sulfa-Michael Addition Research Articles

N-Heterocyclic carbene-catalyzed sulfa-Michael addition of enals.

An efficient N-heterocyclic carbene (NHC) catalyzed sulfa-Michael addition (SMA) between enals and thiols has been developed. Under the catalysis of 10 mol% stable free carbene IPr and with 20 mol% hexafluoroisopropanol (HFIP) as an additive, enals react with a variety of thiols to afford the SMA adducts in 54-98% yields. In this process, the free carbene preferentially interacts with thiols through hydrogen-bonding and no NHC-catalyzed extended Umpolung transformations were observed.

Enantioselective bifunctional iminophosphorane catalyzed sulfa-Michael addition of alkyl thiols to unactivated β-substituted-α,β-unsaturated esters.

The highly enantioselective sulfa-Michael addition of alkyl thiols to unactivated β-substituted-α,β-unsaturated esters catalyzed by a bifunctional iminophosphorane (BIMP) organocatalyst is described. The low acidity of the alkyl thiol pro-nucleophiles is overcome by the high Brønsted basicity of the catalyst and the chiral scaffold/thiourea hydrogen-bond donor moiety provides the required enantiofacial discrimination in the addition step. The reaction is broad in scope with respect to the alkyl thiol and β-substituent of the α,β-unsaturated ester, affords sulfa-Michael adducts in excellent yields (up to >99%) and enantioselectivity (up to 97 : 3 er) and can operate down to 1 mol% catalyst loading.

ChemInform Abstract: Direct Synthesis of γ‐Keto Sulfones from Allylic Alcohols: One‐Pot Palladium(II)‐Catalyzed Generation of Enones Followed by Water‐Mediated 1,4‐Addition of Organosulfinates.

Allylic alcohols were exploited as synthetic precursors of γ-keto sulfones. The reaction involved the one-pot generation of α,β-enones in situ from the allylic alcohols by using a PdII–dioxygen catalytic system and subsequent sulfa-Michael addition in the presence of water. Importantly, water was identified as a sustainable substitute for a toxic copper salt to promote organosulfonyl addition. Diverse examples of aromatic and aliphatic γ-keto sulfones were prepared. Specially, Ar–X (X = Br, Cl) bonds were tolerated, which indicated a chemoselective catalytic system for the preparation of halogen-bearing γ-keto sulfones. This one-pot method does not require an acid, a base, or isolation of any intermediate. Control experiments indicated that the active catalyst of the first step also promoted the subsequent C–S bond-formation reaction. Water was found to accelerate the reaction rate and to be involved in the protonolysis of the σ-alkylpalladium complex, as corroborated by deuterium incorporation.

Asymmetric Catalysis with Iron–Salen Complexes

Iron(III)–salen complexes based on a chiral cis -2,5-diaminobicyclo[2.2.2]octane scaffold are used as catalysts for a variety of stereo­selective reactions. High enantio- and diastereoselectivities can be achieved with these catalysts in sulfa-Michael conjugate addition to acyclic α,β-unsaturated ketones, in regioselective δ-addition of thiols to acyclic α,β,γ,δ-unsaturated ketones, and in Conia-ene carbocyclization of alkynyl-substituted β-dicarbonyl compounds. The use of these chiral iron–salen complexes as catalysts provides a new method for conducting these three important reactions under environmentally sustainable conditions.

Asymmetric Sulfa-Michael Addition of α,β-Unsaturated Esters/Amides Using a Chiral N-Heterocyclic Carbene as a Noncovalent Organocatalyst

We report an asymmetric sulfa-Michael reaction of α,β-unsaturated amides and esters using a chiral N-heterocyclic carbene as the HOMO-raising organocatalyst. We discovered an interesting correlation between ¹³C NMR shifts of substrates and ee of their products. More electron-deficient Michael acceptors afforded higher enantioselectivity.

ChemInform Abstract: Site and Stereoselectivity in Sulfa—Michael Addition to Equivocally Activated Conjugated Dienes.

AbstractIt is found that the product ratio of the competing sulfa—Michael 1,4‐ and 1,6‐addition depends on the potency of the electron withdrawing group and can be to some extend altered by the choice of the activation method.

Bifunctional Iminophosphorane Catalyzed Enantioselective Sulfa-Michael Addition to Unactivated α-Substituted Acrylate Esters.

