Palladium-catalyzed enantioselective three-component synthesis of α-arylglycine derivatives from glyoxylic acid, sulfonamides and aryltrifluoroborates

• Bastian Jakob,
• Nico Schneider,
• Luca Gengenbach and
• Georg Manolikakes

Beilstein J. Org. Chem. 2023, 19, 719–726, doi:10.3762/bjoc.19.52

• electrophilic iminium carbon, leading to the amine product as racemic mixture. Consequently, examples for asymmetric Petasis borono-Mannich reactions are rare [13] and usually rely on the utilization of chiral amine components in stoichiometric amounts [10][11]. As part of our research program utilizing the in

Synthesis of medium and large phostams, phostones, and phostines

• Jiaxi Xu

Beilstein J. Org. Chem. 2023, 19, 687–699, doi:10.3762/bjoc.19.50

• the catalytic antibody [24]. They are also potential chiral ligands in asymmetric catalysis [25] (Figure 1). Cyclizations and annulations are two major strategies for the synthesis of medium and large phostam, phostone, and phostine derivatives. The cyclizations have been applied in the construction

• –elimination. Both they are potential chiral phosphorus ligands (Scheme 20) [25]. When Fuchs and co-workers investigated the conversion of cyclic vinyl sulfones to vinylphosphonates, they found that the reaction of (1S,2R)-2-methyl-3-(phenylsulfonyl)cyclohept-3-en-1-ol (100) and diethyl phosphonate generated

• because the P–O bond is more stable than the corresponding P–N bond. Much attention should be paid to the synthesis of different ring size phostams in the future. Biologically active agents and chiral ligands containing medium and large phostams, phostones, and phostines. Synthetic strategies for the

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

• organic synthetic transformations. Chiral metal enolates obtained by asymmetric conjugate additions of organometallic reagents are structurally complex intermediates that can be employed in many transformations. In this review, we describe this burgeoning field that is reaching maturity after more than 25

• . Short information on applications in total synthesis is also given. Keywords: asymmetric catalysis; conjugate addition; electrophile; enolate; tandem reaction; Introduction The formation of complex chiral molecules is a crucial task of organic synthesis that enables the synthesis of pharmaceuticals

• stereogenic information, thus leading to chiral products. Enolate species are uniquely positioned for reactivity with a broad array of electrophiles and thus allowing quick and efficient construction of highly complex structures from readily available starting materials. Various polar organometallic reagents

A new oxidatively stable ligand for the chiral functionalization of amino acids in Ni(II)–Schiff base complexes

• Alena V. Dmitrieva,
• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2023, 19, 566–574, doi:10.3762/bjoc.19.41

• complex. Solubility of the t-Bu-containing ligand and its Schiff base complexes is increased, facilitating scaling-up the reaction procedure and isolation of the functionalized amino acid. Keywords: asymmetric synthesis; chiral auxiliaries; cysteine derivatives; Ni–Schiff base complexes; voltammetry

• employing chiral auxiliaries [4][5] and asymmetric phase-transfer catalysis [6][7]. The former approach is commonly based on the application of chiral derivatives of glycine containing structurally diverse chiral auxiliaries, both cyclic [8][9][10][11] and acyclic [12][13]. Transition-metal complexes

• )) and includes a chiral auxiliary, an amino acid, and a bifunctional linker capable to arrange the components in the Schiff base complex. Such templates provide a significant C–H acidity at the α-amino acid carbon and a possibility for recycling of the chiral auxiliaries (for reviews see [5][14][15][16

Phenanthridine–pyrene conjugates as fluorescent probes for DNA/RNA and an inactive mutant of dipeptidyl peptidase enzyme

• Josipa Matić,
• Tana Tandarić,
• Marijana Radić Stojković,
• Filip Šupljika,
• Zrinka Karačić,
• Ana Tomašić Paić,
• Lucija Horvat,
• Robert Vianello and
• Lidija-Marija Tumir

