[3 + 2] Cycloaddition with photogenerated azomethine ylides in β-cyclodextrin

• Margareta Sohora,
• Leo Mandić and
• Nikola Basarić

Beilstein J. Org. Chem. 2020, 16, 1296–1304, doi:10.3762/bjoc.16.110

• the macrocyclic host affected the stereochemistry of the reaction. Moreover, we studied photodecarboxylation reactions initiated by the phthalimide chromophore [17][18][19] and applied them in cyclizations with memory of chirality [20] and diastereoselective peptide cyclizations [21

Ferrocenyl-substituted tetrahydrothiophenes via formal [3 + 2]-cycloaddition reactions of ferrocenyl thioketones with donor–acceptor cyclopropanes

• Grzegorz Mlostoń,
• Mateusz Kowalczyk,
• André U. Augustin,
• Peter G. Jones and
• Daniel B. Werz

Beilstein J. Org. Chem. 2020, 16, 1288–1295, doi:10.3762/bjoc.16.109

• -arylcyclopropane dicarboxylates reacted with the corresponding aryl ferrocenyl thioketones in a completely diastereoselective manner to form single products in which (C-2)-Ar and (C-5)-ferrocenyl groups were oriented in a cis-fashion. In contrast, the same cyclopropanes underwent reaction with alkyl ferrocenyl

• practical importance [1][2]. The development of chemo- and diastereoselective syntheses for these compounds is thus a challenging problem. An elegant and highly efficient method for the construction of the tetrahydrothiophene ring is based on 1,3-dipolar cycloadditions of in-situ-generated thiocarbonyl S

• -naphthyl) thioketone (8c) reacted with 5a in a diastereoselective manner yielding the expected product 9c in good yield (65%) as the sole isolated product. Notably, in all reactions performed with aryl-substituted cyclopropanes 5a–f and with thioketones 8a,c,f, the desired tetrahydrothiophenes 9a,c,f–l

Synthesis of pyrrolidinedione-fused hexahydropyrrolo[2,1-a]isoquinolines via three-component [3 + 2] cycloaddition followed by one-pot N-allylation and intramolecular Heck reactions

• Xiaoming Ma,
• Suzhi Meng,
• Xiaofeng Zhang,
• Qiang Zhang,
• Shenghu Yan,
• Yue Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2020, 16, 1225–1233, doi:10.3762/bjoc.16.106

• with 2-bromobenzaldehydes 3 and maleimides 4 (Scheme 3) [30][37]. The cycloaddition reactions were diastereoselective (>20:1 dr for adducts 5 and >6:1 dr for adducts 6). The major diastereomers of 5 and 6 were isolated for following N-allylation and intramolecular Heck reactions. Adduct 5a generated

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• enantioselective and chemoselective oxidations of many organic compounds. Notably, the Gryko’s group recently described an enantio- and diastereoselective approach involving a porphyrin-based photooxygenation of aldehydes with sequential reduction to yield chiral diols in yields up to 91% and significant er (up to

• ). Ferroud’s group showed that the α-photocyanation of amines can be efficiently applied in complex molecules. The authors reported a highly regio- and diastereoselective photocyanation of both catharanthine and 16-O-acetylvindoline alkaloids with TMSCN and using TPP as photocatalyst (Scheme 58) [106][107

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• dienyne precursors in three steps, from (S)- and (R)-citronellal, through a diastereoselective Michael addition, chemoselective dibromoolefination, and a one-pot Wittig olefination/alkyne-bond formation. The enantiopure dienynes were then converted into the enantiomeric hydroazulenes in 53% and 55% yield

• enantiopure trienyne or diene–diyne metathesis precursors were readily obtained from (S)-citronellal by a highly diastereoselective organocatalytic Michael addition. Erogorgiaene An exceptionally stereoselective synthesis of erogorgiaene (12) (95% E-selectivity) was reported by Hoveyda et al. [80]. They