The highly enantioselective sulfa-Michael addition of alkyl thiols to unactivated α-substituted acrylate esters catalyzed by a bifunctional iminophosphorane organocatalyst under mild conditions is described. The strong Brønsted basicity of the iminophosphorane moiety of the catalyst provides the necessary activation of the alkyl thiol pro-nucleophile, while the two tert-leucine residues flanking a central thiourea hydrogen-bond donor facilitate high enantiofacial selectivity in the protonation of the transient enolate intermediate. The reaction is broad in scope with respect to the alkyl thiol, the ester moiety, and the α-substituent of the α,β-unsaturated ester, affords sulfa-Michael adducts in excellent yields (up to >99%) and enantioselectivities (up to 96% ee), and is amenable to decagram scale-up using catalyst loadings as low as 0.05 mol %.

Insights into the diastereoselective control in the sulfa-Michael addition of thiols to nitroalkenes: stereoelectronic effect in the cyclic chelated transition state

The diastereoselective control in the sulfa-Michael addition of nitroalkenes and lithium thiolates followed by protonation was investigated. Lithium thiolates first added to nitroalkenes to afford cyclic lithium-chelated nitronates. The subsequent kinetic protonation of nitronates was proved to be the stereochemical determinant through the chelate-controlled six-membered half-chair transition state bearing two approximately 1,2-diaxial substituents due to stereoelectronic effect control. The stereoelectronic effect in the cyclic chelated transition state was probed and verified by tuning the steric bulkiness of the corresponding substituents. The reaction involving 1-nitrocyclohexene provided perfect support for the proposed diastereoselective control model. The current investigation provided not only comprehensive insights into the diastereoselective control in the sulfa-Michael addition of nitroalkenes and thiolates, but also an important role of the stereoelectronic effect in certain organic reactions involving cyclic chelate transition states.

Cinchona Alkaloid Catalyzed Sulfa-Michael Addition Reactions Leading to Enantiopure β-Functionalized Cysteines.

Sulfa-Michael additions to α,β-unsaturated N-acylated oxazolidin-2-ones and related α,β-unsaturated α-amino acid derivatives have been enantioselectively catalyzed by Cinchona alkaloids functionalized with a hydrogen bond donating group at the C6' position. The series of Cinchona alkaloids includes known C6' (thio)urea and sulfonamide derivatives and several novel species with a benzimidazole, squaramide or a benzamide group at the C6' position. The sulfonamides were especially suited as bifunctional organocatalysts as they gave the products in very good diastereoselectivity and high enantioselectivity. In particular, the C6' sulfonamides catalyzed the reaction with the α,β-unsaturated α-amino acid derivatives to afford the products in a diastereomeric ratio as good as 93:7, with the major isomer being formed in an ee of up to 99%. The products of the organocatalytic sulfa-Michael addition to α,β-unsaturated α-amino acid derivatives were subsequently converted in high yields to enantiopure β-functionalized cysteines suitable for native chemical ligation.

Asymmetric Iron(III)-Catalyzed Sulfa-Michael Addition of Thiols to Dienones

Asymmetric Iron(III)-Catalyzed Sulfa-Michael Addition of Thiols to Dienones

ChemInform Abstract: Stereoselective Synthesis of Organosulfur Compounds Incorporating N‐Aromatic Heterocyclic Motifs and Quaternary Carbon Centers via a Sulfa‐Michael Triggered Tandem Reaction.

AbstractA novel sulfa‐Michael addition (SMA)‐triggered tandem reaction is developed by combining a SMA reaction with a simultaneous rearomatization process utilizing a less reactive carbonyl group as an intramolecular electrophilic partner.

ChemInform Abstract: Diastereoselectivity in the Triethylamine‐Catalyzed sulfa‐Michael Addition of Thiols to Nitroalkenes: Kinetic and Thermodynamic Control.

