Diastereoselective synthesis of 5,5-disubstituted 3,3-difluorotetrahydrofurans

The diastereoselective synthesis of 5,5-disubstituted 3,3-difluorotetrahydrofurans 2 was achieved using β,β-difluorohomoallylic alcohols 1 as the key starting material in the presence of ICl (3.0?equiv) and tert-BuOK (1.5?equiv) in THF. The corresponding iodocyclization products 2 were obtained in good to moderate yields with excellent diastereo- and regioselectivities (d.r.?=?>20/1, 5-endo-trig only).     

Copper-catalyzed synthesis of 1,2-disubstituted benzimidazoles from imidoyl chlorides

A strategy for the synthesis of 1,2-disubstituted benzimidazoles has been developed and a variety of 1,2-disubstituted benzimidazoles were obtained from imidoyl chlorides and o-haloanilines via copper(I)-catalyzed reaction in moderate yields.     

Highly selective Syn acyclic homoaldol chemistry synthesis of cis-3,4-disubstituted butyrolactones

Syn acyclic homoaldol products have been prepared by the conjugate addition reaction of α-alkoxyorganocuprates to enals. Selectivities of up to >250:1 have been obtained.     

Stereoselective synthesis of cis- or trans-2,4-disubstituted butyrolactones from Wynberg lactone

(R)-Wynberg lactone was used to prepare various asymmetric 2,4-disubstituted butyrolactones in three to four steps. Attainment of any possible stereoisomer, based upon commencement from (R)- or (S)-4-trichloromethyl-2-oxetanone, and the capacity to install disparate substituents at C₂ make this approach particularly versatile.     

Stereoselective synthesis of 2,6-disubstituted 3-piperidinols: application to the expedient synthesis of (+)-julifloridine

[reaction: see text] The asymmetric synthesis of 2,6-disubstituted 3-piperidinols having a 2,3-cis and 2,6-trans relative stereochemistry was accomplished in three steps using the following sequence: stereocontrolled nucleophilic addition of an organomagnesium reagent to a chiral pyridinium salt; monohydrogenation of the resulting 2-substituted 1,2-dihydropyridine; and a one-pot, highly diastereoselective epoxidation-nucleophilic addition with a heteroatom nucleophile or an organometallic reagent. This methodology was applied to the expedient asymmetric synthesis of (+)-julifloridine in four steps.     

Copper-catalyzed allylic amination of olefins with nitrosoarenes

The transition metal catalyzed allylic amination of olefins are studied. A screening of catalysts known for the intermediacy of PhNO in the amination of alkene with phenylhydroxylamine reveals that the hydrated copper salt in conjugation with copper powder as reductant has the best catalytic properties using nitrosobenzene as nitrogen-fragment donor. The catalytic system has been studied for a variety of alkenes. Unsymmetrical alkenes react with high regioselectivity with N-functionalization at the less substituted vinylic carbon.     

Convenient route to enantiopure substituted butyrolactones: application in a formal synthesis of both enantiomers of enterolactone

A simple route for the synthesis of enantiopure substituted γ-butyrolactones involving a highly diastereoselective alkylation of an enantiomerically pure substituted latent succinate ester is described. This route provides entry into both enantiomers of 3,4-disubstituted butyrolactones from a single enantiomer, 2,3-di-O-cyclohexylidine-R-(+)-glyceraldehyde. The synthetic potential of this methodology has been demonstrated by a formal synthesis of both enantiomers of enterolactone.     

The application of vinamidinium salts to the synthesis of 2,4-disubstituted thiophenes

The synthesis of 2,4-disubstituted thiophenes by the condensation of symmetrical vinamidinium salts with methyl thioglycolate has been accomplished for the first time. Simple experimental conditions were used to prepare seven different methyl 4-aryl-2-thiophenecarboxylates, three of which are new compounds.     

Efficient and connective synthesis of substituted butyrolactones and exo-methylene butyrolactones

A variety of -(trimethylsilylmethyl)-substituted butyrolactones are readily accessed by a novel tandem ene-reaction/oxidative desilylation of a range of aldehydes. Subsequent functionalisation led to an efficient methodology for the preparation of exo-methylene butyrolactones.     

A mild and general method for the synthesis of 5-substituted and 5,5-disubstituted fulleroprolines

The reductive ring-opening of fullerenyldihydropyrrole yields ethyl N-benzhydryl fullerenyl[60]glycinate, which is deprotected to give ethyl fullerenylglycinate. The free amine is able to react with a variety of aldehydes and ketones in a Mannich-type process to produce 5-substituted and 5,5-disubstituted fulleroprolines and represents a versatile and general strategy to this class of compounds.     

Flexibility in the partial reduction of 2,5-disubstituted pyrroles: application to the synthesis of DMDP

[reaction: see text] The partial reduction of electron-deficient 2,5-disubstituted pyrroles has been developed into a flexible procedure that gives control of relative stereochemistry by variation of the reduction conditions. After the reaction, the pyrroline products were dihydroxylated at C-3,4 to give either the cis or trans isomers; this flexibility means that a variety of polyhydroxylated pyrrolidines can be prepared in a short sequence. Finally, this method was applied to a synthesis of the naturally occurring glycosidase inhibitor DMDP.     