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

• derivatives [113], the cyanoborylation of terminal allenes 382 has also been studied. Using B2pin2 in the presence of N-cyano-N-phenyl-p-toluenesulfonamide (NCTs, 377), under Cu-catalysis led to regio-, chemo-, and diastereoselective trifunctionalized products 383–386. The reaction sequence involves three

• ]. The diastereoselective formation of α-hydroxyboronate esters 477 and 478 starting from cyclic and acyclic ketones 475 and 476) arises from an extensive steric crowding during the insertion reaction of the coordinated L-Cu-Bpin to the aldehyde 479. The observed selectivity from Felkin-Anh-controlled

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

• diastereoselective and enantioselective iterative route, affording the highly desirable deoxypropionate moiety in high 97% de. The Josiphos (L9)/CuBr∙SMe2 catalytic system was also efficient to promote the ECAs of MeMgBr to the less reactive aromatic α,β-unsaturated thioesters (ee values up to >99%) [26]. In order

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• 1994, Zielinski and Schäfer made a vital contribution in the field of asymmetric electrosynthesis in terms of the diastereoselective cathodic reduction of the carbonyl group of chiral phenylglyoxamides 150 and 152 [89][90]. After initial conversion to its corresponding amides using chiral auxiliaries

• diastereoselective Michael addition reactions [103][104]. The glycine–nickel complex 184 was deprotonated using a radical anion generated from the electrochemical reduction of azobenzene. The anionic Ni complex 185 acted as a good C-nucleophile towards Michael acceptors 186 resulting in diastereoisomeric mixtures of

Indium-mediated C-allylation of melibiose

• Christian Denner,
• Manuel Gintner,
• Hanspeter Kählig and
• Walther Schmid

Beilstein J. Org. Chem. 2019, 15, 2458–2464, doi:10.3762/bjoc.15.238

• elongation methodology allows for a short, efficient and diastereoselective approach towards complex glycosylated carbohydrate structures. The stereochemical outcome of the key intermediates, allylated disaccharides, has been determined by X-ray analysis. Ozonolysis of the introduced double bond yielded the

• established as reliable and efficient approach in carbohydrate chemistry, shown by many examples reported in the literature [8][9][10][11][12]. Thus far, this method has been applied to monosaccharides [13][14]. In this context, the development of diastereoselective and efficient synthetic routes to elongated

• a powerful synthetic tool for the efficient and diastereoselective elongation of melibiose (1) without affecting the existing glycosidic linkage, allowing for additional options for further modifications of complex glycosides. Experimental 2’,3’,4’,6’-Tetra-O-acetyl-α-ᴅ-galactopyranosyl-(1’→1

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• Sodeoka [40] reported the first example of an enantioselective monofluorination of α-keto esters catalyzed by Pd-μ-hydroxo complexes with cyclopentyl methyl ether (CPME) as the best solvent (Scheme 6). Also, they achieved the diastereoselective reduction of the remaining keto group with lithium tri(sec

• diastereoselectivities. Based on the PIP auxiliary developed by Shi, Ge’s group [48] developed a similar direct, highly site- and diastereoselective fluorination of aliphatic amides (Scheme 11b). Although the roles of Fe(OAc)2 and Ag2CO3 were unclear, their addition significantly improved the reaction yield. A catalytic

α-Photooxygenation of chiral aldehydes with singlet oxygen

• Dominika J. Walaszek,
• Magdalena Jawiczuk,
• Jakub Durka,
• Olga Drapała and
• Dorota Gryko

Beilstein J. Org. Chem. 2019, 15, 2076–2084, doi:10.3762/bjoc.15.205

• of diarylprolinol silyl ethers is highly diastereoselective and that the configuration of a newly created stereocenter at the α-position depends predominantly on the catalyst structure. The absolute configuration of chiral 1,2-diols has been unambiguously established based on electronic circular

• small molecule size, there are few examples of its use not only in diastereoselective synthesis but also in enantioselective reactions [9][10]. Inspired by Cόrdova’s work [11][12][13], we explored the idea of merging enamine catalysis with photocatalytic oxygenation with singlet oxygen for α

