Stereoselective mechanochemical synthesis of thiomalonate Michael adducts via iminium catalysis by chiral primary amines

• Michał Błauciak,
• Dominika Andrzejczyk,
• Błażej Dziuk and
• Rafał Kowalczyk

Beilstein J. Org. Chem. 2024, 20, 2313–2322, doi:10.3762/bjoc.20.198

• significant advancement in mechanocatalysis. The stereoselective addition of bisthiomalonates 1–4 to cyclic enones and 4-chlorobenzylideneacetone proceeds stereoselectively under iminium activation conditions secured by chiral primary amines, in contrast to oxo-esters as observed in dibenzyl malonate addition

• nitroalkenes or guanidine-mediated addition of bisthiomalonates to maleimides, cyclic enones, and acyclic 1,4-dicarbonylbutenes, albeit at low temperatures and with relatively long reaction times, further limited to a narrow scope of thioesters (Scheme 1) [31]. Recently, we described a cinchona-squaramide

• low conversions and stereoselectivities when applied to benzylidene acetones or cyclic enones (vide infra). In our latest research in establishing a mild organocatalytic protocol for incorporating benzyl malonates and bisthiomalonates into cyclic enones and benzylidene acetones, we have developed a

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• arylaluminium reagents to five-, six-, and seven-membered β-substituted cyclic enones (Scheme 42). It is obvious that the NHC–Cu(I) complexes are generated in situ through transmetallation. For arylation reactions, Me2(Ar)Al reagents were used. The substrates having a variety of substituents (R = CH2Bn, n-Bu

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

• enolate. González-Gómez et al. studied the tandem conjugate addition of dialkylzincs to cyclic enones (9, 12) and the subsequent reaction of the enolate with N-tert-butanesulfinylimines 10 (Scheme 4) [24][25][26]. Their method was applied to a broad range of substrates (5–7-membered rings) with equally

• imines or their synthetic equivalents. Furthermore, we wanted to develop an enantioselective and diastereoselective process without adding chirality elements within the reagents. For our initial studies, we have selected the well-studied cyclic enones as substrates and the Taniaphos ligand (L14) that has

• -mediated epimerization. Guénée et al. described the allylation, benzylation, and propargylation of magnesium enolates. These enolates were generated by a Cu-NHC-catalyzed conjugate addition of Grignard reagents to β-substituted cyclic enones (70) (Scheme 19) [51]. Fox and co-workers developed an intriguing

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

• nucleophilic addition of the hydroxycoumarin. The procedure allowed obtaining products 34 with excellent yields and enantiomeric excesses (Scheme 11). Zhu et al. described the asymmetric Michael addition of substituted 4-hydroxycoumarins (1) to cyclic enones 36, using an in situ formed organocatalyst [44]. The

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• the use of a catalytic amount of DBU in DMSO at room temperature [46]. The cyclic enones 43 were reacted with the α-azidostyrenes 44 containing groups such as Cl, F, and OMe to form the corresponding products (Scheme 16). The o-, m-, and p-tolylvinyl azides facilitated a good to excellent yield of the

• -substituted cyclic enones treated successfully with azidophiles to give good yield of the corresponding double C- and N-vinylated 1,2,3-triazole derivatives 45. Then, the reaction was extended to some aryl and alkyl azides and different cyclic enones. Moreover, a variety of vinyl, alkyl, and aryl azides were

• also applicable in the reaction. In continuation of the study, various alkyl- and aryl-substituted unmodified cyclic enones were explored, and the result was a moderate to good yield of the corresponding products. The reaction was performed well using alkyl-substituted cyclic enone. Finally, acyclic

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• given combination of enone and arylboronic acid. Keywords: asymmetric reaction; boronic acid; conjugated enones; chromones; enantioselective catalysis; Michael addition; Pd complexes; Introduction The asymmetric 1,4-addition of arylboronic acids to conjugated cyclic enones and chromones is a very

