Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition

• Anaïs Rousseau,
• Guillaume Vincent and
• Cyrille Kouklovsky

Beilstein J. Org. Chem. 2022, 18, 1385–1395, doi:10.3762/bjoc.18.143

• preparation and the coupling of three main fragments (Figure 2): the lactone fragment 3, the central fragment 4 and the cyclohexane fragment 5. We have previously described the enantioselective synthesis of the lactone fragment 3 [18]; we now disclose the synthesis of the oxazinone 4 and attempts for coupling

Derivatives of benzo-1,4-thiazine-3-carboxylic acid and the corresponding amino acid conjugates

• Péter Kisszékelyi,
• Tibor Peňaška,
• Klára Stankovianska,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 1195–1202, doi:10.3762/bjoc.18.124

• isolated. Moreover, the coupling of benzothiazines with amino acids was realized. In doing so, an enantioselective synthesis of the nonproteinogenic amino acid 2-amino-3-propylhexanoic acid was accomplished. Keywords: amino acid; benzothiazine; oxidative dimerization; peptide coupling; stereoselective

Synthesis of tryptophan-dehydrobutyrine diketopiperazine and biological activity of hangtaimycin and its co-metabolites

• Houchao Xu,
• Anne Wochele,
• Minghe Luo,
• Gregor Schnakenburg,
• Yuhui Sun,
• Heike Brötz-Oesterhelt and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 1159–1165, doi:10.3762/bjoc.18.120

• hangtaimycin, TDD and the hangtaimycin degradation product HTM222 are given. Keywords: antibiotics; enantioselective synthesis; peptides; racemisation; Streptomyces; Introduction Hangtaimycin (1, Scheme 1) was first isolated from Streptomyces spectabilis and shown to possess weak antimicrobial activity

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

• furnished a chiral thiosquaramide-catalyzed tandem Michael–Henry reaction of phenacylmalononitriles and nitroolefins for the enantioselective synthesis of cyclopent-3-ene-1-carboxamides [32] (reaction 2 in Scheme 1). Mohanan and co-workers reported a PBu3-catalyzed [3 + 2] annulation of

The stereochemical course of 2-methylisoborneol biosynthesis

• Binbin Gu,
• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 818–824, doi:10.3762/bjoc.18.82

• 2-methylisoborneol from (S)-2-Me-LPP may be explained by isomerization to 2-Me-GPP and then to (R)-2-Me-LPP. Keywords: biosynthesis; enantioselective synthesis; enzyme mechanisms; gas chromatography; terpenoids; Introduction After its first discovery from Streptomyces [1][2], it has been

• )-2-Me-LPP is the true pathway intermediate towards compound 1. For this purpose, both enantiomers of 2-Me-LPP were synthesized and enzymatically converted by 2MIBS. Here we report on the enantioselective synthesis of (R)- and (S)-2-Me-LPP and the results from the incubation experiments with 2MIBS

• . Results and Discussion Enantioselective synthesis of 2-methyllinalyl diphosphate The synthesis of (R)- and (S)-2-Me-LPP started with the Horner–Wadsworth–Emmons reaction [34][35] of sulcatone (2) with triethyl 2-phosphonopropionate to obtain ethyl 2-methylgeranate (3) as a mixture of the E and Z

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• anomeric hydroperoxides (HPO) to obtain epoxides 40 with moderate ees (Scheme 11B) [100][101]. Bunge and co-workers used the enantiomerically pure dihydroperoxide 41 in the DBU-mediated epoxidation of menadione (10) for the enantioselective synthesis of epoxide 42 (92% yield and 45–66% ee) (Scheme 11C

Bifunctional thiourea-catalyzed asymmetric [3 + 2] annulation reactions of 2-isothiocyanato-1-indanones with barbiturate-based olefins

