New one-pot synthesis of 4-arylpyrazolo[3,4-b]pyridin-6-ones based on 5-aminopyrazoles and azlactones

• Vladislav Yu. Shuvalov,
• Ekaterina Yu. Vlasova,
• Tatyana Yu. Zheleznova and
• Alexander S. Fisyuk

Beilstein J. Org. Chem. 2023, 19, 1155–1160, doi:10.3762/bjoc.19.83

• aldehyde with thioglycolic acid and aminopyrazole, followed by the extrusion of sulfur from the resulting thiazepine [20] (method C). The three-stage synthesis of 4-arylpyrazolo[3,4-b]pyridin-6-ones, involving the preparation of 3-aryl-N-(1H-pyrazol-5-yl)propiolamides (method D), also leads to the

Five new sesquiterpenoids from agarwood of Aquilaria sinensis

• Hong Zhou,
• Xu-Yang Li,
• Hong-Bin Fang,
• He-Zhong Jiang and
• Yong-Xian Cheng

Beilstein J. Org. Chem. 2023, 19, 998–1007, doi:10.3762/bjoc.19.75

• activities for all the new derivatives. Furthermore, we recall the skeletons in our current study and our previously reported ones [16][22][23][24][25][26], which revealed the SAR. Moreover, eudesmane-type sesquiterpenes constructed with aldehyde groups are more active even in the form of dimers. In the

• present study, it was described that skeletons with 1°-alcohols and/or acid groups suppress activity, which was consistent with the A. sinensis literatures that 1°-alcohols and/or acid groups suppress activity [25][27], and concluded that eudesmane-type sesquiterpenes constructed with aldehyde groups are

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• force the π-nucleophile to approach from the less sterically congested para-position. As ortho-substituents in the phenol derivatives, mainly sterically bulky alkyl, silyl, and iodo groups were incorporated to ensure the complete regioselectivity. On the other hand, various aromatic aldehyde-based

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• shown in Scheme 20b. In this mechanism, calcium nitrate first activates the decomposition process of 2,5-DMTHF (2) from A to B. Further, a nucleophilic attack of amines 42 on B generates imine intermediate C. Finally, intramolecular nucleophilic attack by enamine D on the aldehyde group, dehydration and

Intermediates and shunt products of massiliachelin biosynthesis in Massilia sp. NR 4-1

• Till Steinmetz,
• Blaise Kimbadi Lombe and
• Markus Nett

Beilstein J. Org. Chem. 2023, 19, 909–917, doi:10.3762/bjoc.19.69

• accordance with eight degrees of unsaturation. The NMR data for 4 is closely related with that of compound 3. The carbon atom at 184.9 ppm (C-15) possesses an HSQC correlation to a proton resonance at δH 9.98 (H-15), which is characteristic of an aldehyde function. This is in full accordance with the loss of

• seven degrees of unsaturation. The NMR data of compound 5 are very similar to those of compounds 3 and 4. However, instead of the aldehyde function seen in compound 4, a proton signal at δH 4.63 (H-15) can be observed. Together with its distinct carbon signal at 60.3 ppm (C-15), HMBC correlations to the

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• proximal C–H functionalizations in pyridine substrates under different catalytic systems. However, the intermolecular undirected distal C–H functionalization in pyridine remained unstudied. In these circumstances, the distal C–H alkylation by addition of the pyridine C–H bond to an aldehyde 50 under

• addition of 1 gives the silyl-iridium complex 52. The insertion of aldehyde 50 into the Ir–Si bond of 52 provides the pyridyl alkyl iridium species 53 that finally by C–C formation via reductive elimination furnishes the desired products 51 along with the formation of an iridium hydride species (Scheme 11b

Synthesis of imidazo[1,2-a]pyridine-containing peptidomimetics by tandem of Groebke–Blackburn–Bienaymé and Ugi reactions

• Oleksandr V. Kolomiiets,
• Alexander V. Tsygankov,
• Maryna N. Kornet,
• Aleksander A. Brazhko,
• Vladimir I. Musatov and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2023, 19, 727–735, doi:10.3762/bjoc.19.53

