Sulfinimines Research Articles

Asymmetric Synthesis of syn-α-Substituted β-Amino Ketones by Using Sulfinimines and Prochiral Weinreb Amide Enolates

Syn-alpha-substituted beta-amino Weinreb amides are new chiral building blocks for asymmetric synthesis of syn-alpha-substituted beta-amino acids, aldehydes, and ketones and are prepared by addition of prochiral lithium enolates of Weinreb amides to sulfinimines (N-sulfinyl imines).

Adventures in Sulfur—Nitrogen Chemistry

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Diastereomeric Fluoroolefins as Peptide Bond Mimics Prepared by Asymmetric Reductive Amination of α‐Fluoroenones

Fluoropeptidomimetics: An efficient asymmetric reductive amination of fluoroenones has been developed that affords potential precursors of fluoropeptide isosteres. Stereoselective routes with different reductive agents provided both diastereomers from the same nonracemic sulfinyl imine. The method was applied to the synthesis of different dipeptide analogues.

Aza-Mannich Condensation of Sulfinimine Promoted by Tetrabutyl­ammonium Fluoride: Synthesis of α,β-Unsaturated Sulfinimine

Aza-Mannich Condensation of Sulfinimine Promoted by Tetrabutyl­ammonium Fluoride: Synthesis of α,β-Unsaturated Sulfinimine

Total Synthesis of (−)-Normalindine via Addition of Metalated 4-Methyl-3-cyanopyridine to an Enantiopure Sulfinimine

A concise total asymmetric synthesis of the tetrahydronaphthyridine alkaloid (-)-normalindine has been accomplished via the addition of a laterally metalated 4-methyl-3-cyanopyridine to a sulfinimine (N-sulfinyl imine) as the key step.

Rapid Synthesis of 4-Benzyl-4-aminopiperidines by Addition of Grignard Reagents to N-(1-Boc-Piperidin-4-ylidene)-tert-butanesulfinyl Imine

Two concise methods for the synthesis of aryl-substituted 4-benzyl-4-aminopiperidines by the addition of benzyl Grignard ­reagents to sulfinyl imines were developed. The hydration-prone tert-butanesulfinyl imine derived from N-Boc-piperidin-4-one was trapped as a stable α-(N-sulfinyl)aminonitrile, which underwent displacement of the nitrile on treatment with Grignard reagents. Alternatively, benzyl and allyl Grignards added to the sulfinyl imine in situ in a one-pot procedure. Acid deprotection provided various substituted 4-benzyl-4-aminopiperidines.

Adventures in Sulfur−Nitrogen Chemistry

This account reviews our efforts over the past 37 years to understand the chemistry of a select group of sulfur-nitrogen compounds including sulfinimines (N-sulfinyl imines) and N-sulfonyloxaziridines. Our early exploration of the thermal properties of sulfenamides, a class of sulfur-nitrogen compounds about which little was known, resulted in a new procedure, the silver-assisted method, for the construction of sulfenimines (N-sulfenyl imines). Selective oxidations of these compounds resulted in the production of N-sulfinyl imines (sulfinimines) and N-sulfonyloxaziridines. N-Sulfonyloxaziridines turned out to be a new class of aprotic neutral oxidizing reagents. Enantiomerically pure examples afford high ee values in the oxidation of enolates to alpha-hydroxy carbonyl compounds and in the oxidation of sulfides and selenides to sulfoxides and selenoxides. Additions of organometallic reagents to enantiomerically pure sulfinimines provide the best and most versatile method for the asymmetric construction of the carbon-nitrogen stereocenters found in many biologically active compounds. Sulfinimine-derived chiral building blocks provide efficient access to many classes of nitrogen heterocycles including aziridines, 2H-azirines, pyrrolidines, and piperidines.

Reversal of Diastereofacial Selectivity in Hydride Reductions of N-tert-Butanesulfinyl Imines

A variety of N-tert-butanesulfinyl imines were reduced with NaBH4 in THF containing 2% water to provide the corresponding secondary sulfinamides in high yield and diastereoselectivity. By using the same sulfinyl imine starting materials and changing the reductant to L-Selectride, the stereoselectivity could be efficiently reversed to afford the opposite product diastereomer in high yield and selectivity.

