Stereospecific Elimination Research Articles

Synthesis of Dehydroamino Acids through Stereospecific Elimination

Key words dehydroamino acids - asymmetric synthesis - cyclic sulfamidites - phomopsin - hydroxyamino acids - elimination

Stereoselective Iterative Convergent Synthesis of Z-Oligodiacetylenes from Propargylic Dithioacetals.

A series of (t)Bu-substituted Z-oligodiacetylenes (Z-ODAs) are synthesized from the reactions of allenyl/propargylic zinc reagents, obtained from the corresponding propargylic dithiolanes and BuLi, with dithiolane-substituted propargylic aldehydes followed by stereospecific elimination of β-thioalkoxy alcohols under Mitsunobu conditions. The stereochemical assignments are based on NOE experiments. The X-ray structure of the hexamer further supports the Z configuration for each of the double bonds in these ODAs. The photophysical properties of these Z-ODAs have been examined and are compared with known related E- and Z-ODAs with different substituents.

Practical Synthesis of (±)-Nyasol

A practical total synthesis of racemic nyasol (7) was explored. The α-hydroxyketo compound 3 was prepared from commercially available starting materials in two steps. Chelation-controlled reduction of the α-hydroxyketo compound 3 with Zn(BH4)2 gave the anti-1,2-diol compound 4 as the major product (anti/syn = 11.5:1). Stereospecific elimination reaction of a 1,3-cyclic thionocarbonate intermediate (5) exclusively yielded the Z-alkene compound 6. Our total synthesis is very concise (seven steps), uses commercially available starting materials, and offers good overall yield (40%).

A Practical Chemo-enzymatic Approach to Highly Enantio-Enriched 10-Ethyl-7,8-dihydro-γ-ionone Isomers: A Method for the Synthesis of 4,5-Didehydro-α-Ionone

An efficient and convenient strategy for the enantioselective synthesis of enantiomerically enriched 10-ethyl-7,8-dihydro-γ-ionone isomers (R)-(+)-7, and (S)-(−)-7 are described utilizing a lipase mediated resolution protocol, and reductive elimination of the secondary allylic alcohol as the key step. The enantioselective and diastereoselective lipase kinetic acetylation of 4-hydroxy-γ-ionone derivatives 6a afforded the 4-acetyl-γ-ionone derivatives (−)-8, and the 4-hydrox-γ-ionone derivatives (+)-6a, which are suitable precursors of the desired products. Stereospecific palladium-mediated elimination of allylic acetate provides the target compounds with an excellent enantiomeric excess and yield. Additionally, the novel 4,5-didehydro-α-ionone 13 is obtained from readily prepared (2,6,6-trimethylcyclohexa-2,4-dien-1-yl) methanol 9. The structures of all newly synthesized compounds have been elucidated by 1H, 13C NMR, GC-MS, and IR spectrometry. These compounds represent a new class of odorants that may be of pivotal relevance in industrial perfumery.

ChemInform Abstract: 2‐Alkylidene Oxetanes by Stereospecific Elimination of Mesylates.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

2-Alkylidene oxetanes by stereospecific elimination of mesylates

α-Mesyloxyoxetanes undergo stereospecific elimination to 2-alkylidene oxetanes upon treatment with potassium t-butoxide.

The Crystal Structure of Human Geranylgeranyl Pyrophosphate Synthase Reveals a Novel Hexameric Arrangement and Inhibitory Product Binding

Modification of GTPases with isoprenoid molecules derived from geranylgeranyl pyrophosphate or farnesyl pyrophosphate is an essential requisite for cellular signaling pathways. The synthesis of these isoprenoids proceeds in mammals through the mevalonate pathway, and the final steps in the synthesis are catalyzed by the related enzymes farnesyl pyrophosphate synthase and geranylgeranyl pyrophosphate synthase. Both enzymes play crucial roles in cell survival, and inhibition of farnesyl pyrophosphate synthase by nitrogen-containing bisphosphonates is an established concept in the treatment of bone disorders such as osteoporosis or certain forms of cancer in bone. Here we report the crystal structure of human geranylgeranyl pyrophosphate synthase, the first mammalian ortholog to have its x-ray structure determined. It reveals that three dimers join together to form a propeller-bladed hexameric molecule with a mass of approximately 200 kDa. Structure-based sequence alignments predict this quaternary structure to be restricted to mammalian and insect orthologs, whereas fungal, bacterial, archaeal, and plant forms exhibit the dimeric organization also observed in farnesyl pyrophosphate synthase. Geranylgeranyl pyrophosphate derived from heterologous bacterial expression is tightly bound in a cavity distinct from the chain elongation site described for farnesyl pyrophosphate synthase. The structure most likely represents an inhibitory complex, which is further corroborated by steady-state kinetics, suggesting a possible feedback mechanism for regulating enzyme activity. Structural comparisons between members of this enzyme class give deeper insights into conserved features important for catalysis.