• proved to be inefficient. In addition, we also tested the one-pot method for the synthesis of similar structures [32]. Aminopyridine, aldehyde and Sc(OTf)3 as catalyst were stirred in MeOH/DCM for 45 min at room temperature, then the isocyanide was added and the mixture was stirred for another 8 h

• . Without isolation, the corresponding aldehyde, amine and isocyanide were added to the resulting iminopyridine product and the mixture was then stirred at room temperature for 12 h. But again, the expected compounds could not be obtained. Following this trend and based on published data, we synthesized

Palladium-catalyzed enantioselective three-component synthesis of α-arylglycine derivatives from glyoxylic acid, sulfonamides and aryltrifluoroborates

• Bastian Jakob,
• Nico Schneider,
• Luca Gengenbach and
• Georg Manolikakes

Beilstein J. Org. Chem. 2023, 19, 719–726, doi:10.3762/bjoc.19.52

• palladium-catalyzed three-component reactions between arylboronic or carboxylic acids, amides or sulfonamides and different aldehyde components as attractive and broadly applicable alternative to the classical Petasis borono-Mannich reaction (Scheme 1b) [17][18][19][20][21]. Recently, we were able to extend

Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• precursor 102 and the complementary aldehyde 103. 3.4 Catellani-type reaction The Catellani reaction involves palladium-norbornene cooperative catalysis to functionalise the ortho- and ipso-positions of aryl halides by alkylation, arylation, amination, acylation, thiolation, etc. [63]. Della Ca' et al. [64

• synthesising the tethers and RCM products are reported, the method does not currently allow for the synthesis of unsymmetrical compounds. 3.6 Alkyne–aldehyde metathesis Bera et al. [69] reported on the synthesis of a series of 10-acyldibenzo[b,f]oxepines 125 by alkyne–aldehyde metathesis catalysed by iron(III

• metathesis as key step in the synthesis of dibenzo[b,f]heteropines. Alkyne–aldehyde metathesis in the synthesis of dibenzo[b,f]heteropines. Hydroarylation of 9-(2-alkynylphenyl)-9H-carbazole derivatives. Oxidative coupling of bisphonium ylide intermediate to give pacharin (13). Preparation of 10,11

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

• isolated with equally good yields and excellent stereoselectivities (98–99% ee) (Scheme 41B). Surprisingly, when the aldehyde was exchanged with imine 163, the Mannich product 164 was gained only in 23% yield, however, with excellent enantioselectivity of 94%. In the following year, Aponick et al

• activation of aryl pyrazoles, followed by the asymmetric conjugate addition to the Michael acceptor. Then, the formed cobalt enolate participates in the intermolecular aldol reaction with an aldehyde 207. The stereochemistry of this tandem procedure is controlled by the chiral Co(III) complex C4 bearing

• addition of organozirconium reagent 227 to enone 1. In the presence of the (R)-BINAP ligand, the Michael adduct 228 could be isolated in 97% ee. Finally, the Zr enolate was trapped by aldehyde 229 prepared from ᴅ-ribose. The aldol adduct 230 was isolated in 80% yield and excellent diastereoselectivity (>20

C3-Alkylation of furfural derivatives by continuous flow homogeneous catalysis

• Grédy Kiala Kinkutu,
• Catherine Louis,
• Myriam Roy,
• Juliette Blanchard and
• Julie Oble

Beilstein J. Org. Chem. 2023, 19, 582–592, doi:10.3762/bjoc.19.43

• changing the redox state of the aldehyde function, we have developed a number of directed Ru(0)-catalyzed C3-functionalizations of furfurylimines, such as alkylation [21], arylation [22], alkenylation [23] and acylation [24], as well as an Ir-catalyzed directed C3-silylation (Scheme 1a) [25]. These batch

• starting material had proved to be the most reactive imine in batch, leading, in the presence of 5 mol % of [Ru3(CO)12] and 3 equivalents of triethoxyvinylsilane in toluene at 150 °C after 5 h, to the alkylated aldehyde 2a with 62% yield, after purification on silica gel (Scheme 2) [21][39]. The flow