• er for enantioenriched substrate 1 thus indicating that the organocatalytic photooxygenation of aldehydes with singlet oxygen is highly diastereoselective. In the case, when two chiral compounds participate in a given reaction, they, according to Masamune, may be considered as matching or mismatching

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

• group, the synthesis also provides a new useful approach for the synthesis of other structurally relevant derivatives of triptolide. In 2011, as their ongoing work that devoted to the synthesis of triptolide, Batti and co-workers developed a novel highly diastereoselective methodology that features 6

• trimethylsilyl trifluoromethanesulfonate (TMSOTf) in a diastereoselective and stepwise manner. This novel methodology provides a shorter access to the intermediate 97, which is a key intermediate for the synthesis of triptolide. Recently, photoredox catalysis has emerged as a powerful and high-yielding method

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• ] reported another example of a diastereoselective MCR between a 6-ketosteroid, 2-aminopyridines and an isocyanide, using propylphosphonic acid anhydride (TP3) as catalyst to afford a steroidal derivative with an imidazole-pyridine moiety attached to ring B. This moiety is present in several compounds

• line. A very recent example of a highly diastereoselective Ugi-type MCR was reported by Rivera, Paixão and co-workers using a steroidal isocyanide [31]. As shown in Scheme 9, the procedure comprised the organocatalytic asymmetric synthesis of the chiral bifunctional substrate 30 bearing an masked

• -diketopiperazines based on a diastereoselective Ugi-4CR with an androstanic aldehyde derived from dehydroepiandrosterone (DHEA) [16]. Multicomponent synthesis of a heterocycle–steroid hybrid using a ketosteroid as carbonyl component [18]. Synthesis of peptidomimetic–steroid hybrids using the Ugi-4CR with

Ugi reaction-derived prolyl peptide catalysts grafted on the renewable polymer polyfurfuryl alcohol for applications in heterogeneous enamine catalysis

• Alexander F. de la Torre,
• Gabriel S. Scatena,
• Oscar Valdés,
• Daniel G. Rivera and
• Márcio W. Paixão

Beilstein J. Org. Chem. 2019, 15, 1210–1216, doi:10.3762/bjoc.15.118

• employ a three-component, diastereoselective variant of the Ugi reaction for the synthesis of a prolyl pseudo-peptide catalyst, which proved effective in an organocatalytic conjugate addition reaction [6]. Later, our groups developed an Ugi reaction-based multicomponent approach enabling the structure

Synthesis of aryl cyclopropyl sulfides through copper-promoted S-cyclopropylation of thiophenols using cyclopropylboronic acid

• Emeline Benoit,
• Ahmed Fnaiche and
• Alexandre Gagnon

Beilstein J. Org. Chem. 2019, 15, 1162–1171, doi:10.3762/bjoc.15.113

• diastereoselective [3 + 2] cycloaddition reaction [14][15]. The ring expansion sequence 1 → 2 → 6 → 8 has been used as a key step in the synthesis of (±)-fragranol [16], (±)-grandisol [16], (±)-α-cuparenone [17] and (±)-herbertene [17]. Aryl cycloropyl sulfides 1 are most frequently prepared by cyclopropylation of

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• . This is a good partner for a cycloaddition with an imine such as 99 that would give rise to the spiro β- and γ-lactam derivative 101 in a diastereoselective manner. Indeed, a seminal contribution also made use of a similar Pd-catalysed carbonylation followed by amide formation and cyclization in a

Stereo- and regioselective hydroboration of 1-exo-methylene pyranoses: discovery of aryltriazolylmethyl C-galactopyranosides as selective galectin-1 inhibitors

• Alexander Dahlqvist,
• Axel Furevi,
• Niklas Warlin,
• Hakon Leffler and
• Ulf J. Nilsson

Beilstein J. Org. Chem. 2019, 15, 1046–1060, doi:10.3762/bjoc.15.102

• using a highly diastereoselective hydroboration of C1-exo-methylene pyranosides giving inhibitors with fourfold or better selectivity for galectin-1 over galectin-3, -4C (C-terminal CRD), -4N (N-terminal CRD), -7, -8C, -8N, -9C, and -9N and dissociation constants down to 170 µM. Keywords: C-galactoside