• Jiang-Song Zhai and
• Da-Ming Du

Beilstein J. Org. Chem. 2022, 18, 25–36, doi:10.3762/bjoc.18.3

• or new methodologies to construct the spirobarbiturates with diverse structures. In recent years, good progress has been achieved in the construction of racemates of spirobarbiturates and the enantioselective synthesis [24][25][26][27][28][29], but only limited progress has been made in the

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

• phosphoric acid-catalyzed synthesis of axially chiral compounds and to suggest that much more attention should be paid to these catalysts in order to promote asymmetric synthesis. Review 1. Enantioselective synthesis of atropisomeric biaryls Direct C–H functionalization strategies for the atroposelective

• (Brønsted acidity/basicity, hydrogen-bonding units, and counter-anions toward metals) [48][49]. In 2019, Shi, Lin, and co-workers achieved an enantioselective synthesis of axially chiral quinoline-derived biaryl atropisomers via Pd-catalyzed C–H olefination of 8-phenylquinoline (11) using a novel chiral

• bioactive molecules and chiral catalysts [62][63][64], the construction of this scaffold has recently become valuable and attracted the attention of chemists [2][64]. In this context, Shi and co-workers reported a new strategy for the enantioselective synthesis of axially chiral naphthylindoles via the

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• directly with the presilylated cytosine without any promoter or additive and gave nucleoside 93 in a selective manner (β/α 10:1). The ester group of nucleoside derivative 93 was further reduced with sodium borohydride in ethanol, which gave lamivudine (1). An efficient and enantioselective synthesis 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

• the asymmetric aza-Michael addition reactions. Mahe et al. reported an effective, eco-friendly and cost-effective enantioselective synthesis of 3,5-diarylpyrazolines 49 by using phase-transfer methodology. They carried out a set of reactions between chalcones 46 and N-tert-butoxycarbonylhydrazine (47

• yields ranged 57–89% with ee 70–97% [52]. A similar chiral multifunctional thiourea/boronic acid was used as an organocatalyst by Michigami et al. for the enantioselective synthesis of N-hydroxyaspartic acid derivatives 76 with perfect regioselectivity and high enantioselectivity (Table 17) [53

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• annulation. Recently, there have been several elegant reviews covering the 1,3-enynes chemistry [46][47][48]. For instance, Procter and co-workers reviewed the copper-catalyzed functionalization of enynes [46]. In 2020, the Wang group reviewed the development of 2-activated 1,3-enyne in enantioselective

• synthesis [47]. Further, the Liu group reviewed the synthesis of allenes via transition metal-catalyzed 1,4-functionalizations of unactivated 1,3-enynes [48]. In this review, we will highlight the recent advances in the tandem annulation reactions of 1,3-enyne structural motifs for the construction of

Enantioselective PCCP Brønsted acid-catalyzed aminalization of aldehydes

• Martin Kamlar,
• Robert Reiberger,
• Martin Nigríni,
• Ivana Císařová and
• Jan Veselý

Beilstein J. Org. Chem. 2021, 17, 2433–2440, doi:10.3762/bjoc.17.160

• is the binaphthol (BINOL)-derived phosphoric acid class of catalysts, firstly reported by Akiyama [25] and Terada [26]. Soon after, BINOL-derived phosphoric acids were employed in the enantioselective synthesis of 2,3-dihydroquinazolinones. The initial report in this area was made by List and co

Base-free enantioselective S_N2 alkylation of 2-oxindoles via bifunctional phase-transfer catalysis

• Mili Litvajova,
• Emiliano Sorrentino,
• Brendan Twamley and
• Stephen J. Connon

Beilstein J. Org. Chem. 2021, 17, 2287–2294, doi:10.3762/bjoc.17.146

• report we disclose the outcome of an investigation into the design of an efficient catalytic asymmetric system capable of manipulating this substrate and its application to the enantioselective synthesis of the potent CRTH2 receptor antagonist 6 [32] (Scheme 1C). Results and Discussion We began our

• through the enantioselective synthesis of the (S)-antipode potent CRTH2 receptor antagonist 6 [48] (Scheme 2). Compound 10Al, isolated in 76% ee, was recrystallised in n-hexane to obtain optically pure 10Al. This material was deprotected with benzylamine 11 to afford oxindole 12, which was subsequently N

