Unsymmetrical three-carbon condensations with dimedone

Condensing together equimolecular amounts of dimedone, an aldehyde, and ß-aminocrotonic ester gives derivatives of 3-ethoxycarbonyl-2, 7, 7-trimethyl-5-keto-1, 4, 5, 6, 7, 8-hexahydroquinoline (IVa-c); of these, compounds IVb and IVc can be oxidized by chromic anhydride to 3-ethoxycarbonyl-2, 7, trimethyl-5-keto-5, 6, 7, 8-tetrahydroquinolines (Vb, c). The UV and IR spectra of compounds IVc and Vc are determined. Oxidation splits IVa to bisdimedonylmethane (VI).     

Iterative three-carbon annelations. Synthesis of (±)-hirsutene

A short, flexible approach to the tricyclopentanoid carbon skeleton of the hirsutane group is illustrated by the synthesis of (±)-hirsutene (3).     

A direct three-carbon annelation to cyclopentenone derivatives

Cyclopentenone derivatives were prepared by three-carbon alkylation followed by cyclisation of the ester.     

β-Carbonyl radicals as three-carbon building blocks for carbon-carbon bond forming reactions

From aldehydes, ketones and esters β-carbonyl radicals $\text{47}$ can be generated via enolization, cyclopropanation, solvomercuration and reduction with NaBH₄. Radicals $\text{47}$ react with electron-poor alkenes $\text{27}$ to give products of CC-bond forming reactions (Tables 1–3). Carbonyl compounds are therefore precursors of three-carbon building blocks. The products result from reactions with “Umpolung”.     

Allenes as three-carbon units in catalytic cycloadditions: new opportunities with transition-metal catalysts

Allenes are very versatile synthetic units that are used in many types of catalytic cycloaddition reactions. Most examples reported so far involve their use as 2C-atom components, whereas their participations as 3C-atom components have been much less frequent. In this concept article, we present an overview of this latter strategy, emphasizing on those more recent contributions involving the use of Pt(II) and Au(I) catalysts, which have uncovered new opportunities in this area.     

An extremely stable and orthogonal DNA base pair with a simplified three-carbon backbone

A nucleotide C3HQ with a minimal three-carbon backbone displays unprecedented pairing strength and orthogonality in a homopair C3HQ:C3HQ in the presence of one equivalent of Cu2+. The pairing stability in DNA even exceeds the related base pair having the regular 2'-deoxyribose backbone. This discovery of a synergy between an artificial backbone and base-pairing scheme opens new avenues for the economical design of modified oligonucleotides with tailored properties.     

Application of group separation reaction formalism for analysis of non-valence effects of organic compounds: three-carbon rings

Russian Chemical Bulletin - An authors’ methodology based on the graph theory was used to construct the complete set of group separation reactions (homodesmic reactions, HDRs) for 12 cyclic...     

Differentiation between the ethoxycarbonyl groups in diethyl malate via their titanium-catalyzed reductive cyclopropanation with ethylmagnesium bromide and subsequent site-selective three-carbon ring cleavage

Ethoxycarbonyl groups in O-THP protected racemic diethyl malate 1 were differentiated by their reductive cyclopropanation with ethylmagnesium bromide in the presence of titanium(IV) isopropoxide and subsequent site-selective C1-C2, C2-C3 or both C1-C2 and C1-C3 ring cleavage of the cyclopropyl groups of the resulting bis-cyclopropanol 2.     

A novel synthesis of alkyl vinyl ketones and divinyl ketones from carbonyl compounds by three-carbon homologation

Alkyl vinyl ketones and divinyl ketones are synthesized from carbonyl compounds and 1-chloro-3-phenylthiopropyl phenyl sulfoxide as a three-carbon homologating agent in good overall yields.     

A three-carbon (n+1+2) ring expansion method for the synthesis of macrocyclic enones. Application to muscone synthesis

The three-carbon ring expansion methodology commences with the preparation of a cyclic allene (C9, C11, C13), readily available from the corresponding cycloalkene via dibromocarbene addition and subsequent treatment with methyllithium. Dichloroketene addition to the cyclic allene regioselectively provides the [2+2] cycloadduct, which is reductively dechlorinated with zinc in methanol. The resulting cyclobutanone is then catalytically hydrogenated; cyclobutanone ring opening is affected with trimethylsilyl iodide; immediate dehydroiodination of the resulting β-iodocycloalkanone with diazabicycloundecane (DBU) provides the corresponding macrocyclic enone. The 15-membered enone was converted to d,l-muscone with (CH₃)₂CuLi.     

