Fluorine and sulfur- an old combination with a new lease of life

The use of fluorine and fluorine-containing functional groups in medicinal chemistry, agrochemicals and advanced materials has grown over the past fifty years.1 Not surprisingly this increase in utility tracks with notable developments and refinements in safe and accessible synthetic methodology, both on the discovery and development front and in subsequent manufacturing. A recent example that caught

Osmium (Os, Element 76)

Osmium, a group 8 d-block transition metal discovered in 1803 by the English chemist Smithson Tennant, is the rarest of the stable elements. Concentrations in the Earth’s crust are around 50 parts per trillion. The metal is found in nature uncombinrd or alloyed with its neighbour, iridium, in the alloys iridosmine or osmiridium. Around 500Kg

Intermolecular reductive C-N cross coupling of nitroarenes and boronic acids by P(III) / P(V)=O catalysis

When approaching the synthesis of an aryl- or heteroaryl- amine most people would turn to a suitable transition metal (Pd, Cu or Ni) catalysed C-N cross-coupling reaction- most likely a Buchwald-Hartwig reaction, or, if this has limited success, Ullmann or Chan-Evans-Lam couplings.1 Photoredox approaches using aryloxy amides as a source of amidyl radicals began a trend

Selective N-methylation of amides using (chloromethyl) dimethylchlorosilane / fluoride: Application to the large scale synthesis of a pyrimidone intermediate for Raltegravir

Raltegravir (free base) Selective N- v’s O- alkylation of an amide can be challenging and somewhat unpredictable- the outcome being highly dependent on the structure of the substrate. A good example of this is the N-methylated pyrimidone intermediate (5) en route to Merck’s antiretroviral drug Raltegravir.1 Direct methylation of amide (4) (Figure 1) using MeI gives significant

The Balz-Schiemann Reaction

Aryl- and heteroaryl- diazonium tetrafluoroborate salts, prepared by diazotization of an aniline in the presence of HBF4, are unique in that in many cases they are sufficiently stable to isolate. Thermal decomposition of these salts at elevated temperatures results in fluoro-dediazoniation and formation of the corresponding aryl or heteroaryl fluoride- the Balz-Schiemann reaction.1a,bRadiolabelled 18F compounds

All about the base- or lack of it! Base-free nickel catalysed decarbonylative Suzuki-Miyaura coupling of acid fluorides

Figure 1: Suzuki-Miyaura Coupling   It’s a reaction that most organic chemists have run at some stage in their careers and is almost certainly in the running for the most widely used C-C bond forming reaction. First reported in 1979, the Suzuki-Miyaura cross-coupling between an organoboron nucleophile and an aryl halide electrophile is still ubiquitous in

Heterocyclic phosphonium salts- powerful intermediates for pyridine coupling

Heterocyclic phosphonium salts- powerful intermediates for pyridine coupling:- I’ve always had a keen interest in phosphorus chemistry and have followed the work of the McNally group at Colorado state on heterocyclic phosphonium salts closely. In late 2016 a paper describing synthesis and application of the so called HetPhos salts for C4 (or C2) functionalisation of

Reagent of the month: N-((Methylsulfonyl)oxy) acetimiodyl chloride (The Fier reagent)

Figure 1 I guess to qualify as a reagent of the month the material has to fulfil certain criteria and commercial availability, though not essential, is very desirable. N-((Methylsulfonyl)oxy)acetimiodyl chloride (henceforth known, at least by me, as Fier’s reagent) is now available to buy from Sigma Aldrich (CAS: 1433887-06-9). The compound is an air and