Reductive Rearrangement Research Articles

Stereocontrolled synthesis of all-syn 3,4-disubstituted l-prolines: studies of the reductive rearrangement of unactivated tertiary allylic alcohols

We describe a stereocontrolled method that converts tertiary allylic alcohols in pyrrolidine-2-carboxylic acid derivatives prepared from 3-(S)-hydroxy-l-proline to all-syn 3,4-disubstituted l-prolines. A study of various parameters to optimize the reductive rearrangement of tertiary allylic alcohols to tetrasubstituted olefins was conducted.

Reductive iodonio-Claisen rearrangement of iodothiophene diacetates with allylsilanes: formal synthesis of Plavix®

Iodothiophene diacetates react with allyltrimethylsilanes in the presence of boron trifluoride diethyl etherate to afford corresponding ortho-allyliodothiophenes via reductive iodonio-Claisen rearrangement. This method has been successfully applied to the synthesis of Plavix®, a blood clot inhibitor used to reduce the risk of heart attack and stroke.

Synthesis of β-fluoroenones and their reductive rearrangement in aqueous media

In this paper, a simple and efficient preparation of β-fluoroenones, as a mixture of E/Z isomers with the E-isomer as the main product, from 1,2-allenic ketones by using TBAF·3H2O in water as a nucleophilic fluorination agent has been developed. Moreover, in exploring the synthetic applications of β-fluoroenones, an unprecedented reductive defluorination rearrangement of β-fluoroenones toward enones under mild conditions in aqueous media was also discovered.

Transannular Reductive Rearrangement of α-Amino Ketones: Construction of Aza-tricyclic Frameworks of Several Alkaloids

Transannular reductive rearrangement of bridged cyclic α-amino ketones led to the aza-tricyclic frameworks azepinoindole, hydrolulolidine, and hydrojulolidine of the typical alkaloids of Stemona, Aspidosperma, and Lycopodium, respectively. This facile approach demonstrates the potential applicability of the Clemmensen-Clemo-Prelog-Leonard reductive rearrangement of tricyclic α-amino ketones for the aza-heterocycle synthesis.

Synthesis of Complex ortho‐Allyliodoarenes by Employing the Reductive Iodonio‐Claisen Rearrangement

I(o)dide behind the wheel: Aromatic hypervalent iodine(III) compounds reacted with allyltrimethylsilane in the presence of a Lewis acid to give ortho-allyliodoarenes through a reductive iodonio-Claisen rearrangement (see scheme). An meta-electron-donating group in the λ3-iodanes was indispensable to favor the [3,3]-sigmatropic rearrangement over reductive elimination. The method was successfully used for the concise synthesis of an antifungal natural product, broussin.

Identification of unique mechanisms for triterpene biosynthesis in Botryococcus braunii

Botryococcene biosynthesis is thought to resemble that of squalene, a metabolite essential for sterol metabolism in all eukaryotes. Squalene arises from an initial condensation of two molecules of farnesyl diphosphate (FPP) to form presqualene diphosphate (PSPP), which then undergoes a reductive rearrangement to form squalene. In principle, botryococcene could arise from an alternative rearrangement of the presqualene intermediate. Because of these proposed similarities, we predicted that a botryococcene synthase would resemble squalene synthase and hence isolated squalene synthase-like genes from Botryococcus braunii race B. While B. braunii does harbor at least one typical squalene synthase, none of the other three squalene synthase-like (SSL) genes encodes for botryococcene biosynthesis directly. SSL-1 catalyzes the biosynthesis of PSPP and SSL-2 the biosynthesis of bisfarnesyl ether, while SSL-3 does not appear able to directly utilize FPP as a substrate. However, when combinations of the synthase-like enzymes were mixed together, in vivo and in vitro, robust botryococcene (SSL-1+SSL-3) or squalene biosynthesis (SSL1+SSL-2) was observed. These findings were unexpected because squalene synthase, an ancient and likely progenitor to the other Botryococcus triterpene synthases, catalyzes a two-step reaction within a single enzyme unit without intermediate release, yet in B. braunii, these activities appear to have separated and evolved interdependently for specialized triterpene oil production greater than 500MYA. Coexpression of the SSL-1 and SSL-3 genes in different configurations, as independent genes, as gene fusions, or targeted to intracellular membranes, also demonstrate the potential for engineering even greater efficiencies of botryococcene biosynthesis.

ChemInform Abstract: Synthesis of Amino‐1,2,4‐triazoles by Reductive ANRORC Rearrangements of 1,2,4‐Oxadiazoles.

