The distant and selective activation of unreactive C–H and C–C bonds remains one of the biggest challenges in organic chemistry. In recent years, the development of remote functionalization has received growing interest as it allows for the activation of rather challenging C–H and C–C bonds distant from the initiation point by means of a “metal-walk”. A “metal-walk” or “chain-walk” is defined by an iterative series of consecutive 1,2- or 1,3-hydride shifts of a metal complex along a single hydrocarbon chain. With this approach, simple building blocks or mixtures thereof can be transformed into complex scaffolds in a convergent and unified strategy. A variety of catalytic systems have been developed and refined over the past decade ranging from late-transition-metal complexes to more sustainable iron- and cobalt-based systems. As the possibilities of this field are slowly unfolding, this area of research will contribute considerably to provide solutions to yet unmet synthetic challenges.

Countless natural products of polyketide origin have an E-configured 2-methyl-but-2-en-1-ol substructure. An unconventional entry into this important motif was developed as part of a concise total synthesis of 5,6-dihydrocineromycin B. The choice of this particular target was inspired by a recent study, which suggested that the cineromycin family of antibiotics might have overlooked lead qualities, although our biodata do not necessarily support this view. The new approach consists of a sequence of alkyne metathesis followed by a hydroxy-directed trans-hydrostannation and a largely unprecedented methyl-Stille coupling. The excellent yield and remarkable selectivity with which the signature trisubstituted alkene site of the target was procured is noteworthy considering the rather poor outcome of a classical ring-closing metathesis reaction. Moreover, the unorthodox ruthenium-catalyzed trans-hydrostannation is shown to be a versatile handle for diversity-oriented synthesis.

The known procedures for the conversion of alkenylstannanes into the corresponding fluoroalkenes suffer from largely variable yields and a limited compatibility with functional groups; most notably, protodestannation becomes a serious issue whenever protic sites are present in the substrate. Outlined in this paper is a convenient alternative with a much improved application profile, which is largely unperturbed by free alcohols and amides of all sorts. Key to success is the use of F-TEDA-PF6 in combination with non-hygroscopic and bench-stable silver phosphinate (AgOP(O)Ph₂) that acts as an essentially neutral, non-nucleophilic promotor and effective tin-scavenger at the same time. This new method opens many opportunities for late-stage fluorination of elaborate compounds far beyond the scope of the literature procedures, as witnessed by the preparation of a fluorinated macrolide antibiotic, a fluorinated prostaglandin derivative, and a set of fluorinated amino acid surrogates and peptide isosteres

An iridium-catalyzed tandem olefin migration/Cope rearrangement of alkenyl ω-ene cyclopropanes is reported. By this means, a variety of complex annulenes are obtained as single diastereomers starting from cyclopropyl ester derived from simple 1,ω-dienes and alkenyldiazo compounds. Long-range olefin migration over up to 10 positions could be realized and coupled with an efficient Cope rearrangement to yield valuable scaffolds. Various functional groups are well-tolerated, giving rise to densely functionalized products. Furthermore, the present methodology could be successfully extended to yield bicyclic cycloheptenones starting from readily available alkenyl cyclopropanols via a Kulinkovich reaction.

Treatment of alkenylstannanes with Cu(OAc) /Et N affords the corresponding enol esters or ketones under conditions that proved compatible with many common functionalities; these include groups that would neither survive under the standard Tamao-Fleming conditions for the oxidation of Csp2 -SiR bonds nor under the conditions commonly used to oxidize C-B bonds. Chiral centers adjacent to the unveiled carbonyls are not racemized and competing protodestannation is marginal, even if the substrate carries unprotected -OH groups as internal proton sources. Therefore, the procedure is well suited for the preparation of acyloin and aldol derivatives. These enabling virtues are illustrated by a concise approach to the bicyclic lipid paecilonic acid A.