Preparation of Tetrasubstituted 3‑Phosphonopyrroles through Hydroamination: Scope and Limitations

Phosphonylated pyrroles were obtained by a ZnCl₂-catalyzed 5-<i>exo</i>-<i>dig</i> hydroamination of propargylic enamines. These starting compounds were obtained in two steps from commercially available β-ketophosphonates. The method tolerates a wide variety of substituents at the 1,2- and 5-position of the pyrrole, while further derivatization allows for the introduction of substituents at the 4-position via lithiation or halogenation

Synthetic Entry into 1‑Phosphono-3-azabicyclo[3.1.0]hexanes

3-Azabicyclo­[3.1.0]­hex-2-en-1-yl phosphonates were prepared in a five-step reaction route from β-ketophosphonates. The key steps in this sequence are an atom-transfer radical cyclization and an unforeseen lithium–halogen exchange with <i>n</i>-BuLi. The cyclization reaction proceeds with excellent diastereoselectivity. The resulting cyclic imines were reduced, and 3-azabicyclo[3.1.0]­hexan-1-yl phosphonates were obtained

3‑Imidoallenylphosphonates: <i>In Situ</i> Formation and β‑Alkoxylation

3-Imidoallenylphosphonates, allenes bearing both an electron-withdrawing and -donating group, were isolated for the first time. An alkoxy substituent was introduced into these unprecedented intermediates in a one-pot approach, yielding β-functionalized aminophosphonates in excellent yields and short reaction times. The mechanistic insights gained are important additions to the domain of allene chemistry. Addition of biologically important molecules, including monoglycerides, amino acids, and nucleosides, proves the general applicability of the developed method

Tandem Addition of Phosphite Nucleophiles Across Unsaturated Nitrogen-Containing Systems: Mechanistic Insights on Regioselectivity

The addition of phosphite nucleophiles across linear unsaturated imines is a powerful and atom-economical methodology for the synthesis of aminophosphonates. These products are of interest from both a biological and a synthetic point of view: they act as amino acid transition state analogs and Horner–Wadsworth–Emmons reagents, respectively. In this work the reaction between dialkyl trimethylsilyl phosphites and <i>α,β,γ,δ</i>-diunsaturated imines was evaluated as a continuation of our previous efforts in the field. As such, the first conjugate 1,6-addition of a phosphite nucleophile across a linear unsaturated <i>N</i>-containing system is reported herein. Theoretical calculations were performed to rationalize the observed regioselectivites and to shed light on the proposed mechanism