Synthetic study toward the diterpenoid aberrarone

• Liang Shi,
• Zhiyu Gao,
• Yiqing Li,
• Yuanhao Dai,
• Yu Liu,
• Lili Shi and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2022, 18, 1625–1628, doi:10.3762/bjoc.18.173

• were reported [30][31] and more recently, Carreira and co-workers reported [32] the first total synthesis of aberrarone through an impressive cascade reaction including a gold-catalyzed Nazarov cyclization, a cyclopropanation followed by intramolecular aldol reaction to forge the A, B and D rings

Oxa-Michael-initiated cascade reactions of levoglucosenone

• Julian Klepp,
• Thomas Bousfield,
• Hugh Cummins,
• Sarah V. A.-M. Legendre,
• Jason E. Camp and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2022, 18, 1457–1462, doi:10.3762/bjoc.18.151

• presumed to start with an oxa-Michael initiated aldol reaction promoted by a methoxide nucleophile giving enone 6 via enolate 8 (Scheme 1). A Rauhut–Currier-type reaction of 6 with the addition of another equivalent of 8, followed by a subsequent double β-elimination leads to the observed product 5. When

• tetraketones 11 promoted by base (Scheme 2) [25]. The equivalent reaction has not been reported for dihydrolevoglucosenone (Cyrene™) 12, and it was thought that the chiral 1,5-diketone products could be used to construct catalysts or ligands. The aldol/Michael cascade using conditions for the aldol reaction

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• cycloisomerization of the α-ketoester 22, which can be described as a Friedel–Crafts-type reaction or an aldol reaction of an S,O-ketene acetal (Scheme 4). The required ketoester 22 was synthesized from sulfonylchromenone 20, accessible from dihydroxyacetophenone 19 and thiol 18 derived from known alcohol 17 [11][12

• 27. Subsequent oxidation gave α-ketoester 28 which was used in an intramolecular, Lewis acid-mediated aldol reaction, presumably via tridentate complex transition state III, to give diol 29 as a single diastereomer. Inversion of the secondary alcohol and deprotection gave preussochromone D (30

• (−)-irofulven (87), Movassaghi et al. used a CuII-catalyzed asymmetric aldol reaction of O-silyl ketene S,O-acetal 84 with methyl pyruvate (85) to enantioselectively install the crucial tertiary TMS-protected alcohol in ester 86 (Scheme 14) [29]. Eleven further steps gave (−)-irofulven (87). 2. Mesoxalic

Tosylhydrazine-promoted self-conjugate reduction–Michael/aldol reaction of 3-phenacylideneoxindoles towards dispirocyclopentanebisoxindole derivatives

• Sayan Pramanik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 469–478, doi:10.3762/bjoc.18.49

• Sayan Pramanik Chhanda Mukhopadhyay Department of Chemistry, University of Calcutta, 92 APC Road, Kolkata-700009, India 10.3762/bjoc.18.49 Abstract An efficient tosylhydrazine-mediated conjugate reduction of 3-phenacylideneoxindole and sequential Michael/intramolecular aldol reaction is reported

• dispirocyclopentanebisoxindoles from two molecules of 3-phenacylideneoxindoles, accomplished by reduction of one molecule of 3-phenacylideneoxindole by thiol [24]. In 2017, Thennarasu et al. [25] reported the tandem oxidation/Michel-aldol reaction of 3-phenacyloxindoles for the synthesis of dispirocycliopentanebisoxindoles

Organocatalytic asymmetric nitroso aldol reaction of α-substituted malonamates

• Ekta Gupta,
• Narendra Kumar Vaishanv,
• Sandeep Kumar,
• Raja Krishnan Purshottam,
• Ruchir Kant and
• Kishor Mohanan

Beilstein J. Org. Chem. 2022, 18, 217–224, doi:10.3762/bjoc.18.25

• 226031, India Academy of Scientific and Innovative Research, Ghaziabad, 201002, India 10.3762/bjoc.18.25 Abstract A practical enantioselective N-selective nitroso aldol reaction of α-methylmalonamates with a nitrosoarene is reported. The reaction employs the Takemoto thiourea catalyst for the induction

• of enantioselectivity, and the corresponding optically active oxyaminated malonamates were obtained in reasonably good yields. Keywords: enantioselective; malonamate; nitroso aldol reaction; N-selectivity; Takemoto catalyst; Introduction Nitrosoarenes are versatile building blocks frequently

