An operationally simple nickel-catalyzed hydroarylation reaction for alkynes is described. This threecomponent coupling reaction utilizes commercially available alkynes and aryl bromides, along with water and Zn. An airstable and easily synthesized Ni(II) precatalyst is the only entity used in the reaction that is not commercially available. This reductive cross-coupling reaction displays a fairly unusual anti selectivity when aryl bromides with ortho substituents are used. In addition to optimization data and a preliminary substrate scope, complementary experiments including deuterium labeling studies are used to provide a tentative catalytic mechanism. We believe this report should inspire and inform other Ni-catalyzed carbofunctionalization reactions.

Up to 80% of the fatty acids in Staphylococcus aureus membrane lipids are branched, rather than straight-chain, fatty acids. The branched fatty acids (BCFAs) may have either an even or odd number of carbons, and the branch position may be at the penultimate carbon (iso) or the antepenultimate (anteiso) carbon of the tail. This results in two sets of isomeric fatty acid species with the same number of carbons that cannot be resolved by mass spectrometry. The isomer/isobar challenge is further complicated when the mixture of BCFAs and straight-chain fatty acids (SCFAs) are esterified into diacylated lipids such as the phosphatidylglycerol (PG) species of the S. aureus membrane. No conventional chromatographic method has been able to resolve diacylated lipids containing mixtures of SCFAs, anteiso-odd, iso-odd, and iso-even BCFAs. A major hurdle to method development in this area is the lack of relevant analytical standards for lipids containing BCFA isomers. The diversity of the S. aureus lipidome and its naturally high levels of BCFAs present an opportunity to explore the potential of resolving diacylated lipids containing BCFAs and SFCAs. Using our knowledge of lipid and fatty acid biosynthesis in S. aureus, we have used a stable-isotope-labeling strategy to develop and validate a 30 min C18 reversed-phase liquid chromatography method combined with traveling-wave ion mobility–mass spectrometry to provide resolution of diacylated lipids based on the number of BCFAs that they contain.

A Ni-catalyzed annulation reaction to synthesize indenones is reported. The reaction provides high yields and regioselectivities when aliphatic- and silyl-substituted alkynes are employed. Both have been challenging and underutilized substrate classes. Several mechanistic observations aided in the development of this reaction, including that β-hydride elimination is turnover-limiting for ortho-halogenated aldehyde substrates and that alkyne dissociation is rate-limiting for internal aliphatic alkynes. We anticipate that these methods will be rapidly adopted due to their synthetic ease and inherent versatility. We also anticipate that the mechanistic conclusions will inform further reaction development.

The Paternò–Büchi (PB) reaction is a cycloaddition reaction between a carbon–carbon double bond (CC) and a photochemically excited carbonyl-containing compound. The constrained ring formed between the CC bond and the PB reagent is more susceptible to fragmentation by collision-induced dissociation, which facilitates identification of the CC position within the fatty acyl tails of lipids. Although the original PB reaction using acetone had a low yield of derivatized lipids and therefore a low yield of diagnostic ions, a new generation of PB reagents based on halogenated acetophenones has improved the reaction yield substantially. In this study, we investigated the use of halogenated PB reagents and ion mobility to improve the identification of PB-derivatized lipids by shifting them out of the densely populated lipid region of ion mobility-mass spectrometry (IM-MS) space. Several halogenated PB reagents containing fluorine, chlorine and bromine were investigated for their ability to decrease the collision cross-section (CCS) values of derivatized lipids and yield sufficient intensity for both the derivatized lipid and its diagnostic ions. We found that 4′-chloro-2′,6′-difluoroacetophenone (CDFAP) displayed the best performance, with an average decrease in CCS of 4.4% and yield of derivatized lipids and diagnostic ions comparable to the trifluorinated acetophenone reagent proposed by the Xia group. The unique isotope pattern resulting from the chlorine substituent aided in identification of the derivatized lipids and their diagnostic ions, as well. We further demonstrate that derivatization with CDFAP preserves the separation of lipids classes in IM-MS space.