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.     

A new synthesis of macrocyclic keto-lactones via ring expansion of 2-(3-hydroxypropyl)-2-nitrocycloalkanones

2-(3-Hydroxypropyl0-2-nitrocycloalkanones undergo base-catalysed isomerisation into nitro-lactones containing four more atoms in the ring, which can be smoothly converted to the corresponding keto-lactones.     

Cyclopropylcarbinyl radicals as three-carbon insertion units: easy synthesis of C-15 macrocyclic ketones by three-carbon ring expansion

Thermal isomerization of cyclic 3-cyclopropyl ketones under FVP conditions at 620 °C provides a new and convenient route to δ,ε-unsaturated cycloalkanones. The synthetic potential of this novel three-carbon ring expansion has been demonstrated by the synthesis of (±)-muscone from inexpensive C-12 starting material.     

Palladium-catalyzed ring expansion reaction of 1-alkynylcyclobutanols with aryl iodides: an efficient route to 2-disubstituted methylenecyclopentanones

The reaction of 1-alkynylcyclobutanols with aryl iodides in the presence of Pd(OAc)₂ and Et₃N in acetonitrile at 80°C for 24 h gives 2-disubstituted methylenecyclopentan-1-ones in modest to good yields. The tandem insertion-ring expansion process proceeds via the formation of an alkynyl π-complex, followed by migration of a carbon-carbon bond of the tert-alkanol to form the cyclopentanones stereoselectively.     

Palladium-catalyzed ring expansion reaction of (Z)-1-(1,3-butadienyl)cyclobutanols with aryl iodides. stereospecific synthesis of (Z)-2-(3-aryl-1-propenyl)cyclopentanones

[reaction: see text] A novel type of cascade ring expansion process has been developed by the palladium-catalyzed reaction of (Z)-1-(1,3-butadienyl)cyclobutanols with aryl iodides. The reaction proceeds in a stereospecific manner to produce (Z)-2-(3-aryl-1-propenyl)cyclopentanones. It has also been found that regioselective alpha-arylation of alkenyl cyclopentanones proceeds to afford the alpha-arylated cyclopentanones.     

Pd(CH3CN)2Cl2-catalyzed oxidative heterodimerization reaction of 2,3-allenamides and 1,2-allenyl ketones: an efficient synthesis of 4-(furan-3'-yl)-2(5H)-furanimines

The Pd(II)-catalyzed oxidative heterodimerization reaction of 2,3-allenamides and 1,2-allenyl ketones was studied. It provides an efficient route for the synthesis of the polysubstituted 4-(furan-3'-yl)-2(5H)-furanimines, which are not readily available from the known methods. Due to the application of benzoquinone, the loadings of both the palladium catalyst and ketone have been greatly reduced for the oxidative heterodimerization of 2,3-allenamides and 1,2-allenyl ketones in acetic acid.     

Cu(I) catalyst in DMF: an efficient catalytic system for the synthesis of furans from 2-(1-alkynyl)-2-alken-1-ones

The cyclization of 2-(1-alkynyl)-2-alken-1-ones 1 proceeded very smoothly in the presence of alcohols 2 with a catalytic amount of Cu(I)Br in DMF at 80 degrees C, leading to the formation of highly substituted furans 3. The catalytic system reported herein is easy to handle, compared to the previously known system wherein the reaction between 1 and 2 needed to use moisture sensitive gold(III) chloride.     

A new method for the synthesis of macrocyclic ketones

Summary We have described the synthesis of macrocyclic diacetylene ketones by oxidative condensation of aliphatic ,-diacetyiene ketones.     

An efficient synthesis of highly substituted furans via the electrophilic cyclization of 1-(1-alkynyl)-cyclopropyl ketones

The electrophilic cyclization of 1-(1-alkynyl)-cyclopropyl ketones offers an efficient and straightforward route to highly substituted furans under extremely mild reaction conditions. Iodine, NIS, and PhSeBr have proven successful as electrophiles in this process.     

Macroexpansion methodology: an efficient eight unit ring expansion

An efficient eight unit ring expansion method which is postulated to proceed by either a [5,5] or consecutive [3,3] sigmatropic shifts is described.     

