There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

Organocatalytic Reactions Enabled by N-Heterocyclic Carbenes.

Recent Advances of Catalytic Asymmetric 1,3-Dipolar Cycloadditions

The use of NHCs for generating homoenolate species has gained widespread popularity in recent years. A number of highly stereoselective processes of NHC-homoenolates have emerged. Homoenolate reactions have also been employed as key steps in the total synthesis of a number of natural products. The use of compatible co-catalysts, improved NHC-catalyst design and the use of novel precursors for homoenolate generation are among the major developments in this area that were disclosed recently. This tutorial review organises and presents the advancements in this rapidly growing area of catalysis and in the process updates a previous account published in 2011 in this journal.

Recent advances in employing homoenolates generated by N-heterocyclic carbene (NHC) catalysis in carbon–carbon bond-forming reactions

N-Heterocyclic carbene (NHC) catalysis has emerged as a powerful stratagem in organic synthesis to construct complex molecules primarily by polarity reversal (umpolung) approaches. These unique Lewis bases have been used to generate acyl anions, enolates, and homoenolates in catalytic fashion. Recently, a new strategy has emerged that dramatically expands the synthetic utility of carbene catalysis by leveraging additional activation modes: cooperative catalysis. The careful selection and balance of cocatalysts have led to enhanced reactivity, increased yields, and improved stereoselectivity. In certain cases, these catalytic additives have changed the regioselectivity or diastereoselectivity. This Minireview highlights new advances in NHC cooperative catalysis and surveys the evolution of this field.

Cooperative Catalysis and Activation with N-Heterocyclic Carbenes

A sterically hindered homoenolate has been generated by the NHC-catalyzed conjugate umpolung of β,β-disubstituted enals and successfully employed in a facile stereoselective annulation with isatins. The strategy provides efficient access to spirocyclic oxindoles bearing two highly congested contiguous quaternary carbon centers. The use of a Bronsted acid cocatalyst was found to be crucial for guaranteeing both excellent reactivity and high stereoselectivity.

Conjugate umpolung of β,β-disubstituted enals by dual catalysis with an N-heterocyclic carbene and a Brønsted acid: facile construction of contiguous quaternary stereocenters.

Enantioselective catalytic intermolecular 1,3-dipolar cycloadditions are powerful methods for the synthesis of heterocycles. In contrast, intramolecular enantioselective 1,3-dipolar cycloadditions are virtually unexplored. A highly enantioselective synthesis of natural-product-inspired pyrrolidino-piperidines by means of an intramolecular 1,3-dipolar cycloaddition with azomethine ylides is now reported. The method has a wide scope and yields the desired cycloadducts with four tertiary stereogenic centers with up to 99% ee. Combining the enantioselective catalytic intramolecular 1,3-dipolar cycloaddition with a subsequent diastereoselective intermolecular 1,3-dipolar cycloaddition yielded complex piperidino-pyrrolizidines with very high stereoselectivity in a one-pot tandem reaction.

Highly Enantioselective Intramolecular 1,3‐Dipolar Cycloaddition: A Route to Piperidino‐Pyrrolizidines

2,6-Dimethoxyphenyl-Substituted N-Heterocyclic Carbenes (NHCs): A Family of Highly Electron-Rich Organocatalysts

The frustrated Lewis pair (FLP) mediated hydrosilylation of pentafulvenes is described yielding allyl silanes with high regioselectivity in excellent yields. While phenyl substituted allyl silanes undergo B(C6F5)3-mediated rearrangement to vinyl silanes, dimethyl derivatives experience FLP-catalyzed hydrogenation followed by an unprecedented protodesilylation. This observation allowed the metal-free hydrogenation of 6,6-dimethylfulvene to iso-propyl cyclopentene according to a FLP-catalyzed triple domino reaction consisting of hydrosilylation, hydrogenation and protodesilylation. The mechanisms were investigated by deuteration experiments.

https://pubs.rsc.org/en/content/articlepdf/2014/ob/c4ob01346h

Frustrated Lewis pair catalyzed hydrosilylation and hydrosilane mediated hydrogenation of fulvenes

Ein sterisch gehindertes Homoenolat wurde durch NHC-katalysierte, konjugierte Umpolung von β,β-disubstituierten Enalen generiert und in einer direkten, stereoselektiven Anellierung mit Isatinen eingesetzt. Diese Strategie bietet einen effizienten Zugang zu spirocyclischen Oxindolen, die zwei hochsubstituierte, benachbarte, quartare Stereozentren enthalten. Die Verwendung einer Bronsted-Saure als Cokatalysator erwies sich als entscheidend fur sowohl ausgezeichnete Reaktivitat als auch hohe Stereoselektivitat.

Konjugierte Umpolung von β,β‐disubstituierten Enalen durch duale Katalyse mit N‐heterocyclischen Carbenen und Brønsted‐Säuren: einfacher Aufbau benachbarter, quartärer Stereozentren

Constantin-G. Daniliuc

Papers

Conjugate umpolung of β,β-disubstituted enals by dual catalysis with an N-heterocyclic carbene and a Brønsted acid: facile construction of contiguous quaternary stereocenters.

Highly Enantioselective Intramolecular 1,3‐Dipolar Cycloaddition: A Route to Piperidino‐Pyrrolizidines

2,6-Dimethoxyphenyl-Substituted N-Heterocyclic Carbenes (NHCs): A Family of Highly Electron-Rich Organocatalysts

Frustrated Lewis pair catalyzed hydrosilylation and hydrosilane mediated hydrogenation of fulvenes

Konjugierte Umpolung von β,β‐disubstituierten Enalen durch duale Katalyse mit N‐heterocyclischen Carbenen und Brønsted‐Säuren: einfacher Aufbau benachbarter, quartärer Stereozentren