Current mass spectrometry-based methodologies for synthetic organic reaction monitoring largely use electrospray ionization (ESI), or other related atmospheric pressure ionizationbased approaches. Monitoring of complex, heterogeneous systems may be problematic because of sampling hardware limitations, and many relevant analytes (neutrals) exhibit poor ESI performance. An alternative monitoring strategy addressing this significant impasse is condensed phase membrane introduction mass spectrometry using liquid electron ionization (CP-MIMS-LEI). In CP-MIMS, a semipermeable silicone membrane selects hydrophobic neutral analytes, rejecting particulates and charged chemical components. Analytes partition through the membrane, and are then transported to the LEI interface for sequential nebulization, vaporization, and ionization. CP-MIMS and LEI are both ideal for continuous monitoring applications of hydrophobic neutral molecules. We demonstrate quantitative reaction monitoring of harsh, complex reaction mixtures (alkaline, acidic, heterogeneous) in protic and aprotic organic solvents. Also presented are solvent-membrane compatibility investigations and, in situ quantitative monitoring of catalytic oxidation and alkylation reactions.

Annulations that combine diacceptors with bis-nucleophiles are uncommon. Here, we report the synthesis of 1,4-dioxanes from 3-aryloxetan-3-ols, as 1,2-bis-electrophiles and 1,2-diols. Brønsted acid Tf 2 NH catalyzes both the selective activation of the oxetanol, to form an oxetane carbocation that reacts with the diol, and intramolecular ring opening of the oxetane. High regio- and diastereoselectivity are achieved with unsymmetrical diols. The substituted dioxanes and fused bicyclic products present interesting motifs for drug discovery and can be further functionalized.