Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• tricyclic imidazonaphthyridinone derivative having antibacterial properties, with low catalyst loading (0.1 mol %) (Scheme 20b). Later, in 2014, the same authors, using an amide as directing group (DG), developed a protocol for the regioselective C3-alkenylation of pyridines through syn-addition of alkynes

Sequential hydrozirconation/Pd-catalyzed cross coupling of acyl chlorides towards conjugated (2E,4E)-dienones

• Benedikt Kolb,
• Daniela Silva dos Santos,
• Sanja Krause,
• Anna Zens and
• Sabine Laschat

Beilstein J. Org. Chem. 2023, 19, 176–185, doi:10.3762/bjoc.19.17

• enone building blocks 23 for the synthesis of clifednamides [54][62]. The addition of Schwartz's reagent proceeds as a syn-addition affording (E)-alkenylzirconocenes 24 from terminal alkynes [28]. Based on these precedents from the literature, we surmised that it might be possible to establish a related

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• furylmercurials 91 via syn-addition of acetylene, which on carbonylation yielded the furan-containing carbonyl compound 92 (Scheme 30) [83]. It was proposed that initially mercuration of acetylene bonds via mercurinium like ions or π-complex takes place. Then the structure was stabilized through hydrogen bonding

• between alcohol and carbonyl groups (path a) or by hemiketal formation (path b). Thus, the chloride ion attacks from the frontside, producing syn-addition molecules that, upon dehydration, formed furan rings. Later they had reported similar mercuration of arylacetylenes to synthesize a broad spectrum of

Palladium-catalyzed regio- and stereoselective synthesis of aryl and 3-indolyl-substituted 4-methylene-3,4-dihydroisoquinolin-1(2H)-ones

• Valeria Nori,
• Antonio Arcadi,
• Armando Carlone,
• Fabio Marinelli and
• Marco Chiarini

Beilstein J. Org. Chem. 2020, 16, 1084–1091, doi:10.3762/bjoc.16.95

• -substituted and unsubstituted at the propargylic position) were successfully used as starting materials, affording the corresponding products 4eb, 4fc and 4fj in good yields. According to the literature, the highly stereoselective formation of products 4 resulted from the intramolecular syn-addition of the in

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

•  46). The product featuring the PhMe2Si residue at the β-location 287, however, arises by way of a 1,2-addition to an imine, formed from the same Pd(II) intermediate via elimination [84]. Oestrich and co-workers have recently demonstrated non-directed, asymmetric syn-addition-silylations of 3,3

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

• Heck cyclization reaction between the substituted alkyne and aryl bromide in 133 takes place to form a cyclic palladium intermediate 134 with E-configuration, resulting from a syn-addition mechanism of this step. The addition of a silver salt reduces the probability of isomerization of the double bond

Polyketide stereocontrol: a study in chemical biology

• Kira J. Weissman

Beilstein J. Org. Chem. 2017, 13, 348–371, doi:10.3762/bjoc.13.39

• acid biosynthesis by animal FAS, this reaction proceeds with attack of the 4′-pro-R hydride of NADPH on the 3-re face of the unsaturated thioester intermediate, with stereospecific protonation at the 2-si face, giving an overall syn addition [114]. In the case of polyketide chains, when a C-2 methyl

A detailed view on 1,8-cineol biosynthesis by Streptomyces clavuligerus

• Jan Rinkel,
• Patrick Rabe,
• Laura zur Horst and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 2317–2324, doi:10.3762/bjoc.12.225

• in both cases a syn addition, as could be shown by incubation of (2-13C)geranyl diphosphate in deuterium oxide. Keywords: biosynthesis; enzyme mechanisms; isotopic labelling; stereochemistry; terpenes; Introduction Among all classes of natural products the climax of structural diversity and

• incorporation at C-2 was indicated by a strongly enhanced triplet in the 13C NMR spectrum due to 13C-2H-spin coupling (Figure S4, Supporting Information File 1) [11][20][23]. This finding is in agreement with a syn addition to the olefinic double bond of (S)-7 in the final cyclisation step. It is possible that

• generated by plant enzymes [24][37][38]. Both enzymes from Salvia officinalis and from Streptomyces clavuligerus share the syn addition in the final cyclisation step which can be rationalised by a direct intramolecular proton transfer, circumventing the need of a low-energy neutral intermediate such as α

Garner’s aldehyde as a versatile intermediate in the synthesis of enantiopure natural products

• Mikko Passiniemi and
• Ari M.P. Koskinen

Beilstein J. Org. Chem. 2013, 9, 2641–2659, doi:10.3762/bjoc.9.300

• higher catalyst loading (5% instead of the usual 3%). Fujisawa studied the addition of lithiated dithiane to (S)-1 (Scheme 13) [66]. Without additives the reaction in THF provided alcohols 27 and 28 in a 7:3 ratio (anti/syn). Addition of aggregation braking HMPT slightly improved the selectivity (10:3

