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The dihydrobenzocyclobutene 90 having a 4-hydroxycrotonate unit attached via an ester linkage as an internal dienophile can be cyclized to a 3:1 mixture of the trans lactone 92 (an analogue of podophyllotoxin, 1) and the cis lactone 93.This stereoselective reaction proceeds via the intermediacy of the o-quinodimethane 91 which cyclizes from the endo transition state 91n in preference to the exo-one 91x, presumably because of stabilization of the former by secondary orbital overlap.This result provides evidence that a proposed general route to the synthesis of podophyllotoxin, 1, and its analogues via the internal cycloaddition of the o-quinodimethane 8 to 9n may prove successful.Several possible approaches to the synthesis of the trans-2-aryldihydrobenzocyclobutenol 4 are described.The benzyne 11 was prepared and underwent <2 + 4> but no <2 + 2> cycloadditions.Although the 2-bromobenzocyclobutenone 23 could be synthesized in an efficient manner, it proved impossible to convert it into 4 by means of the aryl organometallic reagents 22ab.The bromo epoxide 52 was prepared and subjected to metal-halogen exchange and Lewis acid catalyzed epoxide rearrangement in an attempt to prepare 4.The aldehyde 56 was obtained in this reaction, clearly indicating that the desired intermediate 54 had been formed but could not be trapped under these conditions.Two ring contraction routes to 4 are also described, both beginning with the 1-indanone 74 prepared in good yield from piperonal 14.The diol monomesylate 78, prepared from 74, suffered base-catalyzed E2 elimination rather than the desired rearrangement to 80.The diazo ketone 83 underwent Wolff rearrangement to give the desired ester 84, but only in 7percent yield.Two interesting transformations were observed in these ring contraction schemes, namely the formation of the oxathiole dioxide 77 on mesylation of the ketol 75 and the preparation of the diazirene 86 on photolysis of the diazo ketone 83 at long wavelengths.The ester 84 was then saponified to the acid 87 which was coupled with methyl 4-hydroxycrotonate, 5, to give 90.The assignment of the structures of the products of thermolysis of 90 was based on high field 1H NMR and analogy to the spectra of similar compounds in the literature.

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Reference:
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

18-Sep News Brief introduction of 4062-60-6

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An efficient N-alkylation reaction of tosylhydrazones was developed in the presence of triphenylphosphine; triphenylphosphine played a key role in the transformation. A range of N-alkylated tosylhydrazones were prepared in good to high yields.

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Reference:
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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A series of 5-hexenyllithiums having a phenyl, trimethylsilyl, or cyclopropyl substituent at the terminal [C(6)] alkene carbon have been prepared from the corresponding iodides by lithium-iodine exchange with t-butyllithium at -78C. Although 6-alkyl-substituted 5-hexenyllithiums do not isomerize to five-membered rings upon warning, terminally substituted 5-hexenyllithiums bearing a moderately activating phenyl or trimethylsilyl group cleanly undergo a totally regiospecific 5-exo cyclization at sub-ambient temperatures to afford five membered rings bearing a CHRLi moiety that may be trapped with an electrophile to deliver high yields of functionalized product. Cyclization of 6-cyclopropyl-5-hexenyllithium is accompanied by ring opening of the three-membered ring.