Stereoselective Synthesis of Highly Enantioenriched (E)‐Allylsilanes by Palladium‐Catalyzed Intramolecular Bis‐Silylation: 1,3‐Chirality Transfer and Enantioenrichment via Dimer Formation.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Stereoretentive Elimination and Trans-olefination of the Dicationic Dipalladium Moiety [Pd2Ln]2+ Bound on 1,3,5-Trienes

The reaction of [Pd(2)(CH(3)CN)(6)][BF(4)](2) (1) with 1,3,5-hexatriene, 1,6-diphenyl-1,3,5-hexatriene (DPHT), or 2,2,9,9-tetramethyl-3,5,7-decatriene (DBHT) afforded bi-eta(3)-allyldipalladium complexes 3, 4, or 5. The reaction of 1 and DBHT proceeded in a stereospecific (syn) manner when the reaction was carried out in CD(2)Cl(2) under aerobic conditions, while a mixture of two diastereomers was formed under N(2) atmosphere. The two diastereomers (5-E,Z,E-antifacial and 5-E,E,E-antifacial) formed from DBHT were isolated, and the structure of 5-E,Z,E-antifacial, which was kinetically formed from the reaction of 1 and (E,E,E)-DBHT, was determined by X-ray diffraction analysis. Addition of phosphine ligands (PPh(3) or dppm) to the dinuclear adduct 5-E,Z,E-antifacial or 5-E,E,E-antifacial in acetonitrile resulted in the stereospecific (syn) elimination of [Pd(2)(PPh(3))(2)(CH(3)CN)(4)][BF(4)](2) (2) or [Pd(2)(dppm)(2)(CH(3)CN)(2)][BF(4)](2) (6). During the PPh(3)-induced dinuclear elimination, the phosphine adducts 7 that retain bi-eta(3)-allyldipalladium structure were observed initially. The phosphine adduct generated from 5-E,E,E-antifacial was isolated and structurally characterized by X-ray diffraction analysis. The reaction of 1 and DPHT in CH(2)Cl(2) afforded unique dipalladium sandwich compounds [Pd(2)(mu-eta(3):eta(3)-DPHT)(2)][BF(4)](2) (8). Interconversion between the sandwich complexes and half-sandwich complexes occurred in a stereoretentive manner. The structure of the sandwich complex 8-E,Z,E formed from 4-E,E,E-antifacial and (E,Z,E)-DPHT was determined by X-ray diffraction analysis. Transfer of the dipalladium moiety [Pd(2)(CH(3)CN)(4)](2+) from DPHT ligand of 4-E,E,E-antifacial onto DBHT ligand proceeded in a stereoretentive manner. The observed stereoretentive dinuclear process is featured by the pairwise behavior of two palladium atoms sitting on the triene pi-plane. In the dinuclear elimination, the two Pd atoms that are initially in the divalent state and bound on the opposite faces (antifacial) come to the synfacial positions to form a Pd-Pd bond prior to dissociation. These results represent the unique property of conjugated olefin as the multidentate ligands for metal-metal moieties.

Asymmetric Synthesis of Axially Chiral cis-Arylmethylenebicyclo[3.3.0]octanes Using α-Thio- and α-Selenoorganolithium Compounds

Abstract Enantioselective reaction of α-thio carbanion derived from 1-phenyl-1-(phenylthio)-1-(tributylstannyl)methane with cis-bicyclo[3.3.0]octane-3,7-dione monoethylene ketals in the presence of bis(oxazoline)s gave products with high diastereoselectivity and with high enantioselectivity. The reaction of α-seleno carbanions derived from bis(phenylseleno)arylmethanes also showed high diastereoselectivity and enantioselectivity. Deprotection and subsequent stereospecific elimination afforded axially chiral cis-arylmethylenebicyclo[3.3.0]octanes with high enantioselectivity (up to 99% ee).

