Acid-catalyzed reaction behavior of 1-silylcyclopropylmethanols

Treatment of 1-silylcyclopropylmethanols with TsOH in methanol gives different homoallyl ethers depending upon the configuration of substituents on cyclopropane ring and the kinds of substituents on carbinyl carbon. Especially, the reaction of cyclopropylmethanols having no substituents on the same side with silyl group on cyclopropane ring proceeds to give the corresponding E-homoallyl ethers with high stereoselectivity. The following protiodesilylation of resulting homoallyl ethers proceeds with retention of configuration.     

Gold-catalyzed cyclization of 1-alkynyl cyclopropyl tert-butyl carbonate to construct multifunctionalized vinyl cyclopropane derivatives

A convenient new method was developed to prepare two types of vinyl cyclopropane derivatives through gold-catalyzed cyclization of 1-alkynyl cyclopropyl tert-butyl carbonates 2. Different from the previous reported 5-exo-dig route, the 6-endo-dig addition is the preferred pathway to provide six-membered cyclized carbonates. Two factors, including stereoelectronic effect and steric effect might affect the regioselectivity. Therefore, low steric aliphatic substrates afforded only six-membered isomers. The synthetic utility of compound 3 was also explored to afford a series of β-carbonyl cyclopropanol derivatives.     

Trimethylsilyl tetrafluoroborate a convenient reagent for solvolysis reactions

Conversions of cyclopropyl carbinols (or their acetates) and ketones into homoallyl and γ-substituted ketone derivatives, respectively, are accomplished by trimethylsilyl tetrafluoroborate efficiently and under mild conditions.     

Brookhart's Acid-Catalyzed Switchable Regioselective N-Alkylation of Arylamines/Heterocyclic Amines with Cyclopropylcarbinols by Temperature Regulation

An unprecedented, Brookhart's acid-catalyzed temperature-switchable regioselective divergent approach for N-alkylation of arylamines and heterocyclic amines by utilising cyclopropylcarbinols is presented herein. The reaction offers N-alkylated cyclopropyl derivatives and homoallyl amines by employing 2.5 mol% catalyst loading at different temperatures in excellent regioselectivity and yields. This method has shown to be relevant with a wide range of cyclopropylcarbinols, including aliphatic ones. Several control experiments and spectroscopic studies have been performed to gain insight into the reaction mechanism. Further, the synthetic utility of the protocol has also been described.     

An asymmetric synthesis of carboxylic acid derivatives,including lactic acid and α-amino acid derivatives,from optically active 1-chlorovinyl p-tolyl sulfoxides and ester lithium enolates with creation of chirality at the α-position

Treatment of optically active 1-chlorovinyl p-tolyl sulfoxides, which were synthesized from symmetrical ketones or methyl formate and (R)-(−)-chloromethyl p-tolyl sulfoxide in three steps, with lithium enolate of carboxylic acid tert-butyl esters gave optically active adducts having a substituent (alkyl, alkoxy, or dibenzylamino group) at the α-position with high 1,4-chiral induction from the sulfur chiral center. The adducts were converted to optically active esters, lactic acid, and α-amino acid derivatives having a chiral center at the α-position. When this addition reaction was carried out with an ester enolate generated from excess carboxylic acid tert-butyl ester with LDA in the presence of HMPA, the diastereomer of the adduct was obtained. By using the two reaction conditions for the generation of the ester enolate, a new method for asymmetric synthesis of both enantiomers of carboxylic acid derivatives having a substituent at the α-position from the one chiral source, (R)-(−)-chloromethyl p-tolyl sulfoxide, was achieved.     

Pd-catalyzed cycloisomerization-allylation of 4-alkynones: synthesis of 5-homoallylfuran derivatives

In the presence of Pd₂(dba)₃-tBu₃P catalyst and Cs₂CO₃, cycloisomerization-allylation reactions of 4-alkynone derivatives with allyl carbonates in MeCN proceed in 5-exo mode to give highly-substituted furans having homoallyl groups at 5-position.     