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• allylic alcohol isomerization in 137 resulting in the aldehyde 138. This aldehyde, in close proximity to the tertiary alcohol, leads to the production of the hemiacetal 139 which can finally undergo an oxidation producing the final bicyclo[2.2.2]lactone product 136. In 2011, the Radhakrishnan laboratory

• salicylaldehydes with EWGs failed to react. The authors hypothesized the reaction mechanism begins with the association of the Rh(III) catalyst with the hydroxy group of salicylaldehyde (151a) resulting in a selective cleavage of the aldehyde C–H bond producing the rhodocycle 153 which side-on coordinates with the

Transition-metal-catalyzed C–H bond activation as a sustainable strategy for the synthesis of fluorinated molecules: an overview

• Louis Monsigny,
• Floriane Doche and
• Tatiana Besset

Beilstein J. Org. Chem. 2023, 19, 448–473, doi:10.3762/bjoc.19.35

• broad range of functional groups such as halogens, ester, aldehyde, cyano, and nitro (36c–g, 36–74% yield). It is noteworthy that a disubstituted compound 35j and a thiophene derivative 35k were also efficiently difluoromethylthiolated (36j and 36k, 72% and 65%, respectively). α-Substituted

Asymmetric synthesis of a stereopentade fragment toward latrunculins

• Benjamin Joyeux,
• Antoine Gamet,
• Nicolas Casaretto and
• Bastien Nay

Beilstein J. Org. Chem. 2023, 19, 428–433, doi:10.3762/bjoc.19.32

• (13,14)-bond of 1 and 2, respectively. Conversely, we envisaged an alternative disconnection to form the (16,17)- or the (14,15)-bond of 1 and 2, through an aldol reaction of aldehyde 8 readily available from ʟ-cysteine, leading to aldol adduct 7 (Figure 2, route B). The methyl ketone partner 9 could be

• formed by the oxidation of an allyl moiety introduced by the asymmetric allylation of an aldehyde derived from (+)-β-citronellene. At this stage, we can speculate that the stereocontrol of this reaction could either follow a polar Felkin–Anh model [14][15][16] based on chiral aldehyde partner 8 [17], or

• 11 in 78% yield (Scheme 1). Due to easier purification, this alcohol was preferred to the aldehyde in our synthetic route, allowing a key stereoselective Krische allylation [21][22] to be envisaged. Applying reported conditions for this allylation – in presence of allyl acetate (10 equiv), [Ir(COD)Cl

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• necessary to give compound 17 in 85% yield after the two steps. Subsequent reaction of the aldehyde 17 following a modified Still–Gennari protocol [29] employing the phosphonate 18 gave the alkene 19 in 90% yield and high selectivity (cis/trans = 25:1). Removal of the silane group with TBAF furnished the

• coupling reaction. Thus, the olefination reaction of aldehyde 15 with phosphonate 23, followed by the reduction of the obtained ester 24 using DIBAL led to the alcohol 25. The latter was submitted to the reaction with carboxylic acid 26 under Mitsunobu conditions [30], giving the corresponding ester 27 in

• ] between halide 37 and phenol 38 leading to the formation of diaryl ether 39, which was subjected to a regioselective iodination reaction to give compound 40. Conversion of the nitrile in compound 40 into the corresponding aldehyde 41 followed by Z-selective Still–Gennari olefination gave the cis α,β

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

• . Alongside this, H-B-9-BBN underwent reduction of the ester or lactone 57, to give a hemiacetal intermediate 58, which underwent B‒O/B‒H transborylation with HBpin to give an O-Bpin hemiacetal 59. Borane-mediated collapse of the O-Bpin hemiacetal gave an aldehyde 60 which reacted with the O-Bpin enolate 52

Continuous flow synthesis of 6-monoamino-6-monodeoxy-β-cyclodextrin

• János Máté Orosz,
• Dóra Ujj,
• Petr Kasal,
• Gábor Benkovics and
• Erika Bálint

