The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

• which although commercially available was expensive and could be generated from 1,3-cyclohexadione (104). The sequence consisted of O-acetylation, a Steglich rearrangement, oxidation and a final methylation reaction. As the use of flow chemistry had already improved the O-acetylation during scale-up

• tests (130 mmol) by avoiding exotherms, it was anticipated that the subsequent Steglich rearrangement could be accomplished in flow using catalytic DMAP instead of stoichiometric AlCl3 as precedented (Scheme 19). This was eventually realised by preparing a monolithic flow reactor functionalised with

Modulating NHC catalysis with fluorine

• Yannick P. Rey and
• Ryan Gilmour

Beilstein J. Org. Chem. 2013, 9, 2812–2820, doi:10.3762/bjoc.9.316

• derivatives are presented and the conformations are discussed. Upon deprotonation, the fluorinated triazolium salts generate catalytically active N-heterocyclic carbenes, which can then participate in the enantioselective Steglich rearrangement of oxazolyl carbonates to C-carboxyazlactones (e.r. up to 87.0

• :13.0). Keywords: catalysis; enantioselectivity; fluorine; gauche effect; organo-fluorine; Steglich rearrangement; Introduction Molecular editing using fluorine is a powerful strategy to modulate the conformation and reactivity of small molecule organocatalysts [1][2][3]. The negligible steric penalty

• substitution is evaluated in the NHC-catalysed, enantioselective Steglich rearrangement of oxazolyl carbonates 3 to C-carboxyazlactones 4 [29], recently reported by Smith and co-workers [30][31][32][33][34][35][36]. Fluorination sites were selected based on their proximity to the ring junction nitrogen of the