Chiral Sulfinyl Group Research Articles

Stereoselective Aminomethylation of β,β-Disubstituted Enesulfinamides: Asymmetric Construction of Less Accessible Acyclic α,α-Disubstituted α-Aminomethylated Ketimines.

β,β-Disubstituted enesulfinamides undergo stereoselective nucleophilic addition to the formaldehyde imines, in situ formed from tosylmethylcarbamates, affording α-aminomethylated ketimines bearing a challenging acyclic quaternary stereocenter substituted by two sterically and electronically similar groups (e.g., Me and Et). The defined geometry of the C═C bond in the enesulfinamides, combined with the strong chiral induction offered by their chiral sulfinyl group, ensures precise stereocontrol during the formation of the new C-C bond.

Insight into Stereocontrol in the Asymmetric Intramolecular Allylation with a tert-Butylsulfinamide Nucleophile: Application in the Synthesis of Chiral Isoindoline-1-Carboxylic Acid Esters.

The asymmetric induction afforded by a chiral sulfinyl group in a palladium/Brønsted-acid-catalyzed intramolecular allylic amination was investigated. Predictions of the diastereoselectivity for various substrates under assumed total thermodynamic control were obtained from density functional theory (DFT), and the correlation with experimental data demonstrates abrupt changes to kinetic control across the substrate scope. The resulting heterocyclic product was readily converted to valuable isoindoline-1-carboxylic acid esters by a two-step oxidation sequence, providing asymmetric access to a key unnatural α-amino acid scaffold.

Diastereoselective Addition of PhSCF2SiMe3 to Chiral N-tert-Butanesulfinyl Ketimines Derived from Isatins: Synthesis of Enantioenriched gem-Difluoromethylenated Spiro-pyrrolidinyl and Spiro-piperidinyl Oxindoles.

A convenient and efficient synthetic strategy to prepare enantioenriched gem-difluoromethylenated spiro-pyrrolidinyl and spiro-piperidinyl oxindoles is described. Fluoride-mediated diastereoselective nucleophilic addition of PhSCF2SiMe3 to chiral N-tert-butanesulfinyl ketimines derived from isatins was a key step and provided diastereomeric adducts, which were readily separable. Removal of the chiral sulfinyl group followed by structural manipulation afforded chiral gem-difluoromethylenated spiro-pyrrolidinyl and spiro-piperidinyl oxindoles.

Synthesis and Resolution of a Chiral Open-Chain Host Having a Partial Structure of p-tert-Butylsulfinylcalix[4]arene

Abstract An open-chain carboxylic acid host with a chiral sulfinyl group (4) was synthesized from 3,3′-thiobis[(5-tert-butyl-2-hydroxyphenyl)acetic acid] (2) by oxidation of the epithio linkage with mCPBA, followed by acid-catalyzed monoesterification with propan-1-ol. The monoester was resolved via diastereomeric salt formation using quinidine as a resolving agent. The absolute configuration of (+)-4 was assigned to be (R) by X-ray analysis.

Diastereoconvergent synthesis of chiral sulfoxides containing vicinal amino alcohol framework

A highly diastereoconvergent synthesis of chiral sulfoxides containing vicinal amino alcohol framework has been achieved in moderate to good yield with up to 99:1 dr. Different from the previous work, the stereochemistry of the new chiral center was determined solely by the configuration of benzyl tert-butyl sulfoxide, while both the chiral sulfinyl group and the tert-butyldimethylsilyl ether (α-OTBS) group at the α-position of imine were not involved in the stereo induction. This approach also provides an efficient synthesis of chiral building blocks of pyrrolidinones.

Stereocontrolled Synthesis of Planar Chiral Carba-Paracyclophanes via Modular Assembly

Described herein is a flexible modular approach to planar chiral carba-paracyclophanes via the stepwise assembly of two distinct side arms and the aromatic core followed by ring-closing olefin metathesis. Planar chirality is induced by one chiral sulfinyl group by forming a hydrogen bond to the phenol in the aromatic unit.

