Diastereoselective radical addition to γ-alkyl-α-methylene-γ-butyrolactams and the synthesis of a chiral pyroglutamic acid derivative

• Tomoko Yajima,
• Eriko Yoshida and
• Masako Hamano

Beilstein J. Org. Chem. 2013, 9, 1432–1436, doi:10.3762/bjoc.9.161

• the reaction were also revealed. This stereoselective radical reaction was used for synthesis of chiral pyroglutamic acid derivatives starting from a commercially available chiral amino acid. Keywords: chelation controlled reaction; diastereoselective reaction; free radical; lactams; pyroglutamic

• -selectivities were not observed for substrates with pivaloyl groups, and it appears that steric hindrance between the pivaloyl group and the lactam γ-alkyl disturbs chelation. Using the acetyl group, which is less sterically hindered than the pivaloyl group, improved the chelate formation of γ-isobutyl or γ

• -substituent on the substrate. The reactions using N-acetyl substrates instead of pivaloyl substrates yielded better trans-selectivities with γ-isobutyl and γ-phenethyl substrates, because acetyl is sufficiently small to allow chelation with the Lewis acid and lactam carbonyl. We used the reaction to

Cascade radical reaction of substrates with a carbon–carbon triple bond as a radical acceptor

• Hideto Miyabe,
• Ryuta Asada and
• Yoshiji Takemoto

Beilstein J. Org. Chem. 2013, 9, 1148–1155, doi:10.3762/bjoc.9.128

• solvent MeOH gave the nearly racemic product, although the high Z-selectivity was maintained (Table 1, entry 10). These results suggest that the rigid chelation of the chiral Lewis acid to the hydroxamate ester functionality occured in CH2Cl2. In the presence of chiral Lewis acid, hydroxamate ester 6C had

Amyloid-β probes: Review of structure–activity and brain-kinetics relationships

• Todd J. Eckroat,
• Abdelrahman S. Mayhoub and
• Sylvie Garneau-Tsodikova

Beilstein J. Org. Chem. 2013, 9, 1012–1044, doi:10.3762/bjoc.9.116

• good pharmacokinetic profile of 124 warrants further investigation in vivo. [Re] and [99mTc]-labeled benzofurans, BAT-Bp-2 (125a,b), were synthesized from 132 by reductive monoamination and O-demethylation to give 135 (Scheme 9D) [88]. Subsequent reaction with the protected chelation ligand TRT-Boc-BAT

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

• give 3c (Table 1, entry 3). Although N-heterosubstituted alkynes were used in all cases, the α-isomer is regioselectively obtained, as confirmed by 1H NMR analysis of the crude reaction mixture after hydrolysis, through an intramolecular chelation between the N-sulfonamide moiety and the organocopper

• species. To improve the chemical yield of this transformation, we considered the copper-catalyzed carbomagnesiation reaction. However, such catalytic reaction requires a transmetallation reaction of the intermediate vinylcopper into vinylmagnesium halide, and due to the intramolecular chelation, it is

• -regioisomer, albeit in moderate yield. On the other hand, in the presence of the 1-adamantylester substituted substrate 7d, the two α/β-isomers were formed in a 8:2 ratio (Table 3, entry 8). This loss of selectivity may be explained either by a competitive chelation of the carbonyl group of the ester

De novo synthesis of D- and L-fucosamine containing disaccharides

• Daniele Leonori and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2013, 9, 332–341, doi:10.3762/bjoc.9.38

• are usually further elongated at the C3 position in P. aeruginosa requiring two orthogonal protecting groups (PGs) at C3 and C4 of the building block in order to differentiate the two hydroxy groups at a later stage. The three carbon C4–C6 fragment of D-fucosamine was introduced by chelation

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

• chiral ligand required to provide high enantiofacial selectivity for a broader range of substrates are still unclear. The intermolecular reactions usually take advantage of chelation and stabilizing effects on the resulting organolithium to obtain high enantioselectivity and avoid polymerization

One-pot tandem cyclization of enantiopure asymmetric cis-2,5-disubstituted pyrrolidines: Facile access to chiral 10-heteroazatriquinanes