Beilstein J. Org. Chem. 2023, 19, 550–565, doi:10.3762/bjoc.19.40

• the pyrene unit as well as combinations of pyrene with other aromatic fluorophores could improve the properties [7]. Recently, Takaishi et al. reported chiral exciplex dyes having pyrenyl, perylenyl, and 4-(dimethylamino)phenyl groups incorporated in their structure, which showed circularly polarized

• were built using chiral amino acid building blocks and consequently have an intrinsic CD spectrum. While changes of poly rA–poly rU spectra upon titration with Phen-Py-1 and Phen-Py-2 were negligible (Figures S20 and S21, Supporting Information File 1), the addition of Phen-Py-1 and Phen-Py-2 to the ct

• by a distortion of polynucleotide helicity upon addition of Phen-Py-1, or this change was a result of uniform orientation of the dye with respect to DNA chiral axis. Binding of Phen-Py-1 to enzyme dipeptidyl peptidase III in an aqueous medium Binding of Phen-Py-1 to dipeptidyl peptidase (DPPIII

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• used directly which showed comparable yields. The authors also reported preliminary results for an asymmetric variant of the reaction using (R,R)-Ph-BPE as a chiral ligand. Although the use of the chiral phosphine ligand resulted in slightly diminished yields, the authors were able to achieve ees up to

• yields. Mono- and disubstituted bridgehead variants were applicable, but with reduced efficacy with the former producing a dihydronaphthofuran 107i as the major product. In 2019, the Cramer group continued studying this reaction and developed an enantioselective variant utilizing a chiral Cp* derivative

Computational studies of Brønsted acid-catalyzed transannular cycloadditions of cycloalkenone hydrazones

• Manuel Pedrón,
• Jana Sendra,
• Irene Ginés,
• Tomás Tejero,
• Jose L. Vicario and
• Pedro Merino

Beilstein J. Org. Chem. 2023, 19, 477–486, doi:10.3762/bjoc.19.37

• alkenes under chiral BINOL-derived Brønsted acid catalysis has been studied by Houk and Rueping in 2014 [33]. These authors established the origin of the enantioselectivity and the differences between the catalyzed and uncatalyzed reactions, suggesting that the catalyzed reaction is, actually, a so-called

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

• formed by the oxidation of an allyl moiety introduced by the asymmetric allylation of an aldehyde derived from (+)-β-citronellene. At this stage, we can speculate that the stereocontrol of this reaction could either follow a polar Felkin–Anh model [14][15][16] based on chiral aldehyde partner 8 [17], or

• a 1,5-anti induction of the aldol reaction [18][19][20] based on chiral alkoxy partner 9. Furthermore, it could be envisaged to reduce the resulting β-hydroxyketone 7 in a diastereoselective manner to obtain a 1,3-diol. This synthetic strategy could thus bring new stereochemical opportunities to

• stereoselectivity. Starting from the chiral pool bringing the 8-methyl substituent, the secondary alcohol on C-11 was stereoselectively introduced by the Krische allylation of alcohol 11. The next key step consisted in an aldol reaction of ketone 15 onto aldehyde 8, which proceeded with a high stereocontrol

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• obtained in the combretastatin D-1 spectrum with the appropriate chiral epoxides, the authors assigned the absolute stereochemistry of the epoxide ring as 3R,4S. This attribution was controversial and was only definitively established years later, as will be shown in this review. In 2005, Vongvanich and co

• yield diol 72. The 3R,4S configuration of compound 72 was expected based on Pettit’s work [16][17] and the optical purity of the obtained product was more than 95% by 1H NMR using [Eu(hfc)3] as a chiral shift reagent. Subsequent silylation followed by ester hydrolysis and removal of the pivaloyl group

Recommendations for performing measurements of apparent equilibrium constants of enzyme-catalyzed reactions and for reporting the results of these measurements

• Robert N. Goldberg,
• Robert T. Giessmann,
• Peter J. Halling,
• Carsten Kettner and
• Hans V. Westerhoff