AbstractThe hydrazinolysis of the oxadiazoles under optimized conditions allows a general synthesis of functionalized aminotriazole products which are of interest due to the biological activity of the heterocyclic system.

Synthesis of Amino-1,2,4-triazoles by Reductive ANRORC Rearrangements of 1,2,4-Oxadiazoles

The reaction of various 1,2,4-oxadiazoles with an excess of hydrazine in DMF has been investigated. 3-Amino-1,2,4-triazoles are produced through a reductive ANRORC pathway consisting of the addition of hydrazine to the 1,2,4-oxadiazole followed by ring-opening, ring-closure, and final reduction of the 3-hydroxylamino-1,2,4-triazole intermediate. The general applicability of 1,2,4-oxadiazoles ANRORC reactivity is demonstrated also in the absence of C(5)-linked electron-withdrawing groups.

ChemInform Abstract: Generation of Allenyliodinanes and Their Reductive Iodonio-Claisen Rearrangement.

Reported for the first time are the generation of allenyliodinanes and their reductive iodonio-Claisen rearrangement. Reaction of propargylsilanes, germanes, and stannanes with aryliodinanes in the presence of BF 3 -Et 2 O undergoes a reductive iodonio-Claisen rearrangement under mild conditions, yielding o-propargyliodoarenes in good yields. The reductive ortho propargylation probably involves the intermediate formation of allenyl(aryl) iodinanes, which undergo [3,3]-sigmatropic rearrangement. The lack of crossover products argues for the intramolecularity of the rearrangement. When both ortho positions of aryliodinanes are occupied with alkyl substituents, the reductive iodonio-Claisen rearrangement affords meta substitution products. This is the first to show that meta-Claisen rearrangement occurs preferentially even when a free para position is available. The reductive ortho propargylation of iodinanes takes place under much milder conditions than the Claisen rearrangement. The lower activation energy associated with the iodonio-Claisen rearrangement of allenyl(aryl) iodinanes can be interpreted in terms of the small bond energy of the breaking apical carbon-iodine (III) bond

ChemInform Abstract: Reductive Rearrangement of Alkyl-1-alkenylacetals Promoted by AlR3: Are Stereoelectronic Effects an Interpretative Key to the Reaction Mechanism?

ChemInform Abstract: Reductive Rearrangement of Alkyl-1-alkenylacetals Promoted by AlR3: Are Stereoelectronic Effects an Interpretative Key to the Reaction Mechanism?

Total syntheses of (+/-)-platencin and (-)-platencin.

The secondary metabolites platensimycin and platencin, isolated from the bacterial strain Streptomyces platensis, represent a novel class of natural products exhibiting unique and potent antibacterial activity. Platencin, though structurally similar to platensimycin, has been found to operate through a slightly different mechanism of action involving the dual inhibition of lipid elongation enzymes FabF and FabH. Both natural products exhibit strong, broad-spectrum, gram-positive antibacterial activity to key antibiotic resistant strains, including methicillin-resistant Staphylococcus aureus, vancomycin-intermediate S. aureus, and vancomycin-resistant Enterococcus faecium. Described herein are our synthetic efforts toward platencin, culminating in both racemic and asymmetric preparation of the natural product. The syntheses demonstrate the power of the cobalt-catalyzed asymmetric Diels-Alder reaction and the one-pot reductive rearrangement of [3.2.1] bicyclic ketones to [2.2.2] bicyclic olefins.

超原子価ハロガンとその有機合成化学反応

This review provides an overview of the chemistry of hypervalent organohalogans, organoiodanes and organobromanes, developed recently in Tokushima. Vinylic S(N)2 reactions, cyclopentene syntheses via 1,5 C-H insertion of alkylidene carbenes, reductive Claisen rearrangements, oxidations with peroxy-lambda(3)-iodanes, iodobenzene-catalyzed oxidations, oxidative cleavage of double bonds, oxidative coupling of alcohols with alkynes, Michael additions, and transylidations are involved. These reactions mostly rely on the hyperleaving group ability of aryl-lambda(3)-iodanyl, -bromanyl, and -chloranyl groups.

Theoretical Study of the AlEt3-Promoted Tandem Reductive Rearrangement of Epoxides

The AlEt3-promoted tandem reductive rearrangement reactions of epoxides was studied at B3LYP/6-31G(d,p) level. For the model compound -hydroxy epoxides, two possible reaction pathways I and II were calculated. The main difference is the order of ethylene release and six- to five-member ring rearrangement. The ring contraction rearrangement in pathway I is the first step and this step is the rate controlling step with a free energy barrier of 116.62 kJ/mol. For pathway II, the ethylene release occurs first, and is followed by a six-member ring opening reaction which is the rate controlling step, and the barrier is 251.38 kJ/mol. The reason for such high barrier is that the ethylene release results in the following reaction being more difficult. The results show that pathway I (CC rearrangement and then ethylene release) is more favorable, which is consistent with experimental results.

