Kornblum-DeLaMare Rearrangement Research Articles

I2 Catalyzed and TBHP/Ammonium-Promoted Conversion of Arylethanone to Nitriles via β-Scission of Iminyl Radicals.

Herein, we report a general I2-catalyzed and TBHP/ammonium-promoted conversion of arylethanone to aromatic nitriles under air. This procedure proceeded with the β-scission of iminyl radical, which was facilitated via quenching the released alkyl radical by tert-butyl peroxyl radical leading to peroxide followed with Kornblum-DeLaMare rearrangement. A series of aryl methyl ketone and alkyl aryl ketone worked well with good functional group tolerance in high yields. As such, this metal-free procedure represents a facile, safe, green, and practical procedure in conversion of arylethanone to aromatic nitriles.

Tunable Reaction Mode of Bifunctional Peroxides with Ketones to Access α-Oxacyclic Ketones and Enals.

A new annulation reaction between allylic/benzylic peroxides and ketones has been developed to provide the α-oxacyclic ketones in moderate yields under the KOtBu basic conditions. Mechanistic studies reveal that these peroxides undergo the Kornblum-DeLaMare rearrangement to release the aldehyde intermediates and subsequently initiate the aldol/etherification tandem process to deliver the final products. Accordingly, these peroxides serving as "masked" enals have also been utilized to prepare the previously hard-to-achieve α-enal-tethered ketones in one step.

From Ring-Expansion to Ring-Contraction: Synthesis of γ-Lactones from Cyclobutanols and Relative Stability of Five- and Six-Membered Endoperoxides toward Organic Bases

AbstractCyclobutanols undergo ring expansion with molecular oxygen in the presence of Co(acac)2 to afford 1,2-dioxane-hemiperoxyketals. In the course of acylation, we observed that endoperoxides rearranged into γ-lactone in the presence of triethylamine. Thus, a generalization of this ring contraction through a Kornblum–DeLaMare rearrangement is here reported. Application of this transformation to monosubstituted 1,2-dioxane derivatives also led to 1,4-ketoaldehydes, in proportions depending on the nature of the substituent. These same conditions applied to five-membered dioxolane analogues led to fragmentation instead, through a retro-aldol type process. This study emphasizes the difference of stability of 1,2-dioxane and 1,2-dioxolane against organic bases, 1,2-dioxolanes having proved to be particularly reactive whereas 1,2-dioxanes showed a relative tolerance under these conditions.

DBU/O2-Mediated Oxidation of Dienones.

Herein, we describe a DBU/O2-promoted novel method for oxidation of dienones to 2,6-dione derivatives. The reaction involves treatment of a dienone with DBU in acetonitrile employing molecular oxygen as the oxidant. Metal free conditions and an eco-friendly reagent are the striking features of this protocol. This transformation proceeds through a peroxide intermediate that upon Kornblum-DeLaMare rearrangement produces 2,6-diones. The method was successfully utilized for the synthesis of (±)-pleodendione with improved yields versus those of the traditional PDC-TBHP method.

Continuous Endoperoxidation of Conjugated Dienes and Subsequent Rearrangements Leading to C-H Oxidized Synthons.

We have investigated the continuous flow photooxidation of several conjugated dienes and subsequent rearrangement using a practical and safe continuous-flow homemade engineered setup. End-to-end approaches involving endoperoxidation, Kornblum-DeLaMare rearrangement, and additional rearrangements are comprehensively detailed with optimization, scope, and scale-up to obtain useful hydroxyenones, furans, and 1,4-dicarbonyl building blocks.

Stereoselective synthesis of hernandulcin, peroxylippidulcine A, lippidulcines A, B and C and taste evaluation.

The first stereoselective synthesis of lippidulcines A, B and C has been accomplished starting from (+)-hernandulcin, which has been prepared on a multigram scale. The previously assigned absolute configurations have been confirmed. The key steps of this synthesis are based on a modified version of the Kornblum–DeLaMare rearrangement, and on a highly regioselective and stereoselective ketone reduction with the MeCBS reagent. The taste evaluations indicate that none of these sesquiterpenes are sweet, instead the lippidulcine A is a cooling agent with a mint after taste.

Radical-polar crossover reactions: oxidative coupling of 1,3-dioxolanes with electron-deficient alkenes and vinylarenes based on a radical addition and Kornblum-DeLaMare rearrangement.

