Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• attempts have been made to replace formaldehyde with dihalomethanes. These can react with certain secondary amines to generate stable aminals, which increase the rate of reaction at higher temperatures or pressures. This gives rise to products derived from iminium ions and therefore, dihalomethanes can

Challenge N- versus O-six-membered annulation: FeCl₃-catalyzed synthesis of heterocyclic N,O-aminals

• Giacomo Mari,
• Lucia De Crescentini,
• Gianfranco Favi,
• Fabio Mantellini,
• Diego Olivieri and
• Stefania Santeusanio

Beilstein J. Org. Chem. 2024, 20, 1412–1420, doi:10.3762/bjoc.20.123

• intermediates through selective FeCl3-catalyzed intramolecular N-annulation. Keywords: α-aminoacetals; fused-ring systems; heterocyclic hemiaminals; heterocyclic N,O-aminals; multicomponent reactions; Introduction N-Fused heterocycles are ubiquitous within crucial molecules, including biologically active

• to afford, by a chemospecific Lewis acid-catalyzed ring-closure protocol, valuable heterocyclic N,O-aminals (Scheme 1). Results and Discussion Since the direct functionalization of N-heterocycles offers an attractive entry to important molecular targets that might otherwise require lengthy synthetic

• dissolved in DCM (10 mL), FeCl3 (30 mol %) added and magnetically stirred at room temperature. Within 2–30 h, the reactions went to completion (TLC monitoring), affording, at last, N,O-aminals 5a–r (42–82%) and the corresponding hemiaminals 6a–p (4–35%) after column chromatography (Scheme 3). An increased

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• building blocks providing an aminomethyl moiety upon adding nucleophiles. Protected formaldehyde aminals are useful synthetic equivalents to formaldehyde imines. The imine functionality can be unmasked (68) in the reaction medium by Lewis acids such as TiCl4. The formed Mg enolates 66 readily react with

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• aminals with allylic or allenylboronic esters (Scheme 25) [117]. The reaction was proposed to proceed by an activation of elemental gallium to a GaI species [(18-crown-6)-GaI·(dioxane)nOTf] 99, which abstracted methoxide from the acetal 100, to give an oxocarbenium 101 and GaIOMe 102. The gallium(I

• , acetals, aminals, and alkyl ethers (Scheme 26) [119][120][121]. The proposed mechanism was analogous to the GaI catalysis by Schneider, with an In‒O/B‒C exchange proposed to drive catalytic turnover. Nakazawa reported an iron–indium cooperative catalytic system for the hydroboration of nitriles with HBpin

• /propargylation of acetals and aminals and the proposed mechanism. Indium(I)-catalysed allylation/propargylation of acetals, aminals, and alkyl ethers. Iron–indium cocatalysed double hydroboration of nitriles and the proposed mechanism. Funding S.P.T. thanks the Royal Society for a University Research Fellowship

Enantioselective PCCP Brønsted acid-catalyzed aminalization of aldehydes

• Martin Kamlar,
• Robert Reiberger,
• Martin Nigríni,
• Ivana Císařová and
• Jan Veselý

Beilstein J. Org. Chem. 2021, 17, 2433–2440, doi:10.3762/bjoc.17.160

• from preformed imines instead of aldehydes catalyzed by BINOL-phosphoric acid [17]. The corresponding aminals were prepared with a wide range of substitutions using aromatic, α,β-unsaturated, or aliphatic imines. Apart from chiral phosphoric acids, chiral quaternary ammonium salts were successfully

• as the optimal catalyst. With the optimized reaction conditions in our hands, we continued investigating the scope of the reaction. First, we focused on the reactivity of anthranilamide (1a) with various aldehydes 2a–j (Scheme 1). Generally, aliphatic aldehydes delivered the cyclic aminals 3a–d in

• of 70% ee. On the other hand, when m- or o-tolualdehyde were employed in aminalization reaction, a significant drop in the enantioselectivity was observed. Aminals 3g and 3h were obtained with 36 and 20% ee, respectively. We have also tested the reaction between anthranilamide (1a) and