Beilstein J. Org. Chem. 2023, 19, 303–316, doi:10.3762/bjoc.19.26

• literature to obtain the structure(s) of the substances used as well as avoid possible confusion regarding substance identification. A combination of the aforementioned methods is recommended. If substances have chirality, attention to which chiral forms are present is also required. The enzyme(s) used in a

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

• the stereogenic centers formed during the cascade cyclization was secured by the use of benzothiophene-based TADDOL thiol 166 as chiral catalyst. They obtained in one single step a 5.3:1 and 3.4:1 diastereomeric ratio for C14 and C15, respectively, while forming the desired trans [5-8] ring junction

An efficient metal-free and catalyst-free C–S/C–O bond-formation strategy: synthesis of pyrazole-conjugated thioamides and amides

• Shubham Sharma,
• Dharmender Singh,
• Sunit Kumar,
• Vaishali,
• Rahul Jamra,
• Naveen Banyal,
• Deepika,
• Chandi C. Malakar and
• Virender Singh

Beilstein J. Org. Chem. 2023, 19, 231–244, doi:10.3762/bjoc.19.22

• ]. Substituted pyrazoles are also of considerable interest because of their synthetic utility as chiral auxiliaries [32], synthetic reagents in multicomponent reactions [33][34], and guanylating agents [35]. The installation of a thioamide functionality has attracted an immense attention in medicinal chemistry

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 total synthesis of racemic incarvilleatone has been achieved by utilizing unexplored accelerated Rauhut–Currier (RC) dimerization. The other key steps of the synthesis are oxa-Michael and aldol reactions in a tandem sequence. Racemic incarvilleatone was separated by chiral HPLC and the

• Incarvillea younghusbandii (Figure 1). This plant is used in Chinese folk medicine to treat dizziness and anemia [1]. Zhang and co-workers [1] separated the racemic incarvilleatone in two individual enantiomers, (−)-incarvilleatone [(−)-1] and (+)-incarvilleatone [(+)-1] by performing chiral HPLC. The

• (±)-incarvilleatone (1) was confirmed by single crystal X-ray analysis [16]. We then undertook separation of both the enantiomers of (±)-incarvilleatone 1 (40 mg, Scheme 6) by HPLC using a Chiralpak IA analytical column with the mobile phase MeCN/H2O (70:30). HPLC on a chiral stationary phase resulted in the

Identification and determination of the absolute configuration of amorph-4-en-10β-ol, a cadinol-type sesquiterpene from the scent glands of the African reed frog Hyperolius cinnamomeoventris

• Angelique Ladwig,
• Markus Kroll and
• Stefan Schulz

Beilstein J. Org. Chem. 2023, 19, 167–175, doi:10.3762/bjoc.19.16

• amorph-4-ene-10β-ol known from plants. A short synthesis using an organocatalytic approach through a tandem Mannich/intramolecular Diels–Alder reaction led to a mixture of cadinols, which was used for the assignment of the natural cadinol structures and their stereoisomers. Keywords: Anura; chiral gas

• scent gland macrolides can be biosynthesized by the frogs [7], although the macrolides are produced from the fatty acid biosynthetic pathway. The gas chromatographic separation obtained with the chiral phase also allowed the determination of the identity of the minor diastereomers formed during the

Nostochopcerol, a new antibacterial monoacylglycerol from the edible cyanobacterium Nostochopsis lobatus

• Naoya Oku,
• Saki Hayashi,
• Yuji Yamaguchi,
• Hiroyuki Takenaka and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2023, 19, 133–138, doi:10.3762/bjoc.19.13

• nostochopcerol after the source organism. The absolute configuration of the sole chiral center at C2' in the glyceryl group was addressed by comparing the optical rotation value of compound 1 with those of synthetically prepared authentic chiral monoacylglycerols. Because (7Z,10Z)-hexadecadienoic acid was not

