxide/Ni(II)-catalyzed Diels–Alder reactions

Catalytic Michael/Ring‐Closure Reaction of α,β‐Unsaturated Pyrazoleamides with Amidomalonates: Asymmetric Synthesis of (−)‐Paroxetine

N,N'-dioxide/nickel(II)-catalyzed asymmetric inverse-electron-demand hetero-diels-alder reaction of β,γ-unsaturated α-ketoesters with enecarbamates.

N,N′-Dioxide/nickel(II)-catalyzed asymmetric Diels–Alder reaction of cyclopentadiene with 2,3-dioxopyrrolidines and 2-alkenoyl pyridines