Rearrangement of Threonine- and Serine-Based N-(3-Phenylprop-2-yn-1-yl) Sulfonamides Yields Chiral Pyrrolidin-3-ones

Abstract

N-(3-Phenylprop-2-yn-1-yl)-sulfonamides derived from serine and threonine were synthesized using solid-phase synthesis and subjected to reaction with trimethylsilyl trifluoromethanesulfonate (TMSOTf). In contrast to the previously reported formation of 1,4-oxazepanes, this reaction afforded pyrrolidin-3-ones. A mechanistic explanation for this unexpected outcome is proposed, and the limitations and scope of the rearrangement are outlined.

Copper‐Free Solid‐Phase Synthesis of Triazolo[1,5‐a][1,4]diazepin‐6‐ones

“…Product was isolated as yellow solid after lyophilization of residual solvents. Analytical data were consistent with published data [27,28] …”

“…In the case of alkynols, we included an aromatic analogue (3‐phenyl‐prop‐2‐yn‐1‐ol) and its alternatives bearing both electron‐donating (3‐( p ‐tolyl)prop‐2‐yn‐1‐ol and 3‐(4‐methoxy)phenyl‐prop‐2‐yn‐1‐ol) and electron‐withdrawing (3‐(4‐trifluoromethyl)phenyl‐prop‐2‐yn‐1‐ol) and (3‐(4‐chloro)phenyl‐2‐yn‐1‐ol) functional groups. The substituted 3‐phenyl‐prop‐2‐yn‐1‐ols were synthesized using slightly modified previously reported approaches [27,28] . Finally, but‐2‐yn‐1‐ol was selected to receive the aliphatic R 2 moiety.…”

Synthesis of Polycyclic Tetrahydroisoquinolines and Tetrahydrobenzo[d]azepines from Polymer-Supported Allylglycine

“…The synthesis of N-(3-phenylprop-2yn-1-yl)-nitrobenzenesulfonamides 2a−m was performed according to the reported protocol. 27 The LC−MS analyses were carried out on a UHPLC-MS system consisting of UHPLC chromatograph Acuity with a photodiode array detector and single quadrupole mass spectrometer (Waters), using an X-Select C18 column with the mobile phase consisting of 10 mM ammonium acetate (AmAc) in H 2 O and CH 3 CN. The ESI source operated at a discharge current of 5 μA, vaporizer temperature of 350 °C, and capillary temperature of 200 °C.…”

Reagent-Based Diversity-Oriented Synthesis of Triazolo[1,5-a][1,4]diazepine Derivatives from Polymer-Supported Homoazidoalanine

“…All reactions were carried out at ambient temperature (23 °C) unless stated otherwise. The synthesis of Fmoc-AHA, 18 its immobilization on the resin, 21 and the synthesis of N-(3-phenylprop-2-yn-1-yl)-nitrobenzenesulfonamides 2a−i 21,27 were performed according to protocols. The LC−MS analyses were carried out on a UHPLC−MS system consisting of a UHPLC chromatograph Acuity with a photodiode array detector and single quadrupole mass spectrometer (Waters), using an X-Select C18 column with the mobile phase consisting of 10 mM ammonium acetate (AmAc) in H 2 O and CH 3 CN.…”

“…On the other hand, despite the potential interference of an azide with triphenylphosphine, immobilization using Mitsunobu conditions was successful and furnished resin 1 with sufficient loading of Fmoc-AHA ranging from 0.21 to 0.37 mmol/g. The formation of the triazolodiazepine scaffold was accomplished according to a previously reported strategy (Scheme 1): 8 Cls), the resulting sulfonamides were subjected to Mitsunobu alkylation 21 with 3-phenylprop-2-yn-1-ol as the representative alkynol followed by catalyst-free Huisgen cycloaddition of resins 2a and 2b, which afforded key intermediates 3a and 3b. Synthesis of Spiro-indoline-1,2,3-triazolodiazepine Derivatives.…”