Acetaldehyde in the Enders triple cascade reaction via acetaldehyde dimethyl acetal

• Alessandro Brusa,
• Debora Iapadre,
• Maria Edith Casacchia,
• Alessio Carioscia,
• Giuliana Giorgianni,
• Giandomenico Magagnano,
• Fabio Pesciaioli and
• Armando Carlone

Beilstein J. Org. Chem. 2023, 19, 1243–1250, doi:10.3762/bjoc.19.92

• because of its high reactivity. Herein, we report the Enders-type cascade reaction using acetaldehyde dimethyl acetal, as a masked form of acetaldehyde. This strategy directly converts acetaldehyde, nitroalkenes and enals into stereochemically dense cyclohexenals in good yield and excellent

• . Although the scope is limited to aromatic nitroalkenes and enals, the yields are good considering the complexity of the domino process that involves highly reactive partners, and the ees are consistently very high. Finally, albeit there is low diastereocontrol, the diastereomers can be easily separated by

Sequential hydrozirconation/Pd-catalyzed cross coupling of acyl chlorides towards conjugated (2E,4E)-dienones

• Benedikt Kolb,
• Daniela Silva dos Santos,
• Sanja Krause,
• Anna Zens and
• Sabine Laschat

Beilstein J. Org. Chem. 2023, 19, 176–185, doi:10.3762/bjoc.19.17

• condensation of enals 6 with aldehydes 7a or ketones 7b [6][7][8][9][10][11], isomerization of alkynones 8 [12][13][14][15], Horner–Wadsworth–Emmons reaction of unsaturated phosphonates 9 and aldehydes 10 [16][17], and dehydrogenation of enones 11 [18]. Further, Claisen rearrangement of vinyl propargylic

• via Corey–Fuchs reaction (Table 1) [63]. Starting from different substituted, (E)-configurated enals 28, the respective dibromo-olefines 29 were formed by reaction of 28 with 4 equiv of PPh3 and 2 equiv of CBr4 for 3 h. Treating 29 with 2.2 equiv of n-butyllithium for 1 h resulted in the desired

• ] starting from (E)-configurated enals 28a and 28f forming 29a and 29f in 95% and 86% yield, respectively (Scheme 4). The dibromo-olefines 29a and 29f were then each treated with 2.2 equiv of n-butyllithium for 1 h to form enynes 25a and 25f in 48% yield. Whereas treating 29a and 29f with 2.2 equiv of n

Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation

• Lukáš Ďurina,
• Anna Ďurinová,
• František Trejtnar,
• Ľuboš Janotka,
• Lucia Messingerová,
• Jana Doháňošová,
• Ján Moncol and
• Róbert Fischer

Beilstein J. Org. Chem. 2021, 17, 2781–2786, doi:10.3762/bjoc.17.188

• )-enantiomer [18]. We have used ᴅʟ-proline for three reasons: first, it provides the target compounds 1 and 2 in their racemic form, second, it is able to catalyze the conjugate addition between N-EWG-protected hydroxylamines and enals effectively, and third, based on our experience, the products obtained by

• the proline catalysis are of higher purity (after purification by silica gel column chromatography), than those synthesized by other methods [16]. Definitely, the effective asymmetric organocatalytic conjugate additions of hydroxylamines to enals using various catalysts provide access to

Solvent-free synthesis of enantioenriched β-silyl nitroalkanes under organocatalytic conditions

• Akhil K. Dubey and
• Raghunath Chowdhury

Beilstein J. Org. Chem. 2021, 17, 2642–2649, doi:10.3762/bjoc.17.177

• ][35][36]. In this context, Huang, Fu and co-workers reported carbene-catalyzed enantioselective formal [4 + 2] annulation reactions of β-silyl enones with enals and with active acetic esters (Scheme 1g) for the preparation of chiral organosilanes [34][35][36]. Very recently, during the final stage of

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

• chiral N-triflylphosphoramide. Aza-Michael addition of primary amines to β-trifluromethyl-β-phenylnitroolefin catalyzed nitrogen heterocyclic carbene. Asymmetric aza-Michael additions of pyrroles to protected (E)-4-hydroxybut-2-enals. Asymmetric aza-Michael addition of purine bases to aliphatic α,β