Use of α-Chlorinated N-(tert-Butanesulfinyl)imines in the Synthesis of Chiral Aziridines

[reaction: see text] Reaction of chiral alpha-chloro tert-butanesulfinyl aldimines with Grignard reagents efficiently afforded beta-chloro N-sulfinamides in high diastereomeric excess. The latter compounds were cyclized toward the corresponding chiral aziridines in a high-yielding one-pot reaction or after separate treatment with base. The diastereoselectivity obtained in the newly synthesized beta-chloro sulfinamides is explained via the coordinating ability of the alpha-chloro atom with magnesium resulting in the opposite stereochemical outcome as generally observed for nonfunctionalized N-sulfinyl imines.

Asymmetric Conjugate Addition to α,β-Unsaturated Chiral Sulfinyl Imines

Asymmetric 1,4-addition to enones is a very versatile method of the enantioselective construction of a new C-C bond. tert-Butyl sulfinimines are easily removable chiral auxiliaries which allow a number of useful synthetic transformations. This work represents a practical method for the enantioselective 1,4-addition of an alkyl group to α,β-enones mediated by organocopper reagents. Moderate to good diastereoselectivities of the resulting Michael adducts can be achieved by this approach. The addition products can be hydrolyzed to ketones or aldehydes, or used in further transformations employing the chiral tert-butanesulfinyl imine chemistry.

Stereoselective Synthesis of β-Substituted β-Amino Sulfones and Sulfonamides via Addition of Sulfonyl Anions to Chiral N-Sulfinyl Imines

[reaction: see text] A highly stereoselective synthesis of beta-amino sulfones and sulfonamides via addition of sulfonyl anions to chiral N-sulfinyl imines is described. The addition reaction proceeds in good yield (75-99%) and stereoselectivity.

Stereoselective Synthesis of 3-Aminoindan-1-ones and Subsequent Incorporation into HIV-1 Protease Inhibitors

A new method for the stereoselective synthesis of 3-aminoindan-1-ones from triflates of salicylic sulfinyl imines and ethylene glycol vinyl ether has been developed. The reaction sequence starts with a regioselective Heck reaction followed by stereoselective Lewis acid mediated annulation. Acidic cleavage of the sulfinamides produced pure (R)- and (S)-3-aminoindan-1-ones, which were successfully isolated and incorporated into active HIV-1 protease inhibitors.

Stereoselective Reductive Coupling of Chiral Sulfinyl Imines with Aldehydes

A reductive cross-coupling reaction between aliphatic aldehydes and chiral N-tert-butanesulfinimines in the presence of SmI2 leads to the formation of β-amino alcohols with excellent enantiomeric and diastereomeric excesses and good yields. The products can be used as chiral ligands or auxiliaries in asymmetric synthesis. The method allows also the preparation of important natural compounds like statine, a structural moiety of novel protease blockers, very perspective for pharmacology.

A Lewis Acid Promoted Asymmetric Umpolung Reaction with Chiral N‐Sulfinyl Imines as the Electrophiles.

ChemInformVolume 36, Issue 35 Preparative Organic Chemistry A Lewis Acid Promoted Asymmetric Umpolung Reaction with Chiral N-Sulfinyl Imines as the Electrophiles. Xin Xu, Xin Xu Dep. Chem. Biochem., Tex. Tech. Univ., Lubbock, TX 79409, USASearch for more papers by this authorJun-ying Liu, Jun-ying Liu Dep. Chem. Biochem., Tex. Tech. Univ., Lubbock, TX 79409, USASearch for more papers by this authorDian-jun Chen, Dian-jun Chen Dep. Chem. Biochem., Tex. Tech. Univ., Lubbock, TX 79409, USASearch for more papers by this authorCody Timmons, Cody Timmons Dep. Chem. Biochem., Tex. Tech. Univ., Lubbock, TX 79409, USASearch for more papers by this authorGuigen Li, Guigen Li Dep. Chem. Biochem., Tex. Tech. Univ., Lubbock, TX 79409, USASearch for more papers by this author Xin Xu, Xin Xu Dep. Chem. Biochem., Tex. Tech. Univ., Lubbock, TX 79409, USASearch for more papers by this authorJun-ying Liu, Jun-ying Liu Dep. Chem. Biochem., Tex. Tech. Univ., Lubbock, TX 79409, USASearch for more papers by this authorDian-jun Chen, Dian-jun Chen Dep. Chem. Biochem., Tex. Tech. Univ., Lubbock, TX 79409, USASearch for more papers by this authorCody Timmons, Cody Timmons Dep. Chem. Biochem., Tex. Tech. Univ., Lubbock, TX 79409, USASearch for more papers by this authorGuigen Li, Guigen Li Dep. Chem. Biochem., Tex. Tech. Univ., Lubbock, TX 79409, USASearch for more papers by this author First published: 02 August 2005 https://doi.org/10.1002/chin.200535034Read 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. Volume36, Issue35August 30, 2005 RelatedInformation