• brackets refers to reaction conducted at 3 °C, using 10 mol % of catalyst. dPerformed in PhCH3. ePerformed using 7c as the catalyst. A) SN2 alkylation of 3-subtituted-2-oxindoles not readily functionalisable; B) Previous work: enantioselective synthesis of a malleable 2-oxindole capable of further

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• have been provided by the group of Jacobsen in the nucleophilic addition of indoles 17 to pyranones 62 (Scheme 14a) [71], as well as in the enantioselective synthesis of α-allyl amino esters 67 by the reaction of α-chloro amino acid derivatives 65 with allyltin and allylsilane 66 nucleophiles [72

Enantioenriched α-substituted glutamates/pyroglutamates via enantioselective cyclopropenimine-catalyzed Michael addition of amino ester imines

• Zara M. Seibel,
• Jeffrey S. Bandar and
• Tristan H. Lambert

Beilstein J. Org. Chem. 2021, 17, 2077–2084, doi:10.3762/bjoc.17.134

• Zara M. Seibel Jeffrey S. Bandar Tristan H. Lambert Department of Chemistry, Columbia University, New York, New York 10027, USA Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA 10.3762/bjoc.17.134 Abstract A procedure for the enantioselective synthesis

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

• a specific target, i.e., it gives access to a greater diversity of compounds to be explored [26]. In this work, a compilation of the enantioselective synthesis of coumarin derivatives using asymmetric organocatalysis is presented, highlighting the proposed mechanism pathways for the formation of the

• substitution reaction between the coumarin and the activated MBH substrate, it is possible to obtain functionalized coumarins 41 (Scheme 13). Furthermore, the absolute configuration of the stereogenic center was determined by X-ray crystallography. The enantioselective synthesis of cyclopropa[c]coumarins 45

• -hydroxycoumarin (1) with the chiral catalyst 48, as shown in Scheme 15 [48]. The enantioselective synthesis of dihydrocoumarins 51 from an inverse demand [4 + 2] cycloaddition of ketenes 50 with o-quinone methides 49 using carbene catalyst (NHC) 52 was described by Ye and co-workers [49].This transformation

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

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

• literature, several strategies are reported using the sulfinyl group [84][85][86][87][88]. In this context, an enantioselective synthesis of 4-substituted azetidin-2-ones 52 was also accomplished starting from chiral imines 14 and dimethyl malonate (49). A diastereoselective coupling of these components

• ) [105]. Li and Xu reported a method for the enantioselective synthesis of β,γ-unsaturated α-amino acids 100, by a Lewis acid-promoted diastereoselective Petasis reaction of vinylboronic acids 98, (R)-N-tert-butanesulfinamide and glyoxylic acid (99). They found that the best results were obtained working

• high yields of 95% and 94%, respectively [132] (Scheme 42). Pinto and co-workers reported recently the enantioselective synthesis of natural alkaloids (−)-cermizine B 171 and (+)-serratezomine E 172. A key step of the synthetic strategy is the allylation with allylmagnesium bromide of N-tert

Menthyl esterification allows chiral resolution for the synthesis of artificial glutamate analogs

• Kenji Morokuma,
• Shuntaro Tsukamoto,
• Kyosuke Mori,
• Kei Miyako,
• Ryuichi Sakai,
• Raku Irie and
• Masato Oikawa

Beilstein J. Org. Chem. 2021, 17, 540–550, doi:10.3762/bjoc.17.48

• studies will straightforwardly focus on the enantioselective synthesis of only the (2R)-isomer. The asymmetric Ugi reaction recently developed [29] is of interest for the selective preparation of (2R)-6 (Scheme 1 and Scheme 5) [6][8]. Studies are in progress to develop an asymmetric Ugi/Diels–Alder