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

• resulted in products with moderate to excellent yields and enantiomeric excesses as shown in Scheme 16. Enders et al. developed the enantioselective synthesis of cyclopenta[c]-fused chromenones 54 starting from hydroxylated malonate 53 with enals 2 [50]. The reaction stands out for its good to excellent

• reaction between 3-cyano-4-methylcoumarins 39 and MBH carbonates 40. Enantioselective synthesis of cyclopropa[c]coumarins 45. NHC-catalyzed lactonization of 2-bromoenals 46 with 4-hydroxycoumarin (1). NHC-catalyzed enantioselective synthesis of dihydrocoumarins 51. Domino reaction of enals 2 with

• hydroxylated malonate 53 catalyzed by NHC 55. Oxidative [4 + 2] cycloaddition of enals 57 to coumarins 56 catalyzed by NHC 59. Asymmetric [3 + 2] cycloaddition of coumarins 43 to azomethine ylides 60 organocatalyzed by quinidine 62. Synthesis of α-benzylaminocoumarins 64 through Mannich reaction between 4

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

NHC-catalyzed enantioselective synthesis of β-trifluoromethyl-β-hydroxyamides

• Alyn T. Davies,
• Mark D. Greenhalgh,
• Alexandra M. Z. Slawin and
• Andrew D. Smith

Beilstein J. Org. Chem. 2020, 16, 1572–1578, doi:10.3762/bjoc.16.129

• using NHCs, the azolium enolate has been widely used [27][28]. Methods to generate azolium enolates from a number of precursors have been reported, including the use of ketenes [29][30], α-functionalized aldehydes [31][32][33][34][35], enals [36][37][38], aryl esters [39][40][41][42], or aldehydes [43

Copper-catalyzed enantioselective conjugate addition of organometallic reagents to challenging Michael acceptors

• Delphine Pichon,
• Jennifer Morvan,
• Christophe Crévisy and
• Marc Mauduit

Beilstein J. Org. Chem. 2020, 16, 212–232, doi:10.3762/bjoc.16.24

• , or trialkylaluminium reagents toward those challenging substrates and their fruitful application in the total synthesis of natural products. Review Enantioselective conjugate addition to challenging Michael acceptors Copper-catalyzed ECA to α,β-unsaturated aldehydes Nowadays, β-substituted enals

• . However, as depicted in Scheme 1, due to their stronger reactivity than that of usual esters or ketones, a competitive 1,2-addition to the carbonyl function of enals could occur, leading to the corresponding alcohol as a byproduct. Moreover, even if the 1,4-addition is favored, thanks to the copper/ligand

• and 89% ee with EtMgBr (Scheme 2b). To overcome the low regioselectivity, the authors took into account previous works showing that the 1,4-regioselectivity in the addition of cuprates to enals could be improved in the presence of a slight excess of TMSCl [15][16][17][18][19]. Indeed, using TMSCl in

Rapid, two-pot procedure for the synthesis of dihydropyridinones; total synthesis of aza-goniothalamin

• Thomas J. Cogswell,
• Craig S. Donald and
• Rodolfo Marquez

Beilstein J. Org. Chem. 2020, 16, 135–139, doi:10.3762/bjoc.16.15

• described above. Rewardingly, Hosomi–Sakurai allylation of the conjugated imine intermediate proceeded to afford the desired diene 10 in working yield (35%). The formation of diene 10 is significant as the corresponding α,β-enones and α,β-enals undergo exclusive conjugate addition under Hosomi–Sakurai

Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure

• Denisa Vargová,
• Rastislav Baran and
• Radovan Šebesta

Beilstein J. Org. Chem. 2018, 14, 553–559, doi:10.3762/bjoc.14.42

• . Stereoselective Michael addition, one of the most important organocatalytic reactions [8] usually serves as a key stereoinduction transformation. Earlier studies, performed by Hayashi and Wang employed iminium activation to perform the enantioselective addition of nitromethane to enals for syntheses of baclofen

