Mechanism and the Origins of Stereospecificity in Copper-Catalyzed Ring Expansion of Vinyl Oxiranes: A Traceless Dual Transition-Metal-Mediated Process

Abstract

Density functional theory computations of the Cu-catalyzed ring expansion of vinyloxiranes is mediated by a traceless dual Cu(I)-catalyst mechanism. Overall, the reaction involves a monomeric Cu(I)-catalyst, but a single key step, the Cu migration, requires two Cu(I)-catalysts for the transformation. This dual-Cu step is found to be a true double Cu(I) transition state rather than a single Cu(I) transition state in the presence of an adventitious, spectator Cu(I). Both Cu(I) catalysts are involved in the bond forming and breaking process. The single Cu(I) transition state is not a stationary point on the potential energy surface. Interestingly, the reductive elimination is rate-determining for the major diastereomeric product, while the Cu(I) migration step is rate-determining for the minor. Thus, while the reaction requires dual Cu(I) activation to proceed, kinetically, the presence of the dual-Cu(I) step is untraceable. The diastereospecificity of this reaction is controlled by the Cu migration step. Suprafacial migration is favored over antarafacial migration due to the distorted Cu π-allyl in the latter.

The Spermine Phosphate-Bound Cyclooctaoxygen Sodium Epigenetic Shell of Euchromatin DNA is Destroyed by the Epigenetic Poison Glyphosate

“…The chiral (S)-2-vinyloxirane structure rearranges to a chiral (R)-2-alkyl-2,5-dihydrofuran due to 3,4-epoxyolefin rearrangement [111,112] We therefore conclude that the sperminium phosphate/cyclooctaoxygen sodium complex serves to protect ssDNA from nucleic acid-mediated intrinsic low intranuclear micro-pH-induced depurination, including KGBF, creating apurinic sites and concomitant DNA single-strand breaks at eukaryotic genome regions engaged in active transcription. The precisely calculated intranuclear micro-pH gain, obtained by sperminium phosphate/cyclooctaoxygen sodium complexation of B-DNA individual strands, is essentially the same as the intranuclear micro-pH gain for condensed B-DNA strand-overarchingly covered by sperminium tetracations.…”

“…A mechanism for the kinetin formation in, or from, DNA was proposed [107,108], but it seems not to be conclusive in chemical reason, since furfural does not react with the adenine 6-NH2 group under condensation to a Schiff base [106]. We therefore propose a chemical mechanistic deduced logical scheme [109][110][111][112] for the generation of kinetin from DNA by proton catalysis (kinetin-generating "base flip", KGBF) (Figure 14), based on proton-catalysed depurination and subsequent inverted adenine 6-NH2 N-glycosylation [109,110], in consequence leaving back a DNA single-strand break. It is proposed that the cyclooctaoxygen sodium-bridged spermine phosphate epigenetic shell protects ssDNA from low pH-induced depurination, including, in part, generation of kinetin by KGBF.…”

“…Protonation of the adenine nucleobase of the shown d(pApApAp) sequence at purine N-7 induces depurination [103,104], creating an apurinic site [103][104][105]. Proton-catalysed N-glycosylation [110,111] at the 6-NH2 of adenine regenerates a nucleobase-inverted 2'-deoxynucleotide which is in furanose ring-opening equilibrium with its ald(os)imine form. Two eliminations simultaneously follow, the first (autocatalysed by 3'-O-phosphate conjugate base proton reception) by SN2-nucleophilic eliminative epoxide formation, the second by proton-catalysed (auto-catalysed by the previously liberated 3'-Omonohydrogen phosphate conjugate acid) β-elimination (E1 unimolecular elimination), which leads to an 3,4-…”

The Spermine Phosphate-Bound Cyclooctaoxygen Sodium Epigenetic Shell of Euchromatin DNA Is Destroyed by the Epigenetic Poison Glyphosate

“…[58] and Kuhn & Kuhn [59] [pK′a,HG = apparent acid dissociation constant (25 °C) of haploid H. sapiens genome B-DNA double helix; pKa,R-OH = 1.29 = theoretical pKa (25 °C) [86] of one isolated internucleotide phosphodiester (R-OH) proton; s = 1 = number of statistical subunits on thread molecule [59]; j = 6 = number of spacing atoms (at least distance) in one dsDNA repeating unit [59]; b = 0.334 × 10 -7 cm (0.334 ± 0.01 nm [87]) = length rise in cm of one B- [103,104], creating an apurinic site [103][104][105]. Proton-catalysed N-glycosylation [110,111] at the 6-NH2 of adenine regenerates a nucleobase-inverted 2'-deoxynucleotide which is in furanose ring-opening equilibrium with its ald(os)imine form. Two eliminations simultaneously follow, the first (auto-catalysed by 3'-Ophosphate conjugate base proton reception) by SN2-nucleophilic eliminative epoxide formation, the second by proton-catalysed (auto-catalysed by the previously liberated 3'-O-monohydrogen phosphate conjugate acid) -elimination (E1 unimolecular elimination), which leads to an 3,4-epoxyolefin: N-{(1E,2E)-3-[(2S)-oxiran-2-yl]prop-2-en-1-ylidene}-9H-purin-6-amine.…”

“…Two eliminations simultaneously follow, the first (auto-catalysed by 3'-Ophosphate conjugate base proton reception) by SN2-nucleophilic eliminative epoxide formation, the second by proton-catalysed (auto-catalysed by the previously liberated 3'-O-monohydrogen phosphate conjugate acid) -elimination (E1 unimolecular elimination), which leads to an 3,4-epoxyolefin: N-{(1E,2E)-3-[(2S)-oxiran-2-yl]prop-2-en-1-ylidene}-9H-purin-6-amine. The chiral (S)-2-vinyloxirane structure rearranges to a chiral (R)-2-alkyl-2,5-dihydrofuran due to 3,4-epoxyolefin rearrangement [111,112]: N-[(2R)-2,5-dihydrofuran-2-ylmethyl]-9H-purin-6-amine. The latter compound rearranges to kinetin through facile double bond migration driven by aromatization to a furan.…”