• Ping-An Wang,
• Sheng-Yong Zhang and
• Henri B. Kagan

Beilstein J. Org. Chem. 2013, 9, 265–269, doi:10.3762/bjoc.9.32

• substance class in organic chemistry containing nitrogen and three fused five-membered rings [1][2][3]. Due to the unique rigid bowl-shaped structure with one noninversible electron lone pair at the bottom of the central nitrogen (“centro-N”) atom, 10-azatriquinane analogues are used as efficient chelation

Alternaric acid: formal synthesis and related studies

• Michael C. Slade and
• Jeffrey S. Johnson

Beilstein J. Org. Chem. 2013, 9, 166–172, doi:10.3762/bjoc.9.19

• glyoxylate 1a under previously optimized conditions, high efficiency was achieved along with excellent (>20:1) stereochemical control for the formation of three-component-coupling product 17 (Scheme 7) [41][42][43][44]. To verify that the dithiane was acting in the desired fashion, and to rule out chelation

Chemical–biological characterization of a cruzain inhibitor reveals a second target and a mammalian off-target

• Jonathan W. Choy,
• Clifford Bryant,
• Claudia M. Calvet,
• Patricia S. Doyle,
• Shamila S. Gunatilleke,
• Siegfried S. F. Leung,
• Kenny K. H. Ang,
• Steven Chen,
• Jiri Gut,
• Juan A. Oses-Prieto,
• Jonathan B. Johnston,
• Michelle R. Arkin,
• Alma L. Burlingame,
• Jack Taunton,
• Matthew P. Jacobson,
• James M. McKerrow,
• Larissa M. Podust and
• Adam R. Renslo

Beilstein J. Org. Chem. 2013, 9, 15–25, doi:10.3762/bjoc.9.3

• TcCYP51. For 4, the ligand, the protein, and the heme group are shown in green, pink, and grey, respectively. For (R)-5, the ligand, the protein, and the heme group are shown in cyan, purple, and white, respectively. Heme-iron chelation and hydrophobic binding interactions dominate in the models. (B

Intramolecular carbolithiation of N-allyl-ynamides: an efficient entry to 1,4-dihydropyridines and pyridines – application to a formal synthesis of sarizotan

• Wafa Gati,
• Mohamed M. Rammah,
• Mohamed B. Rammah and
• Gwilherm Evano

Beilstein J. Org. Chem. 2012, 8, 2214–2222, doi:10.3762/bjoc.8.250

• , which can dramatically affect both the regio- and stereochemical outcomes due to the polarization of the triple bond and/or the formation of chelation-stabilized vinylmetal species. The carbometallation of O-, N-, P-, S-, and Si-substituted alkynes has indeed been quite extensively studied and shown to

• assumptions: According to the remarkable work of the Beak group on the α-lithiation of Boc-protected amines [34][35][36][37][38], N-allyl-ynamides 1 should be readily deprotonated to afford a transient chelation-stabilized allyllithium 2 and, provided that a metallotropic equilibrium exists between this

• intermediate and the less-stable allyllithium 3, an intramolecular carbometallation may then occur to yield a chelation-stabilized vinyllithium 4 and drive the overall process to the formation of the heterocyclic ring system. Further reaction with an electrophile followed by aqueous workup or hydrolysis under

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

• are minimized and Li-chelation stabilizes the conformation (Scheme 3), regardless of the base that was used [30][31]. Reaction of the Z-enolates via a cyclic chelated six-membered chairlike transition-state model TS-6a, would have resulted in anti-addition products anti-5 in analogy with our

• the glycinamides 4, as compared to the reaction with glycine esters, is attributed to the α-coordinating ability of the chlorine atom with the lithium of the incoming enolate as depicted in transition state TS-6b. The coordinating α-chloro atom in TS-6b overrides the chelation of the sulfinyl oxygen

Design and synthesis of quasi-diastereomeric molecules with unchanging central, regenerating axial and switchable helical chirality via cleavage and formation of Ni(II)–O and Ni(II)–N coordination bonds

• Vadim A. Soloshonok,
• José Luis Aceña,
• Hisanori Ueki and
• Jianlin Han

Beilstein J. Org. Chem. 2012, 8, 1920–1928, doi:10.3762/bjoc.8.223

• difference between the designed quasi-diastereomers 5 and 6 is that the noncoordinated arm CDE and the substituent R on the stereogenic coordination site C in 5 are on the same side of the metal chelation plane, while in structure of 6 the arm CBA and the substituent R are on the opposite sides. In contrast