A new radical-polar crossover reaction has been developed involving the combination of a tandem radical reaction and Kornblum-DeLaMare rearrangement in a one-pot process. This simple methodology allows for the construction of polyfunctionalized carbonyl compounds via the oxidative coupling of 1,3-dioxolanes with electron-deficient alkenes and vinylarenes in the presence of Co(salen) and TBHP under mild conditions. This reaction also exhibited high functional group tolerance, wide substrate scope, and operational simplicity.

ChemInform Abstract: Total Synthesis of Sandresolide B and Amphilectolide.

The total synthesis of the diterpenoids sandresolide B and amphilectolide from a common furan building block is presented. Key steps include palladium-mediated carbonylation, lanthanide catalyzed ring closure, Myers alkylation, intramolecular Friedel–Crafts acylation, photooxygenation, and a Kornblum–DeLaMare rearrangement.

Total Synthesis of Sandresolide B and Amphilectolide

The total synthesis of the diterpenoids sandresolide B and amphilectolide from a common furan building block is presented. Key steps include palladium-mediated carbonylation, lanthanide catalyzed ring closure, Myers alkylation, intramolecular Friedel-Crafts acylation, photooxygenation, and a Kornblum-DeLaMare rearrangement.

Stereoselective Total Synthesis of Hainanolidol and Harringtonolide via Oxidopyrylium-Based [5 + 2] Cycloaddition

The tetracyclic carbon skeleton of hainanolidol and harringtonolide was efficiently constructed by an intramolecular oxidopyrylium-based [5 + 2] cycloaddition. An anionic ring-opening strategy was developed for the cleavage of the ether bridge in 8-oxabicyclo[3.2.1]octenes derived from the [5 + 2] cycloaddition. Conversion of cycloheptadiene to tropone was realized by a sequential [4 + 2] cycloaddition, Kornblum-DeLaMare rearrangement, and double elimination. The biomimetic synthesis of harringtonolide from hainanolidol was also confirmed.

Photooxygenation of a Microbial Arene Oxidation Product and Regioselective Kornblum–DeLaMare Rearrangement: Total Synthesis of Zeylenols and Zeylenones

We report the enantioselective total syntheses of zeylenol (+)-1, as well as its congeners (-)-7 and 16, and of 3-O-debenzoylzeylenone 28. To this end, a new variant of the Kornblum-DeLaMare rearrangement, which utilises neighbouring-group participation to impart regioselectivity, has been developed. The approach employs photooxygenation of building blocks derived from a microbial arene oxidation product.

Total Synthesis of Epicoccin G

An expedient enantioselective total synthesis of epicoccin G and related dithiodiketopiperazines through a strategy featuring direct two-directional sulfenylation, photooxygenation, and Kornblum-DeLaMare rearrangement is described.

(±)-trans,cis-4-Hydroxy-5,6-di-O-isopropylidenecyclohex-2-ene-1-one: Synthesis and Facile Dimerization to Decahydrodibenzofurans

An efficient synthesis of (±)-trans,cis-4-hydroxy-5,6-di-O-isopropylidenecyclohex-2-ene-1-one (3) has been developed from acetonide-protected meso-1,2-dihydrocatechol derivative 1 via photooxygenation, then Kornblum-DeLaMare rearrangement. The product is unstable unless its 4-hydroxy group is protected, as it undergoes facile dimerization in solution to a 1:1 mixture of diastereoisomeric decahydrodibenzofurans 8 and 9. A new synthesis of the dihydrocatechol 1 from 1,3-cyclohexadiene has also been developed.

A Novelbis-Lactonisation of Naphtho- and Phenanthro-1,2-Dioxines with Malonate­ Nucleophiles

Malonate nucleophiles add in a conjugate fashion to substituted naphtho- and phenanthro-1,2-dioxines to furnish functionalised bis-lactones in high yield and with high de. The basicity of the malonate nucleophile is sufficiently mild to rearrange the 1,2-dioxines to yield the transient cis-γ-hydroxy enone species with no further Kornblum-DeLaMare rearrangement. The cis-γ-hydroxy enones readily undergo conjugate addition by malonate nucleophiles in a highly diastereoselective fashion. An intramolecular domino cyclisation then ensues yielding the observed bis-lactones. The relative configuration of the bis-lactone series was established by 1- and 2-D 1H, 13C NMR techniques and further confirmed by single crystal X-ray analysis.

The mechanism of the tertiary amine catalysed isomerisation of endoperoxides to hydroxyketones: synthesis and chemistry of the intermediate postulated in the peroxide attack mechanism

Evidence is presented which demonstrates that the Kornblum–DeLaMare rearrangement does not proceed via nucleophilic attack of the peroxide linkage.