Application of carbene chemistry in the synthesis of organofluorine compounds

TMSCF2Br‐Enabled Fluorination–Aminocarbonylation of Aldehydes: Modular Access to α‐Fluoroamides

“…Our investigation commenced with addressing the first issue. TMSCF 2 Br, a mild difluorocarbene reagent introduced by our group in 2011, [21] has become an important tool for the development of novel difluorocarbene chemistry due to its great versatility in the generation of difluorocarbene [9e–g, 14, 21, 22] . Of note is that its side product TMSBr can be used as both a Lewis acidic promoter and a source of bromide ion nucleophile.…”

Metabolic and Pharmaceutical Aspects of Fluorinated Compounds

“…Thus, the [ 18 F] isotope has become the preferred radionuclide for PET imaging studies. Procedures to install [ 18 F] into organic molecules must proceed rapidly and with high radiochemical yield to be useful, and the number of suitable reactions is increasing. − One such reaction involves the displacement of a good leaving group by [ 18 F]­fluoride at an aliphatic or aromatic position. However, since it is often difficult to incorporate an [ 18 F] label into an aromatic compound in the final synthetic step, the addition of a larger appendage, such as an aromatic ring incorporating a [ 18 F]­fluoroalkyl substituent, is used as an alternative approach .…”

“…The inclusion of fluorine in drugs, drug candidates, and agricultural chemicals continues to grow, a trend that is being driven by a deeper understanding of this remarkable element and its effects on molecular properties and biological activity. − The first fluorinated drug was introduced in 1955, and with the exceptions of 1960–1969 and 2000–2009, the presence of fluorine in approved drugs has increased every decade since, as summarized by the statistics presented in Figure . Many new synthetic methods to install fluorine have been developed over the last 15 years, providing access to a range of interesting and potentially useful fluorinated motifs. − The frequent use of fluorine in both drug and agricultural chemical design is also a function of its wide ranging effects on molecular properties. − ,− Patterns of fluorination can enhance potency and/or specificity, increase membrane permeability, modulate metabolism, moderate the p K a of proximal functionalities, influence conformation, stabilize inherently reactive functionalities, and create higher-order bioisosteres that offer advantages, all of which are dependent on context. − ,, In turn, studies of the metabolism and disposition of fluorinated compounds have advanced our knowledge and understanding of metabolic pathways. These efforts have not only provided insight into why fluorine can be advantageous but also identified structural arrangements that can present cryptic liabilities. , In this Perspective, we provide a survey of the metabolism of fluorinated compounds and capture observations that highlight potentially problematic structural arrangements.…”

“…41,44 The normal function of aconitase is to convert citric acid (19) to isocitric acid (21) by the pathway outlined in Scheme 3A. The initial step is the dehydration of 19 to afford cis-aconitate (20), which is believed to flip in the active site of the enzyme to set the stage for the addition of H 2 O to deliver 21. 44 However, aconitase also catalyzes the dehydration of (−)-erythro-(2R,3R)-2-fluorocitric acid (24) in a manner that is analogous to its dehydration of the natural substrate (Scheme 3B).…”

In Vitro Biocompatibility of Diazirine‐Grafted Biomaterials

“…Mild UVA light (365 nm, 10–20 J) irradiation results in reactive carbene and diazoalkane intermediates for covalent crosslinking ( Figure A). [ 14,15 ] Light‐stimulated CaproGlu end groups (aryl‐diazirine) form intermolecular crosslinks as well as interfacial binding with protein functional groups (Figure 1B,C). PCL is a known biodegradable material used in numerous medical devices, [ 12 ] however there is a lack of data available in terms of standardized in vitro genotoxicity and sensitization tests recommended by International Standards Organization (ISO) [ 16 ] and Organization for Economic Co‐operation and Development (OECD).…”