General Method For Asymmetric Synthesis Research Articles

Metalloradical activation of carbonyl azides for enantioselective radical aziridination

Organic azides have been increasingly employed as nitrogen sources for catalytic olefine aziridination due to their ease of preparation and generation of benign N2 as the only byproduct. Among common organic azides, carbonyl azides have not been previously demonstrated as effective nitrogen sources for intermolecular olefin aziridination despite the synthetic utilities of N-carbonyl aziridines. As a new application of metalloradical catalysis, we have developed a catalytic system that can effectively employ the carbonyl azide TrocN3 for highly asymmetric aziridination of alkenes at room temperature. The resulting enantioenriched N-Trocaziridines have been shown as valuable chiral synthons for stereoselective synthesis of other chiral aziridines and various chiral amines. The Co(II)-based metalloradical system, which proceeds with distinctive stepwise radical mechanism, may provide a general method for asymmetric synthesis of chiral aziridines from alkenes with organic azides.

Elaborating Complex Heteroaryl-Containing Cycles via Enantioselective Palladium-Catalyzed Cycloadditions.

A general method for asymmetric synthesis of heteroaryl-containing cycles via palladium-catalyzed cyclization is reported. Most classes of nitrogen-containing aromatics, including pyridines, quinolines, pyrimidines, various azoles and the derivatives of nucleobases are compatible substrates, offering various heteroaryl-substituted cyclopentane, pyrrolidine, furanidine and bicyclo[4.3.1]decadiene derivatives with good to excellent enantioselectivity and diastereoselectivity.

ChemInform Abstract: Asymmetric Synthesis of Homoallylic Amines via 1,2‐Addition of Grignard Reagent to Aliphatic N‐Phosphonyl Hemiaminal.

Abstract A general method for asymmetric synthesis of alkylated homoallylic amines was developed via a one-pot three-component reaction of easily available N-phosphonyl amides, aliphatic aldehydes, and allylic Grignard reagents. As anticipated the reaction proceeds through six-membered chelation controlled mechanism, allowing 1,2-nucleophilic addition to directly give chiral homoallylic amines with high yields and excellent diastereoselectivity.

Asymmetric synthesis of homoallylic amines via 1,2-addition of Grignard reagent to aliphatic N-phosphonyl hemiaminal

A general method for asymmetric synthesis of alkylated homoallylic amines was developed via a one-pot three-component reaction of easily available N-phosphonyl amides, aliphatic aldehydes, and allylic Grignard reagents. As anticipated the reaction proceeds through six-membered chelation controlled mechanism, allowing 1,2-nucleophilic addition to directly give chiral homoallylic amines with high yields and excellent diastereoselectivity.

Enantioselective Synthesis of syn/anti-1,3-Amino Alcohols via Proline-Catalyzed Sequential α-Aminoxylation/α-Amination and Horner−Wadsworth−Emmons Olefination of Aldehydes

A novel and general method for asymmetric synthesis of both syn/anti-1,3-amino alcohols is described. The method uses proline-catalyzed sequential alpha-aminoxylation/ alpha-amination and Horner-Wadsworth-Emmons (HWE) olefination of aldehydes as the key step. By using this method, a short synthesis of a bioactive molecule, (R)-1-((S)-1-methylpyrrolidin-2-yl)-5-phenylpentan-2-ol, is also accomplished.

A Facile Asymmetric Synthesis of Either Enantiomer of 2-Substituted Pyrrolidines

A new and general method for asymmetric synthesis of either enantiomer of 2-substituted pyrrolidines from a single starting material is described. Reductive cyclization of (S(S))-gamma-chloro-N-tert-butanesulfinyl ketimines with LiBHEt(3) in THF at -78 to 23 degrees C afforded (S(S),R)-N-tert-butanesulfinyl-2-substituted pyrrolidines in excellent yields (88-98%) and with high diastereoselectivity (99:1). The diastereoselectivity is controlled effectively by the choice of reducing agent. Thus, the corresponding epimers of (S(S),S)-2-substituted pyrrolidines were synthesized in good yields (87-98%) and with high diastereoslectivity (1:99) by simply switching the reducing agent from LiBHEt(3) to DIBAL-H/LiHMDS. Deprotection of N-tert-butanesulfinyl-2-substituted pyrrolidines using 4 N HCl in dioxane and MeOH gave the corresponding enantiomers of 2-substituted pyrrolidines in quantative yield. This method was found to be effective for a variety of substrates including aromatic, heteroaromatic, and aliphatic substituents. Extension of this methodology to the formation of 2-substituted piperidines is also illustrated. Reductive cyclization of (S(S))-delta-chloro-N-tert-butanesulfinyl ketimine with LiBHEt(3) in THF at -78 to 23 degrees C or DIBAL-H/LiHMDS in toluene at -78 to 0 degrees C afforded the (S(S),R)-N-tert-butanesulfinyl-2-substituted piperidines in excellent yield (98%) and with high diastereoselectivity (99:1) or (S(S),S)-N-tert-butanesulfinyl-2-substituted piperidines in good yield (98%) and with high diastereoselectivity (1:99), respectively.