Beilstein J. Org. Chem. 2023, 19, 294–302, doi:10.3762/bjoc.19.25

• - [16], hydroxylamino- [17], or alkylamino-CDs [18], monosubstituted at position C-6. In addition, the tosyl functional group can be oxidized to an aldehyde using a non-nucleophilic base in dimethyl sulfoxide (DMSO) [19]. The monoaldehyde CDs can be further oxidized selectively to afford the

Synthesis, α-mannosidase inhibition studies and molecular modeling of 1,4-imino-ᴅ-lyxitols and their C-5-altered N-arylalkyl derivatives

• Martin Kalník,
• Sergej Šesták,
• Juraj Kóňa,
• Maroš Bella and
• Monika Poláková

Beilstein J. Org. Chem. 2023, 19, 282–293, doi:10.3762/bjoc.19.24

• -benzyl group with the Cbz group, trityl ether hydrolysis, oxidation of the liberated OH group, and stereoselective addition of MeMgBr to the resulting aldehyde functionality. Hydrogenolysis of the Cbz protecting group in 13 followed by N-alkylation afforded pyrrolidines 14–16 which after acidic

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• 31 and oxazolidinone 32 (Scheme 5) [26]. Subsequently, compound 33 was converted in four steps into aldehyde 34 which was engaged in a coupling reaction with bromoketone 35 according to Utimoto conditions to furnish the A-C-D adduct 36 as a single stereoisomer in high yield. Of note, the Utimoto

• functionalized alkyne moiety prefiguring the aldehyde function of ophiobolin A (8). These two compounds were submitted to the EYRCM in the presence of G-II catalyst and furnished two different outcomes. Indeed, compound 102 gave the expected product 104 in 78% yield, whereas precursor 103, bearing hindered gem

• –Hiyama–Kishi (NHK) reaction is an interesting coupling reaction involving the addition of a halogeno derivative (either bromide or iodide) to an aldehyde in the presence of nickel and chromium salts, typically NiCl2/CrCl2, generating an alcohol. In its original version, the stereochemistry of the adduct

Identification and determination of the absolute configuration of amorph-4-en-10β-ol, a cadinol-type sesquiterpene from the scent glands of the African reed frog Hyperolius cinnamomeoventris

• Angelique Ladwig,
• Markus Kroll and
• Stefan Schulz

Beilstein J. Org. Chem. 2023, 19, 167–175, doi:10.3762/bjoc.19.16

• in a Michael addition with methyl acrylate, affording aldehyde 4 (Scheme 1). Instead of the original Wittig reaction [13], a Horner–Wadsworth–Emmons reaction using diethyl (2-methylallyl)phosphonate and BuLi led to a higher yield and formation of the pure (E)-isomer 5. The required phosphonate was

• cleanly obtained in 75% yield from triethyl phosphite and 3-chloro-2-methylpropene by addition of NaI [14]. Subsequent reduction of the ester with LiAlH4 and oxidation with IBX gave aldehyde 7 in 95% yield. Grignard addition of vinylmagnesium bromide afforded the alcohol 8, which comprised the desired

• , such a synthetic approach would shorten the synthesis from eight to four steps and allow access to both enantiomers of the compounds 12–14. The synthesis started with an enantioselective Michael addition of aldehyde 1 to methyl vinyl ketone (15) catalyzed by (S)-Jørgensen’s organocatalyst S-16, to

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• reactions, as pseudo-heteroarylzinc reagents. Another example developed by Knochel uses the zincated 1,4-dithiin 22 as a nucleophile to add across the N–O bond in anthranil [44], which spontaneously cyclizes to a heterocycle-fused quinoline via a Friedel–Crafts-type pathway onto the released aldehyde moiety

• synthesis starts from a carbonyl compound, wherein an aldehyde can undergo ‘umpolung’ into a cis-vinyl anion equivalent via a 1,3-dithiolane-to-1,4-dithiane rearrangement (Scheme 10b). The potential of the method is demonstrated by the synthesis of (Z)-9-tricosene or muscalure (59), which is the natural sex

• pheromone of the common house fly [58]. The aldehyde 55 is converted into a vinyl anion equivalent 57 in two high yielding and operationally simple steps. The alkylation of this dihydrodithiin intermediate proceeds extremely smoothly, yielding the 1,4-dithiane-tethered version of the target molecule (58). A