• noteworthy and widely explored transformations of nitrosoarenes include nitroso ene reactions [9][10][11], Diels–Alder cycloadditions [12][13][14][15][16][17][18], and nitroso aldol reactions [19][20][21][22][23]. Among the various applications of nitrosoarenes, the asymmetric nitroso aldol reaction to

The enzyme mechanism of patchoulol synthase

• Houchao Xu,
• Bernd Goldfuss,
• Gregor Schnakenburg and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 13–24, doi:10.3762/bjoc.18.2

• proceeded with full retainment of the labelling in both cases (Scheme 1B). Subsequent chemical degradation through acid catalysed conversion into 5, oxidative cleavage to the diketone 13, BF3∙OEt2 mediated ring closure by aldol reaction and catalytic hydrogenation gave 14. For both experiments a full

• experiment with [12,13-14C,1-3H]FPP was expected for the aldol reaction of 13, but is more difficult to understand in the experiment with [12,13-14C,6-3H]FPP. In this case the loss of 3H was explained by an exchange against 1H during catalytic hydrogenation [9]. One year later, Akhila et al. proposed an

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• catalyst developed by our group is critical for increasing the enantioselectivity in this cascade reaction [38]. This catalyst can facilitate the aldol reaction to generate a stereocenter (I-7), which can then be converted to axial chirality (I-8 to I-10) and finally aromatized to give 31 (Scheme 11) [60

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• al. reported cinchona-based primary amine catalyzed cascade aza-Michael-aldol reaction of α,β-unsaturated ketones 6 with 2-(1H-pyrrol-2-yl)-2-oxoacetates 5 where triphenylacetic acid was used as an additive. This cascade reaction afforded highly functionalized chiral pyrrolizines 8 in good yields (70

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• starting material in the asymmetric organocatalyzed reaction, the Enders group described the use of (S)-proline as catalyst in an intramolecular aldol reaction, enabling a new strategy to obtain coumarin natural products [34]. As for example, the total synthesis of (+)-smyrindiol (17), a linear

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• aldol reaction (Scheme 22B), which was confirmed by the observation of the aldol product in low yield. The ET step initially proposed by Baran has undergone insightful discussions about its nature, and a recent theoretical study postulated a proton-coupled electron transfer (PCET) pathway (Scheme 22C

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

• been demonstrated to yield superior results to batch. Higher yields and rates of reaction, and greater selectivities can often be achieved in flow. For example, the rate of the aldol reaction of a silyl enol ether 13 with 4-bromobenzaldehyde (14) showed a marked increase upon transposition to flow [87

• to fragrance chemists. This section investigates the aldol reaction as this is a vital C–C and C=C bond forming tool within this class of reactions. Other sequences such as the Knoevenagel and Darzens condensation, however, will also be considered as part of the evaluation. The condensation of

• reaction [93]. A common synthesis of dihydrojasmone (35) uses an intramolecular aldol reaction to simultaneously form the cyclopentanone ring and the double bond in the correct positions [94][95]. Aldol reactions are most often exothermic, especially those involving highly reactive aldehydes (e.g

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• number of classical methodologies have been used for their synthesis, in which the key step is the generation of the six-membered ring, including the aldol reaction, the reductive amination, Mannich reaction, ring closing metathesis, Diels–Alder reaction with imines as dienophiles, aza-Prins cyclization

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• . A similar tandem strategy of an addition of vinylsilane 196, followed by silyl-Prins cyclization with an aldehyde 197 in the presence of 5 mol % BiBr3, was reported by Hinkle and co-workers to give the corresponding compound 198 (Scheme 47) [18]. The authors further investigated the Mukaiyama aldol

• reaction between the β,γ-unsaturated aldehyde 199 and acetal 200 in the presence of 10 mol % BiBr3 to obtain aldol product 201. However, the addition of 2 equiv of phenylacetaldehyde (189) and 10 mol % BiBr3 afforded dihydropyran 202 in 64% yield as a single isomer, as shown in Scheme 48 [91]. The cis-2,6

Direct synthesis of anomeric tetrazolyl iminosugars from sugar-derived lactams

• Michał M. Więcław and
• Bartłomiej Furman

Beilstein J. Org. Chem. 2021, 17, 115–123, doi:10.3762/bjoc.17.12

• as the aldol reaction [30], Michael addition [31], Mannich reaction [32], and hydrogenation [33]. Results and Discussion Quite recently Xie and Dixon showed that it is possible to synthesize α-tetrazolylamines from simple and linear tertiary amides using an iridium-based catalytic protocol [19]. They