New electroactive asymmetrical chalcones and therefrom derived 2-amino- / 2-(1H-pyrrol-1-yl)pyrimidines, containing an N-[ω-(4-methoxyphenoxy)alkyl]carbazole fragment: synthesis, optical and electrochemical properties

• Daria G. Selivanova,
• Alexei A. Gorbunov,
• Olga A. Mayorova,
• Alexander N. Vasyanin,
• Igor V. Lunegov,
• Elena V. Shklyaeva and
• Georgii G. Abashev

Beilstein J. Org. Chem. 2017, 13, 1583–1595, doi:10.3762/bjoc.13.158

• of POCl3, DMF and methylketones 3a and 3b resulted in formation of the corresponding 3-aryl-3-chloroprop-2-enals 4a,b, with subsequent sequential treating with Na2S and chloroacetone has given rise to 5-aryl-2-acetylthiophenes 5a,b [21] (Scheme 2). Compounds 2 and 5 (Scheme 2) were further used to

• region corresponding to the π−π* electron transition. The absorption spectra of 3-aryl-3-chloroprop-2-enals 4a,b are of particular interest since there are practically no data concerning optical properties of such structures. The absorption maxima in the spectra of chloropronenals 4a,b located within the

Synergistic chiral iminium and palladium catalysis: Highly regio- and enantioselective [3 + 2] annulation reaction of 2-vinylcyclopropanes with enals

• Haipan Zhu,
• Peile Du,
• Jianjun Li,
• Ziyang Liao,
• Guohua Liu,
• Hao Li and
• Wei Wang

Beilstein J. Org. Chem. 2016, 12, 1340–1347, doi:10.3762/bjoc.12.127

• enals and a transition metal promoting to open the 2-vinylcyclopropanes for highly regio- and enantioselective [3 + 2] cycloaddition reaction of 2-vinylcyclopropanes with α,β-unsaturated aldehydes has been developed. Keywords: [3 + 2] annulation; enals; synergistic catalysis; vinylcyclopropanes

• ]. However, it is difficult to apply the catalytic system for the regio-controlled reaction with C=C bonds in α,β-unsaturated carbonyl compounds, particularly enals. The highly active aldehyde functionality reacts more favorably with the D–A cyclopropane resulting 1,3-dipoles, as elegantly demonstrated by

• Johnson and Waser for the formation of chiral tetrahydrofurans (Scheme 1, reaction 1) [36][38]. Achieving a regioselective control at the C=C bond rather than at C=O in enals represents a challenge and has not been reported. Synergistic catalysis is a very important and useful strategy in organic

1H-Imidazol-4(5H)-ones and thiazol-4(5H)-ones as emerging pronucleophiles in asymmetric catalysis

• Antonia Mielgo and
• Claudio Palomo

Beilstein J. Org. Chem. 2016, 12, 918–936, doi:10.3762/bjoc.12.90

• been very scarcely used as pronucleophiles in asymmetric catalysis. Only few examples have been reported, some of them involving the use of rhodanines of type 44 (Scheme 7a), which act directly as pronucleophiles against enones [78] (Scheme 7a,1), enals [79] (a,2) and azodicarboxylates [80] (a,3). In

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• ] cycloaddition of enals 237 with nitroalkenes 238 to obtain the oxabicyclo product 239 (Scheme 74) [93]. A combination of catalysts was used, with catalysts 23 and 214. This reaction affords the desired product in 38–91% yield and 85–95% ee. Furthermore, a thiourea catalyzed reaction via a cationic

Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions

• Rajeev S. Menon,
• Akkattu T. Biju and
• Vijay Nair

Beilstein J. Org. Chem. 2016, 12, 444–461, doi:10.3762/bjoc.12.47

• problem was successfully addressed by using a hindered base, pentamethyl piperidine, which was inert towards the products (Scheme 24) [40]. In 2013, Ye disclosed a remarkable NHC-catalysed enantioselective aza-benzoin reaction of enals and activated ketimines leading to the formation of functionalised α

