Complete Field Guide to Asymmetric BINOL-Phosphate Derived Brønsted Acid and Metal Catalysis: History and Classification by Mode of Activation; Brønsted Acidity, Hydrogen Bonding, Ion Pairing, and Metal Phosphates

Iron Catalysis in Organic Synthesis

Isatins As Privileged Molecules in Design and Synthesis of Spiro-Fused Cyclic Frameworks

Flow chemistry involves the use of channels or tubing to conduct a reaction in a continuous stream rather than in a flask Flow equipment provides chemists with unique control over reaction parameters enhancing reactivity or in some cases enabling new reactions This relatively young technology has received a remarkable amount of attention in the past decade with many reports on what can be done in flow Until recently, however, the question, “Should we do this in flow?” has merely been an afterthought This review introduces readers to the basic principles and fundamentals of flow chemistry and critically discusses recent flow chemistry accounts

The Hitchhiker's Guide to Flow Chemistry

The legacy of Gilbert Newton Lewis (1875-1946) pervades the lexicon of chemical bonding and reactivity. The power of his concept of donor-acceptor bonding is evident in the eponymous foundations of electron-pair acceptors (Lewis acids) and donors (Lewis bases). Lewis recognized that acids are not restricted to those substances that contain hydrogen (Bronsted acids), and helped overthrow the "modern cult of the proton". His discovery ushered in the use of Lewis acids as reagents and catalysts for organic reactions. However, in recent years, the recognition that Lewis bases can also serve in this capacity has grown enormously. Most importantly, it has become increasingly apparent that the behavior of Lewis bases as agents for promoting chemical reactions is not merely as an electronic complement of the cognate Lewis acids: in fact Lewis bases are capable of enhancing both the electrophilic and nucleophilic character of molecules to which they are bound. This diversity of behavior leads to a remarkable versatility for the catalysis of reactions by Lewis bases.

Lewis Base Catalysis in Organic Synthesis

A highly enantioselective 1,3-dipolar cycloaddition of nitrile oxides with 3-arylidene-oxindoles was realized by a chiral N,N′-dioxide–nickel(II) complex catalyst under mild reaction conditions. A series of spiro-isoxazoline-oxindole derivatives were obtained in moderate yields (up to 65%) with good regioselectivities (up to 99:1), excellent enantioselectivities (up to 99% ee), and exclusive diastereoselectivity as well.

Asymmetric synthesis of spiro[isoxazolin-3,3'-oxindoles] via the catalytic 1,3-dipolar cycloaddition reaction of nitrile oxides.

The catalytic asymmetric Strecker reaction has attracted much attention and a number of successful protocols have been disclosed for its great importance in the synthesis of chiral a-amino acids and their derivatives. However, in contrast to the relatively well-developed cyanation of aldimines, limited reports were related to the cyanation of ketoimines to afford pharmaceutically important disubstituted a-amino nitriles. Especially, it is not easy to promote cyanation of ketoimines with organocatalyst. Since the first successful example reported by Jacobsen’s group using chiral urea as catalyst, two types of N,N’-dioxides have been developed by our group for the Strecker reaction of ketoimines and moderate to good results were obtained. Herein, we reported a novel kind of N,N’-dioxide with an axial chirality for the enantioselective cyanation of N-Ts-protected ketoimine, providing excellent results (Figure 1). Before, the linkers of the previously used N,N’-dioxides for the Strecker reaction of ketoimines were achiral moieties. We speculated that the stereocontrol would be enhanced by employing a suitable chiral linker. On the basis of this idea, we designed and synthesized the N,N’-dioxide catalyst derived from BINOL and prolinamide. The general route was given in Scheme 1. Firstly, (S)-BINOL was formylated via three steps to afford A1 which was subsequently subjected to the condensation reaction with l-prolinamide. Then the product B1 was oxidized to achieve the desired novel N,N’-dioxide 1a. Notably, the absolute configuration of the newly formed chiral center in catalyst 1a was identified as R based on the observation of strong NOE signal between H1 and H2 (see Supporting Information). However, the attempt to synthesize the similar structure from (R)-BINOL and lprolinamide was failed, which might be attributed to the instability of the corresponding N,N’-dioxide. Interestingly, when two hydroxyl groups of B1 were replaced by two methoxy group, N,N’-dioxide 1c could not be prepared as diastereomerically pure form in the oxidation step. Instead, the mixture of the two epimers with a ratio of 1:1.8 was obtained (see Supporting Information). Other catalysts displayed in Figure 1 were prepared in a similar process (Scheme 1) for the preparation of 1a. To examine the initial hypothesis, we evaluated these catalysts in the asymmetric Strecker reaction of N-tosyl ketoimines with TMSCN. It was found that a promising result (80 % ee) was obtained by employing 5 mol% N,N’-dioxide 1a as catalyst, while inferior asymmetric induction was ob[a] Z. Hou, J. Wang, Dr. X. Liu, Prof. Dr. X. Feng Key Laboratory of Green Chemistry & Technology (Sichuan University), Ministry of Education College of Chemistry, Sichuan University Chengdu 610064 (PR China) and State Key Laboratory of Oral Diseases, Sichuan University Chengdu 610041 (PR China) Fax: (+86) 28-8541-8249 E-mail : xmfeng@scu.edu.cn Supporting information for this article is available on the WWW under http://www.chemistry.org or from the author. Figure 1. Catalysts used in this research.

Highly enantioselective strecker reaction of ketoimines catalyzed by an organocatalyst from (S)-BINOL and L-prolinamide.

A highly efficient asymmetric Mannich-type reaction between α-tetralone-derived β-keto esters/amides and 1,3,5-triaryl-1,3,5-triazinanes was realized in the presence of chiral N,N′-dioxide–Ni(II) or Mg(II) complex. A variety of optically active β-amino compounds with all-carbon quaternary stereocenters were obtained in good yields with excellent enantioselectivities. A possible transition state was proposed based on these experiments and previous reports.

/pdf/a-new-approach-to-the-asymmetric-mannich-reaction-catalyzed-3nfb5qs8ci.pdf

Xiaohua Liu

Papers

Asymmetric synthesis of spiro[isoxazolin-3,3'-oxindoles] via the catalytic 1,3-dipolar cycloaddition reaction of nitrile oxides.

Highly enantioselective strecker reaction of ketoimines catalyzed by an organocatalyst from (S)-BINOL and L-prolinamide.

A new approach to the asymmetric Mannich reaction catalyzed by chiral N , N ′-dioxide–metal complexes

Asymmetric Three-Component Reaction for the Synthesis of Tetrasubstituted Allenoates via Allenoate-Copper Intermediates

Organocatalytic Enantioselective Michael Addition of 4‐Hydroxycoumarin to α,β‐Unsaturated Ketones: A Simple Synthesis of Warfarin