• widely used as organocatalysts. Such moieties are employed in a number of important synthetic transformations, including the aldol reaction [30], Michael addition [31], Mannich reaction [32], and hydrogenation [33]. We plan to test these possibilities in the near future. Stereochemistry and configuration

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• phosphonate reagent 50 proceeded stereoselectively to give ester 51 in excellent yield (94%). Subsequent DIBAL-H reduction of ester 51 followed by tetrapropylammonium perruthenate (TPAP) oxidation afforded aldehyde (Z,E)-52 as a single isomer in 83% yield over two steps. The asymmetric aldol reaction aldehyde

• ). The total synthesis of inthomycin C ((+)-3) was achieved by using a Stille coupling between (E,E,)-67 and vinyl iodide 48 followed by directed asymmetric aldol reaction under Mukaiyama–Kiyooka aldol reaction conditions (Scheme 6). Initially, (E)-3-(tributylstannyl)propenal (65) was converted into (E,E

• asymmetric aldol reaction in the presence of oxazaborolidinone derivative 68 and silyl ketene acetal 53 to produce the required α-hydroxy ester (+)-11 in 50% yield and 76% ee ((R)-stereochemistry of the major enantiomer). A competitive reduction of 71 was also observed to produce alcohol 72 in 43% yield

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• of the C=C double bond of 170b gave a keto aldehyde (not shown), which was subjected to an acid-mediated aldol reaction to give conidiogenone B (171) in 53% yield. The undesired isomer with β,γ-C=C double bond (not shown) was formed in 34% yield and can be isomerized to the more stable α,β

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• -aldol reaction affording the final product (Scheme 34). This mechanism was experimentally supported by the beneficial effect of water and the observation of HF-loss by 19F NMR. The catalytic version of this process was also studied. The best results in terms of efficiency and stereoselectivity were

• Diels-Alder reactions [70]. Tentative mechanism for the nucleophilic addition/retro-aldol reaction sequence. Catalytic PKR with norbornadiene [70]. Scope of the PKR of trifluoromethylalkynes with norbornadiene [72]. DBU-mediated detrifluoromethylation [72]. A simple route to enone 67, a common

A simple and easy to perform synthetic route to functionalized thienyl bicyclo[3.2.1]octadienes

• Dragana Vuk,
• Irena Škorić,
• Valentina Milašinović,
• Krešimir Molčanov and
• Željko Marinić

Beilstein J. Org. Chem. 2020, 16, 1092–1099, doi:10.3762/bjoc.16.96

• were synthesized through Wittig reactions and subjected to photochemical cyclization, in terms of obtaining the new annulated structures. As part of this study, the aldol reaction of the starting 2-substituted carbaldehyde with acetone was also performed, which produced the thieno-fused benzobicyclo

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• -metal-catalyzed transformations were needed to achieve the total synthesis of des-epoxy-amphidinolide N, including a palladium asymmetric allylic alkylation (Pd-AAA), a Mukaiyama aldol reaction (with Sn), and a Krische allylation (with Ir) [72]. As special feature of this procedure, an Evans aldol

• reaction generated the syn aldol adduct, having the steric configuration imposed in des-epoxy-amphidinolide N. Also, in the last step of their work, Trost et al. managed to install the C14-OH via a finely tuned Rubottom oxidation that finalized the total synthesis of des-epoxy-amphidinolide N. Strikingly

A green, economical synthesis of β-ketonitriles and trifunctionalized building blocks from esters and lactones

• Daniel P. Pienaar,
• Kamogelo R. Butsi,
• Amanda L. Rousseau and
• Dean Brady

Beilstein J. Org. Chem. 2019, 15, 2930–2935, doi:10.3762/bjoc.15.287

• alkoxide anions. This reduces the occurrence of undesirable side-reactions, e.g., intermolecular aldol reaction, lactone/ketonitrile product dimerization and ring-opening polymerization. The application of this method to produce the analogous hemiketal 6 from γ-butyrolactone was not as efficient. Although

