Ring Expansion of Alkylidenecarbenes Derived from Lactams, Lactones, and Thiolactones into Strained Heterocyclic Alkynes: A Theoretical Study

Strained cycloalkynes are of considerable interest to theoreticians and experimentalists, and possess much synthetic value as well. Herein, a series of cyclic alkylidenecarbenes—formally obtained by replacing the carbonyl oxygen of four-, five-, and six-membered lactams, lactones, and thiolactones with a divalent carbon—were modeled at the CCSD(T)/cc-pVTZ//B3LYP/6-311+G** and CCSD(T)/cc-pVTZ//CCSD/6-311+G** levels of theory. The singlet carbenes were found to be more stable than the triplets. The strained heterocyclic alkynes formed by ring expansion of these singlet carbenes were also modeled. Interestingly, the C≡C bonds in the five-membered heterocycles, obtained from the rearrangement of β-lactam- and β-lactone-derived alkylidenecarbenes, displayed lengths intermediate between formal double and triple bonds. Furthermore, 2-(1-azacyclobutylidene)carbene was found to be nearly isoenergetic with its ring-expanded isomer, and 1-oxacyclopent-2-yne was notably higher in energy than its precursor carbene. In all other cases, the cycloalkynes were lower in energy than the corresponding carbenes. The transition states for ring-expansion were always lower for the 1,2-carbon shifts than for 1,2-nitrogen or oxygen shifts, but higher than for the 1,2-sulfur shifts. These predictions should be verifiable using carbenes bearing appropriate isotopic labels. Computed vibrational spectra for the carbenes, and their ring-expanded isomers, are presented and could be of value to matrix isolation experiments.

Identification of site-specific isotopic labels by vibrational spectroscopy in the electron microscope

The identification of isotopic labels by conventional macroscopic techniques lacks spatial resolution and requires relatively large quantities of material for measurements. We recorded the vibrational spectra of an α amino acid, l-alanine, with damage-free “aloof” electron energy-loss spectroscopy in a scanning transmission electron microscope to directly resolve carbon-site–specific isotopic labels in real space with nanoscale spatial resolution. An isotopic red shift of 4.8 ± 0.4 milli–electron volts in C–O asymmetric stretching modes was observed for 13C-labeled l-alanine at the carboxylate carbon site, which was confirmed by macroscopic infrared spectroscopy and theoretical calculations. The accurate measurement of this shift opens the door to nondestructive, site-specific, spatially resolved identification of isotopically labeled molecules with the electron microscope.

Encoding matter with regiospecific 12C/13C isotopic labels

Molecules offer excellent vehicles for encoding messages. This article demonstrates how the regiospecific incorporation of non-natural isotope ratios provides a superb signal for molecular encryption.

Correction: Encoding matter with regiospecific 12C/13C isotopic labels

Correction for ‘Encoding matter with regiospecific 12C/13C isotopic labels’ by James J. La Clair et al., Chem. Commun., 2018, 54, 2611–2614.