• adduct. A variety of trifluoromethylated α-aminoketones could be synthesised in enantiomerically pure form using this method (Scheme 25). Isatin derived ketimines 41 were employed as electrophiles in the NHC-catalysed chemo- and stereoselective cross-aza-benzoin reaction with enals by Chi. The reaction

• . This is followed by a redox esterification of the latter (47) with enals. The overall process constitutes a one-pot synthesis of hydroxamic esters 48 [45]. Notably, both steps can be performed using the single NHC catalyst 22 under same reaction conditions (Scheme 29). This two-step, one-pot synthesis

Facile synthesis of 4H-chromene derivatives via base-mediated annulation of ortho-hydroxychalcones and 2-bromoallyl sulfones

• Srinivas Thadkapally,
• Athira C. Kunjachan and
• Rajeev S. Menon

Beilstein J. Org. Chem. 2016, 12, 16–21, doi:10.3762/bjoc.12.3

• extend the annulation reaction to phenols with other Michael acceptors at the ortho-position (such as unsaturated esters, enals and nitroolefins) were not successful. Additionally, a very low yield (ca. 10%) of the product 8aa was obtained when the chalcone formation (7a) and its annulation reaction with

Multivalent polyglycerol supported imidazolidin-4-one organocatalysts for enantioselective Friedel–Crafts alkylations

• Tommaso Pecchioli,
• Manoj Kumar Muthyala,
• Rainer Haag and
• Mathias Christmann

Beilstein J. Org. Chem. 2015, 11, 730–738, doi:10.3762/bjoc.11.83

• tested in the asymmetric Friedel–Crafts alkylation of N-methylpyrrole with α,β-unsaturated aldehydes. A variety of substituted enals was investigated to explore the activity of the catalytic system which was also compared with monovalent analogues. The catalyst 4b showed excellent turnover rates and no

• transformation, the most active catalyst 4b was selected for a screening of different enals in the alkylation reaction of N-methylpyrrole (11). A study on the substrate scope was further carried out under the established conditions (see Table 4, entry 4). A variety of substituted α,β-unsaturated aldehydes 14a–e

• was employed using 2 mol % PG-57 (4b) in THF/H2O 98.5:1.5 (v/v) (Table 5). Multivalent catalyst 4b showed good to excellent activities in a range of substrates and moderate to good enantiomeric ratios for the formation of products 15a–e, as shown in Table 5. Electron-deficient aromatic enals 14d,e

Olefin cross metathesis based de novo synthesis of a partially protected L-amicetose and a fully protected L-cinerulose derivative

• Bernd Schmidt and
• Sylvia Hauke

Beilstein J. Org. Chem. 2014, 10, 1023–1031, doi:10.3762/bjoc.10.102

• 21 and acetal 23 in a 1.7:1 ratio (Table 4, entry 3). By increasing the amount of catalyst precursor to 1 mol %, conversion to acetal 23 was complete, and this product could be isolated in 82% yield (Table 4, entry 4). Although the Pd(II)-catalyzed acetalization of aldehydes, including enals, is

Establishing the concept of aza-[3 + 3] annulations using enones as a key expansion of this unified strategy in alkaloid synthesis

• Aleksey I. Gerasyuto,
• Zhi-Xiong Ma,
• Grant S. Buchanan and
• Richard P. Hsung

Beilstein J. Org. Chem. 2013, 9, 1170–1178, doi:10.3762/bjoc.9.131

• employ vinylogous amides tethered to α,β-unsaturated ketones, or enones 1b (R ≠ H) (Scheme 1). Conceptually, employing enals or enones in an aza-[3 + 3] annulation appears to constitute very little difference, with the major difference lying in the R group in their respective products 3 and 4. While

• , although stereoselectivity for the reduction was modest. We ultimately elected not to force our way toward propyleine using the enone aza-[3 + 3] annulation, as we succeeded in total syntheses of other members of the azaphenalene alkaloid family through annulations with enals [30][31]. While it is

Organocatalytic tandem Michael addition reactions: A powerful access to the enantioselective synthesis of functionalized chromenes, thiochromenes and 1,2-dihydroquinolines

