On the discovery and development of tandem 1,4- and 1,2-addition of phosphites to 1-azadienes

Over the past 15 years we have developed a one-step protocol for the synthesis of 3-phosphonylated aminophosphonates from alpha,beta-unsaturated imines through tandem 1,4-1,2-phosphite addition. This account covers the initial development, mechanistic implications of using different phosphite nucleophiles and the expansion towards oximes, hydrazones and unsaturated imines included in aromatic sextets, e. g. quinolines, phenanthrolines and napthyridines

Direct regio- and diastereoselective diphosphonylation of cyclic enamines : one-pot synthesis of α,α′-bis(diphenylphosphoryl)- and α,α′-bis(diphenylphosphorothioyl)cycloalkanones

A straightforward regio- and diastereoselective process has been developed for the synthesis of unprecedented symmetrical trans-alpha,alpha '-bis(diphenylphosphoryl)- and alpha,alpha '-bis(diphenylphosphorothioyl)cycloalkanones, through the reaction of cyclic enamines with excess P-chlorodiphenylphosphine in the presence of triethylamine, followed by oxidation or sulfurization and hydrolytic workup

Preparation of phosphines through C–P bond formation

Phosphines are an important class of ligands in the field of metal-catalysis. This has spurred the development of new routes toward functionalized phosphines. Some of the most important C–P bond formation strategies were reviewed and organized according to the hybridization of carbon in the newly formed C–P bond

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 n-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-Imidoallenylphophonates: in situ 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 beta-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

Gold superacid-catalyzed preparation of benzo[c]thiophenes

A three-step synthesis of benzo[c] thiophenes is presented in which the key transformation is the gold-catalyzed 5-exo-dig migratory cycloisomerization of a diallyl thioacetal. It was shown that a small amount of in situ generated HAuCl4 from AuCl3 is the active catalytic species. A mechanism was proposed

Thiol-ene coupling in a continuous photo-flow regime

Photoinitiated thiol-ene chemistry is a promising technique for use in chemical synthesis and related sciences. In view of scaling, the process was successfully transferred to a continuous flow regime with compelling results in terms of selectivity, efficiency, and productivity. A series of selected thiols and enes were reacted using 2,2-dimethoxy-2-phenylacetophenone as radical initiator to respond to the 365nm UV-LED source. Process parameters were evaluated and chemical cross-reactivity of the different substrates was assessed. Optimization of conditions gave high productivity of the thio-ether resulting from the model reaction between benzyl thiol and 1-decene when performed under neat conditions. The robustness of this method was demonstrated by running it under continuous operation for an extended period of time, with product output reaching constant yields of 90-92% as soon as the steady-state regime was installed. The corresponding space-time yield was 9.75kgl(-1)h(-1), an impressive value that further demonstrates scale-up potential

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

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 alpha,beta,gamma,delta-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 N-containing system is reported herein. Theoretical calculations were performed to rationalize the observed regioselectivites and to shed light on the proposed mechanism