• synthesis pathway involving a diastereoselective hydroboration towards (aryltriazolyl)methyl galactopyranosyl derivatives and determined the viability of this as a scaffold for galectin inhibitors by screening a library of fourteen different products against galectins -1, -3, -4C (C-terminal CRD), -4N (N

An efficient synthesis of the guaiane sesquiterpene (−)-isoguaiene by domino metathesis

• Yuzhou Wang,
• Ahmed F. Darweesh,
• Patrick Zimdars and
• Peter Metz

Beilstein J. Org. Chem. 2019, 15, 858–862, doi:10.3762/bjoc.15.83

• (−)-Isoguaiene was prepared from (S)-citronellal in only 9–10 steps with good overall yields. Either a trienyne or a dienediyne metathesis and highly diastereoselective organocatalytic Michael additions of aldehydes derived from (S)-citronellal served as the key transformations. Keywords: domino reactions

• sesquiterpene (−)-isoguaiene (1) using either a trienyne or a dienediyne metathesis and highly diastereoselective organocatalytic Michael additions of aldehydes derived from 5 as the key steps. Structures of the sesquiterpene (−)-isoguaiene (1) and the trisnorsesquiterpene clavukerin A (2). Retrosynthetic

A diastereoselective approach to axially chiral biaryls via electrochemically enabled cyclization cascade

• Hong Yan,
• Zhong-Yi Mao,
• Zhong-Wei Hou,
• Jinshuai Song and
• Hai-Chao Xu

Beilstein J. Org. Chem. 2019, 15, 795–800, doi:10.3762/bjoc.15.76

• Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450001, People’s Republic of China 10.3762/bjoc.15.76 Abstract A diastereoselective approach to axially chiral imidazopyridine-containing biaryls has been developed. The reactions proceed through a radical cyclization cascade to construct

• diastereoselective approach for the synthesis of axially chiral biaryls through an electricity-powered cyclization cascade. The reactions employ easily assembled starting materials and afford functionalized imidazopyridine-based biaryls in good to high yields and diastereoselectivity. Reaction design. Scope of

Stereochemical investigations on the biosynthesis of achiral (Z)-γ-bisabolene in Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 789–794, doi:10.3762/bjoc.15.75

• and was reported from different sources such as the liverwort Dumortiera hirsuta [19]. Its (Z)-configured exocyclic double bond has also attracted the attention of synthetic chemistry for a diastereoselective total synthesis [20][21][22]. The wide occurrence of 5 is likely connected to the simple

Diastereo- and enantioselective preparation of cyclopropanol derivatives

• Marwan Simaan and
• Ilan Marek

Beilstein J. Org. Chem. 2019, 15, 752–760, doi:10.3762/bjoc.15.71

• Marwan Simaan Ilan Marek The Mallat Family Laboratory of Organic Chemistry, Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Haifa, 32000, Israel 10.3762/bjoc.15.71 Abstract The diastereoselective carbocupration reaction of alkoxy-functionalized cyclopropene derivatives

• ). First, we checked that the carbometalation reaction was regio- and diastereoselective by addition of lower order cyanocuprate, easily obtained from the corresponding organolithium and a stoichiometric amount of CuCN (Scheme 4) [68][69][70]. The addition reaction proceeds similarly for the addition of

• when the same sequence of diastereoselective carbometalation/oxidation was performed on cyclopropenyl ester 1, the in situ-formed donor–acceptor cyclopropanol undergoes a selective ring-opening to provide the acyclic product possessing a quaternary carbon stereocenter [57]. As the enantioselective

A chemoenzymatic synthesis of ceramide trafficking inhibitor HPA-12

• Seema V. Kanojia,
• Sucheta Chatterjee,
• Subrata Chattopadhyay and
• Dibakar Goswami