• Chittaranjan Bhanja,
• Satyaban Jena,
• Sabita Nayak and
• Seetaram Mohapatra

Beilstein J. Org. Chem. 2012, 8, 1668–1694, doi:10.3762/bjoc.8.191

• alcohol. Córdova and co-workers [73] in 2007 first reported an asymmetric organocatalytic tandem aza-Michael–aldol reaction for the synthesis of 1,2-dihydroquinolines through the iminium activation strategy. Thus, the aza-Michael–aldol reaction between 2-aminobenzaldehydes 52 and enals 2 in the presence

• α,β-unsaturated oxazolidinones, as presented by Wang and co-workers. Domino Michael–aldol reaction of 2-mercaptobenzaldehydes with maleimides catalyzed by cinchona alkaloid thiourea, as reported by Wang’s group. Domino thio-Michael–aldol reaction between 2-mercaptoacetophenone and enals developed by

N-Heterocyclic carbene/Brønsted acid cooperative catalysis as a powerful tool in organic synthesis

• Rob De Vreese and
• Matthias D’hooghe

Beilstein J. Org. Chem. 2012, 8, 398–402, doi:10.3762/bjoc.8.43

• -unsaturated aldehydes [18], the enantioselective synthesis of cyclopentenes from α,β-unsaturated aldehydes and α,β-unsaturated ketones [19], and the preparation of cyclopentanes through the reaction of enals and β,γ-unsaturated α-ketoesters [20]. Discussion Recently, Rovis et al. reported that the acetate

• Bode et al., who showed that there is no need to add a base when employing azolium catalysts with more basic counterions [22]. As mentioned in the introduction, the reaction of NHCs with enals is known to produce homoenolates [13][14], which have found useful applications as vinylogous acyl anions

• be formed in good yield and high diastereo- and enantioselectivity. A number of different enals 15 as suitable substrates has been explored as well (variation of R3), affording the trans-γ-lactam products 16 in moderate to good yields and stereoselectivities. It is important to underline the fact

Recent advances in the gold-catalyzed additions to C–C multiple bonds

• He Huang,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2011, 7, 897–936, doi:10.3762/bjoc.7.103

• ). Similar strategies [145][146] were applied to synthesize arylated (Z)-enones, -enals or dihydrocyclohepta[b]indole skeletons 277 by gold-catalyzed cascade Friedel–Crafts/furan (or indole)–alkyne cycloisomerizations (Scheme 48). The polysubstituted butenolides 281 could be obtained through a gold-catalyzed

When cyclopropenes meet gold catalysts

• Frédéric Miege,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2011, 7, 717–734, doi:10.3762/bjoc.7.82

• corresponding tert-allylic ethers 9a–9f with very high regioselectivity (>99%). Other catalysts such as AuCl3 or Rh2(OAc)4 provided mixtures of compounds containing traces of allylic ethers 9 and 9’ and mostly oxidation products (vide infra, enals 16 and 17). AgOTf was less efficient and led to an incomplete

• attack of diphenylsulfoxide at C1 followed by elimination of diphenylsulfide to afford a 55:45 mixture of the E and Z enals 16 and 17, respectively (66%) (Scheme 9) [18][19]. Other examples of nucleophilic attack on organogold species resulting from the ring-opening of cyclopropenes in the presence of

Synthesis of chiral mono(N-heterocyclic carbene) palladium and gold complexes with a 1,1'-biphenyl scaffold and their applications in catalysis

• Lian-jun Liu,
• Feijun Wang,
• Wenfeng Wang,
• Mei-xin Zhao and
• Min Shi

Beilstein J. Org. Chem. 2011, 7, 555–564, doi:10.3762/bjoc.7.64

• allylic acetates [75][76], carbene-transfer reactions from ethyl diazoacetate [77], formation of conjugated enones and enals [78], regio- and stereoselective synthesis of fluoroalkenes [79], and so on [80][81][82][83][84][85]. However, reports on NHC–Au catalyzed asymmetric reactions are rare [86]. The