Diethyl (2-(4-phenyl-1H-1,2,3-triazol-1-yl)benzyl) phosphate

Here we describe a full structural elucidation of the diethyl (2-(4-phenyl-1H-1,2,3-triazol-1-yl)benzyl) phosphate. This compound is a common by-product present in the synthetic protocols to access the α-hydroxy phosphonate compounds through of a Phospha-Brook rearrangement. Thus, a complete NMR structural characterization of this rearrangement by-product was performed by 1H, 13C{1H}, 31P{1H}, COSY, HSQC, and HMBC NMR experiments. Additionally, we have demonstrated that the 1H-31P HMBC is a 2D heteroatom NMR experiment which combines the simple identification by 31P chemical shift with the detection sensitivity by 1H spectrum in a practical procedure.

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

Pyrrolidones are common heterocyclic fragments in various biologically active compounds. Here, a two-step radical-based approach to γ-lactams bearing three to four stereocenters starting from epoxides, N-allylic silylacetamides and TEMPO is reported. The sequence starts with a new tandem nucleophilic substitution/Brook rearrangement/single electron transfer-induced radical oxygenation furnishing orthogonally protected α,γ-dioxygenated N-allylamides with wide scope, mostly good yields, and partly good diastereo- and enantioselectivity for defined combinations of chiral epoxides and chiral amides. This represents a very rare example of an oxidative geminal C–C/C–O difunctionalization next to carbonyl groups. The resulting dioxygenated allylic amides are subsequently subjected to persistent radical effect-based 5-exo-trig radical cyclization reactions providing functionalized pyrrolidones in high yields as diastereomeric mixtures. They converge to 3,4-trans-γ-lactams by base-mediated equilibration, which can be easily further diversified. Stereochemical models for both reaction types were developed.