De Novo Asymmetric Synthesis and Biological Evaluation of the Trisaccharide Portion of PI-080 and Vineomycin B2

A highly enantio- and diastereoselective synthesis of an alpha-L-aculose, alpha-L-rhodinose, and beta-D-olivose trisaccharide is described. The key transformations include the palladium-catalyzed glycosylation, Myers' reductive rearrangement, diastereoselective dihydroxylation, and regioselective Mitsunobu inversion. Significant apoptotic antitumor activity was found for this trisaccharide, which has implication for vineomycin B2 and PI-080 structure-activity relationship.

De Novo Synthesis of the Trisaccharide Subunit of Landomycins A and E

A highly enantio- and diastereoselective synthesis of alpha- -rhodinose, beta-d-olivose as well as the trisaccharide portion of landomycin A from achiral acetyl furan has been developed. The key transformations include the palladium-catalyzed glycosylation, Myers' reductive rearrangement, diastereoselective dihydroxylation, and regioselective Mitsunobu inversion. A Mitsunobu reaction on a six member ring cis-1,2-diol was found to chemoselectively discriminate between equatorial and axial alcohols and to stereoselectively convert cis-1,2-diol into anti-1,2-diol.

ChemInform Abstract: A Novel Hydride‐Mediated Reductive Rearrangement of Amide: A Facile Synthesis of Pyrimidyl and Triazinyl Amines.

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.

Exocyclic vinyl ethers of ketofuranosides

Exocyclic vinyl ether derivatives of sugars are found in biosynthetic pathways and may serve as useful synthetic intermediates. The ketose subfamily of sugars is the least characterized in this field. Thus, the synthesis of exocyclic vinyl ether derivatives of ketohexoses via β-elimination was studied with respect to the nature of the 6- O leaving group and the protection of the 4-hydroxy group. We applied this study to protected l-sorbofuranoside and d-tagatofuranoside sugar derivatives in which the 4-hydroxy group and the 6- O-leaving group are in the syn configuration. Some reactions involving deprotection and reductive rearrangement of the tagatose-derived vinyl ether product were also studied.

An unexpected aminocyclopropane reductive rearrangement

A reductive rearrangement of aminocyclopropanes is described for the synthesis of cis- or trans-fused bicyclic 1,2-diaminocyclobutanes. Ionization of a cyclic aminal using BF 3·OEt 2 induces rearrangement to a cyclobutyl iminium ion, which is subsequently reduced by Et 3SiH. Substitution with allyltrimethylsilane allows carbon incorporation, giving a quaternary center. Silyloxy-substituted cyclopropanes rearrange rapidly to cyclobutanones which react with NaBH 4 to provide 1,2-aminohydroxycyclobutanes. These aminals were generated by the reduction of a Boc-imide with DIBAL-H or LiBH 4.

A novel hydride-mediated reductive rearrangement of amide: a facile synthesis of pyrimidyl and triazinyl amines

LiAlH 4 and NaBH 4 were found to mediate the conversion of 2-(pyrimidyl-2-ylsulfanyl)- N-arylbenzamides and 2-(triazinyl-2-ylsulfanyl)- N-arylbenzamides into pyrimidyl and triazinyl amines under notably mild conditions via a novel reductive rearrangement mechanism. These reactions invent a new route to prepare amines, which are a kind of important biologically active compounds and provide the first insight into a novel hydride-promoted reductive rearrangement of amides.

A Mixed‐valent Heterometallic [Mn4Co4] Complex from Reductive Rearrangement of a [Mn4] Single‐Molecule Magnet

AbstractThe synthesis, crystal structure and magnetic properties of the mixed‐metal aggregate [Mn4Co4(hmp)6(pic)9(H2O)2(OH)](ClO4)3·xH2O·yCH3CN (3·xH2O·yCH3CN) are reported. This complex was prepared by the reaction of a [Mn4] single‐molecule magnet and a cobalt monomeric complex, [Co(pic)2(H2O)2]·2H2O (1). Complex 3 crystallizes in the triclinic ${\rm P}{\bar 1}$ space group and consists of a cationic [MnII4CoIII3CoII] octaheteronuclear complex that possesses a symmetric equilateral triangle‐based pyramid core with a cobalt main base and a manganese minor base.