• (phosphines, NHC-carbenes, bisoxazolines, pyridine-oxazolines, and miscellaneous) is used. Review Catalytic systems based on phosphine ligands A pioneering work on the enantioselective addition of boron-derived carbon nucleophiles to cyclic enones was published by the group of Miyaura et al. in 2005 [32

• ]. Specifically, they have dealt with the addition of potassium aryltrifluoroborates to conjugated cyclic enones differing in ring size [32]. The catalysts PdL1a,b exhibited great conversion and enantioselectivities (up to 99% and up to 96% ee) for various combinations of nucleophiles and enones (Table 1). The

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

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• ratios. Both cyclic (117 and 118) and acyclic (119,120) ketones could be silylated efficiently (Scheme 23). Interestingly, cyclic enones conjugated to an external double bond, as in 121, upon exposure to these conditions resulted in an excellent selectivity for the 1,6-addition and in high ee for product

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

• for the generation of carbon radicals via single-electron transfer (SET). In 2016, Barriault and co-workers reported a methodology that features the utilization of dimeric gold complex [Au2(dppm)2]Cl2 and ultraviolet A (UV, 365 nm) light to direct arylation of bromide-substituted butenolides or cyclic

• enones [51]. Photoexcitation (UV, 365 nm) of [Au-Au]2+ generated [Au-Au]2+*, which could then effectively reduce the vinyl C–Br bond via a SET to generate the vinyl radical. This radical then cyclizes with an aryl group to generated a tricyclic intermediate bearing a tertiary radical. A simultaneous

Et₃B-mediated and palladium-catalyzed direct allylation of β-dicarbonyl compounds with Morita–Baylis–Hillman alcohols

• Ahlem Abidi,
• Yosra Oueslati and
• Farhat Rezgui

Beilstein J. Org. Chem. 2016, 12, 2402–2409, doi:10.3762/bjoc.12.234

• addition of Grignard reagents onto α-methyl cyclic enones, affording mainly the trans-2,3-disubstituted cyclohexanones as being the thermodynamic products [52]. Similarly, we believe that the intramolecular conjugate addition of carbanion 3j onto α-substituted enone moiety is under thermodynamic control

Cupreines and cupreidines: an established class of bifunctional cinchona organocatalysts

• Laura A. Bryant,
• Rossana Fanelli and
• Alexander J. A. Cobb

Beilstein J. Org. Chem. 2016, 12, 429–443, doi:10.3762/bjoc.12.46

• vinylogous Michael addition reaction [48]. In this process, cyclic enones 52 are added to nitroalkenes 41 using dienamine catalysis (Scheme 13). Although no model is suggested with respect to how the 6’-OH is involved, it is clearly of importance as the analogous 6’-OMe derived cupreine catalyst gives

Copper-catalyzed asymmetric conjugate addition of organometallic reagents to extended Michael acceptors

• Thibault E. Schmid,
• Sammy Drissi-Amraoui,
• Christophe Crévisy,
• Olivier Baslé and
• Marc Mauduit

Beilstein J. Org. Chem. 2015, 11, 2418–2434, doi:10.3762/bjoc.11.263

• cyclic enones. Enynone 69 was reacted to assess the versatility of the reaction, and a full 1,4-regioselectivity was recorded, leading to compound 70 in 71% yield and 91% ee (Scheme 19). Another example of trialkylaluminium addition onto a cyclic extended Michael acceptor was reported in 2013, using a

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

• , enantioselective tandem conjugate addition–aldol reaction of cyclic enones [19]. While tandem conjugate addition–α-functionalization reactions were well known prior to Feringa’s publication [20] (Scheme 1), this work was unique because of the high enantioselectivity that was observed through the use of a chiral

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• ][40]. Asymmetric conjugate additions using P-chiral phosphonamides were reported by Denmark [2][3][4] and Hua [5][6], with remarkable differences in selectivity depending on the configuration of the P-stereogenic center (Scheme 5). Thus, the addition of the Li-anion of trans-40a to cyclic enones 41

