Suzuki cross-coupling reactions of an unprecedented array of unactivated primary and secondary alkyl halides (including challenging alkyl chlorides) can be accomplished through the use of nickel/amino alcohol-based catalysts. Both the nickel precatalyst and the amino alcohols (prolinol or trans-2-aminocyclohexanol) are commercially available and air-stable. In view of the remarkable diversity of amino alcohols that are readily accessible, this discovery may open the door to the rapid development of versatile catalysts for a wide range of cross-coupling processes.

The use of bis(pyridine)iodonium tetrafluoroborate (IPy(2)BF(4)) as an oxidizing agent towards different types of alcohols is reported. The observed reactivity involves different reaction pathways, as a function both of the structures of the starting materials and of the experimental conditions. Interestingly, the title iodine-containing compound is capable of a tuneable reaction with simple cycloalkanols, providing straight and selective access either to omega-iodocarbonyl compounds or to ketones, a previously unreported and chemoselective range of oxidation potential. Furthermore, appropriate conditions for the preparation of aldehydes and esters from primary alcohols by easily performed experimental procedures were also established. The beta-scission reactions of cycloalkanols and the alpha-oxidation processes of primary, secondary and benzylic alcohols are discussed.

Ring-closing metathesis (RCM) has become indispensable in organic synthesis for both academic investigations and industrial applications. This review provides an overview of RCM reactions, focusing on the practical aspects that researchers in an industrial environment may find of interest. Key elements of reaction design and lessons learned from these applications are discussed to help those considering implementing RCM reactions on scale, particularly in manufacturing active pharmaceutical ingredients (APIs). Advances in the development of more effective catalysts and new methodologies, such as enantioselective RCM and stereoselective macrocyclic RCM, are also briefly discussed.

We describe the development and scale-up of a nickel-catalyzed reductive cross-electrophile coupling reaction between a substituted 2-chloropyridine and ethyl 3-chloropropanoate using manganese dust as the terminal reductant. Several additives were screened for the activation of the manganese reductant in situ, and chlorotriethylsilane (TESCl) was found to provide the optimal conversion. A focused beam reflectance measurement (FBRM) probe was utilized to monitor particle attrition as well as manganese activation during the reaction. Modeling was employed to garner an understanding of mixing requirements that would ensure effective suspension of the manganese during scale-up. The process was successfully demonstrated on a 7 kg scale and afforded 2 in 64% yield.

Abstract:The outstanding ability of dirhodium a,a,a',a'-tetramethyl-1,3-benzenedipropanoate