Ex situ gas generation for lab scale organic synthesis

Abstract

This review discusses recent examples of ex situ generated gaseous reagents, and their use in organic synthesis.

SuFEx-Enabled, Chemoselective Synthesis of Triflates, Triflamides and Triflimidates

“…[30] We envisaged the generation of CF3SO2F in a two-chamber reactor as the most convenient way to employ this gas safely on lab scale. [31] Inspired by the aforementioned results, we set out to develop a CF3SO2F gas generation method using PhNTf2 as a bench-stable and easily handled solid precursor (for optimization, see SI). To our delight, the final reaction conditions allowed conversion of the model substrate 4-fluoro-4'-hydroxybiphenyl into product 1 in 85% yield after 4 hours at room temperature (Scheme 2A).…”

“…Tailoring the reactive system to more physiologically relevant conditions, the triflation of L-tyrosine was tested on a 4 µmol scale in organic solvent/buffer mixtures. After modifying and optimizing the conditions (see SI), L-tyrosine (30), Leu-enkephalin (31) and endomorphin-1 (32) underwent triflation in good to excellent conversion (average over two runs, Scheme 2F).…”

Membrane Microreactors for the On‐Demand Generation, Separation, and Reaction of Gases

“…Gases can also be formed in situ or ex situ from solid or liquid reagents, known as gas surrogates. [5,6] Some gases are highly reactive and therefore need to be prepared on-site and only shortly before use. Dangerous purification operations (e.g.,d istillation) are often necessary for isolation of these gases with sufficient purity.T he main limitation of an in situ approach is that there are often chemicalc ompatibilityi ssues between the gas forming reaction and the organic transformation consuming the gas.…”

“…The condensation of a gas can be highly hazardous due to flammability issues. Gases can also be formed in situ or ex situ from solid or liquid reagents, known as gas surrogates . Some gases are highly reactive and therefore need to be prepared on‐site and only shortly before use.…”

Carboxyboronate as a Versatile In Situ CO Surrogate in Palladium‐Catalyzed Carbonylative Transformations

“…[8] To circumvent this challenge,Skrydstrup [11] and Wu [15] developed COware and In-Ex tube,r espectively,t hat effectively separates the CO generation process and the main carbonylation reaction in different chambers that are connected via the headspace. [16] Although the two-chamber approach circumvents the incompatibility issues described thus far, it requires the use of specialized twochamber glassware and sophisticated experimental setups. TheW ug roup reported benzene-1,3,5-triyl triformate (TFBen) as as uitable in situ CO surrogate for metalcatalyzed carbonylations.…”