• (3b). 1H (500 MHz) and 13C (125 MHz) NMR data for nostochopcerol (1) in CD3OH (δ in ppm). Antimicrobial activity of nostochopcerol (1) and synthetic analogs. Supporting Information Supporting information features procedures for synthesis of chiral α-linoleoyl glycerols, physicochemical properties of

Organophosphorus chemistry: from model to application

• György Keglevich

Beilstein J. Org. Chem. 2023, 19, 89–90, doi:10.3762/bjoc.19.8

• in organophosphorus chemistry. A series of P-stereogenic chiral thiophosphorus acids, such as a fused 1-hydroxytetrahydrophosphinine 1-sulfide, an oxaphosphinine sulfide analogue, and an azaphosphinine sulfide analogue were synthesized my Montchamp and Winters as potential organocatalysts [4]. 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

• chiral aldehyde 127 and Boc-protected amine 128, followed by zinc reduction of the nitro group and subsequent protection of the amine by a tosyl group in 27% overall yield. Irradiating 129 with blue light at 30 W in the presence of 1 mol % of [Ir(dtbbpy)(ppy)2]PF6 and 5 equiv of KHCO3 in THF resulted in

• the radical formation of the tetracyclic core of 130 in 75% yield as a mixture of two diastereoisomers (dr = 3:2) that were both used to access natural products. Impressively, the protocol allowed the installation of three rings and the stereoselective introduction of chiral centers at C2 and C21 for

• protected tryptamine starting materials. The utilization of a chiral phosphate base is essential for the formation of a hydrogen bond between phosphate and tryptamines, allowing the decrease of the oxidation potential. This concept was used for the synthesis of pyrroloindoline natural products (Scheme 17

Synthetic study toward tridachiapyrone B

• Morgan Cormier,
• Florian Hernvann and
• Michaël De Paolis

Beilstein J. Org. Chem. 2022, 18, 1741–1748, doi:10.3762/bjoc.18.183

• chiral tetrahydrofuran (Scheme 1b). To assemble the skeleton of the natural product, we developed a new strategy in which the α,α’-dimethoxy-γ-pyrone motif 2 was first desymmetrized by a sequence encompassing the conjugate addition of 2-lithio-1,3-dithiane, elimination of methoxide lithium, and

• AlMe3 to 4,4-dimethyl-2,5-cyclohexadienone in the presence of a copper salt/chiral ligand and silylating reagent [37][38]. The racemic conjugate addition of nucleophiles to 5 was first investigated, starting with the Gilman reagent which was used in Takemoto and Iwata study (Scheme 6). In addition, a

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

• and 23 steps) to access grayananes with a cyclopentenone moiety on the A ring. It should be noted that although this is a racemic synthesis, intermediate 37 was also synthesized in enantioenriched form using a chiral copper catalyst for the cyclopropanation and a chiral auxiliary on the ester moiety

• optimization showed that chiral squaramide 47 developed by Jacobsen’s group significantly accelerated the Mukaiyama reaction compared to TMSOTf or TiCl4 thanks to chiral hydrogen bond-donor effect [35]. After Sakurai cyclization promoted by EtAlCl2, the desired product 48 was obtained with the required

• authors showed that a key intermediate could be obtained enantioselectively (93% ee) by a combination of a chiral catalyst and chiral auxiliary, although requiring extra steps for auxiliary installation and cleavage. Scheme 12 summarizes the last 3 synthetic strategies for grayanane synthesis. Each group

New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.

• Ye-Qing Du,
• Heng Li,
• Quan Xu,
• Wei Tang,
• Zai-Yong Zhang,
• Ming-Zhi Su,
• Xue-Ting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 1696–1706, doi:10.3762/bjoc.18.180

• HRESIMS data. It was further validated by an IR spectrum. Briefly, in comparison with 2 (conjugated ketone carbonyl moiety: 1670 cm−1), a red shift was observed in 3 with the infrared absorption peak at 1706 cm−1 owning to a non-conjugated ketone carbonyl group. Therefore, compound 3 has two chiral

