Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• pikromycin and the aglycones in this family, 10-deoxymethynolide (24) and norbonolide (25), using asymmetric aldol reaction, Yamaguchi esterification, and ring-closing metathesis as key steps [65][66]. Nevertheless, the inherent complexity of these natural products demands high step counts, leading to low

Evaluation of the enantioselectivity of new chiral ligands based on imidazolidin-4-one derivatives

• Jan Bartáček,
• Karel Chlumský,
• Jan Mrkvička,
• Lucie Paloušová,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2024, 20, 684–691, doi:10.3762/bjoc.20.62

• also tested in asymmetric aldol reactions. Under the optimised reaction conditions, aldol products with enantioselectivities of up to 91% ee were obtained. Keywords: asymmetric aldol reaction; asymmetric Henry reaction; chiral ligands; enantioselective catalysis; imidazolidine derivatives

• acids producing chiral isotetronic acids. However, the application of compound IV as the organocatalyst in these reactions proceeded sluggishly, and the corresponding products were obtained in only moderate ees [24]. Herein, the aldol reaction was chosen as a standard asymmetric reaction to explore the

• . Thus, early attempts at the aldol reaction of 4-nitrobenzaldehyde with cyclohexanone were performed to evaluate the reaction parameters, i.e., solvent, reaction temperature, and amount of acidic additive (Table 5). Hence, using DMF at −25 °C were the most convenient conditions regarding diastereo- and

α-(Aminomethyl)acrylates as acceptors in radical–polar crossover 1,4-additions of dialkylzincs: insights into enolate formation and trapping

• Angel Palillero-Cisneros,
• Paola G. Gordillo-Guerra,
• Fernando García-Alvarez,
• Olivier Jackowski,
• Franck Ferreira,
• Fabrice Chemla,
• Joel L. Terán and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2023, 19, 1443–1451, doi:10.3762/bjoc.19.103

• (MgSO4), and concentrated under reduced pressure to provide the crude product which was then purified by column chromatography on silica gel. 3. Procedure for the air-promoted tandem 1,4-addition–aldol reaction between dialkylzinc reagents, α-(aminomethyl)acrylates and carbonyl derivatives (preparation

Sulfate radical anion-induced benzylic oxidation of N-(arylsulfonyl)benzylamines to N-arylsulfonylimines

• Joydev K. Laha,
• Pankaj Gupta and
• Amitava Hazra

Beilstein J. Org. Chem. 2023, 19, 771–777, doi:10.3762/bjoc.19.57

• their unique stability, defined reactivity, and versatility in organic synthesis [2]. Leveraging their electron-deficient nature, N-arylsulfonylimines are widely used in organic transformations including nucleophilic addition, cycloaddition, imino-aldol reaction, ene reactions, aza-Friedel–Crafts

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

• Following the seminal work of Feringa in 1997 [21], the tandem asymmetric organozinc conjugate addition followed by subsequent aldol reaction was scarcely applied in the last decade. Welker and Woodward studied the reaction of zinc enolates 2 with chiral acetals 3 (Scheme 2) [22]. The Lewis acid (TiCl4 or

• successfully applied in the Mukiyama aldol reaction to gain the originally desired aldol adducts with improved yields and still good dr. Finally, the cerium ammonium nitrate (CAN) promoted one-step oxidative removal of the chiral auxiliary group was also successfully demonstrated. In 2012, Aikawa et al

• benzaldehyde (51) (Scheme 13a). Related to this work, Feringa´s team realized also the conjugate addition to chromone (53) [44]. The enolate was again trapped with benzaldehyde in an aldol reaction (Scheme 13b). Naphthol derivatives 55 bearing an α,β-unsaturated ester group undergo a copper(I)-catalyzed

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

• analogue synthesis, starting from (+)-β-citronellene. Key stereoselective transformations involve an asymmetric Krische allylation, an aldol reaction under 1,5-anti stereocontrol, and a Tishchenko–Evans reduction accompanied by a peculiar ester transposition, allowing to install key stereogenic centers of

• the natural products. Keywords: allylation; aldol reaction; latrunculins; stereocontrol; total synthesis; Introduction Latrunculins constitute a class of marine polyketide natural products isolated from Sponges like Negombata (= Latrunculia) magnifica [1][2]. They are characterized by the presence

• disconnection strategies for the macrocycle or the lactol formation (Figure 2, left), and for the aldol reaction leading to 4, using a 4-acetyl-1,3-thiazolidin-2-one 5 as ketone partner (Figure 2, route A). Strikingly, this last disconnection was adopted in all previous syntheses to form the (15,16)- or the

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

• could not obtain the desired tricyclic compound possessing the required eight-membered ring, but instead they recovered the starting material 47, together with a dimeric product or an eleven-membered ring resulting from a RCM and a retro-aldol reaction. Assuming that the allylic alcohol may induce a

An accelerated Rauhut–Currier dimerization enabled the synthesis of (±)-incarvilleatone and anticancer studies

• Tharun K. Kotammagari,
• Sweta Misra,
• Sayantan Paul,
• Sunita Kunte,
• Rajesh G. Gonnade,
• Manas K. Santra and
• Asish K. Bhattacharya

Beilstein J. Org. Chem. 2023, 19, 204–211, doi:10.3762/bjoc.19.19

• ). The formation of (±)-incarvilleatone (1), perhaps due to RC dimerized product (±)-4, first undergoes oxa-Michael followed by aldol reaction in one-pot. The aldol reaction take place with intermediate 5 in basic medium due to the close proximity of the two carbonyl groups. Finally, the structure of

• achieved the total synthesis of (±)-incarvilleatone (1) starting from rac-rengyolone (3) through accelerated RC intermolecular dimerization catalyzed by TBAF to synthesize a heterochiral dimerized product (±)-4, followed by a one-pot oxa-Michael and aldol reaction sequence using KHMDS as a base. The

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

• total synthesis of (−)-FR901483 (160) through an aldol reaction, and an intramolecular condensation resulted in the synthesis of (+)-TAN1251C (162, Scheme 13). Divergent synthesis of bipolamine alkaloids (Maimone 2022) [88]: Bipolamines were isolated from the fungi Curvularia sp. IFB Z10 and Bipolaris

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

• 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

Rhodium-catalyzed intramolecular reductive aldol-type cyclization: Application for the synthesis of a chiral necic acid lactone

• Motoyuki Isoda,
• Kazuyuki Sato,
• Kenta Kameda,
• Kana Wakabayashi,
• Ryota Sato,
• Hideki Minami,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1642–1648, doi:10.3762/bjoc.18.176

• aldol reaction is one of the most powerful tools to achieve this transformation [1][2][3][4][5][6][7][8]. In particular, the intramolecular aldol condensation is an important approach to the formation of ring systems such as cyclic β-hydroxy carbonyl products or cyclic α,β-unsaturated carbonyl products

• aldol-type reactions, and reductive Mannich-type reactions using RhCl(PPh3)3 with Et2Zn [41][42][43][44][45][46][47]. The rhodium-catalyzed reductive aldol reaction of α,β-unsaturated esters with aldehydes or ketones gives aldol-type products in good to excellent yields (Scheme 1) [43][44]. In addition

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