Beilstein J. Org. Chem. 2019, 15, 490–496, doi:10.3762/bjoc.15.42

• synthesis of the title compound has been developed using an efficient and highly enantioselective lipase-catalyzed acylation in a hydrophobic ionic liquid, [bmim][PF6], followed by a diastereoselective asymmetric dihydroxylation as the key steps for incorporating the stereogenic centers. The further

• (1R,3S)-HPA-12 (2) used the chiral pool approach [15][16], crystallization-induced asymmetric transformation [17], diastereoselective reduction of γ-aryl-γ-oxo-β-amino alcohol [18], cycloaddition of oxime with alkenes [19], enantioselective carbonyl reduction followed by an organocatalyzed α-amination

• /aza-Michael reaction of 3,6-dihydro-1,2-dioxines followed by diastereoselective reduction [25]. Most of these methods employ starting materials or catalysts, which are not commercially available, and also require operationally demanding reaction conditions. Hence a need to develop a simple, efficient

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• (Scheme 1, reaction 3) [23][26][27][28][29][30][31][32][33]. Thus, methylenecyclopropanes have been prepared by diastereoselective addition of Grignard reagents to cyclopropenylmethyl ethers, possessing a hydroxymethyl directing substituent at C3, in the absence or in the presence of a catalyst (copper or

• previously with alkylidene(aminocyclopropane) derivatives, diastereoselective hydrogenation reactions of alkylidenecyclopropanes possessing a single substituent at C2 can be carried out with complementary face selectivities, depending on the conditions and substrates. Thus, the hydrogenation of 58a catalyzed

• out in the presence of Crabtree’s catalyst [58], thereby allowing access to cyclopropylcarbinol 73’ with high diastereoselectivity (73’/73 = 97:3, Scheme 25). By taking advantage of the directing effect of a hydroxy group, diastereoselective hydrogenations of alkylidenecyclopropanes possessing two

Ruthenium-based olefin metathesis catalysts with monodentate unsymmetrical NHC ligands

• Veronica Paradiso,
• Chiara Costabile and
• Fabia Grisi

Beilstein J. Org. Chem. 2018, 14, 3122–3149, doi:10.3762/bjoc.14.292

• 24b showed activities similar to that of GII-SIMes. They also exhibited different E/Z selectivities in CM transformations (e.g., Table 1, entry 2), and gave improved selectivities in a diastereoselective RCM reaction (Table 1, entry 3). Ledoux, Verpoort et al. described a series of phosphine

• diastereoselective ring-rearrangement metathesis (dRRM) of cyclopentene 131 (Scheme 12). The presence of a nitro group at the ortho or para positions of the benzyl substituent (134 and 135 in Figure 24), reported by Malinowska and co-workers [45], led to higher activities in the RCM of 7 and 9 (Schemes 1 and 2

Stereodivergent approach in the protected glycal synthesis of L-vancosamine, L-saccharosamine, L-daunosamine and L-ristosamine involving a ring-closing metathesis step

• Pierre-Antoine Nocquet,
• Aurélie Macé,
• Frédéric Legros,
• Jacques Lebreton,
• Gilles Dujardin,
• Sylvain Collet,
• Arnaud Martel,
• Bertrand Carboni and
• François Carreaux

Beilstein J. Org. Chem. 2018, 14, 2949–2955, doi:10.3762/bjoc.14.274

• vinyl ethers as key step of reaction sequences developed. Keywords: 3-amino glycals; diastereoselective additions to aldehydes; pluramycins; ring-closing metathesis; vinyl ethers; Introduction Several classes of medicinally useful molecules with antibiotic and anticancer activity contain in their

• corresponding alkenes 13a,b in 90% and 63% yield, respectively, over two steps. Alternatively, we envisioned that, from the same α-substituted chiral aldehyde 5, compound 13b could be obtained in a more straightforward manner employing a strategy based on a diastereoselective allylboration reaction (Scheme 2

• metathesis of vinyl ethers as key step for the preparation of several carbamate-protected 3-aminoglycals. Evans aldol reaction for the preparation of diastereomeric compounds 13a and 13b. Alternative preparation of 13b based on a diastereoselective allylboration. O-Vinylation-ring-closing metathesis sequence