• . Initial assignment of the structures of compounds 19/20 by NMR was not possible because of the very fast exchange between Ni–O=C and Ni–NH=C chelation. Thus, due to fast interconversion between compounds 19 and 20, only broad signals were observed in the 1H NMR spectra recorded at ambient temperature

Palladium-catalyzed dual C–H or N–H functionalization of unfunctionalized indole derivatives with alkenes and arenes

• Gianluigi Broggini,
• Egle M. Beccalli,
• Andrea Fasana and
• Silvia Gazzola

Beilstein J. Org. Chem. 2012, 8, 1730–1746, doi:10.3762/bjoc.8.198

• moderate to good yield (Scheme 6). A mechanism including an electrophilic palladation involving the pyridinyl chelation was thought to be plausible taking into account the outcome of the reaction performed on isotopically labeled substrates as well as by kinetic studies of variously substituted indoles

A simple and efficient dual optical signaling chemodosimeter for toxic Hg(II)

• Sabir H. Mashraqui,
• Sapna A. Tripathi,
• Sushil S. Ghorpade and
• Smita R. Britto

Beilstein J. Org. Chem. 2012, 8, 1352–1357, doi:10.3762/bjoc.8.155

• presently conceived the design of simple and easily accessible 10-methylthioacridone – designated as acrithion 2 – as a new chemodosimeter for the highly selective colorimetric and fluorescence signaling of Hg2+. The chemodosimeter mechanism, illustrated in Scheme 1, is proposed to proceed via chelation of

On the proposed structures and stereocontrolled synthesis of the cephalosporolides

• Sami F. Tlais and
• Gregory B. Dudley

Beilstein J. Org. Chem. 2012, 8, 1287–1292, doi:10.3762/bjoc.8.146

• Sami F. Tlais Gregory B. Dudley Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306-4390 USA, Fax: (850) 644-8281 10.3762/bjoc.8.146 Abstract The synthesis of four candidate stereoisomers of cephalosporolide H is described, made possible by a zinc-chelation

• strategy for controlling the stereochemistry of oxygenated 5,5-spiroketals. The same strategy likewise enables the first stereocontrolled synthesis of cephalosporolide E, which is typically isolated and prepared admixed with its spiroketal epimer, cephalosporolide F. Keywords: cephalosporolides; chelation

• structures of cephalosporolide E and F. Results and Discussion We recently reported the stereocontrolled synthesis of cephalosporolide H (reported structure) and its spiroketal isomer [32]. Our strategy featured the use of zinc salts to control the spiro-center using either steric biases or chelation

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

• chain at C5 through chelation. We chose Crabtree’s iridium catalyst ([Ir(cod)PCy3(py)]PF6) which has been reported to furnish excellent facial selectivities during directed hydrogenations of cyclic olefins [32][33][34]. Hydrogenation of acetate 16 in the presence of 11 mol % of Crabtree’s catalyst under

(How) does 1,3,5-triethylbenzene scaffolding work? Analyzing the abilities of 1,3,5-triethylbenzene- and 1,3,5-trimethylbenzene-based scaffolds to preorganize the binding elements of supramolecular hosts and to improve binding of targets

• Xing Wang and
• Fraser Hof

Beilstein J. Org. Chem. 2012, 8, 1–10, doi:10.3762/bjoc.8.1

• first took advantage of this kind of steric gearing by leaving ethyl groups in positions 1,3,5 and replacing the substituents in positions 2,4,6 with metal-coordinating ligands, which by design were directed toward the same face of the central scaffold and therefore preorganized for metal chelation

Directed aromatic functionalization in natural-product synthesis: Fredericamycin A, nothapodytine B, and topopyrones B and D

• Charles Dylan Turner and
• Marco A. Ciufolini

Beilstein J. Org. Chem. 2011, 7, 1475–1485, doi:10.3762/bjoc.7.171

• chlorinated benzamides undergo ortho-deprotonation without difficulty [104], implying that the resistance of 57 cannot be attributed to the chloro substituent per se. Nor can the problem be ascribed to sequestration of the base through coordination/chelation [33] effects involving the chlorine atom. Such a