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Metal catalyst and ligand design,
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The equilibrium acidities (pK(a)s) of six families of remotely substituted benzyl onium salts (i.e., 4-G-C6H4CH2-E+·Br-, where E+ = Ph3P+, Ph2PO, Et3N+, Me2S+, Me2Se+, and Bu2Te+ and G = H, Me, CF3, CO2Me, CN, and NO2), one family of alpha-E+ substituted acetophenones (i.e., PhCOCH2-E-·Br-, where E+ = Me2S+, Bu2Te+, Bu3P+, and Ph3As+), and one family of 9-E+-substituted fluorenes (i.e., 9-E+- FlH·Br-, where E+ = Bu2S+, Me2Se+, Bu2Te+, Bu3P+, and Ph3As+) have been determined in a single solvent, dimethyl sulfoxide (DMSO). This allowed meaningful comparisons of the thermodynamic stabilities for an extensive range of Group VB and VIB ylides covering up to six elements (N, P, As; S, Se, Te) to be made for the first time on the basis of a unified standard. A comparison of the pK(a) values of onium salts with those of their parents shows that all the onium substituents studied in the present work are strongly ylide-stabilizing, covering an anion stabilization energy range of 17-35 kcal/mol (i.e., DeltapK = 12-25 pK units). A further examination of the pK(a) values also reveals that the thermodynamic stabilities of the Group VB onium ylides are in a decreasing order of P+-C- > As+-C- > N+-C- and of the Group VIB onium ylides in a decreasing order of S+-C- > Se+-C- ~ Te+-C-, if the substituents on the onium atoms are kept similar. The stability order for the ylides of the third-row elements was found to be S+- C- > P+-C-, as implied by the DeltapKs of 1.7-4.2 for the three R3P+-C- /R2S+-C- pairs compared (see text). The pK(a)s of the eight remotely substituted E+-CH2Ar series all correlate well with the sigma- constants (see Table 3) with a decreasing order of slopes as (E+ =) Ph2P(O) (-5.86) > Ph3As+ (-5.35) > Bu3P+ (-5.00) > Ph3P+(-4.46) and Bu2Te+ (-5.50) > Me2Se+ (-5.03) > Me2S+ (-3.40), suggesting a similar trend for the extent of charge localization at the carbanions next to the E+ group. All these observations are consistent with the assumption that at least part of the gained stabilization in the phosphonium and sulfonium ylide cases (especially the latter) has to be attributed to the backbonding stabilization involving the sigma* and/or 3d orbital participation. Discussion for elucidating this view is presented.

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Reference:
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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The specific nonpurely thermal effects of microwaves were evidenced according to neutral or charged leaving groups during nucleophilic substitution of benzylic electrophiles with triphenylphosphine and tributylphosphine. Microwave (MW) irradiation considerably enhanced the reactions with charged alkylating agents, especially under solvent-free conditions. Results are interpreted considering the magnitude of MW effects according to the position of the transition state along the reaction coordinates.

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Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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A palladium (Pd)-catalyzed endo-selective Heck reaction of iodomethylsilyl ethers of phenols and aliphatic alkenols has been developed. Mechanistic studies reveal that this silyl methyl Heck reaction operates via a hybrid Pd-radical process and that the silicon atom is crucial for the observed endo selectivity. The obtained allylic silyloxycycles were further oxidized into (Z)-alkenyldiols.

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Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

9-Sep-2021 News The important role of C10H24N2

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A wide variety of 6-aryl-5-phenyl-1,2-dithiafulvenes and 6-aroyl-5-phenyl-1,2-dithiafulvenes (4) have been synthesized by the interaction of 5-phenyl-1,2-dithiol-3-one (3a) and phosphonium ylides (2).The synthesis of these dithiafulvenes has also been carried out by an alternative route involving the condensation of 2 with 5-phenyl-1,2-dithiol-3-thione (3b).The spectral data ara consistent with the proposed structures for the products.

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Metal catalyst and ligand design,
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Five newly designed organic small molecules (DSBTs, 1?5) with 3,3?-bithienyl unit had been successfully synthesized with 3-bromothiophene as the starting material. In both UV?vis absorption and fluorescence emission investigation, compound 3 with nitro-substitution exhibited the largest bathochromic shift and narrowest optical bandgap among 1?5. Further photophysical studies showed that 3 had obvious solvatochromism and aggregation-induced emission (AIE) property. The electrochemical properties and thermal stabilities studies demonstrated that 3 had high electron affinity and good thermal stability, which in combination with favorable optical properties indicated the prospect of 3 as a promising material in optoelectronic devices. Finally, theoretical calculations on structures, frontier molecular orbitals, UV?vis spectra and electronic transitions gave a good acknowledge of the relationship between optoelectronic properties and molecular structures.

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Metal catalyst and ligand design,
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A short synthesis of the phytosphingosine derivatives and their stereoisomers by using asymmetric dihydroxylation of the optically active olefins derived from L-serine is described.

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Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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A palladium-catalyzed benzannulation with o-bromobenzyl alcohols enabled the facile construction of phenanthrene skeletons via the sequential multiple carbon-carbon bond formations. A variety of multisubstituted phenanthrenes were synthesized by the reaction of (Z)-beta-halostyrenes with o-bromobenzyl alcohols as well as by the three-component coupling of alkynes, aryl bromides, and o-bromobenzyl alcohols. The electron-deficient phosphine ligand played an important role to control the sequential oxidative addition of two different organic halides employed, which realized the selective formation of the desired phenanthrenes in good yields. This synthetic protocol was also applicable to the synthesis of the highly fused polycyclic aromatic hydrocarbons such as tetraphenes.

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Reference:
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI