New advances in asymmetric organocatalysis II

• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 766–769, doi:10.3762/bjoc.21.60

• contributions in stereoselective organocatalytic transformations. The collection contains nine articles featuring various aspects of asymmetric organocatalysis. In the first contribution, Waser et al. examined how chiral phase-transfer catalysts promote β-selective additions of azlactones to allenoates. Maruoka

Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

Towards an asymmetric β-selective addition of azlactones to allenoates

• Behzad Nasiri,
• Ghaffar Pasdar,
• Paul Zebrowski,
• Katharina Röser,
• David Naderer and
• Mario Waser

Beilstein J. Org. Chem. 2024, 20, 1504–1509, doi:10.3762/bjoc.20.134

• , Iran 10.3762/bjoc.20.134 Abstract We herein report the asymmetric organocatalytic addition of azlactones to allenoates. Upon using chiral quaternary ammonium salt catalysts, i.e., Maruoka’s binaphthyl-based spirocyclic ammonium salts, the addition of various azlactones to allenoates proceeds in a β

• -selective manner with moderate levels of enantioselectivities (up to 83:17 er). Furthermore, the obtained products can be successfully engaged in nucleophilic ring opening reactions, thus giving highly functionalized α-amino acid derivatives. Keywords: allenoates; amino acids; azlactones; organocatalysis

• studies we also realized that the masked β-AA derivatives 2 undergo enantioselective β-addition to allenoates 3 under chiral ammonium salt catalysis (Scheme 1B) [18]. Interestingly, hereby we also found that the use of alternative catalyst systems (i.e., tertiary phosphines) allows for a γ-selective

Molecular diversity of the base-promoted reaction of phenacylmalononitriles with dialkyl but-2-ynedioates

• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 991–998, doi:10.3762/bjoc.18.99

• phenacylmalononitriles and allenoates for the tunable synthesis of multifunctionalized cyclopentene carboxamides and cyclopentenols [33] (reaction 3 in Scheme 1). Recently, Zhang and Ban reported a NaHCO3-promoted reaction of phenacylmalononitriles and N-alkylmaleimides to give the novel cyclopenta[c]pyrrole-4

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

• , Wang and co-workers reported the organocatalytic asymmetric synthesis of tetrasubstituted α-amino allenoates by a dearomative γ-addition reaction of 2,3-disubstituted indoles 99 to β,γ-alkynyl-α-imino esters 100 [103]. In the presence of chiral phosphoric acid CPA 13, a series of tetrasubstituted α

• -amino allenoates 101 was prepared in moderate to excellent yields (69–99%), dr (9:1 to >20:1), and excellent enantioselectivity (91–99% ee, Scheme 34). The mechanistic studies showed that the substituents at the second and third positions of the indole play a crucial role in the chemo- and

• regio- and stereoselective γ-addition reaction of isoxazol-5(4H)-ones 103 to β,γ-alkynyl-α-imino esters 102 for the synthesis of axially chiral tetrasubstituted α-amino allenoates 104 containing an adjacent quaternary carbon stereocenter and an axially chiral tetrasubstituted allene scaffold [104

Highly chemo-, enantio-, and diastereoselective [4 + 2] cycloaddition of 5H-thiazol-4-ones with N-itaconimides

• Shuai Qiu,
• Choon-Hong Tan and
• Zhiyong Jiang

Beilstein J. Org. Chem. 2016, 12, 2293–2297, doi:10.3762/bjoc.12.222

• [6], allylation [7], conjugate addition to enones [8], and γ-addition with allenoates [9]. All these examples focused on nucleophilic addition reactions of the C5 atom of 5H-thiazol-4-ones. Recently, we described an organocatalytic asymmetric [4 + 2] cyclization of 5H-thiazol-4-ones with a series of

Enantioconvergent catalysis

• Justin T. Mohr,
• Jared T. Moore and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2016, 12, 2038–2045, doi:10.3762/bjoc.12.192

• with multiple racemic starting materials are rare since each additional racemic substrate exponentially increases the number of stereochemical combinations. However, Kalek and Fu have demonstrated that racemic allenoates (±)-26 and racemic azalactones (±)-25 may be combined in the presence of an

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

• of thiazol-4(5H)-ones as pronucleophiles in asymmetric catalytic reactions has been investigated in the Michael addition reaction to nitroalkenes and α-silyloxyenones, phosphine-catalyzed γ-addition to allenoates and alkynoates, α-amination reactions and iridium-catalyzed allylic substitution

• interaction. In addition, adducts 76 and 77 were easily transformed into the corresponding carboxylic acids 79 and 80 by treatment with periodic acid (Scheme 14) and thiolactone 81 by simple ring opening of the latter under mild acidic conditions. Phosphine-catalyzed γ-addition to allenoates and alkynoates

• . Chiral phosphine-mediated nucleophilic catalysis has attracted considerable attention in the recent years [98][99][100][101]. However, few examples of phosphine-mediated γ-addition reactions have been reported. Pioneering studies on γ-additions of pronucleophiles to allenoates or alkynoates were first

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

• + 2] adduct 92, albeit achieved in a step-wise manner (Scheme 21c) [65]. Disappointingly, though not uninteresting, is the fact that there is no enantioinduction for either of these processes. β-Isocupredeine has also been used in the [2 + 2]-addition between 2-thioxoacetates 94 and allenoates 95 to

Enantioselective [3 + 2] annulation of α-substituted allenoates with β,γ-unsaturated N-sulfonylimines catalyzed by a bifunctional dipeptide phosphine

