Cyano phosphate: an efficient intermediate for the chemoselective conversion of carbonyl compounds to nitriles

Development of New Synthetic Reactions Using Hetero-Heavy Atoms and Their Application to Synthesis of Biofunctional Molecules

“…In addition, we investigated dephosphorylation of CPs by reduction with lithium in liquid ammonia, as outlined in Table 3. 18,19) Reduction of a CP derived from citral 19 with lithium in liquid ammonia at −78°C and quenching of the reaction mixture with isoprene afforded β,γ-unsaturated nitrile 20 (86%, entry 1, Table 3), while quenching of the CP derived from α-ionone (21) using octyl iodide yielded the α-alkylated nitrile 22 (83%, entry 2). Furthermore, reduction of the CP derived from 4-isobutylacetophenone (23) under refluxing conditions (at −33°C) followed by quenching with ammonium chloride (NH 4 Cl) yielded 1-ethyl-4-isobutylbenzene (24, 89%) (entry 3), thus giving a deoxygenated derivative of an aromatic ketone.…”

“…Furthermore, reduction of the CP derived from 4-isobutylacetophenone (23) under refluxing conditions (at −33°C) followed by quenching with ammonium chloride (NH 4 Cl) yielded 1-ethyl-4-isobutylbenzene (24, 89%) (entry 3), thus giving a deoxygenated derivative of an aromatic ketone. 19) Interestingly, no isomerized or reduced alkenes were formed in the reduction stages. 18,19) Thus, these reductive dephosphorylation reactions have potential for application in the preparation of CPs derived from enones and aromatic ketones.…”

“…19) Interestingly, no isomerized or reduced alkenes were formed in the reduction stages. 18,19) Thus, these reductive dephosphorylation reactions have potential for application in the preparation of CPs derived from enones and aromatic ketones. 1) We further developed the reductive cyanation of CPs using SmI 2 , which is a moderate reducing agent 20,21) (Table 4).…”

Cycloaddition and one-carbon homologation studies in the synthesis of advanced iridoid precursors

“…36 Reaction conditions whereby the cyanohydrin hydroxyl group is trapped as a phosphate ester 37, 38 to give a cyanohydrin O,O¢-diethyl phosphate (cyanophosphate) were attractive here because there is literature precedent for the reductive elimination of the phosphate group to give a nitrile. 39 The reaction of 4 with diethylchlorophosphate and lithium cyanide 38 afforded cyanophosphate 27 as a single diastereomer. Surprisingly, the treatment of 27 with SmI 2 in the presence of tert-butyl alcohol gave 28 as the major product instead of the expected nitrile.…”

Total Synthesis of (±)-Marsupellins A and B via Acetoxymarsupellone Using an Intramolecular Reductive Cyclization of Epoxycyanohydrin Derivative with Cp2TiI

“…In route B, the seven-membered ring would be constructed by a Negishi coupling reaction of acryloyl chloride and a zinc reagent, which could be synthesized from 10 and Zn, and then the six- and seven-membered ring would be constructed by an intramolecular Diels–Alder reaction (IMDA) of 9 . In this synthetic strategy, the reductive cyclization of 7 to 6 is challenging because the removal of oxygen functional groups in cyanohydrin derivatives has been reported, whereas the formation of C–C bonds using the resulting nitrile enolate has not.…”