Asymmetric synthesis of α-mercapto-β-amino acid derivatives: application to the synthesis of polysubstituted thiomorpholines

Tandem conjugate addition of homochiral lithium N-benzyl-N-(α-methyl-p-methoxybenzyl)amide to tert-butyl cinnamate and enolate trapping with TsS^tBu proceeds with high diastereoselectivity to give a homochiral anti-α-tert-butylthio-β-amino ester. Stepwise deprotection gives the corresponding free α-tert-butylthio-β-amino acid without epimerisation. Tandem conjugate addition of homochiral lithium N-allyl-N-(α-methylbenzyl)amide to tert-butyl cinnamate and enolate trapping with TsS^tBu followed by conversion of the S-tert-butyl group to a disulphide, and reduction with Lalancette’s reagent generates polysubstituted thiomorpholine derivatives.     

(−)-Fenchone derived epoxy alcohols—preparation and configuration

Several chiral diastereoisomerically pure epoxy alcohols were prepared diastereoselectively in high yields after epoxidation of allyl and homoallyl alcohols containing the 1R-fenchone skeleton with VO(acac)₂/t-butyl hydroperoxide. The configurations of some of the new chiral compounds were determined by NMR methods. An interesting rearrangement reaction of an epoxy alcohol to an olefinic diol catalyzed by V⁵⁺ ions was observed.     

Samarium dienolate mediated stereoselective synthesis of anti-1,3-diol monoesters via aldol-Tishchenko reaction

The reaction of an (E)-samarium dienolate, generated by the regioselective reductive cleavage of a phenylsulfonyl activated cyclopropyl ketone with samarium(II) iodide, with aliphatic and aromatic aldehydes gives the 2-substituted anti-1,3-diol monoester derivatives, stereoselectively, in good to excellent yields. The results represent the first report of a dienolate in the aldol-Tishchenko reaction and also provide an optically active polyol with (R)-glyceraldehyde.     

Analogs of pyrimidine mono- and polynucleotides

Phosphorylation of N₁-(1,4-dihydroxy-2-butyl) derivatives of uracil and thymine with polyphosphoric acid or Β-cyanoethyl phosphate in the presence of dicyclohexylcarbodiimide gives the corresponding diphosphates as the chief reaction products.     

An efficient synthesis of tert-butyl ethers/esters of alcohols/amino acids using methyl tert-butyl ether

A facile synthesis of a wide variety of tert-butyl ethers and tert-butyl ester derivatives under mild conditions is described. Alcohols etherified with tert-butyl methyl ether as tert-butyl source and solvent, in the presence of sulfuric acid. Many amino acid tert-butyl esters have been synthesized by this procedure. The reaction is simple, inexpensive, easily scaled up, and proceeds without observable racemization. A green method was developed for the deprotection of this group using Amberlite resin IR 120-H as catalyst.     

Mono- and di-t-butyl substituted 2,2′-bis(1,3-dithia[3]ferrocenophane-2-ylidene) derivatives: TTF-like ferrocene analogs

Mono- and di-t-butyl substituted 2,2′-bis(1,3-dithia[3]ferrocenophane-2-ylidene) derivatives were prepared. These derivatives showed the E_1/2(1) in lower potential region than that of differrocenyl-ethene and -ethyne. Also, the ΔE_1/2 value declined according to the increase of a t-butyl group.     

A synthesis of bicyclo[n.1.0]alkanes having tert-butyl carboxylate or acetamide moiety via the intramolecular 1,3-CH insertion of magnesium carbenoids

Treatment of 1-chlorovinyl p-tolyl sulfoxides, derived from various cyclic ketones and chloromethyl p-tolyl sulfoxide, with lithium enolate of carboxylic acid tert-butyl esters or N,N-dimethylacetamide gave adducts in high yields. The adducts were treated with ether solution of isopropylmagnesium chloride in dry toluene to give bicyclo[n.1.0]alkane derivatives having tert-butyl carboxylate or acetamide moiety on the bridgehead carbon in high to quantitative yields via magnesium carbenoid 1,3-CH insertion reaction. The 1,3-CH insertion reaction proved to be regioselective and stereospecific. The reaction mechanism and origin of the selectivity and specificity are discussed.     

