A.-E. Dascalu, et al.
Molecular Catalysis 470 (2019) 32–39
Fig. 1. Structures containing cyclic N,N’-aminals or N,O-acetals.
white precipitate is filtered and discarded. The filtrate is evaporated
and then dichloromethane (40 mL) is added, followed by acidified
water (pH = 5). The organic phase is separated and the aqueous phase
is acidified by citric acid and extracted by dichloromethane. The or-
ganic phases are combined and evaporated at 50 °C under vacuum. The
oily crude product obtained rapidly crystallized into white pure pter-
olactam 3 in quantitative yield.
2.3. General procedure for the synthesis of products 4-44
To a mixture of 5-methoxypyrolidone 3 (17.4 mmol, 1 eq) and CsF
(
0.086 mmol, 5 mol%) was added the nucleophilic reactant (17.4 mmol,
1
8
eq). The mixture was stirred under moderate vacuum (30 mmHg) at
0 °C, until the NMR conversion showed no more progression or after
Scheme 1. Previously reported pathway to 5-substituted pyrrolidin-2-one de-
rivatives from pyroglutamic acid 1 [30] and current work.
caking of the medium. Then, the crude product was precipitated by
Et O and recrystallized from EtOH or purified by flash liquid chroma-
2
tography (silica gel, gradient of ethyl acetate in n-heptane), to afford
the target compounds. All products 4-44 were identified by comparing
their spectral date with those of authentic samples or by elemental
analysis for new compounds.
2
. Experimental
2.1. General informations
Starting materials are commercially available and were used
2
.4. Protocol for the recording of pH
without further purification. Melting points were measured on a MPA
®
1
00 OptiMelt apparatus. Nuclear magnetic resonance (NMR) spectra
45 g of pterolactam 3 (0.395 mol) was dissolved in 20 mL of water
1
13
were acquired at 400 MHz for H NMR, 100 MHz for C NMR and
and heated under low stirring at 80 °C. The pH was recorded thanks a
combined electrode (calomel reference) which was calibrated just be-
fore the set of experiments. The pH was recorded every minute for
1
9
3
76 MHz for F NMR on a Varian 400-MR spectrometer, at 25 °C.
Chemical shifts (δ) are quoted in parts per million (ppm) and are re-
ferenced to TMS as an internal standard. Coupling constants (J) are
quoted in hertz. Comparisons with known or reported compounds and
1
5 min as soon as the cesium salt (CsF or Cs
2 3
CO , 5 mol%) was added in
the solution at 80 °C under stirring (200 rpm) (see Graph in SI).
2
D methods (HMBC and HSQC experiments) have been used to confirm
the NMR peak assignments. Organic solutions have been concentrated
under reduced pressure using a Büchi rotary evaporator. Column
chromatography was performed with a CombiFlash Rf Companion
3
. Results and discussion
3.1. 3.1Preliminary screening
(
Teledyne-Isco System) using RediSep packed columns. IR spectra were
recorded on a Varian 640-IR FT-IR Spectrometer. Elemental analyses
C, H, N, S) of new compounds were determined on a Thermo Electron
Pterolactam 3 was prepared in quantitative yield by electrochemical
(
decarboxylation of pyroglutamic acid as described by our group after
slight modifications of literature process [30], and used as substrate
model with benzyl amine and furfuryl alcohol as nucleophiles. In a first
approach, various catalysts, reported as active for related reactions
were screened to promote the reaction (Table 1). At first, furfuryl al-
cohol was used as oxygenated nucleophile. Without any solvent nor
catalyst, the conversion is low and only an 11% yield of the target
compound 4 is obtained (Table 1, entry 1). Acids, known to favor
iminium salts formation, were then attempted as catalysts (Table 1,
entries 2-5). Methanesulfonic acid, Amberlyst H15 resin or Lewis acids
led to a total degradation of pterolactam 3 (Table 1, entries 2-5). As a
consequence, some basic promoters were attempted.
apparatus by ‘Pôle Chimie Moléculaire-Welience’, Faculté de Sciences
Mirande, Université de Bourgogne, Dijon, France. Yield refers to the
isolated analytically pure material.
2.2. General procedure for the synthesis of pterolactam 3
A mixture of pyroglutamic acid 1 (5.16 g, 0.04 mol) and 30% so-
dium methoxide in methanol (1.15 g) in methanol (500 mL) was placed
in a beaker equipped with 6 graphite-rods anodes and 6 graphite-rods
cathodes and a stirring bar. The carbon rods, immersed 100 mm into
the solution were spaced 10 mm apart. During the electrolysis, the
temperature of the reaction mixture was maintained at 15 °C by using a
water bath. The current intensity was fixed at 0.5 amperes, and the cell
voltage was initially 5.4 volts. The electrolysis was performed for 6 h. A
Triethylamine did not lead to any conversion nor degradation
(Table 1, entry 6). Interestingly, addition of cesium carbonate led to a
complete conversion of pterolactam 3 and the target compound 4 was
33