ABSTRACT
The effect of acidic media on the formation of the 3,4-dihydro-2H-3-phenyl-1,3-benzoxazine Bz is evaluated, focusing on the differentiation of intermediates and products formed by the distinct pathways observed in the presence and absence of acid. The use of real-time mass spectrometry (PSI-ESI-MS) coupled to tandem MS and infrared multiple photon dissociation (IRMPD) allowed the differentiation of the species observed during the synthesis of benzoxazines in these different conditions. The results suggest that formic acid promotes the formation of aniline and phenol condensation products (IC and IIC) by protecting the aniline amino group and enhancing the formaldehyde electrophilicity. The results also suggest that although the presence of acid allow a more efficient potential energy landscape to be accessed, the last cyclization step for the formation of benzoxazines cannot be mediated by the protonation route intermediate (ROP Bz). Overall, the conclusions presented here provide important information about the synthesis of benzoxazines under acidic conditions, allowing the development of optimal reaction conditions.
ABSTRACT
The regio- and diastereoselective synthesis of oxazolidinones via a Pd-catalyzed vicinal C-N/C-Cl bond-forming reaction from internal alkenes of allylic carbamates is reported. The oxazolidinones are obtained in yields of 44 to 95% with high to excellent diastereoselectivities (from 6 : 1 to >20 : 1 dr) from readily available precursors. This process is scalable, and the products are suitable for the synthesis of useful amino alcohols. A detailed theoretical and experimental mechanistic study was carried out to describe that the reaction proceeds through an anti-aminopalladation of the alkene followed by an oxidative C-Pd(ii) cleavage with retention of the carbon stereochemistry to yield the major diastereomer. The role of Cu(ii) in a C-Cl bond-forming mechanism step has also been proposed.
