Enantioselektive α‐Fluorierung von Carbonylverbindungen: Organo‐ oder Metallkatalyse?

Pihko, Petri M.

doi:10.1002/ange.200502425

Cited by 66 publications

(7 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The electrophilic fluorination reaction whetted the scientific appetite of many chemists. [77] The large electronegativity and small van der Walls radius of the fluorine atom clearly differentiates it from the other halogens. This helps explain the great interest in this reaction.…”

Section: Enantioselective Fluorination Reactionsmentioning

confidence: 99%

Asymmetric Aminocatalysis—Gold Rush in Organic Chemistry

Marigo²,

et al. 2008

View full text Add to dashboard Cite

Catalysis with chiral secondary amines (asymmetric aminocatalysis) has become a well-established and powerful synthetic tool for the chemo- and enantioselective functionalization of carbonyl compounds. In the last eight years alone, this field has grown at such an extraordinary pace that it is now recognized as an independent area of synthetic chemistry, where the goal is the preparation of any chiral molecule in an efficient, rapid, and stereoselective manner. This has been made possible by the impressive level of scientific competition and high quality research generated in this area. This Review describes this "Asymmetric Aminocatalysis Gold Rush" and charts the milestones in its development. As in all areas of science, progress depends on human effort.

show abstract

Section: Enantioselective Fluorination Reactionsmentioning

confidence: 99%

Asymmetric Aminocatalysis—Gold Rush in Organic Chemistry

Marigo²,

et al. 2008

View full text Add to dashboard Cite

show abstract

“…There are obvious advantages in medicinal chemistry in replacing hydrogen with fluorine at metabolically vunerable carbon atoms and at enolizable centers in drugs, to lengthen in vivo half‐lives. The quest for methods to mediate the introduction of the CF bond with high enantioselectivity and with catalytic efficiency has been intense, and successes have been emerging rapidly as illustrated by related Highlights in 20066, 7 and in other recent reviews 8–10. The major focus in asymmetric CF bond formation has involved catalytic enolate/α‐carbonyl fluorination of amides, β‐cyano‐, β‐nitro‐, and β‐keto esters, as well as malonates.…”

Section: Methodsmentioning

confidence: 99%

Catalytic Asymmetric Fluorination Comes of Age

2008

View full text Add to dashboard Cite

asymmetric catalysis · electrophilic substitution · fluorinated substituents · fluorinationThe CÀF bond is a fundamental unit of organic chemistry, and its introduction into organic compounds has been widely deployed to optimize the properties of performance materials.[1] Important contemporary applications are in organic materials such as liquid crystals for display technologies, [2] the refinement of catalysts for asymmetric transformations, [3] as well as the important role of strategic fluorination for lead optimization in the pharmaceuticals sector.[4] Although fluorine is very often found on aromatic rings in, for example, pharmaceutical and agrochemical products, the enantioselective introduction of the C À F bond at a stereogenic center has emerged as a clear goal in organic chemistry ever since the first asymmetric fluorination reagents, N-fluorocamphorsultams 1 a, b, were reported by Differding and Lang [5] in 1988 (Scheme 1).There are obvious advantages in medicinal chemistry in replacing hydrogen with fluorine at metabolically vunerable carbon atoms and at enolizable centers in drugs, to lengthen in vivo half-lives. The quest for methods to mediate the introduction of the C À F bond with high enantioselectivity and with catalytic efficiency has been intense, and successes have been emerging rapidly as illustrated by related Highlights in 2006 [6,7] and in other recent reviews. [8][9][10] The major focus in asymmetric C À F bond formation has involved catalytic enolate/a-carbonyl fluorination of amides, b-cyano-, b-nitro-, and b-keto esters, as well as malonates. In 2005 there were a flurry of papers reporting the successful asymmetric fluorination of aldehydes using pyrrolidine or imidazolidinone organocatalysts in combination with electrophilic fluorinating reagents.[11] This progress has recently been reviewed in a Highlight.[6] Developments in asymmetric fluorination were slow for a decade after the discovery of the N-fluorosultams 1 a, b, [5] but subsequent progress has been rapid and impressive, particularly in using selectfluor (2) and N-fluorodibenzenesulfonimide (NFSI, 3) as electrophilic fluorine-transfer reagents for catalytic processes. The first efficient enantioselective fluorinations used reagents derived from cinchona alkaloid, which were independently discovered in 2000 in the laboratories of Cahard [12] and Shibata.[13] These protocols demonstrated high enantioselectivities (up to 91 % ee) but with stochiometric reagents. Catalytic fluorinations using selectfluor/NFSI as transfer reagents were demonstrated; however, they were not efficient.Asymmetric Lewis acid based catalysts also emerged in 2000.[13] Hintermann and Togni were the first to demonstrate such fluorination reactions, [14] using taddol-titanium complexes in combination with selectfluor to mediate the afluorination of b-keto esters. Such an approach has evolved to the present, in that chiral ligand-metal complexes have been discovered which can now mediate catalytic and highly enantioselective fluorination protocols. This ...

show abstract

“…Nowhere is this perturbation more important than for organic compounds, where fluorination can impart substantial metabolic stability to prospective pharmaceutically active species 1. However, because of their stability and inertness,1c, 2 facile synthesis of CF bonds still provides a considerable challenge for chemists 1a. 3…”

Section: Fluorination Reactions Observed Following Reactions Of Sf42+mentioning

confidence: 99%

Fast and Efficient Fluorination of Small Molecules by SF₄²⁺

2010

View full text Add to dashboard Cite

Doubly charged, highly efficient: The use of a mass spectrometric technique specifically designed to monitor the reactions of dications has revealed that gaseous SF42+ is a powerful fluorinating agent. The fluorination of different classes of compounds (Ar, CO, CH4, C2H4, and H2) has been efficiently achieved in the gas phase (see picture). Of particular note is the formation of CF bonds in the reactions with organic compounds.

show abstract

Enantioselektive α‐Fluorierung von Carbonylverbindungen: Organo‐ oder Metallkatalyse?

Cited by 66 publications

References 45 publications

Asymmetric Aminocatalysis—Gold Rush in Organic Chemistry

Asymmetric Aminocatalysis—Gold Rush in Organic Chemistry

Catalytic Asymmetric Fluorination Comes of Age

Fast and Efficient Fluorination of Small Molecules by SF₄²⁺

Contact Info

Product

Resources

About

Enantioselektive α‐Fluorierung von Carbonylverbindungen: Organo‐ oder Metallkatalyse?

Cited by 66 publications

References 45 publications

Asymmetric Aminocatalysis—Gold Rush in Organic Chemistry

Asymmetric Aminocatalysis—Gold Rush in Organic Chemistry

Catalytic Asymmetric Fluorination Comes of Age

Fast and Efficient Fluorination of Small Molecules by SF42+

Contact Info

Product

Resources

About

Fast and Efficient Fluorination of Small Molecules by SF₄²⁺