• Huanzhen Ni,
• Weijun Yao and
• Yixin Lu

Beilstein J. Org. Chem. 2016, 12, 343–348, doi:10.3762/bjoc.12.37

• Huanzhen Ni Weijun Yao Yixin Lu Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore, 117543 10.3762/bjoc.12.37 Abstract The first enantioselective [3 + 2] annulation of α-substituted allenoates with β,γ-unsaturated N-sulfonylimines is described. In the presence

• allenoates and activated alkenes by Lu in 1995, this type of annulation reaction has received considerable attention due to its high efficiency and versatility in creating five-membered ring systems [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]. However, most of the earlier

• examples make use of allenoates without an α-substitution. As demonstrated by Yu, Kwon and their co-workers [34][35][36], this is due to the requirement of a hydrogen atom at the α-position for a proton shift during the reaction cycle. Instead, α-substituted allenoates were shown to interact with phosphine

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

• (allenoates) in numerous useful reactions (see for examples [18][19][20]). The propensity of allenyl sulfones to oligomerise and display anomalous reactivity profiles in presence of base has, to some extent, dissuaded chemists from devising synthetic applications of allenyl sulfones [21][22]. We envisaged

Reaction of allene esters with Selectfluor/TMSX (X = I, Br, Cl) and Selectfluor/NH₄SCN: Competing oxidative/electrophilic dihalogenation and nucleophilic/conjugate addition

• A. Srinivas Reddy and
• Kenneth K. Laali

Beilstein J. Org. Chem. 2015, 11, 1641–1648, doi:10.3762/bjoc.11.180

• A. Srinivas Reddy Kenneth K. Laali Department of Chemistry, University of North Florida, 1 UNF Drive, Jacksonville, Florida 32224, USA 10.3762/bjoc.11.180 Abstract Reaction of benzyl and ethyl allenoates with TMSX (X = I, Br, Cl) and with NH4SCN were investigated in MeCN, DMF, and in imidazolium

• ) is diminished in allenoates, most significantly in reactions with TMSCl, and essentially disappearing in reactions with NH4SCN, in favor of nucleophilic/conjugate addition. The study underscores the contrasting reactivity patterns in 1-arylallenes and allenoates toward electrophilic and nucleophilic

• ionic liquids (ILs) as solvent in which Selectfluor is soluble. Previous studies have shown that the major products arising from the reaction of 2,3-allenoates with MX/HX are hydrohalogenated compounds [19][20][21]. Similarly, reactions with NuH lead to Michael-type nucleophilic additions, but in the

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

• chiral bicyclic phosphine A2 to achieve asymmetric [3 + 2] annulations between several allenoates and electron-deficient olefins in benzene at room temperature with excellent regioselectivities (1:2 >94/6) and enantioselectivities (1, 69–93% ee). This catalyst features a rigid bridged [2.2.1] bicyclic

• + 2] annulations of allenoates with activated alkenes. In the presence of chiral phosphine B2, the [3 + 2] annulations between allenoates and 2-aryl-1,1-dicyanoethylenes allowed convenient syntheses of functionalized cyclopentenes with both aryl and heteroaryl substituents on the stereogenic carbon

• atom, in high yields and with up to 90% ee (Scheme 4) [37]. 3-Alkylideneindolin-2-ones underwent [3 + 2] annulations with allenoates, affording various biologically relevant spirocyclic oxindolic cyclopentanes in excellent yields and greater than 97% ee (Scheme 5) [38]. Enantioselective [3 + 2

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• by Jia and co-workers [99]. The authors got inspired by the recent development of the phosphine-catalyzed [3 + 2] cycloaddition of allenoates with electron-deficient species such as olefins and imines, which involves the in situ formation of a zwitterionic intermediate from the nucleophilic addition

• [2 + 2 + 1] cycloaddition of allenoates 84, dual activated olefins 85, and isocyanides 83 (Scheme 39). It is noteworthy, that only the external double bond of the allenic fragment is embedded in the final carbocyclic ring, whereas in the phosphine-catalyzed [3 + 2] cycloadditon process the allene

Chiral multifunctional thiourea-phosphine catalyzed asymmetric [3 + 2] annulation of Morita–Baylis–Hillman carbonates with maleimides

• Hong-Ping Deng,
• De Wang,
• Yin Wei and
• Min Shi

Beilstein J. Org. Chem. 2012, 8, 1098–1104, doi:10.3762/bjoc.8.121

• ] annulation catalyzed by chiral phosphines, Zhang and co-workers first reported the asymmetric [3 + 2] annulation of allenoates with acrylates catalyzed by a bicyclic chiral phosphine in 1997 [21]. Moreover, Fu [22][23][24], Marinetti [25][26][27][28], Lu [29][30][31] and other researchers [32][33][34][35][36

• ] have also developed asymmetric [3 + 2] annulations of allenoates to give the corresponding cyclopentene derivatives in good yields with excellent enantioselectivities [37]. On the other hand, some examples of phosphine-catalyzed [3 + 2] annulation of MBH carbonates with electron-deficient alkenes have

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

• rearrangement to produce naphthalen-2(1H)-ones or naphthalenes 305, 307, 309, and 311 selectively (Scheme 53) [155]. The synthesis of indole 313 [156] and tricyclic dihydroindenofuranone-type product 315 from 2-(tosylamino)phenylprop-1-yn-3-ol 312 [157] and allenoates 314 [158], respectively, has been reported

• allenoates 364 and various terminal alkynes [172]. The González group developed an intermolecular reaction of internal alkynes and imines, in which the propargyl tosylates 367 react with N-tosylaldimines 368 to afford cyclopent-2-enimines 369 [173]. The final product was achieved through a 1,2-migration of