A complementary approach to conjugated N-acyliminium formation through photoredox-catalyzed intermolecular radical addition to allenamides and allencarbamates

• Olusesan K. Koleoso,
• Matthew Turner,
• Felix Plasser and
• Marc C. Kimber

Beilstein J. Org. Chem. 2020, 16, 1983–1990, doi:10.3762/bjoc.16.165

• in the synthesis of N,N’-aminals [50]. Therefore, photoredox-catalysis would be employed to generate an electrophilic radical that would add to the central carbon of the allenamide 1 to give a transient radical 13, whose oxidation, facilitated by the photoredox catalyst [47][48], would provide the

• very challenging and we can account for this instability by the identification of 14a in the 1H NMR spectrum of the crude reaction mixture. A comparable instability profile was observed in the formation of N-acyl-N’-aryl-N,N’-aminals derived from enamides [50]; however, to our knowledge, there are no

Experimental and theoretical investigations into the stability of cyclic aminals

• Edgar Sawatzky,
• Antonios Drakopoulos,
• Martin Rölz,
• Christoph Sotriffer,
• Bernd Engels and
• Michael Decker

Beilstein J. Org. Chem. 2016, 12, 2280–2292, doi:10.3762/bjoc.12.221

• Theoretische Chemie, Julius-Maximilians-Universität Würzburg, Emil-Fischer-Straße 42, D-97074 Würzburg, Germany 10.3762/bjoc.12.221 Abstract Background: Cyclic aminals are core features of natural products, drug molecules and important synthetic intermediates. Despite their relevance, systematic

• investigations into their stability towards hydrolysis depending on the pH value are lacking. Results: A set of cyclic aminals was synthesized and their stability quantified by kinetic measurements. Steric and electronic effects were investigated by choosing appropriate groups. Both molecular mechanics (MM) and

• density functional theory (DFT) based studies were applied to support and explain the results obtained. Rapid decomposition is observed in acidic aqueous media for all cyclic aminals which occurs as a reversible reaction. Electronic effects do not seem relevant with regard to stability, but the magnitude

Antibacterial structure–activity relationship studies of several tricyclic sulfur-containing flavonoids

• Lucian G. Bahrin,
• Henning Hopf,
• Peter G. Jones,
• Laura G. Sarbu,
• Cornelia Babii,
• Alina C. Mihai,
• Marius Stefan and
• Lucian M. Birsa

Beilstein J. Org. Chem. 2016, 12, 1065–1071, doi:10.3762/bjoc.12.100

• ][18] through the reaction of phenacyl carbodithioates 2a–f with aminals 3a–e as presented in Scheme 1. Phenacyl carbodithioates 2a–f, obtained from the appropriately substituted ω-bromoacetophenones and ditihiocarbamates according to previously described procedures [19][20], and aminals 3a–e

• , synthesized by reacting morpholine with halogenated benzaldehydes [21][22], are collected in Table 1. The individual substitution patterns and yields for flavonoids 4a–m and 5a–m are presented in Table 2. The reaction between brominated and iodinated phenacyl carbodithioates 2a–f and halogenated aminals 3a–e

• ). Ellipsoids represent 50% probability levels [26]. Synthesis of flavanones 4a–m and tricyclic flavonoids 5a–m. Conditions: i) EtOH, reflux, 4 h; ii) H2SO4/CH3COOH (1:3 v/v), 20 min; iii) NaBF4 aq. Phenacyl carbodithioates 2a–f and halogenated aminals 3a–e. Substitution patterns and yields for flavonoids 4a–m

Selective copper(II) acetate and potassium iodide catalyzed oxidation of aminals to dihydroquinazoline and quinazolinone alkaloids

• Matthew T. Richers,
• Chenfei Zhao and
• Daniel Seidel

Beilstein J. Org. Chem. 2013, 9, 1194–1201, doi:10.3762/bjoc.9.135

• to affect the selective oxidation of ring-fused aminals to dihydroquinazolines and quinazolinones, respectively. These methods enable the facile preparation of a number of quinazoline alkaloid natural products and their analogues. Keywords: aminal; copper; oxygen; tert-butylhydroperoxide