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• developed by the authors conferred an excellent methodology to obtain the 9-azabicyclo[3.3.1]nonane ring present in (±)-euphococcinine (2). Kibayashi synthesis – 2002 Kibayashi et al. performed the enantioselective synthesis of (−)-adaline (1). Their approach had as key steps SN2-type alkynylation

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• fragmentation to afford alkene 72 in 61% yield. Marcfortine B (8) was synthesized from alkene 72 in seven steps. The enantioselective synthesis of marcfortine C (9) commenced with a catalytic asymmetric cyano-substituted TMM cycloaddition of oxindole 73 and TMM donor 75 with Pd(dba)2/74 as catalyst to give a

• enantioselective synthesis of marcfortine C (9, Scheme 4B). Another brilliant example is the development of a chiral-phosphine-catalyzed [3 + 2] annulation reported by Lu in 2019, in which the chiral phosphine catalyst confers high stereocontrol on the formation of a spiro adduct bearing two vicinal all-carbon

• carboxylatve TMM [3 + 2] cycloaddition [38][39]. (B) Enantioselective synthesis of marcfortine C (9) features a palladium-catalyzed asymmetric cyano-substituted TMM [3 + 2] cycloaddition [39]. (A) Phosphine-catalyzed [3 + 2] cycloaddition [17]. (B) The proposed mechanism. Lu’s [3 + 2] cycloaddition in natural

3-Acetoxy-fatty acid isoprenyl esters from androconia of the ithomiine butterfly Ithomia salapia

• Florian Mann,
• Daiane Szczerbowski,
• Lisa de Silva,
• Melanie McClure,
• Marianne Elias and
• Stefan Schulz

Beilstein J. Org. Chem. 2020, 16, 2776–2787, doi:10.3762/bjoc.16.228

• catalysis [33]. Final acetylation of the hydroxy esters delivered the target compound isoprenyl 3-acetoxyoctadecanoate (11). Comparison of mass spectra and retention index confirmed the identity of the naturally occurring compound and 11. An enantioselective synthesis of isoprenyl (Z)-3-acetoxyoctadec-13

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

• transformative synthetic strategy, including in enantioselective synthesis. From the pioneering work by MacMillan [1] and Bach [2], enantioselective photocatalysis has grown into a well-established field of its own. A large proportion of photocatalysis focuses on photoredox catalysis, which involves single

• to allenes 80 to give complex bicyclic products 81 in moderate yields and good enantioselectivities (20 examples, up to 92:8 er) (Scheme 9b) [47]. The Bach group recently developed an enantioselective synthesis of cyclobutane 82 from enal 83 and diene 84 (Scheme 11a) [48]. Most of the examples

• dual catalytic mode. Ooi et al. reported an enantioselective synthesis of 1,2 diamines 247 from tertiary amines 248 and aldimines 249 (Scheme 39) [100]. The proposed mechanism involves a reductive quenching pathway with 248 to produce radical cations 248•+, which following deprotonation and a [1,2

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• can not only be useful for enantioselective synthesis of π-bowls but also to produce novel building blocks for molecular switches, chemical machines, molecular motor, ferroelectric memories, molecular devices, and sensory materials etc. Interestingly, electronic switching, thermal transport and

Controlling the stereochemistry in 2-oxo-aldehyde-derived Ugi adducts through the cinchona alkaloid-promoted electrophilic fluorination

• Yuqing Wang,
• Gaigai Wang,
• Anatoly A. Peshkov,
• Ruwei Yao,
• Muhammad Hasan,
• Manzoor Zaman,
• Chao Liu,
• Stepan Kashtanov,
• Olga P. Pereshivko and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2020, 16, 1963–1973, doi:10.3762/bjoc.16.163

• alkaloid-promoted electrophilic fluorination producing enantioenriched post-Ugi adducts fluorinated at the peptidyl position. Keywords: cinchona alkaloids; electrophilic fluorination; enantioselective synthesis; 2-oxo-aldehydes; Ugi reaction; Introduction Multicomponent reactions (MCRs) [1][2][3][4][5][6