Stereoselective Construction of Tertiary Homoallyl Alcohols and Ethers by Nucleophilic Substitution at Quaternary Carbon Stereocenters

An efficient method for the stereoselective construction of tertiary C−O bonds via a stereoinvertive nucleophilic substitution at the quaternary carbon stereocenter of cyclopropyl carbinol derivatives using water, alcohols and phenols as nucleophiles has been developed. This substitution reaction proceeds under mild conditions and tolerates several functional groups, providing a new access to the stereoselective formation of highly congested tertiary homoallyl alcohols and ethers.     

A novel method for asymmetric synthesis of both enantiomers of α-substituted carboxylic acid derivatives from optically active 1-chlorovinyl p-tolyl sulfoxides and lithium ester enolates with 1,4-chiral induction from the sulfur chiral center

Treatment of optically active 1-chlorovinyl p-tolyl sulfoxides, which were synthesized from symmetrical ketones and (R)-(−)-chloromethyl p-tolyl sulfoxide in three steps, with lithium enolate of carboxylic acid tert-butyl esters gave optically active adducts having a substituent at the α-position with high 1,4-chiral induction from the sulfur chiral center in high yields. The adducts were converted to optically active esters and carboxylic acids having a chiral center at the α-position. When this addition reaction was carried out with the ester enolate generated from excess carboxylic acid tert-butyl ester with LDA in the presence of HMPA, the diastereomer of the adduct was obtained. By using the two reaction conditions for the generation of the ester enolates, a new method for asymmetric synthesis of both enantiomers of carboxylic acid derivatives having a substituent at the α-position from the one chiral source, (R)-(−)-chloromethyl p-tolyl sulfoxide, was realized.     

BiCl3 promoted aza-Prins type cyclization: a rapid and efficient synthesis of 2,4-disubstituted piperidines

Several N-protected homoallyl amines and epoxides were subjected to an aza-Prins cyclization. A rapid and efficient BiCl₃ promoted stereoselective synthesis of trans-2,4-disubstituted piperidine derivatives was achieved.     

Oxidation of β-dicarbonyl compounds with tert-butyl hydroperoxide in the presence of vanadyl acetylacetonate

Oxidation of β-dicarbonyl compounds with tert-butyl hydroperoxide in the presence of vanadyl acetylacetonate (benzene, 20°C) involves the activated methylene group with intermediate formation of trioxo derivatives and is accompanied by decomposition of carbon skeleton. The oxidation products are carbon dioxide, carboxylic acids, and tert-butyl and peroxy esters derived from the latter.     

An efficient synthesis of 5-silyl-2,3-dihydrofurans via acid-catalyzed ring-enlargement of cyclopropyl silyl ketones and their functionalization

Treatment of cyclopropyl silyl ketones with trimethylsilyl trifluoromethanesulfonate as a strong acid having low nucleophilic counter anion gives the corresponding 5-silyl-2,3-dihydrofuran derivatives, exclusively, regardless of substituents on the cyclopropane ring or silicon atom. The resulting 5-silyl-2,3-dihydrofuran derivatives exhibit both reactivities of the vinylsilane and the cyclic enol ether in the subsequent reaction with electrophilic reagents or Heck type reaction.     

An efficient synthesis of cyclopropyl silyl ketones

The reaction of silylcyclopropyl bromides with dichloromethyl methyl ether in the presence of n-butyllithium is investigated. Under basic reaction conditions, the corresponding cyclopropylidene derivatives are exclusively obtained. The resulting cyclopropylidene compounds are subjected to protonolysis or trapping with electrophiles in a one-pot to give the cyclopropyl silyl ketone derivatives in good yields. Acidic treatment of derived cyclopropyl silyl ketone allows isomerization to give the thermodynamically favorable trans form exclusively.