Head-to-tail peptide macrocyclisations are significantly improved, as measured by isolated yields, reaction rates and product distribution, by substitution of one of the backbone amide CO bonds with an oxetane ring.

The lithiation/borylation-protodeboronation of a homoallyl carbamate was applied to the synthesis of (+)-sertraline and (+)-indatraline. Due to the presence of the alkene, significant modifications of the methodology were required (use of 12-crown-4, TMSCl, H(2)O), or a solvent switch to CHCl(3), to achieve high yields and high selectivities.

A continuous-flow method for the regioselective arylation of fluoroarenes and fluoropyridines has been developed. The telescoped procedure reported here consists of a three-step metalation, zincation, and Negishi cross-coupling sequence, providing efficient access to a variety of functionalized 2-fluorobiaryl products. Precise temperature control of the metalation step, made possible by continuous-flow technology, allowed for the efficient preparation of the arylated products in high yields and short residence times. Additionally, several examples of the regioselective arylation of benzotrifluoride derivatives are also provided.

Highly hindered benzylic carbamates have been reacted with hindered boronic esters to give tertiary boronic esters with very high diastereo- and enantiocontrol and the methodology has been applied to otherwise difficult-to-access molecules.

The substrate-directed regiochemistry of the cobaltcatalysed 1,4-hydrovinylation reaction is described. A variety of symmetrical and unsymmetrical 2,3-disubstituted 1,3-dienes are synthesised by ruthenium-catalysed enyne metathesis, and then reacted with a terminal alkene catalysed by cobalt(II) bromide-[1,2-bis(diphenylphosphino)ethane] [CoBr 2 (dppe)] under reductive conditions. The regiochemistry of the branched 1,4-diene products is influenced by the nature of the substituents on the unsymmetrical 2,3-disubstituted 1,3-dienes. The influence of steric and electronic effects is also discussed.Among atom economic cobalt-catalysed carbon-carbon bond-forming processes, 1 the cobalt-catalysed 1,4-hydrovinylation reaction of symmetrical 1,3-dienes with a terminal alkene is a convenient method for the synthesis of 1,4-dienes such as 1, under mild reaction conditions. 2 This efficient and atom economic reaction utilising a cobalt catalyst system [abbreviated as Co(I)] makes use of a mixture of cobalt(II) bromide-[1,2-bis(diphenylphosphino)ethane] [CoBr 2 (dppe)], zinc iodide (ZnI 2 ) and zinc powder in dichloromethane at ambient temperature. This catalyst system tolerates a variety of functional groups leading to functionalised 1,4-dienes. These dienes are of significant synthetic value and products such as 1,3-dicarbonyl compounds 2 are easily accessible via ozonolysis (Scheme 1). In this context, the 1,4-hydrovinylation reaction has been used as the key step in the synthesis of small natural products containing a 1,4-diene subunit as in 1, or a 1,3-dicarbonyl moiety as found in 2. 3 Scheme 1 Synthesis of 1,3-dicarbonyl compounds via cobalt-catalysed 1,4-hydrovinylation of 2,3-dimethyl-1,3-butadiene with terminal alkenes followed by ozonolysis When unsymmetrical 1,3-dienes were used as starting materials in the cobalt-catalysed 1,4-hydrovinylation reaction, a mixture of two different regioisomers (e. g. 3 and 4) was obtained (Scheme 2). The regiochemical outcome of the reaction is determined in the ligand sphere of the cobalt centre during formation of the carbon-carbon bond. The regiochemistry might therefore be influenced by either the steric or electronic effects of the 1,3-diene. In this study the influence of a variety of substituents bound to an unsymmetrical 2,3-disubstituted 1,3-diene was investigated in order to control the regiochemistry of the cobaltcatalysed 1,4-hydrovinylation reaction.Scheme 2 Cobalt-catalysed 1,4-hydrovinylation of 2-substituted 1,3-butadienes with terminal alkenes followed by ozonolysis for the synthesis of 1,3-dicarbonyl compounds The motivation behind this study was the need to develop a regioselective cobalt-catalysed 1,4-hydrovinylation reaction for the synthesis of 1,3-dicarbonyl compounds utilising a regiodirecting substituent on the 1,3-diene. Thereby, 'valuable' substituents (R 1 ) would remain in the carbon chain, attached to R 2 , as in compound 5, after ozonolysis. The cobalt-catalysed 1,4-hydrovinylation leading to 4 would result in undesired scission of the R 1 and R 2 su...

Short and highly stereoselective total syntheses of the sesquilignan natural product tatanan A and its C3 epimer are described. An assembly‐line synthesis approach, using iterative lithiation–borylation reactions, was applied to install the three contiguous stereocenters with high enantio‐ and diastereoselectivity. One of the stereocenters was installed using a configurationally labile lithiated primary benzyl benzoate, resulting in high levels of substrate‐controlled (undesired) diastereoselectivity. However, reversal of selectivity was achieved by using a novel diastereoselective Matteson homologation. Stereospecific alkynylation of a hindered secondary benzylic boronic ester enabled completion of the synthesis in a total of eight steps.

A high yielding, flexible strategy to hydrazine based chemical libraries is reported. Using a single stereogenic center, good shape diversity and three dimensionality is achieved by exploitation of the fluxional behavior of the two nitrogens.

The synthesis of primary and secondary pinacol boronic esters via lithiation-borylation of carbamates and benzoates with pinacolborane is described. This new protocol enables the highly selective synthesis of enantioenriched and geometrically defined boronic esters that cannot otherwise be accessed by alternative methodologies.