Regio- and Stereoselective Aminopentadienylation of Carbonyl Compounds

A simple and robust protocol is detailed for the preparation of enantioenriched α-substituted (1,4-pentadien-3-yl)amine derivatives. The methodology involves the addition of an in situ formed pentadienyl indium reagent to chiral tert-butylsulfinimines, previously formed in the same pot. The addition takes place with excellent γ-regio- and diastereoselectivity for a wide range of carbonyl compounds, including α-unsubstituted aldehydes and methyl alkyl ketones. The catalytic hydrogenation of the sulfinamines obtained provides a convenient access to chiral α-substituted (3-pentyl)amines. The hydroboration-oxidation of the α-(1,4-pentadien-3-yl)amine derivatives, followed by a cyclization under Mitsunobu conditions, takes place with an excellent diastereoselectivity governed by the chiral sulfinyl group.

Transition Metal Catalyzed Asymmetric Oxidation of Sulfides: From Discovery to Recent Trends

In the past decades, chiral sulfoxides have been finding increasing use, reflecting a wide interest in both convenient auxiliaries in asymmetric synthesis and products with biological properties containing a chiral sulfinyl group. Since the breakthrough of the groups of Kagan and of Modena (1984) who discovered that modified titanium(IV) isopropoxide - diethyltartrate catalyst systems (known as “modified Katsuki-Sharpless reagents”) are capable of asymmetric oxidizing of prochiral sulfides by alkylhydroperoxides, plethora of modifications and practical applications of titanium based catalyst systems for the asymmetric oxidation of sulfides to sulfoxides emerged. Diverse catalysts based on titanium complexes with other chiral ligands as well as on other transition metal complexes appeared, especially in the last fifteen years. The aim of this review is to cover the progress in transition metal catalyzed asymmetric sulfides oxidations achieved since the milestone discoveries of early 1980s and to bring out the main trends of this important field of modern catalytic chemistry.

ChemInform Abstract: Asymmetric Synthesis of Ethoxydienamines in Superbasic Medium Mediated by Chiral Sulfinyl Group.

AbstractIt provides a highly enantioselective approach to ethoxydienamines.

Asymmetric Synthesis of Ethoxydienamines in Superbasic Medium Mediated by Chiral Sulfinyl Group

The direct addition of metalated alkoxydiene 2, obtained from α,β-unsaturated acetal 1 through a LIC-KOR-promoted conjugated elimination reaction, to enantiopure sulfinimines 3 (both R and SN-sulfinyl imines) afforded N-sulfinyl alkoxydienyl amines 4 with high diastereoselectivity. Functionalized enantiopure alkoxydienyl amines 5 were then easily obtained upon the selective removal of the chiral auxiliary under mild conditions. Moreover, the further hydrolysis of the alkoxydienyl moiety gave access to protected enantiopure β-keto amines 7.

ChemInform Abstract: A New Approach to the Asymmetric Cyclopropanation via a Chiral Sulfinyl Group.

ChemInform 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.

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.

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.

N-Phosphano nitrogen-containing five-membered aromatic chiral α-sulfoxides as new chiral ligands in asymmetric palladium-catalyzed allylic alkylation: stereoelectronic effects of the substituents on the aromatic rings

New chiral ligands, N-diphenylphosphano nitrogen-containing five-membered aromatic compounds bearing chiral sulfinyl groups as the sole chiral source has been developed. The structure of a palladium intermediate derived from the new chiral sulfoxide ligand was determined as a palladium complex with a five-membered chelate ring formed by coordination of the phosphano group and the sulfinyl sulfur atom involved. The stereoelectronic effects of substituents on the aromatic rings are discussed.

Novel chiral sulfur-containing ferrocenyl ligands for palladium-catalyzed asymmetric allylic substitution.

New chiral ferrocenyl ligands having chiral sulfinyl and phosphinyl groups were prepared. The palladium-catalyzed allylic substitution reaction using these chiral ligands showed good enantioselectivity. The mechanism for the asymmetric reaction is proposed on the basis of the stereochemical outcome.

Recent developments in chiral non-racemic sulfinyl group chemistry in asymmetric synthesis

Chiral sulfinyl groups have been widely used in organic synthesis as a stereo- and enantiodirecting functionality and the high efficiency of the selectivity has received much attention in recent years. In this review we wish to cover the work published in the literature since 1996. The participation of a chiral sulfinyl function in a wide range of reactions as well as the application of these methodologies to the synthesis of natural products are reported.