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

• Bilge Banu Yagci,
• Selin Ezgi Donmez,
• Onur Şahin and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6

• the β-silicon effect in this aza-Nazarov cyclization. During the course of our studies, we observed occasionally the formation of aldehyde-containing side products, the amount of which increased when the aza-Nazarov cyclizations did not proceed efficiently. We proposed that, if the aza-Nazarov

• cyclization of an in situ-formed iminium intermediate is not efficient under certain reaction conditions, then its hydrolysis with adventitious water, which might be present in the reaction medium, would lead to the formation of an aldehyde side product. Unfortunately, our attempts to isolate such a side

• product in pure form from a crude reaction mixture failed. However, when a mixture of imine 5a and methacryloyl chloride (31) was stirred in a biphasic mixture of CH2Cl2 and aqueous NaHCO3 solution, we were able to isolate and fully characterize aldehyde 32 which would form via the hydrolysis of iminium

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• pyrone meroterpenoids on sclareolide (29). Key reaction of this strategy was the formal [3 + 3] cycloaddition, catalyzed by phosphoric acid 33, followed by addition of a pyrone residue 32 to sclareolide-derived aldehyde 31, which served as the common synthetic intermediate for the synthesis (Scheme 3

• commenced with the generation of 107 from cyclopentenone 105 and aryl aldehyde 106 in a three-step sequence. An oxidative dearomatization induced a [5 + 2] cycloaddition–pinacol rearrangement of 107 to 109, according to previous studies of the same group (Scheme 9) [59][60][61]. The key HAT-mediated

• chiral aldehyde 127 and Boc-protected amine 128, followed by zinc reduction of the nitro group and subsequent protection of the amine by a tosyl group in 27% overall yield. Irradiating 129 with blue light at 30 W in the presence of 1 mol % of [Ir(dtbbpy)(ppy)2]PF6 and 5 equiv of KHCO3 in THF resulted in

Synthetic study toward tridachiapyrone B

• Morgan Cormier,
• Florian Hernvann and
• Michaël De Paolis

Beilstein J. Org. Chem. 2022, 18, 1741–1748, doi:10.3762/bjoc.18.183

• ’-methoxy-γ-pyrone in one step. To construct the quaternary carbon of the 2,5-cyclohexadienone of the target, a strategy based on the Robinson-type annulation of an aldehyde derived from α-crotyl-α’-methoxy-γ-pyrone was applied. The grafting of the simplified target’s side chain was demonstrated through an

• of an aldehyde resulting in a regioselective aldolization [29]. Thereafter, we hypothesized converting cyclopentadiene 6b into 2,5-cyclohexadienone 5 by a sequence involving the oxidation into dialdehyde 7 and treatment with pentan-3-one to enable sequential steps of aldolization and crotonization

• to 2,5-cyclohexanedione 5 was accordingly updated and an approach to make use of the Robinson-type annulation was devised from aldehyde 9, prepared by oxidation of α-crotyl-α’-methoxy-γ-pyrone 8 (Scheme 4). While its synthesis was initially investigated by the coupling of tri(n-butyl)crotylstannane

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• on the obtainment of two distinct fragments, a racemic bicyclo[3.2.1]octane unit 25 corresponding to rings C and D, and an enantioenriched cyclopentyl aldehyde derivative 29, corresponding to ring A. These fragments were successfully coupled under basic conditions, and the ring B was later

• afforded fragment 25 with 73% yield over 3 steps. On the other hand, the enantioenriched cyclopentyl aldehyde fragment 29 was obtained starting from commercially available 2,2-dimethylcyclopentane-1,3-dione (26). The dione was submitted to a sequence involving a monoreduction, protection of the alcohol as

• into dimethylacetal 45 by Vilsmeier reaction followed by aldehyde protection in 54% yield over two steps. A Mukaiyama aldol reaction between trimethylsilyl enol ether 46 and dimethylacetal 45 followed by Sakurai cyclization provided an inseparable mixture of C9 epimers (dr = 2:1). A catalyst