New developments in gold-catalyzed manipulation of inactivated alkenes

• Michel Chiarucci and
• Marco Bandini

Beilstein J. Org. Chem. 2013, 9, 2586–2614, doi:10.3762/bjoc.9.294

• concerted SN2’ pathway was judged energetically unfavourable, two possible mechanistic channels were supposed to account for the observed stereoselectivity: anti addition followed by anti-elimination or syn addition followed by syn-elimination. Calculations showed that the former pathway was energetically

Carbolithiation of N-alkenyl ureas and N-alkenyl carbamates

• Julien Lefranc,
• Alberto Minassi and
• Jonathan Clayden

Beilstein J. Org. Chem. 2013, 9, 628–632, doi:10.3762/bjoc.9.70

• established by X-ray crystallography of urea 6c (Figure 1). The stereochemical outcome of the reaction is consistent with syn-addition of the organolithium across the double bond (as is typical for carbolithiation [9][19]) followed by retentive protonation. The relative configuration of the carbolithiation

Regio- and stereoselective carbometallation reactions of N-alkynylamides and sulfonamides

• Yury Minko,
• Morgane Pasco,
• Helena Chechik and
• Ilan Marek

Beilstein J. Org. Chem. 2013, 9, 526–532, doi:10.3762/bjoc.9.57

• alkenes is the carbometallation reaction of alkynes [16][17][18], ynamide should be a suitable substrate for the regio- and stereoselective synthesis of enamide through carbometallation reaction [19][20][21][22]. Although the stereoselectivity of the carbocupration is usually controlled through a syn

• -addition of the organocopper reagent on the triple bond [23], the regioselectivity is dependent on the nature of the α-substituent on the alkyne 1. The presence of a donor substituent (XR = OR, NR2, Path B, Scheme 1) leads generally to the β-isomer in which the copper atom adds to the carbon β of the

Inter- and intramolecular enantioselective carbolithiation reactions

• Asier Gómez-SanJuan,
• Nuria Sotomayor and
• Esther Lete

Beilstein J. Org. Chem. 2013, 9, 313–322, doi:10.3762/bjoc.9.36

• to 58% ee) (Scheme 5) [16]. The enantiofacial differentiation can be explained through the formation of the complexed conformers by the coordination of the organolithium and the chiral ligand, which will react with the double bond in an intramolecular syn-addition to form benzyllithium derivatives 15

•  10) [40]. The stereochemical outcome is explained assuming that the (−)-sparteine-mediated enantioselective deprotonation leads to an (S)-configurated (α-carbamoyloxy)alkyllithium intermediate 26. Then, the cycloisomerization occurs through a syn addition to the π-bond to give a stabilized

Recent advances in transition-metal-catalyzed intermolecular carbomagnesiation and carbozincation

• Kei Murakami and
• Hideki Yorimitsu

Beilstein J. Org. Chem. 2013, 9, 278–302, doi:10.3762/bjoc.9.34

• nicely controlled by the organomagnesium reagents and electrophiles employed. The reaction with arylmagnesium reagents provided alkenylmagnesium intermediate 1a. The reaction of 1a with allyl bromide provided syn-addition product 1b in 70% yield while the reaction with benzaldehyde afforded anti-addition

• product 1c in 59% yield. In contrast, allylmagnesiated intermediate 1d reacted with benzaldehyde to give syn-addition product 1e stereoselectively. Marek reported copper-catalyzed carbometalation of alkynyl sulfoximines and sulfones using organozinc reagents of mild reactivity [41]. Various organozinc

• ]. Recently, Ready reported an intriguing iron-catalyzed carbomagnesiation of propargylic and homopropargylic alcohols 2b to yield syn-addition intermediates 2c with opposite regioselectivity (Scheme 7) [64]. They assumed that the key organo-iron intermediate 2A underwent oxygen-directed carbometalation to

Asymmetric synthesis of γ-chloro-α,β-diamino- and β,γ-aziridino-α-aminoacylpyrrolidines and -piperidines via stereoselective Mannich-type additions of N-(diphenylmethylene)glycinamides across α-chloro-N-sulfinylimines

• Gert Callebaut,
• Sven Mangelinckx,
• Pieter Van der Veken,
• Karl W. Törnroos,
• Koen Augustyns and
• Norbert De Kimpe

Beilstein J. Org. Chem. 2012, 8, 2124–2131, doi:10.3762/bjoc.8.239

• α-coordinating group [37][38][39]. The resulting syn-addition products syn-5 were subsequently cyclized to the corresponding N-sulfinyl-β,γ-aziridino-α-aminocarboxylamides 8 upon treatment with K2CO3 in acetone under reflux in a moderate to very good yield (36–90%, Scheme 4). The conversion of the

Stereoselective synthesis of trans-fused iridoid lactones and their identification in the parasitoid wasp Alloxysta victrix, Part II: Iridomyrmecins

• Robert Hilgraf,
• Nicole Zimmermann,
• Lutz Lehmann,
• Armin Tröger and
• Wittko Francke

Beilstein J. Org. Chem. 2012, 8, 1256–1264, doi:10.3762/bjoc.8.141

• a directed hydrogenation for a “syn” addition of hydrogen as represented in 6 [16][17][18]. Subsequent to the hydrogenation step, the synthesis of trans-fused iridomyrmecins could be completed after some standard functional group modifications. The synthesis of the corresponding enantiomers followed

