Reversing the polarity in molecules is a versatile tool for expanding the boundaries of structural space. Despite a manifold of different umpolung methods available today, overcoming the inherent reactivity still remains a constant challenge in organic chemistry. The oxidative α-functionalization of ketones by external nucleophiles constitute such an example. Herein, we present a hypervalent F-iodane mediated umpolung of pyridyl ketones triggered by Lewis base/Lewis acid noncovalent interactions. A wide variety of external nucleophiles are introduced with high regioselectivity applying this substrate-directing concept.

Our recent studies of the diastereo- and enantioselective formation of strained alkylidenecycloalkanes drove us to more-thoroughly investigate the formation of four-membered rings for which only few efficient methods are described. We first developed a strategy to diversify the saturated part of the four-membered ring and applied it to a highly diastereoselective synthesis of more-elaborate alkylidenecyclobutanes, which completed our precedent studies. In parallel, cyclobutene structures were built employing simple organometallic methods and further functionalized to give a diverse range of new substitution patterns, which consequently enriched the pool of cyclobutene-based building blocks.

Fluorination reactions facilitated by hypervalent F‐iodanes have experienced vivid attention recently, since they often lead to novel, fluorinated scaffolds not accessible with common electrophilic fluorination reagents. The fluorocyclization of styrenes equipped with an amide functionality in the ortho position using F‐iodanes represents a transformation with unusual chemoselectivity. Within this context, the conversion of pyridine derivatives to fluoropyridyloxazepines, which constitutes a particular challenge due to the deactivating properties of the aza heterocycle, was accomplished in this work using the bench‐stable λ3‐F‐benzoiodoxole under Lewis acid catalysis. The versatility of the obtained F‐heterocycles as building blocks in organic synthesis was demonstrated by their straightforward conversion into azaindoles in a one‐pot, three‐step reaction sequence.

Enantioenriched alkylidenecyclobutanes possessing a quaternary stereogenic center, usually difficult to access, have been synthesized by combining a double boron-homologation and an allylboration through a highly efficient and diastereoselective one-pot process. Starting from commercially available substrates, this protocol represents a simple way of accessing chiral unsaturated four-membered ring systems with excellent stereoisomeric ratios.

Reversing the polarity in molecules is a versatile tool for expanding the boundaries of structural space. Despite a manifold of different umpolung methods available today, overcoming the inherent reactivity still remains a constant challenge in organic chemistry. The oxidative α-functionalization of ketones by external nucleophiles constitute such an example. Herein, we present a hypervalent F-iodane mediated umpolung of pyridyl ketones triggered by Lewis base Lewis acid non-covalent interactions. A wide variety of external nucleophiles are introduced with high regioselectivity applying this substratedirecting concept.<br>