ChemInform Abstract: General Method for Asymmetric Synthesis of Substituted 2,2′‐Biaryldiols via Asymmetric Desymmetrization of 2,2′,6,6′‐Tetrahydroxybiphenyl with l‐Menthone.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

General method for asymmetric synthesis of substituted 2,2′-biaryldiols via asymmetric desymmetrization of 2,2′,6,6′-tetrahydroxybiphenyl with l-menthone

Asymmetric desymmetrization of prochiral 2,2′,6,6′-biphenyltetrol by acetalization with l-menthone affords isomenthonide 5b of S-axial chirality. A variety of ( S)-6,6′-dialkoxy-2,2′-biphenyldiols of high enantiomeric purities are synthesized by using 5b as an intermediate. Thus, etherification of the hydroxy groups of 5b followed by hydrolysis of the isomenthonide moiety give the corresponding 6,6′-dialkoxy-2,2′-biphenyldiols ( 12). Intermolecular cyclization of 5b with 1,ω-dibromoalkanes followed by hydrolysis yields 2,2′-biphenyldiols 13 with alkylenedioxy bridges at the 6 and 6′ positions. Regioselective functionalization of 13 leading to 3,3′-dimethyl, -diphenyl, and -bis(TBS) derivatives is achieved either via directed lithiation of a carbamate derivative or via regioselective bromination reaction of 13. Origin of the stereoselectivity in acetalization reaction as well as thermal stability of the axial chirality of 2,2′-biphenyldiols is also discussed.

ChemInform Abstract: General Method for Asymmetric Synthesis of α‐Methylsulfinyl Ketones: Application to the Synthesis of Optically Pure Oxisuran (IV) and Bioisosteres.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

General Method for Asymmetric Synthesis of alpha-Methylsulfinyl Ketones: Application to the Synthesis of Optically Pure Oxisuran and Bioisosteres.

The first asymmetric synthesis of oxisuran [1, (methylsulfinyl)methyl 2-pyridyl ketone], a synthetic immunosuppressive drug, is described. Both enantiomers were efficiently synthesized, in optically pure form, using DAG methodology for the key condensation step. Attempts to couple metal enolates of aryl methyl ketones with chiral sulfinyl compounds led to some epimerization at sulfur. This loss of chirality was circumvented by reacting the alpha-lithio derivatives of the N,N-dimethylhydrazones derived from these ketones with either the (R)- or the (S)-methanesulfinate of diacetone D-glucose, to yield the corresponding alpha-(methylsulfinyl)methylhydrazones, with complete inversion of chirality at sulfur. Hydrolysis of the resulting hydrazones with copper(II) chloride gave 1 in optically pure form. The generality of the method was demonstrated by the preparation of the optically active oxisuran analogs, 2-4, in which the pyridyl moiety was replaced by phenyl, furyl, and thienyl moieties, respectively. The optical purities of these products were determined by proton NMR spectroscopy, using chiral shift reagents, following conditions established by the study of racemic mixtures of the beta-keto sulfoxides.

ChemInform Abstract: General Method for Asymmetric Synthesis of α‐Amino Acids via Alkylation of Glycine in Chiral Ni(II) Complexes.

ChemInformVolume 18, Issue 15 Natural Products ChemInform Abstract: General Method for Asymmetric Synthesis of α-Amino Acids via Alkylation of Glycine in Chiral Ni(II) Complexes. YU. N. BELOKON', YU. N. BELOKON' Inst. elementoorg. soed. im. Nesmeyanova AN SSSR, MoskvaSearch for more papers by this authorN. I. CHERNOGLAZOVA, N. I. CHERNOGLAZOVA Inst. elementoorg. soed. im. Nesmeyanova AN SSSR, MoskvaSearch for more papers by this authorN. S. GARBALINSKAYA, N. S. GARBALINSKAYA Inst. elementoorg. soed. im. Nesmeyanova AN SSSR, MoskvaSearch for more papers by this authorM. B. SAPOROVSKAYA, M. B. SAPOROVSKAYA Inst. elementoorg. soed. im. Nesmeyanova AN SSSR, MoskvaSearch for more papers by this authorK. A. KOCHETKOV, K. A. KOCHETKOV Inst. elementoorg. soed. im. Nesmeyanova AN SSSR, MoskvaSearch for more papers by this authorV. M. BELIKOV, V. M. BELIKOV Inst. elementoorg. soed. im. Nesmeyanova AN SSSR, MoskvaSearch for more papers by this author YU. N. BELOKON', YU. N. BELOKON' Inst. elementoorg. soed. im. Nesmeyanova AN SSSR, MoskvaSearch for more papers by this authorN. I. CHERNOGLAZOVA, N. I. CHERNOGLAZOVA Inst. elementoorg. soed. im. Nesmeyanova AN SSSR, MoskvaSearch for more papers by this authorN. S. GARBALINSKAYA, N. S. GARBALINSKAYA Inst. elementoorg. soed. im. Nesmeyanova AN SSSR, MoskvaSearch for more papers by this authorM. B. SAPOROVSKAYA, M. B. SAPOROVSKAYA Inst. elementoorg. soed. im. Nesmeyanova AN SSSR, MoskvaSearch for more papers by this authorK. A. KOCHETKOV, K. A. KOCHETKOV Inst. elementoorg. soed. im. Nesmeyanova AN SSSR, MoskvaSearch for more papers by this authorV. M. BELIKOV, V. M. BELIKOV Inst. elementoorg. soed. im. Nesmeyanova AN SSSR, MoskvaSearch for more papers by this author First published: April 14, 1987 https://doi.org/10.1002/chin.198715347Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume18, Issue15April 14, 1987 RelatedInformation