Control of Diastereoselectivity by Solvent Effects in the Addition of Grignard Reagents to Enantiopure t-Butylsulfinimine: Syntheses of the Stereoisomers of the Hydroxyl Derivatives of Sibutramine

[reaction: see text] An efficient method has been developed to prepare all four isomers of the hydroxyl derivatives of sibutramine by addition of Grignard reagents (R)- or (S)-5 to a single enantiomer of sulfinyl imine (R)-1 simply by tuning the reaction solvent. The phenomenon of the reversed diastereoselectivity in CH(2)Cl(2) and THF implied that the reaction may proceed through a chelated cyclic transition state in CH(2)Cl(2) and nonchelated acyclic transition state in THF.

Asymmetric Synthesis of α-Substituted β-Amino Ketones from Sulfinimines (N-Sulfinyl Imines). Synthesis of the Indolizidine Alkaloid (−)-223A

Of the possible four stereoisomers, addition of the lithium enolate of 4-heptanone to sulfinimines resulted in only the syn- and anti-alpha-substituted beta-amino ketones. The formation of the major syn-beta-amino ketone was rationalized in terms of addition of the E-enolate to the C-N double bond of the sulfinimine via a six-member chelated chairlike transition state. The enolates of 4-heptanone were generated using LiHMDS in THF where a 1:2.5 E:Z enolate ratio was noted. In diethyl ether the E:Z ratio was 15:1 in favor of the E-enolate and explained in terms of Ireland's transition state model. Here increased steric interactions between the ethyl group and the carbonyl-LiN(TMS)(2) moiety destabilize the transition state leading to the Z-enolate in the poorly coordinating diethyl ether solvent. This new synthesis of syn-alpha-substituted-beta-amino ketones was applied to the concise enantioselective total synthesis of indolizidine (-)-223A, a 5,6,8-trisubstituted alkaloid isolated from the skin of the dendrobatide frog.

A Lewis Acid Promoted Asymmetric Umpolung Reaction with ChiralN‐Sulfinyl Imines as the Electrophiles

AbstractAn new asymmetric umpolung reaction has been developed by reacting N‐sulfinyl imines with 2‐lithio‐2‐phenyl‐1,3‐dithiane. The reaction was conducted at between –20 and–25 °C in THF in the presence of Et2AlCl as the Lewis acid promoter. Excellent diastereoselectivities (up to >95 % de) and chemical yields (64–95 %) have been achieved for nine substrates with all individual isomers separated and characterized. The absolute structure of the chiral products has been unambiguously determined by synthetic conversions to a known sample. 2‐Lithio‐2‐phenyl‐1,3‐dithiane was found to be much less reactive than its 2‐methyl counterpart, which was reported very recently. All individual isomers have been readily separated by column chromatography. The absolute structure of the chiral products has been unambiguously determined by conversion into a known compound. This method provides an easy access to enantiomerically pure α‐amino ketones. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Asymmetric Synthesis of β-Amino Carbonyl Compounds with N-Sulfinyl β-Amino Weinreb Amides

[reaction: see text] Diverse organometallic reagents readily add to enantiopure N-sulfinyl beta-amino Weinreb amides providing the corresponding, stable, N-sulfinyl beta-amino carbonyl compounds in good to excellent yields. This new methodology represents a general solution to the problem of beta-amino carbonyl syntheses, which are important chiral building blocks and constituents of natural products. N-Sulfinyl beta-amino Weinreb amides are prepared by reaction of the potassium enolate of N-methoxy N-methylacetamide with sulfinimines (N-sulfinyl imines) or lithium N,O-dimethylhydroxylamine with N-sulfinyl beta-amino esters.

Highly Diastereoselective Addition of Ketone Enolates to N‐Sulfinyl Imines: Asymmetric Synthesis of syn‐ and anti‐1,3‐Amino Alcohol Derivatives

AbstractFor Abstract see ChemInform Abstract in Full Text.

Highly Stereoselective Addition of Organometallic Reagents to N‐tert‐Butanesulfinyl Imines Derived from 3‐ and 4‐Substituted Cyclohexanones.

AbstractFor Abstract see ChemInform Abstract in Full Text.