A Novel Method for the Preparation of Benzylidenecyclohexanes with High Optical Purity.

AbstractFor Abstract see ChemInform Abstract in Full Text.

A novel method for the preparation of benzylidenecyclohexanes with high optical purity

The enantioselective reaction of the α-thio carbanion derived from 1-phenyl-1-(phenylthio)-1-(tributylstannyl)methane with 4-substituted cyclohexanones in the presence of bis(oxazoline)s gave the products as a diastereomeric mixture. Each diastereomer obtained had high optical purity. The reaction of the α-seleno carbanion derived from the bis(phenylseleno)acetal also showed high enantioselectivity. The stereospecific elimination of the isolated diastereomers on treatment with methanesulfonyl chloride and triethylamine afforded axially chiral benzylidenecyclohexanes with high enantioselectivities up to 99% ee.

Synthesis of 2,5-disubstituted tetrahydrofurans by stereospecific elimination-cyclization of 1-iodomethyl-1,5-bis-epoxides.

[reaction: see text] Treatment of 1-iodomethyl-1,5-bis-epoxides with zinc in refluxing ethanol affords cis or trans 2-vinyl-5-(1-hydroxyethy)-substituted tetrahydrofurans stereospecifically in high yield.

A New Horner−Wadsworth−Emmons Type Coupling Reaction between Nonstabilized β-Hydroxy Phosphonates and Aldehydes or Ketones

Treatment of nonstabilized beta-hydroxy phosphonic acid mono methyl esters with diisopropyl carbodiimide at ambient temperature leads to clean stereospecific elimination. The phosphonic acid mono alkyl esters are accessible by the selective partial saponification of dimethyl or diethyl alkyl phosphonates with NaOH or MgBr(2). Isolated yields over both hydrolysis and elimination steps average 55-75%.

Convergent Stereocontrol in Peterson Olefinations. Application to the Synthesis of (±)-3-Hydroxybakuchiol and Corylifolin

The iron-catalyzed Kirmse reaction was used to generate neopentyl alpha-silyl thioethers that were elaborated to meroterpenes using two complementary routes: one route involved a sila-Pummerer rearrangement, and the other route involved a Peterson olefination. While severe eclipsing interactions undermined the efficiency of the stereospecific sila-Pummerer rearrangement, they made it possible to stereoselectively generate E olefins without isolation or separation of syn- and anti-beta-silyl alkoxides. Addition of a neopentyl alpha-silyl alkyllithium intermediate to an aryl aldehyde generated a mixture of syn- and anti-beta-silyl alkoxides. The syn-beta-silyl alkoxide eliminated stereospecifically at -78 degrees C to give an E olefin, whereas the anti-beta-silyl alkoxide was unreactive. The reaction mixture was then acidified and heated to induce stereospecific elimination of the anti isomer to give the same E olefin via a complementary cationic pathway. This route was used to complete the first synthesis of the meroterpene (+/-)-3-hydroxybakuchiol. In addition, we synthesized another meroterpene corresponding to the natural product corylifolin and offer evidence that the structure of corylifolin was misassigned.

Stereospecific or Stereoselective Elimination of vicinal-Alkoxyiodoalkanes by Means of Organometallic Reagents

Stereospecific or Stereoselective Elimination of <i>vicinal</i>-Alkoxyiodoalkanes by Means of Organometallic Reagents

Stereospecific elimination of dihydropyran from protonated tetrahydropyranyl (THP) difunctional derivatives upon chemical ionization and collision-induced dissociation: intramolecular interactions in polyfunctional ions

Tetrahydropyranyl (THP) ethers of cis-1-methoxymethyl-, 1-benzyloxymethyl-, and 1-hydroxymethyl-4-cyclohexane methanols and of cis-1,4-dihydroxycyclohexane, and THP ester of cis-1,3-cyclohexane dicarboxylic acid (cis-3–cis-7, respectively) exhibit low abundance MH+ ions and undergo efficient elimination of dihydropyran (DHP) upon isobutane chemical ionization (CI). In contrast to this behavior, the trans isomers give rise to highly abundant MH+ ions, whereas the elimination of dihydropyran affords low abundance [MH−DHP]+ ions. A similar stereospecific behavior has been also observed under collision-induced dissociation (CID) conditions. Tetrahydropyranylium ion (m/z 85), obtained by a simple C-O bond dissociation, is abundant in the CI and CID mass spectra of both stereoisomers in all the examined systems. The high stereoselectivity suggests intermediacy of internal proton bridging of the two adjacent basic sites in the formation of the [MH−DHP]+ ions from the MH+ ions of the cis isomers. Thermochemical analysis indicates stabilized proton bridged structures for the [MH−DHP]+ ions. A mechanistic pathway has been proposed for the DHP elimination, based on the stereospecificity of this process and on its thermochemistry.