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• the formal synthesis of triptolide (Figure 2, route N) [43]. This synthesis highlighted the palladium-catalyzed asymmetric addition of arylboronic acid 37 to 3-methylcyclohex-2-en-1-one (38) to form the C-10 quaternary chiral center, and a subsequent Claisen rearrangement and an aldol reaction to

Application of chiral 2-isoxazoline for the synthesis of syn-1,3-diol analogs

• Juanjuan Feng,
• Tianyu Li,
• Jiaxin Zhang and
• Peng Jiao

Beilstein J. Org. Chem. 2019, 15, 1840–1847, doi:10.3762/bjoc.15.179

• boronic acid had been widely utilized to disconnect the N–O bond as well as to hydrolyze the resulting imine into a ketone [52]. We applied this method to deprotect the isoxazoline 3. However, the desired β-hydroxy ketone was never obtained. In one instance, the methyl ketone from a retro-aldol reaction

New α- and β-cyclodextrin derivatives with cinchona alkaloids used in asymmetric organocatalytic reactions

• Iveta Chena Tichá,
• Simona Hybelbauerová and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2019, 15, 830–839, doi:10.3762/bjoc.15.80

• as the promoter (not in a catalytic amount) of a Henry reaction and obtained the product with 99% ee. Subsequently, Doyagüez et al. [17] attached L-proline to β-CD via different linkers (including a triazole linker) and used the resulting organocatalysts in an aldol reaction in water, albeit with a

• lower enantiomeric excess (54% ee). Conversely, Shen et al. [18] performed an aldol reaction in a buffer using L- and D-proline-derived CDs connected through a pyrrolidine skeleton as catalysts and observed 94% ee. More recently, Liu et al. [19] reported the excellent enantioselectivity of 99% ee in an

• aldol reaction catalyzed by β-CD with L-proline attached through a urea moiety. Therefore, mainly proline-derived CDs have been previously tested as organocatalysts and mainly in aldol-type reactions. The limited number of functional groups attached to CD comprising mainly L-proline restricts the

Mechanistic studies of an L-proline-catalyzed pyridazine formation involving a Diels–Alder reaction with inverse electron demand

• Anne Schnell,
• J. Alexander Willms,
• S. Nozinovic and
• Marianne Engeser

Beilstein J. Org. Chem. 2019, 15, 30–43, doi:10.3762/bjoc.15.3

• -proline-catalyzed aldol reaction. Organocatalysis has become a major research field with many applications and has proven to be a valuable complementary approach to organometallic or enzymatic catalysis [29][30][31][32][33][34]. The advantages especially in comparison to organometallic catalysis lie in a

• inexpensive and easily available. The work of List and Barbas in 2000 was groundbreaking for L-proline-catalyzed reactions [40]. They published a L-proline-catalyzed asymmetric aldol reaction and suggested that the essential catalytic step is the enamine formation between the secondary amine function of L

• aldol reaction [17]. In our case, it unfortunately does not accumulate in sufficient amounts for detection. Thus, the reaction was setup differently: instead of premixing L-proline (0.05 equiv) and tetrazine substrate 2 (1 equiv) in solution and then adding acetone (4 equiv) to start the reaction as

Stereodivergent approach in the protected glycal synthesis of L-vancosamine, L-saccharosamine, L-daunosamine and L-ristosamine involving a ring-closing metathesis step

• Pierre-Antoine Nocquet,
• Aurélie Macé,
• Frédéric Legros,
• Jacques Lebreton,
• Gilles Dujardin,
• Sylvain Collet,
• Arnaud Martel,
• Bertrand Carboni and
• François Carreaux

Beilstein J. Org. Chem. 2018, 14, 2949–2955, doi:10.3762/bjoc.14.274

• derivatives, from the same source of chirality. Results and Discussion Synthesis of vancosamine and saccharosamine glycals. The chiral (−)-lactic methyl ester was identified as the privileged starting material considering that the Evans aldol reaction via boron enolates [26][27][28] with an appropriately O

• -protected aldehyde should afford the desired aldol adduct with a syn relative configuration between the two newly created chiral centers [29][30]. Moreover, the boron-mediated stereoselective aldol reaction is all the more interesting for our synthetic plan as stereochemical diversity can be generated

• strategy based on an Evans’ aldol reaction. Mildly oxidizing conditions using 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) were used for the removal of the p-methoxybenzyl (PMB) group to provide alcohols 14 (Scheme 3). Several palladium(II) catalysts have been tested for the conversion of alcohols to