Chiral Sulfinyl Research Articles

ChemInform Abstract: Diastereoselective Diels-Alder Reactions with Chiral Sulfinyl Derivatives as Dienophiles Under High Pressure.

Abstract Using the high pressure technique, asymmetric Diels-Alder reaction utilizing chiral 2-nitro-1-sulfinylolefins and dienes proceeded smoothly to give highly functionalized cyclohexene derivatives with satisfactory chemical yield and high diastereomeric excess.

ChemInform Abstract: Asymmetric Synthesis of Aminophosphonic Acids Mediated by Chiral Sulfinyl Auxiliary: Recent Advances

AbstractReview: 14 refs.

ChemInform Abstract: Stereoselective Synthesis of α‐Methylene‐γ‐butyrolactams from Ethyl 2‐(Bromomethyl)arcylate and Chiral Sulfinyl Aldimines Mediated by Indium.

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.

ChemInform Abstract: Asymmetric Synthesis of Fluorine‐Containing Amines, Amino Alcohols, α‐ and β‐Amino Acids Mediated by Chiral Sulfinyl Group

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.

Asymmetric synthesis of aminophosphonic acids mediated by chiral sulfinyl auxiliary: Recent advances

New approaches to asymmetric synthesis of α-, β- and γ-aminophosphonic acids using enantiopure p-toluenesulfinimines as key reagents are reported. The utility of the devised methods is illustrated by the syntheses of enantiomeric aminophosphonic acids such as AP4, AP3, and its 3-amino isomer.

Stereoselective Synthesis of α-Methylene-γ-butyrolactams from Ethyl 2-(Bromomethyl)acrylate and Chiral Sulfinyl Aldimines Mediated by Indium

The reaction of ethyl 2-(bromomethyl)acrylate (1) with chiral N-tert-butylsulfinyl aldimines 2 and indium powder in THF at 100 °C for 48 h affords, after hydrolysis, a mixture of N-tert-butylsulfinyl aminoesters 3 and α-methylene-y-butyrolactams 4. From the reaction mixture, compounds 3 were quantitatively converted to the expected butyrolactams 4 after removal of the tert-butylsulfinyl group under acidic conditions and final basic workup. The whole process takes place in high overall yields and with fairly good stereoselectivities.

ChemInform Abstract: Synthesis of Chiral Aziridines Through Decarboxylative Generation of Sulfur Ylides and Their Reaction with Chiral Sulfinyl Imines.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 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.

Synthesis of Chiral Aziridines Through Decarboxylative Generation of Sulfur Ylides and Their Reaction with Chiral Sulfinyl Imines

Reaction of sulfur ylides with a series of aryl substituted chiral nonracemic sulfinyl imines afforded the corresponding aziridines in good yields with good stereoselectivity. The sulfur ylides were generated by the thermally induced decarboxylation of carboxymethylsulfonium betaines. A drop in the diastereomeric ratio was observed when going from electron-deficient to electron-releasing aryl substituted imines. S-Methylene aziridinations involving the decarboxylation of carboxymethylsulfonium betaine functionality complements existing technologies with the advantages of the reaction protocol, levels of conversion, and scope.

Relaying stereochemistry through aromatic ureas: 1,9 and 1,15 remote stereocontrol

The well-defined conformation of an N,N'-diarylurea allows a chiral sulfinyl substituent to influence diastereoselectivity in the formation of new stereogenic centres up to 14 bond lengths away.

Helix Persistence and Breakdown in Oligoureas of Metaphenylenediamine: Apparent Diastereotopicity as a Spectroscopic Marker of Helix Length in Solution

Oligomeric ureas derived from m-phenylenediamine with chain lengths of up to seven urea linkages were made by iterative synthetic pathways. Three families were synthesized: 4 and 20, bearing a terminal chiral sulfinyl group; 24, bearing a terminal rotationally restricted amide group, and 30 bearing a terminal achiral bromophenyl group. The distal end of the oligomers was capped with an N-benzyl group to act as a diastereotopic probe. With a terminal sulfinyl group, the 1H NMR signals arising from the CH2 group of the diastereotopic probe remained anisochronous even when separated from the stereogenic center by up to 24 bonds (in 20c). With a rotationally restricted amide, anisochronicity was no longer apparent beyond 17 bond lengths (in 24c). No anisochronicity was observable with a terminal bromophenyl group. We interpret these results as indicating that the oligoureas of short lengths adopt a defined helical secondary structure in solution, but that in longer oligomers the helicity breaks down and transmission of chirality in these systems is limited to about 24 bond lengths. We propose that "apparent diastereotopicity" (anisochronicity) provides a general empirical method for identifying secondary structure in solution.

Total diastereoselectivity in the one-pot multistep reaction of ( RS)-(+)-{[(4-methylphenyl)sulfinyl]methyl}-1-oxa-4-azaspiro[4.5]dec-3-ene and E-methyl cinnamate. An approach to (2 S,4 S,5 R,6 R)-2-(hydroxymethyl)-4,6-diphenyl-1-azabicycle[3.3.1]nonane

The base-mediated reaction of enantiomerically pure α-sulfinylketimine (+)- 1 with ( E)-methyl cinnamate afforded (+)- 5a in a one-pot procedure with complete diastereoselectivity. A sole diastereomer of the eight possible ones was isolated which revealed the stereocontrol of the chiral sulfinyl group in the construction of the three new stereogenic centres. The absolute configuration of stereocentres introduced in (+)- 5a was assigned on the basis of 1H NMR data and a single X-ray structure.