Copper-catalyzed tandem reaction directed toward synthesis of 2,2-disubstituted quinazolinones from vinyl halides and 2-aminobenzamides

A copper-catalyzed tandem reaction with vinyl halides and 2-aminobenzamides has been developed. In this synthetic route, cross-coupling reaction of the amide moiety with vinyl halides initially progresses, followed by hydroamination, to provide 2,2-disubstituted quinazolinone derivatives. Moreover, the tandem reaction is used in a one-pot synthesis beginning with alkyne hydroiodination by PPh₃, I₂, and H₂O.     

A route to 1,4-disubstituted aromatics and its application to the synthesis of the antibiotic culpin

A method is described for converting tert-butyl benzoates or tert-butyl 1-naphthoates into derivatives having an alkyl or substituted alkyl group in a 1,4-relationship to an alkyl, aryl, alkenyl, or alkynyl group. Key steps in the sequence are (i) addition of an organometallic species to a cross-conjugated cyclohexadienone obtained by Birch alkylation of a tert-butyl benzoate or a tert-butyl 1-naphthoate, followed by allylic oxidation, and (ii) treatment with BiCl3 x H2O, which results in removal of the tert-butyl group and spontaneous decarboxylative aromatization. The method was applied to the synthesis of the antimicrobial fungal metabolite culpin.     

Conformation of 5,5-disubstituted 2,2-dimethyl-1,3-dioxanes

It was established by PMR spectral data that in solutions of derivatives of 5-acetoxymethyl-, 5-methyl-, and 5-hydroxymethyl-2,2-dimethyl-1,3-dioxanes with nitrogen-containing substituents (2,4-disubstituted 1,3,5-triazin-6-ylamino, benzamido, and nitro groups) with an N-C₍₅₎ bond the 1,3-dioxane ring exists in the chair conformation with primarily an axial orientation of the nitrogen-containing substituent. Depending on the nature of the substituents attached to the C₍₅₎ atom, the 1,3-dioxane ring may exist either in the stable chair conformation or may undergo rapid inversion of the chair-chair type at 20 °C.The author sincerely thanks A. I. Kol'tsov for his assistance in recording and interpreting the PMR spectra.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 468–473, April, 1985.     

Rh-catalyzed asymmetric hydroformylation of functionalized 1,1-disubstituted olefins

The first method for the highly enantioselective rhodium-catalyzed hydroformylation of 1,1-disubstituted olefins has been developed. By employing either of the P-chirogenic phosphine ligands BenzP* and QuinoxP*, linear aldehydes with β-chirality can be prepared in a highly enantioselective fashion with good chemo- and regioselectivities.     

Copper-catalyzed synthesis of vinyl sulfides

[reaction: see text] We report a method for the synthesis of vinyl sulfides using the soluble copper(I) catalyst [Cu(phen)(PPh3)2]NO3. The desired vinyl sulfides are obtained in good to excellent yields, with retention of stereochemistry. This protocol tolerates a wide variety of functional groups or substrates, is palladium-free, and does not require the use of expensive or air-sensitive additives.     

Copper-catalyzed synthesis of unsymmetrical triarylphosphines

Various triarylphosphines have been prepared by coupling diphenylphosphine with aryl iodides with catalytic amounts of CuI in the presence of either K(2)CO(3) or Cs(2)CO(3), in good yields. This method can tolerate a variety of functional groups and does not require the use of expensive additives, or harsh reaction conditions, and is palladium free.     

Versatile approach to enantiopure 2,6-disubstituted piperidin-3-ol framework: application to the total synthesis of (+)-deoxoprosopinine

An efficient synthesis of enantiopure 2,6-disubstituted piperidin-3-ol 19 is developed featuring two key steps: (a). Julia olefination of (2R)-3-phenylsulfonyl-2-tert-butyloxycarbamoylpropanol benzyl ether 9B and (2R,3S)-2-tert-butyldiphenyl-3,4-O-isopropylidine-2,3,4-trihydroxybutyraldehyde 8 and (b). intramolecular N-alkylation. A straightforward asymmetric synthesis of (+)-deoxoprosopinine(2) from 19 is described demonstrating the versatility of this novel approach.     

Stereoselective synthesis of cis-2,5-disubstituted THFs: application to adjacent bis-THF cores of Annonaceous acetogenins

The iodocyclization of γ,δ-unsaturated alcohols in the presence of a silyl enol ether produced cis-2,5-disubstituted tetrahydrofurans in one pot via siloxy intermediates. N-Iodosuccinimide (NIS) effectively worked as an activator of the double bonds in the substrates and the silyl enol ether. Application to an expedient synthesis of the adjacent bis-tetrahydrofuran core of Annonaceous acetogenins with a cis/threo/cis relative stereochemistry is also described.