Stereospecific Toxicokinetics of Bromochloro- and Chlorofluoroacetate: Effect of GST-ζ Depletion

The chloro- and bromohaloacetates are drinking water disinfection by-products and rodent carcinogens. Chloro—bromo dihaloacetates are also mechanism-based inhibitors of glutathione S-transferase-ζ (GSTZ1–1). We studied the stereospecific toxicokinetics and in vitro metabolism of two chiral dihaloacetates in male F344 rats: (−),(+)-bromochloroacetate (BCA) and racemic chlorofluoroacetate (CFA), a non-GST-ζ-inhibiting dihaloacetate. These experiments were repeated in animals that had previously been treated with dichloroacetate (DCA) to deplete GST-ζ activity. Results indicated that the elimination half-life of (−)-BCA was 0.07 compared to 0.40 h for (+)-BCA in naive rats. A comparable difference in elimination half-life was also observed for the CFA stereoisomers (0.79 vs 0.11 h). In GST-ζ-depleted rats, stereospecific elimination of (−),(+)-BCA was absent, with both stereoisomers having an elimination half-life of approximately 0.4 h. This finding was in contrast to results for CFA, which still maintained the same relative difference in elimination rate between its stereoisomers, although overall elimination was diminished in GST-ζ-depleted rats. Results of in vitro metabolism experiments indicated (−)-BCA was affected by modulating GST-ζ activity, with the intrinsic metabolic clearance decreasing from 2.81 to 0.15 ml h−1 mg·protein−1 (naive, GST-ζ depleted) compared with values for (+)-BCA (0.30 and 0.31 ml h−1 mg·protein−1). Incubations with 350 μM diethyldithiocarbamate preferentially decreased (+)-BCA metabolism in naive and GST-ζ-depleted cytosol. These results indicate (+)-BCA is a poor substrate for GST-ζ and its metabolism is controlled by an additional GST isoenzyme.

Stereospecific multi-step elimination of methanol involving 1,4-methoxyl migration from the MH+ ion of 2,3-cis-3-methoxytricyclo[6.2.2.02,7]dodeca-9-ene

The eilmination of methanol from the MD + ion of 2,3-cis-3-methoxytricyclo[6.2.2.0 2,7 ]dodeca-9-ene, endo-2, upon chemical ionization (CI) gives rise to both [MD - MeOD] + and [MD - MeOH] + ions. Only the [MD - MeOH] + ion is formed under collision-induced dissociation (CID) conditions. This is in contrast with the behavior of the 2,3-trans-stereoisomer exo-2 and with saturated analogs which undergo exclusive elimination of MeOD. The unusual elimination of MeOH from endo-2 indicates transfer of the external deuteron in the MD + ion from the oxygen atom to the interior of the organic moiety and a back transfer of a hydrogen from the organic moiety to the oxygen atom prior to the C-O bond dissociation step. A deuterium labeling study showed that the hydrogen atom involved in this elimination process originates at position 3 (formal 1,1-elimination). These results suggest a multi-step mechanism for this unique stereospecific methanol elimination, initiated by a proton transfer from the methoxy group to the double bond followed by a 1,4-methoxyl migration from C-3 to C-10. The proposed mechanism finds support in the Cl and CID study of deuterium-labeled analogs which have a methoxy group at position 10.

Stereospecific multi-step elimination of methanol involving 1,4-methoxyl migration from the MH+ ion of 2,3-cis-3-methoxytricyclo[6.2.2.02,7]dodeca-9-ene Dedicated to the memory of Willi Richter

Stereospecific multi-step elimination of methanol involving 1,4-methoxyl migration from the MH+ ion of 2,3-cis-3-methoxytricyclo[6.2.2.02,7]dodeca-9-ene Dedicated to the memory of Willi Richter