Transition Metal Catalyzed Asymmetric Oxidation of Sulfides

In the past two decades, chiral sulfoxides have been finding increasing use, reflecting growing interest both in convenient auxiliaries in asymmetric synthesis and products with biological properties containing a chiral sulfinyl group. In 1984, groups of Kagan and Modena discovered that titanium(IV) isopropoxide - diethyltartrate based systems (also known as “modified Katsuki-Sharpless reagents”) are capable of asymmetric oxidizing of prochiral sulfides by alkylhydroperoxides. Later, catalytic versions of the titanium tartrate systems were developed (with up to 90 % yield and 90 % ee for certain sulfides) that remain the most applied systems for asymmetric sulfoxidations. However, the low turnover numbers (5-20), complexity and expensiveness of such systems stimulated the search for other transition metal based catalytic systems. This review will cover the progress in transition metal catalyzed asymmetric sulfides oxidations achieved since the discoveries of early 1980s to the present days.

Stereoselective Palladium-Catalyzed Addition of Boronic Acids onto Aldehydes

The authors of this report used palladium catalysis to diastereoselectively generate diaryl methanols with moderate selectivity. One attractive feature is the ability to apply the slightly less expensive palladium catalyst (compared to rhodium). The use of boronic acid substrates as coupling partners is also an interesting aspect. The authors must first convert 2-bromobenzaldehyde in a two-step sequence into the chiral sulfinyl compound.

Highly stereoselective aziridination of imines with ( S)-dimethylsulfonium-( p-tolylsulfinyl)methylide

Addition of ( S)-dimethylsulfonium-( p-tolylsulfinyl)methylide to N-tosyl imines afforded the corresponding sulfinyl aziridines with full enantio- and diastereoselectivity. The chiral sulfinyl substituent was removed without ring opening leading to enantiopure 2-substituted aziridines.

New Multicomponent Approach for the Creation of Chiral Quaternary Centers in the Carbonyl Allylation Reactions

The combined regio- and stereo-controlled carbometalation reaction of alkynyl sulfoxide followed by a zinc homologation and finally an allylation reaction led, in a single-pot operation, to chiral homoallylic alcohols in excellent yields and diastereoselectivities for the creation of chiral quaternary and tertiary centers. The key features in all of the reactions that are described in this article are the high degree of stereocontrol, the level of predictability, and "the ease of execution" which ensures success in the application of such methods. The chiral sulfinyl moiety can be finally removed by simple treatment with alkyllithiums, which allows further functionalizations of the carbon skeleton. By using one of these methods, the creation of chiral quaternary centers with the smallest possible difference, namely CD3 versus CH3 and 13CH3 versus CH3, was easily performed.

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.

Remote asymmetric trifluoromethylation induced by chiral sulfinyl group: synthesis of enantiomerically pure 1-(2-naphthyl)-2,2,2-trifluoroethanol

The reaction of 1-[(2,4,6-triisopropylphenyl)sulfinyl]-2-naphthaldehyde with (trifluoromethyl)trimethylsilane using tetramethylammonium fluoride gave trifluoromethylated compounds in high yield with high diastereoselectivity. Desilylation and subsequent recrystallization yielded the enantiomerically and diastereomerically pure trifluoroethanol, which afforded chiral 1-(2-naphthyl)-2,2,2-trifluoroethanol after removal of the sulfinyl group.

Diastereoselective synthesis of 3,4-disubstituted 5-( p-tolylsulfinyl)-5,6-dehydropiperidin-2-ones: chirality transfer in the enantioselective synthesis of ethyl (+)-(3 S,4a S,7a S)-1-oxo-octahydro-1 H-cyclopenta[ c]pyridine-3-carboxylate

The base-mediated reaction of enantiomerically pure α-sulfinylketimine (+)- 1 with ( E)-α,β-disubstituted propenoate esters afforded 3,4-disubstituted-5-( p-tolylsulfinyl)-5,6-dehydropiperidin-2-ones 9α- 13α and 14 with high or complete diastereoselectivity. A sole diastereomer of the four possible ones, with regard to the nature of ester, was isolated, which revealed the stereocontrol of the chiral sulfinyl group in the Michael reaction and transenolization steps. In addition, the enantioselective synthesis of ethyl (+)-(3 S,4a S,7aS)-1-oxo-octahydro-1 H-cyclopenta[ c]pyridine-3-carboxylates (+)- 17α is described (five steps; 47% yield; ee ⩾97%). The absolute configuration of stereocentres introduced in (+)- 17α was assigned on the basis of 1H NMR data.

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.

Cis‐ and trans‐N‐(Benzylsulfinyl)hexahydrobenzoxazolidin‐2‐ones as Novel Chiral Sulfinyl Transfer Reagents.

AbstractFor Abstract see ChemInform Abstract in Full Text.