• requires a subsequent reduction of the amide. In 2008, our group reported the syntheses of deoxyvasicinone (4) and rutaecarpine (6) by the potassium permanganate promoted oxidation of aminals, which in turn were obtained from the condensation of ortho-aminobenzaldehydes and simple secondary amines [31][32

• dihydroquinazolines vasicine (1) and deoxyvasicine (2) can be synthesized from their corresponding aminals by using an iodine-promoted oxidation [34]. While resulting in good yields, these oxidations have the drawback of requiring large amounts of a strong oxidant for the permanganate oxidation and the necessity of

C–C Bond formation catalyzed by natural gelatin and collagen proteins

• Dennis Kühbeck,
• Basab Bijayi Dhar,
• Eva-Maria Schön,
• Carlos Cativiela,
• Vicente Gotor-Fernández and
• David Díaz Díaz

Beilstein J. Org. Chem. 2013, 9, 1111–1118, doi:10.3762/bjoc.9.123

• further cycles, albeit unfortunately with gradual deactivation of the catalyst in both organic and aqueous media (Figure 1). This result may be associated with (1) gradual loss of catalyst loading between cycles and/or (2) possible formation of linear or cyclic aminals [12]. Interestingly, when water/TBAB

Tricyclic flavonoids with 1,3-dithiolium substructure

• Lucian G. Bahrin,
• Peter G. Jones and
• Henning Hopf

Beilstein J. Org. Chem. 2012, 8, 1999–2003, doi:10.3762/bjoc.8.226

• Chemistry, Technical University of Braunschweig, Hagenring 30, D-38106 Braunschweig, Germany 10.3762/bjoc.8.226 Abstract The synthesis of new 3-dithiocarbamic flavonoids has been accomplished by the reaction of the corresponding 2-hydroxyaryl dithiocarbamates with aminals. These flavonoids were obtained as

• a mixture of diastereoisomers, the anti isomer being the major one. The heterocyclization of these compounds provided novel tricyclic flavonoids bearing a 1,3-dithiolium-2-yl ring fused at the 3,4-carbon positions of the benzopyran moiety. Keywords: aminals; benzopyrans; dithiocarbamates

• flavonoids bearing a 1,3-dithiolium-2-yl ring fused at the 3,4-carbon positions of the benzopyran moiety, utilizing the heterocyclization of corresponding 3-substituted dithiocarbamic flavonones. Results and Discussion The treatment of several dithiocarbamates of type 4 with aminals has been reported to

Organocatalytic C–H activation reactions

• Subhas Chandra Pan

Beilstein J. Org. Chem. 2012, 8, 1374–1384, doi:10.3762/bjoc.8.159

• ]. One well-known example of the “tert-amino effect” is the cyclization of N,N-dialkyl-substituted anilines with imines to generate cyclic aminals. The groups of Seidel and Akiyama independently reported mild organocatalytic approaches to cyclic aminals involving aminobenzaldehydes and primary amines [10

• ][11]. Previously, only preformed imines were used for this purpose, and the reactions were mostly thermally controlled [12][13][14][15]. Seidel and co-workers found that the combination of triflic acid and ethanol provided an effective system for the formation of cyclic aminals (Scheme 1), whereas the

• more organocatalytic non-asymmetric and asymmetric sp3 C–H activation processes are expected [37]. Triflic acid-catalysed synthesis of cyclic aminals. PTSA-catalysed synthesis of cyclic aminals. Plausible mechanism for cyclic aminal synthesis. Annulation cascade reaction with double nucleophiles

2-Phenyl- tetrahydropyrimidine- 4(1H)-ones – cyclic benzaldehyde aminals as precursors for functionalised β²-amino acids

• Markus Nahrwold,
• Arvydas Stončius,
• Anna Penner,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2009, 5, No. 43, doi:10.3762/bjoc.5.43

• , Universitätsstr. 25, 33615 Bielefeld, Germany 10.3762/bjoc.5.43 Abstract Novel procedures have been developed to condense benzaldehyde effectively with β-amino acid amides to cyclic benzyl aminals. Double carbamate protection of the heterocycle resulted in fully protected chiral β-alanine derivatives. These