Meta-metallation of N,N-dimethylaniline: Contrasting direct sodium-mediated zincation with indirect sodiation-dialkylzinc co-complexation

• David R. Armstrong,
• Liam Balloch,
• Eva Hevia,
• Alan R. Kennedy,
• Robert E. Mulvey,
• Charles T. O'Hara and
• Stuart D. Robertson

Beilstein J. Org. Chem. 2011, 7, 1234–1248, doi:10.3762/bjoc.7.144

• chelation of the Na atom results in a longer and thus weaker Na–NMe2 secondary interaction (increase from 2.289 to 2.501 Å), while the meta- and para- isomers benefit from TMEDA’s participation with the energies of TMEDA coordination equal to −20.86 and −20.74 kcal mol−1, respectively. Tellingly, although

Directed aromatic functionalization

• Victor Snieckus

Beilstein J. Org. Chem. 2011, 7, 1215–1218, doi:10.3762/bjoc.7.141

• causing a revolution in how we think about the preparation of aromatic/heteroaromatic molecules. Here, conceptually similar to the complex-induced proximity effect (CIPE) [31], which is operational in DoM reactivity, chelation of heteroatom groups to transition metals may be invoked, with an important

Homoallylic amines by reductive inter- and intramolecular coupling of allenes and nitriles

• Peter Wipf and
• Marija D. Manojlovic

Beilstein J. Org. Chem. 2011, 7, 824–830, doi:10.3762/bjoc.7.94

• dimethylzinc, both (E)- and (Z)-allylzinc species can exist in the solution. The chelation of the zirconocene to the ether oxygen and the imine nitrogen leads to a preference for the (Z)-TS species, paving the way for the formation of the observed cis-product. To further elaborate on the utility of this

Metathesis access to monocyclic iminocyclitol-based therapeutic agents

• Ileana Dragutan,
• Valerian Dragutan,
• Carmen Mitan,
• Hermanus C.M. Vosloo,
• Lionel Delaude and
• Albert Demonceau

Beilstein J. Org. Chem. 2011, 7, 699–716, doi:10.3762/bjoc.7.81

• atom economy. However, before carrying out the RCM reaction, the basic amino group (incompatible with most metathesis catalysts because of chelation to the metal center) [48] must either be protected (as N–Boc, N–Cbz, etc.), masked by incorporation into a cleavable heteroatom-containing cycle

A gold-catalyzed alkyne-diol cycloisomerization for the synthesis of oxygenated 5,5-spiroketals

• Sami F. Tlais and
• Gregory B. Dudley

Beilstein J. Org. Chem. 2011, 7, 570–577, doi:10.3762/bjoc.7.66

• the reported structure of cephalosporolide H (1) is outlined in Scheme 2. We recently demonstrated the use of inter-cycle chelation effects to control the spiroketal stereochemistry [28][29]. However, formation of the requisite oxygenated spiroketals (by cycloisomerization) posed significant

• single diastereomer upon chelation with zinc chloride. TEMPO oxidation gave lactone 1, which corresponds to the reported structure of cephalosporolide H. A more detailed discussion is found in our earlier report [28]. Two mechanistic alternatives (Scheme 7) are proposed for the conversion of 6 → 17 in

Stereoselective synthesis of four possible isomers of streptopyrrolidine

• Debendra K. Mohapatra,
• Barla Thirupathi,
• Pragna P. Das and
• Jhillu S. Yadav

Beilstein J. Org. Chem. 2011, 7, 34–39, doi:10.3762/bjoc.7.6

• determined by HPLC), which were easily separated by silica gel column chromatography. The stereochemical outcome in both the cases was explained by Crams’ rule, i.e., for a non-chelation model, the (R)-aldehyde would give rise to the (3S,4R) isomer. Alternatively, in a chelation model, the metal imposes a

The allylic chalcogen effect in olefin metathesis

• Yuya A. Lin and
• Benjamin G. Davis

Beilstein J. Org. Chem. 2010, 6, 1219–1228, doi:10.3762/bjoc.6.140

• sulfide could be explained with a sulfur relayed mechanism (Scheme 9a), where sulfur pre-coordination to the ruthenium center increases the effective concentration between the alkylidene and the alkene substrate. For the allyl sulfides this can occur without detrimental chelation, which is thought to be