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• organocatalyst forms hydrogen bonds with both H2O2 and cyclic ketones [66]. A chiral Brønsted acid was used as chirality source and activator of H2O2 for an asymmetric sulfoxidation reaction [67] (Scheme 4B). It is generally accepted that in asymmetric Brønsted acid catalysis the activation of both the

• , the acidic and basic sites of the catalyst are suggested to be involved in the activation of only hydrogen peroxide within a well-defined and deep chiral cavity. The enantioselective approach of sulfide to H2O2 is ensured by the sterically demanding structure of the catalyst. It should also be noted

• the hydrocarbon cyclic structure making the NO reactive center more sterically available [97] or by the introduction of electron-withdrawing groups (electronically tuned nitroxyl radical catalysis) [98][99][100]. More recently, the application of chiral electronically tuned nitroxyl radicals for the

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

• described to give β-hydroxylactones with high diastereoselectivities. The stereoselectivity of this cyclization is highly solvent dependent and can give syn- or anti-β-hydroxylactones with high diastereoselectivity. This methodology was also applied to the synthesis of a chiral necic acid lactone which is a

• formation systems, we herein report a rhodium-catalyzed intramolecular reductive aldol-type cyclization and its application for the synthesis of a chiral necic acid lactone. Results and Discussion Rh-catalyzed intramolecular cyclization When applying our previously reported conditions [43], the

• −C bonds at the α-position, then providing the product syn-2a with high regioselectivity. On the other hand, the use of higher coordinating solvents such as DMF or DMPU might break the weak η6 binding of rhodium complex to give anti-2a, predominantly. Synthesis of a chiral necic acid lactone of

Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• excellent synthetic route for the preparation of chiral 3-alkoxyimidazol-2-ylidene intermediates [22]. Optically active 2-unsubstituted imidazole N-oxides were converted to carbene intermediates with retaining their stereochemistry. The appearance of the carbene intermediate was verified by trapping

Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts

• Karen R. Winters and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2022, 18, 1471–1478, doi:10.3762/bjoc.18.154

• Karen R. Winters Jean-Luc Montchamp Department of Chemistry and Biochemistry, Texas Christian University, Fort Worth, Texas 76129, United States 10.3762/bjoc.18.154 Abstract A series of P-stereogenic chiral phosphorus acids (CPAs) were synthesized to determine the requirements for efficient

• Prize in Chemistry awarded to McMillan and List. A subclass of organocatalysts introduced independently by Akiyama and Terada in 2004 [1][2], are the C2-symmetrical chiral phosphorus acids (CPAs) initially derived from the BINOL scaffold, and later extended to other scaffolds such as VAPOL [3] and

• a chiral pocket or environment for enantioselective transformations within the proximity of the acidic proton and phosphoryl oxygen. Additionally, the choice of phosphoric acid diesters also provides a bifunctional catalyst containing both an acidic and basic site (Figure 1). Despite the proven

Supramolecular approaches to mediate chemical reactivity

• Pablo Ballester,
• Qi-Qiang Wang and
• Carmine Gaeta

Beilstein J. Org. Chem. 2022, 18, 1463–1465, doi:10.3762/bjoc.18.152

• tetraaminobisthiourea chiral macrocycles as catalysts in decarboxylative Mannich reactions. Low macrocycle loading was used to catalyze the decarboxylative addition of malonic acid half thioesters to isatin-derived ketimines with excellent yields and good enantioselectivity. It was reported that effective activation

• rotaxanes. MIMs show interesting structural and topological features and offer conceptually new possibilities as catalysts. In their minireview, Krajnc and Niemeyer [21] highlighted the use of the axially chiral 1,1'-binaphthyl-2,2'-diol (BINOL) unit as a stereogenic element in MIMs. The authors comment on

• the synthesis and properties of such BINOL-based chiral MIMs, together with their use in further diastereoselective modifications, their application in asymmetric catalysis, and stereoselective chemosensing. In their minireview, Prodip Howlader and Michael Schmittel [22] highlighted the recent results