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

Enantioselective Vinylogous Michael-Aldol Reaction To Synthesize Spirocyclohexene Pyrazolones in Aqueous Media.

The homologation of ketones with diazo compounds is a useful strategy to synthesize one-carbon chain-extended acyclic ketones or ring-expanded cyclic ketones. However, the asymmetric homologation of acyclic ketones with α-diazo esters remains a challenge due to the lower reactivity and complicated selectivity. Herein, we report the enantioselective catalytic homologation of acetophenone and related derivatives with α-alkyl α-diazo esters utilizing a chiral scandium(III) N,N'-dioxide as the Lewis acid catalyst. This reaction supplies a highly chemo-, regio-, and enantioselective pathway for the synthesis of optically active β-keto esters with an all-carbon quaternary center through highly selective alkyl-group migration of the ketones. Moreover, the ring expansion of cyclic ketones was accomplished under slightly modified conditions, affording a series of enantioenriched cyclic β-keto esters. Density functional theory calculations have been carried out to elucidate the reaction pathway and possible working models that can explain the observed regio- and enantioselectivity.

Catalytic Asymmetric Homologation of Ketones with α-Alkyl α-Diazo Esters.

Highly efficient kinetic resolution of 2H-azirines by an asymmetric imine amidation was achieved in the presence of a chiral N,N'-dioxide/Sc(III) complex, thus providing a promising method to obtain the enantioenriched 2H-azirine derivatives and protecting-group free aziridines at the same time. It is rare to find an example of N1 of an oxindole participating in a reaction over C3. Moreover, chiral 2H-azirines were stereospecifically transformed into an unprotected aziridine and α-amino ketone.

Kinetic Resolution of 2H-Azirines by Asymmetric Imine Amidation.

Asymmetric cascade double Michael additions to construct 2'-substituted 3,3'-spirooxindoles by using a chiral guanidine organocatalyst has been developed. A series of spirooxindole derivatives containing dihydrofuran or pyrrolidine subunits were obtained with good to excellent diastereo- and enantioselectivities. The method showed great tolerance of a number of aromatic and aliphatic alkynones. The strategy gave access to the asymmetric synthesis of (-)-salacin for the first time.

Asymmetric Catalytic Double Michael Additions for the Synthesis of Spirooxindoles

A catalytic asymmetric ring-opening reaction of cyclopropyl ketones with β-naphthols has been accomplished. In the presence of a chiral N,N′-dioxide/scandium(III) complex, a series of aromatic or vinyl substituted cyclopropyl ketones reacted with 2-naphthols, providing efficient access to chiral β-naphthol derivatives in good yields (up to 99%) with good enantioselectivities (up to 97% ee). Notably, using the mixture of 2-naphthol substrates did not affect the efficiency of this catalytic system.

Xiaohua Liu

Papers

Enantioselective Vinylogous Michael-Aldol Reaction To Synthesize Spirocyclohexene Pyrazolones in Aqueous Media.

Catalytic Asymmetric Homologation of Ketones with α-Alkyl α-Diazo Esters.

Kinetic Resolution of 2H-Azirines by Asymmetric Imine Amidation.

Asymmetric Catalytic Double Michael Additions for the Synthesis of Spirooxindoles

Asymmetric ring-opening of cyclopropyl ketones with β-naphthols catalyzed by a chiral N,N′-dioxide–scandium(III) complex