Transition metal-catalyzed “cut-and-sew” reactions offer an efficient approach to construct bridged and fused scaffolds; however, the substrates have been primarily restricted to cyclic ketones and ac...

Nature Catalysis - Directing group strategies for selective dearomatization of unactivated aromatic π-systems have remained elusive. Now a homogeneous ruthenium catalyst, aided by a removable...

Direct introduction of two carbon substituents to less functionalized aromatic cores has been an attractive objective for late-stage modification and …

[2394994-09-1] C9H13NO (MW 151.21) InChI = 1S/C9H13NO/c1-10-9(11)8-5-6-2-3-7(8)4-6/h5-7H,2-4H2,1H3,(H,10,11) InChIKey = BYXAMVZFVXOYIF-UHFFFAOYSA-N (reagent used as a co-catalyst...

Nature Synthesis - An enantioconvergent approach for direct asymmetric insertion of racemic carbon-, oxygen-, nitrogen-, sulfur- and silicon-substituted carbenoids into carbon–boron bonds is...

Aldehyde α-alkylation remains a challenging transformation. On the other hand, given the wide availability of alkenes, it has been an attractive objective to use unactivated alkenes as alkylating agen...

In drug development, replacement of a skeletal carbon with a sulfur atom can result in analogs of bioactive compounds with improved properties. Currently, the sulfur analogs are almost exclusively pre...

Ring-contraction reactions are valuable transformations to access harder-to-synthesize smaller-sized rings from more-available larger-sized precursors…

Given the increasing demand for diverse alkyl fluorides for various applications, it would be beneficial to enrich the fluorination toolbox by including more kinds of common functional groups, such as ketones, as fluoride surrogates. Here we report a Cu-mediated deacylative fluorination approach that can convert a wide range of methyl ketones to the corresponding alkyl fluorides. The reaction is enabled by a ketone activation reagent and a nucleophilic fluoride source. It features broad functional group tolerance, capability for the late-stage fluorination, fluoro-annulation, synthesis of α,α-dideuterated fluorides, and degree-controlled synthesis of mono-, di-, and trifluoro alkanes from a single ketone starting material. The computational studies suggest interesting Cu(III)-mediated C–F bond forming pathways via either fluorine atom transfer or an SN2 process.

Fully automated preparation of diverse small organic molecules remains a formidable challenge due to the inherent constraints of conventional synthetic philosophies. The existing automation approaches require access to either almost unlimited kinds of chemical reagents or custom-made building blocks (BBs). Herein we propose atom-by-atom iterative synthesis (AIS) as a new synthetic logic to tackle this challenge. By viewing complex organic molecules as assemblies of single-carbon- or heteroatom-based units, AIS aims to construct molecular skeletons through iterative coupling of simple atomic-scale BBs by a unified type of reaction─boron homologations. Compared with conventional approaches, the AIS strategy uses only a few types of chemical reactions and a small set of BBs, making it more suitable for automation and artificial intelligence-assisted synthetic route design. To date, enormous progresses have been made on the synthetic chemistry that serves for the purpose of AIS, such as introducing heteroatoms and sp2-carbons, forming ring structures, developing thermostable carbenoid reagents, and achieving stereochemical controls. On the other hand, substantial challenges and limitations remain to be overcome for realizing fully automated construction of diverse molecules. This Outlook article describes the AIS concept, recent progress, current limitations, and future opportunities in this field.