Stereospecific synthesis and characterization of oligodeoxyribonucleotides containing an N2-(1-carboxyethyl)-2'-deoxyguanosine

Methylglyoxal is a highly reactive alpha-ketoaldehyde that is produced endogenously and present in the environment and foods. It can modify DNA and proteins to form advanced glycation end products (AGEs). Emerging evidence has shown that N2-(1-carboxyethyl)-2'-deoxyguanosine (N2-CEdG) is a major marker for AGE-linked DNA adducts. Here, we report, for the first time, the preparation of oligodeoxyribonucleotides (ODNs) containing individual diastereomers of N2-CEdG via a postoligomerization synthesis method, which provided authentic substrates for examining the replication and repair of this lesion. In addition, thermodynamic parameters derived from melting temperature data revealed that the two diastereomers of N2-CEdG destabilized significantly the double helix as represented by a 4 kcal/mol increase in Gibbs free energy for duplex formation at 25 degrees C. Primer extension assay results demonstrated that both diastereomers of N2-CEdG could block considerably the replication synthesis mediated by the exonuclease-free Klenow fragment of Escherichia coli DNA polymerase I. Strikingly, the polymerase incorporated incorrect nucleotides, dGMP and dAMP, opposite the lesion more preferentially than the correct nucleotide, dCMP.     

Intramolecular Lewis-acid promoted (2+2) cycloadditions: An efficient total synthesis of (±)-coronafacic acid via an internal Diels-Alder reaction.

Internal (2+2) cycloaddition of the ester $\text{7}$ gave the cyclobutene $\text{8}$ in fair yield; cyclization of the readily derived trienone $\text{4}$ and hydrolysis produced coronafacic acid in 7% overall yield.     

A practical synthesis of (E)-2-cyclopentadecen-1-one: an important precursor of macrocyclic muscone

A practical synthesis of (E)-2-cyclopentadecen-1-one (E)-2 which is an important precursor of macrocyclic muscone (1) was investigated. Olefination of 2-mesyloxycyclopentadecanone (7c) with strong acid such as sulfuric acid or trifluoromethanesulfonic acid afforded the desired (E)-2 in high yield with extremely high stereoselectivity, which was treated with methylmagnesium cuprate to furnish the dl-muscone in good yield.     

Chemoselective synthesis of highly substituted 1,2-allenyl ketones, furans, and 2-alkynyl ketones from reaction of lithium selenolates with 1-(1-alkynyl)cyclopropyl ketones and electrophiles

A homo-Michael addition reaction of lithium selenolates with 1-(1-alkynyl)cyclopropyl ketones and the subsequent reaction with electrophiles such as PhSeBr, NFSI and NCS is reported. Based on the nature of electrophiles, this reaction may afford highly substituted 1,2-allenyl ketones or furans (E(+) = PhSe(+)) and 2-alkynyl ketones (E(+) = F(+), Cl(+), active halides) as the final products, respectively.     

Total synthesis of (-)-(alpha)-kainic acid via a diastereoselective methylenecyclopropane ring expansion

[reaction: see text] A concise and enantioselective synthesis of (-)-(alpha)-kainic acid in 13 steps with an overall yield of 15% is reported. The pyrrolidine kainoid precursor with the required C2/C3 trans stereochemistry was prepared with excellent diastereoselectivity (>20:1) via a MgI(2)-mediated ring expansion of a tertiary methylenecyclopropyl amide. A selective hydroboration was then employed to set the remaining stereochemistry at the C4 position en route to (-)-(alpha)-kainic acid.     

Diastereoselective construction of quaternary carbons directed via macrocyclic ring conformation: formal synthesis of (-)-mesembrine

In this article, we report a highly diastereoselective new method for the generation of quaternary carbon centers through an anionic oxy-Cope/alkylation sequence where the diastereoselectivity is induced by the conformation of a macrocyclic tetrasubstituted enolate. The use of our methodology culminated in the formal total synthesis of (-)-mesembrine (34) in 11 steps from known starting materials.     

New synthesis of 2-aryl-3-hydroxy(alkoxy)-4-quinolones by ring expansion of 1-acetyl-2-arylmethylene-3-indolinones

Translated from Khimiya Geterotsiklicheskikh Soedinenii,'No. 2, pp. 279–280, February, 1992.