Telescoping Reactions with Trifluorodiazoethane‐Derived Aza‐Wittig Reagents and Allenyl esters

Abstract

A telescoping process involving the consecutive addition of four reagents (trifluorodiazoethane, phosphine, allenyl ester, and acetic acid) into a single reactor was developed for the novel functionalization of allenyl esters. First, new phosphazenes derived from trifluorodiazoethane and phosphines were generated and reacted with allenyl esters to give unexpected α-iminophosphoranes through the creation of C=P, C=N, and C-H bonds at the α-, β-, and γ-carbon atoms, respectively, of the allenyl esters. The α-iminophosphoranes did not react with aldehydes in a classic Wittig reaction, but instead β-enamino esters were obtained. The overall sequence of reactions offered a formal hydrohydrazonation of allenyl esters. The method was extended to other related diazo compounds and applied to the preparation of novel 5-pyrazolone derivatives. Not only is the telescoping process described herein an effective approach for truncating the multistep synthesis, but also each step has been dissected to understand and support the reaction mechanisms.

Phosphine‐Relayed Aldehyde‐Olefination and Aza‐Wittig Reaction with 2,2,2‐Trifluorodiazoethane

“…This hydrazone was assumed to be produced from aza-Wittig reaction of phosphazine intermediate with 2-naphthaldehyde (see the proposed mechanism in Scheme 3). [14] With this hypothesis in mind, 1a was then treated with CF 3 CHN 2 and phosphine in the absence of iron catalyst. Pleasingly, trifluoromethylated hy-drazone 3a could be smoothly obtained as a single isomer in 90% yield.…”

“…[16] On the other hand, in the absence of iron catalyst (Scheme 3b), phosphazene intermediate P-1 would be generated while adding CF 3 CHN 2 to PPh 3 . [14] In this scenario, an aza-Wittig process of this intermediate with aldehyde will proceed to yield trifluoromethylated hydrazone. Control experiments between Fe(TPP)Cl and phosphazene intermediate P-1 or hydra-zone 3a were performed, while no olefination product 2a was observed in either case (Scheme 3c).…”

Expedient Synthesis of 2‐Iminothiazolidines via Telescoping Reactions Including Iron‐Catalyzed Nitrene Transfer and Domino Ring‐Opening Cyclization (DROC)

“…When p-OMe phenyl isothiocyanate is used, good yields were obtained with styrene and p-halogenated styrenes (Table 4, entries [14][15][16][17]. As observed with phenyl isothiocyanate, the reaction with styrenes bearing electronwithdrawing substituents led to lower yields (Table 4, entries [18][19][20].…”

“…Their operation simplicity and solvent‐ and time‐saving make them more economically attractive [16] . As a matter of fact, they were described as the best way to ‘‘clean up’’ organic synthesis [17] and have sharply emerged as a synthetic route for the construction of a large range of compounds, [18–27] including numerous heterocycles of pharmaceutical and agrochemical interest [28–30] …”

“…[15] Their operation simplicity and solvent-and time-saving make them more economically attractive. [16] As a matter of fact, they were described as the best way to ''clean up'' organic synthesis [17] and have sharply emerged as a synthetic route for the construction of a large range of compounds, [18][19][20][21][22][23][24][25][26][27] including numerous heterocycles of pharmaceutical and agrochemical interest. [28][29][30] Therefore, we intended to use telescoping reactions integrating the in situ generation of the aziridine followed by its ring-opening and insertion of an organic isothiocyanate.…”