Metal-mediated aminocatalysis provides mild conditions: Enantioselective Michael addition mediated by primary amino catalysts and alkali-metal ions

• Matthias Leven,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2013, 9, 155–165, doi:10.3762/bjoc.9.18

• % whereas the trans-diaminocyclohexane derivatives could only reach up to 47% ee (Table 1, entry 5). There is a strong preference for 7 to produce higher ee’s if cyclic enones are used, whereas diaminocyclohexane derivatives perform better with the acyclic trans-enone 9 (Table 1, entry 4 versus Table 2

Organocatalytic cascade aza-Michael/hemiacetal reaction between disubstituted hydrazines and α,β-unsaturated aldehydes: Highly diastereo- and enantioselective synthesis of pyrazolidine derivatives

• Zhi-Cong Geng,
• Jian Chen,
• Ning Li,
• Xiao-Fei Huang,
• Yong Zhang,
• Ya-Wen Zhang and
• Xing-Wang Wang

Beilstein J. Org. Chem. 2012, 8, 1710–1720, doi:10.3762/bjoc.8.195

• explored by several groups [72][73]. In 2007, Jørgensen et al. reported that the organocatalyzed asymmetric aza-Michael addition of hydrazones to cyclic enones had been achieved in good yield and stereoselectivity [74]. In 2011, the Deng group developed a highly enantioselective organocatalytic synthesis

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

• to 56%) and enantioselectivities in the range of 85–91% ee (Scheme 9). Mechanistically the reaction involves the iminium activation of the α,β-unsaturated cyclic enones by the chiral pyrrolidine catalyst. Very recently, Xu and co-workers [51] reported an improved protocol for the same reaction

• employing a chiral pyrrolidine bearing a 2-mercaptopyridine moiety as organocatalyst (VII) and simple α-amino acids, such as tert-leucine, as co-catalyst. The asymmetric transformation proceeds by simultaneous activation of cyclic enones 13 and aldehyde 1 by the bifunctional catalyst VII and the amino acid

Construction of cyclic enones via gold-catalyzed oxygen transfer reactions

• Leping Liu,
• Bo Xu and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2011, 7, 606–614, doi:10.3762/bjoc.7.71

• chemistry. This mini-review focuses on the most recent achievements on gold-catalyzed oxygen transfer reactions of tethered alkynones, diynes or alkynyl epoxides to cyclic enones. The corresponding mechanisms for the transformations are also discussed. Keywords: alkyne–carbonyl metathesis; cyclic enones

• cyclic enones from alkynyl ketones Yamamoto and co-workers were the first to report the gold-catalyzed formation of conjugated cyclic enones under mild conditions using tethered alkynyl ketones as substrates (Scheme 2) [43]. Both, aromatic and aliphatic groups substituted on alkynyl ketones 1 were

• case, the gold catalyst exhibited a dual role, namely the activation of alkyne and carbonyl moieties. Yamamoto and co-workers attempted to utilize their protocol to build five-membered cyclic enones, however, when they employed alkynyl ketone 9 as the substrate, the gold catalyst did not show good

Asymmetric synthesis of tertiary thiols and thioethers

• Jonathan Clayden and
• Paul MacLellan

Beilstein J. Org. Chem. 2011, 7, 582–595, doi:10.3762/bjoc.7.68

• demonstrated by the catalytic asymmetric additions of thiols to α,β-unsaturated ketones [44]. (R)-LaNa3tris(binaphthoxide) (LSB) catalyses asymmetric addition to cyclic enones (Scheme 16), and products of addition 43 are isolated in good yields and enantiomeric ratios. However, addition to the substituted

• thioether 29. Thioethers 33 prepared from phosphinites 31. Preparation of enantiomerically pure thiol 39. Thioethers prepared by a modified Mitsunobu reaction. Nucleophilic conjugate addition. Asymmetric addition to cyclic enones. Preparation of thioether 45. Catalytic kinetic resolution of the enantiomers