• hydrogenations: A transfer hydrogenation for a formal “anti” delivery of hydrogen and the use of Crabtree’s catalyst in a directed hydrogenation for a “syn”-addition of hydrogen. Starting from pure enantiomers of limonene [1] these novel synthetic routes provided iridomyrmecins A, A' and B, B' in 2–3% yield over

Stereoselective synthesis of trans-fused iridoid lactones and their identification in the parasitoid wasp Alloxysta victrix, Part I: Dihydronepetalactones

• Nicole Zimmermann,
• Robert Hilgraf,
• Lutz Lehmann,
• Daniel Ibarra and
• Wittko Francke

Beilstein J. Org. Chem. 2012, 8, 1246–1255, doi:10.3762/bjoc.8.140

• reactions proceed via “syn”-addition of hydrogen to olefinic double bonds. Only subsequent isomerization processes may lead to a formal “anti”-addition. To obtain a suitable precursor, which, due to enolization of the hydrogenation product, might allow this formal “anti”-addition of hydrogen, the key

• synthesis of the cis,trans dihydronepetalactone c, a cis,trans-configuration between the substituents at C5-C1 and C1-C2 of the cyclopentane backbone needed to be established. With acetate 16 as the key intermediate, a stereoselective “syn”-addition of hydrogen from the same side as the (R)-configured side

Valence isomerization of cyclohepta-1,3,5-triene and its heteroelement analogues

• Helen Jansen,
• J. Chris Slootweg and
• Koop Lammertsma

Beilstein J. Org. Chem. 2011, 7, 1713–1721, doi:10.3762/bjoc.7.201

• , such as with N-phenylmaleimide and dimethyl acetylenedicarboxylate, providing single anti-adducts (e.g., 14; Scheme 4) [61][69]. Theoretical calculations on model structures showed the anti cycloaddition to be the kinetically controlled path and the syn addition the thermodynamically favoured one [40

Recent advances in carbocupration of α-heterosubstituted alkynes

• Ahmad Basheer and
• Ilan Marek

Beilstein J. Org. Chem. 2010, 6, No. 77, doi:10.3762/bjoc.6.77

• change the stereochemical outcome of the reaction. Representative examples are given in this mini-review. Keywords: alkynes; carbocupration; enamides; regioselectivity; stereoselectivity; syn-addition; vinylcopper; ynamides; ynol ether; Review The addition of a carbon-metal bond of an organometallic

• organocopper 3 must have a reactivity different from that of 1 in order to avoid oligomerization of the carbometalated product 3 (Scheme 1) [1][2][3]. For most carbocupration reactions, a strict syn-addition prevails but the regioselectivity is usually dependent of the substitution pattern of the alkyne [4

• stereoisomer via syn addition under mild conditions in either THF or Et2O (Scheme 20) and the reaction could be expanded to incorporate a large variety of functionalized alkylzinc bromide and dialkylzinc species [52]. Copper-catalyzed carbozincation could also be performed under very different conditions

Polar tagging in the synthesis of monodisperse oligo(p-phenyleneethynylene)s and an update on the synthesis of oligoPPEs

• Dhananjaya Sahoo,
• Susanne Thiele,
• Miriam Schulte,
• Navid Ramezanian and
• Adelheid Godt

Beilstein J. Org. Chem. 2010, 6, No. 57, doi:10.3762/bjoc.6.57

• oligoPPEs. R denotes solubilising substituents such as hexyl. Synthesis of the building blocks 11, 21, and 31. The depicted alkene configuration of 5 was chosen assuming a carbometalation process for the formation of 5 and thus a syn addition of the alkyne onto the hydroxypropyne moiety. Carbometalation, an

• occasionally detected side reaction. The depicted alkene configuration was chosen assuming a carbometalation process and thus a syn addition of the alkyne onto the hydroxypropyne moiety. Iodination of 1,4-dihexylbenzene. Different routes to compound 14, a representative of the large group of functionalized

Synthesis of a new class of aminocyclitol analogues with the conduramine D-2 configuration

• Latif Kelebekli,
• Yunus Kara and
• Murat Celik

Beilstein J. Org. Chem. 2010, 6, No. 15, doi:10.3762/bjoc.6.15

• between H1, H2, H3 and H4 protons. We assume that the stereochemical course of the hydroxylation of 27 proceeds through syn addition as previously observed in the hydroxylation of 13, a quite similar structure to 27. The all cis-configuration of the acetate and amino groups attached to the six-membered

Allylsilanes in the synthesis of three to seven membered rings: the silylcuprate strategy

• Asunción Barbero,
• Francisco J. Pulido and
• M. Carmen Sañudo

Beilstein J. Org. Chem. 2007, 3, No. 16, doi:10.1186/1860-5397-3-16

• key step is the syn addition of the tin cuprate to the acetylene, which controls the cis stereochemistry required for cyclization. [23] Seven Membered Carbocycles The use of nitriles and imines as electrophiles in the silylcupration of allene provides new alternatives for carbocyclization. Recently