Total synthesis of the sesquiterpene (±)β-cuparenone: use of three-carbon annulation in synthesis

A total synthesis of β-cuparenone, which highlights the advantages and disadvantages of the three-carbon annulation process, is described.     

A new three-carbon synthon for efficient synthesis of benzannelated and 1-(2-arylethenyl) heterocycles

The novel three-carbon synthon 1-(1H-1,2, 3-benzotriazol-1-yl)-3-chloroacetone for the synthesis of benzothiazoles, pyrido[1,2-a]indoles, and styryl-substituted indolizines and imidazo[1,2-a]pyridines is reported. The proposed routes are a general and efficient approach for heterocyclizations followed by benzannelations or attachment of arylethenyl pharmacophores.     

Consecutive three-component synthesis of 3-(hetero)aryl-1H-pyrazoles with propynal diethylacetal as a three-carbon building block

A novel consecutive three-component synthesis of 3-(hetero)aryl-1H-pyrazoles via room temperature Sonogashira arylation of propynal diethylacetal used as a propargyl aldehyde synthetic equivalent has been disclosed. The final acetal cleavage-cyclocondensation with hydrazine hydrochloride at 80 °C rapidly furnishes the title compounds in a one-pot fashion.     

Synthesis of indolizines and pyrrolo[2,1-b]azoles from 2-pyridylmagnesium bromide and 2-lithiated azoles using tris(alkylthio)-cyclopropenyl cations as a three-carbon building block

A convenient method for the preparation of indolizines 3 and 4 and pyrrolo[2,1-b]azoles 7a-e from 2-pyridylmagnesium bromide and 2-lithiated azoles 6a-e , respectively, was developed by using tris(tert-butylthio)- and tris(isopropylthio)cyclopropenyl cations 1 and 2 as a three-carbon building block.     

Thermal,three-carbon + two-atom cycloaddition of cyclopropenone ketals with carbon-heteroatom double bonds: Butenolide,furan, and γ-keto ester preparation.

A preliminary study of the thermal reaction of cyclopropenone ketals with carbon-heteroatom double bonds is detailed. The reaction with aldehyde and keto carbonyls provide butenolide ortho esters, the product of a formal three-carbon + two-atom cycloaddition of the cyclopropenone ketal across the carbon-oxygen double bond.     

Dianion of sulfinylacetone as a synthetic equivalent of beta-enolate of propionic acid: a novel synthesis of carboxylic acids from alkyl halides with three-carbon elongation

The reaction of the dianion of phenylsulfinylacetone with alkyl halides afforded beta-keto sulfoxides, which were first chlorinated with hexachloroethane and then treated successively with KH and t-BuLi to give carboxylic acids in three-steps in moderate overall yields from the alkyl halides. This procedure affords a good method for a synthesis of carboxylic acids from alkyl halides with three-carbon elongation.     

Analogues of a locked nucleic acid with three-carbon 2',4'-linkages: synthesis by ring-closing metathesis and influence on nucleic acid duplex stability and structure

Two bicyclic 2'-deoxynucleoside analogues containing a saturated and an unsaturated three-carbon 2',4'-linkage, respectively, have been synthesized using a ring-closing metathesis-based linear strategy starting from uridine. Both analogues have been incorporated into oligodeoxynucleotide sequences and increased the stability of DNA:RNA hybrid duplexes (DeltaT(m) approximately 2.5-5.0 degrees C per modification) and decreased the stability of dsDNA duplexes (DeltaT(m) approximately 2.5-1.0 degrees C per modification). CD spectroscopy revealed that the bicyclic nucleosides induced formation of A-type-like duplexes albeit to a lesser degree than found for locked nucleic acid (LNA) monomers. From the CD data and UV melting analysis, we propose that the 2'-oxygen atom of the bicyclic moiety is essential for the formation of stabilized A-type-like dsDNA but not for the formation of a stabilized A-type DNA:RNA hybrid.