ChemInformVolume 46, Issue 37 Preparative Organic Chemistry ChemInform Abstract: Diastereoselectivity in the Triethylamine-Catalyzed sulfa-Michael Addition of Thiols to Nitroalkenes: Kinetic and Thermodynamic Control. Jiandong Wang, Jiandong Wang State Key Lab. Chem. Resour. Eng., Beijing Univ. Chem. Technol., Beijing 100029, Peop. Rep. ChinaSearch for more papers by this authorNing Chen, Ning Chen State Key Lab. Chem. Resour. Eng., Beijing Univ. Chem. Technol., Beijing 100029, Peop. Rep. ChinaSearch for more papers by this authorJiaxi Xu, Jiaxi Xu State Key Lab. Chem. Resour. Eng., Beijing Univ. Chem. Technol., Beijing 100029, Peop. Rep. ChinaSearch for more papers by this author Jiandong Wang, Jiandong Wang State Key Lab. Chem. Resour. Eng., Beijing Univ. Chem. Technol., Beijing 100029, Peop. Rep. ChinaSearch for more papers by this authorNing Chen, Ning Chen State Key Lab. Chem. Resour. Eng., Beijing Univ. Chem. Technol., Beijing 100029, Peop. Rep. ChinaSearch for more papers by this authorJiaxi Xu, Jiaxi Xu State Key Lab. Chem. Resour. Eng., Beijing Univ. Chem. Technol., Beijing 100029, Peop. Rep. ChinaSearch for more papers by this author First published: 27 August 2015 https://doi.org/10.1002/chin.201537029Read 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. Volume46, Issue37September, 2015 RelatedInformation

ChemInform Abstract: Enantioselective Synthesis of Trifluoromethylated Tertiary Thioethers Through Organocatalytic Sulfa‐Michael Addition of Thiols to β‐Trifluoromethyl β,β‐Disubstituted Enones.

An organocatalytic asymmetric sulfa-Michael addition of thiols to β-trifluoromethyl β,β-disubstituted (E)-enones in the presence of 10 mol% of a cinchona alkaloid-derived thiourea catalyst provides direct and simple access to chiral trifluoromethyl tertiary thioethers in high yields and up to 76% ee.

Quaternary Stereocenters via NHC-Catalyzed Sulfa-Michael Addition

Key words NHC catalysis - sulfa-Michael addition - non-covalent interactions

Diastereoselectivity in the triethylamine-catalyzed sulfa-Michael addition of thiols to nitroalkenes: kinetic and thermodynamic control

The diastereoselectivity in the triethylamine-catalyzed sulfa-Michael addition of nitroalkenes and thiols was investigated. The sulfa-Michael addition is kinetic control at the beginning and thermodynamic control at the end for less bulky reactants. Thus, kinetic and thermodynamic-controlled adducts can be obtained as major products by controlling the reaction time in those cases. Linear nitroalkenes generally produce anti-adducts as major kinetic products due to favorable steric and stereoelectronic effects, but the diastereoselectivity decreases obviously with steric increase of the substituent located in the vicinal olefinic carbon to the nitro group, even leading to syn-adducts as major kinetic products. 1-Nitrocyclohexene gives rise stereospecifically to kinetic cis-adduct, which epimerizes into more stable trans-adduct as major product through the thermodynamic equilibrium. However, the Michael additions involving bulky reactants are generally slow, resulting in the direct generation of thermodynamic adducts.

Asymmetric Synthesis of Dihydronaphthoquinones Containing Adjacent Stereocenters via a Sulfa-Michael Addition Triggered Ring-Expansion Approach.

A novel asymmetric synthetic approach for the construction of enantioenriched functionalized dihydroquinones incorporating adjacent quaternary and tertiary stereocenters has been reported, in which enantioenriched 3-allylic phthalides engaged in an unprecedented sulfa-Michael addition-triggered stereoselective ring-expansion reaction, and furnished the desired sulfur-incoporated dihydronaphthoquinones with high stereoselectivity.

ChemInform Abstract: Asymmetric Sulfa‐Michael Addition to α‐Substituted Vinyl Ketones Catalyzed by Chiral Primary Amine.

The first effective example of asymmetric conjugate addition–protonation reactions of thiols to α-substituted vinyl ketones by chiral primary amine catalysis is reported. A simple chiral primary–tertiary diamine catalyst derived from l-phenylalanine was found to promote the sulfa-Michael addition–protonation reactions with good to excellent enantioselectivity.

Enantioselective Synthesis of Trifluoromethylated Tertiary Thioethers through Organocatalytic Sulfa-Michael Addition of Thiols to β-Trifluoromethyl β,β-Disubstituted Enones

An organocatalytic asymmetric sulfa-Michael addition of thiols to β-trifluoromethyl β,β-disubstituted (E)-enones in the presence of 10 mol% of a cinchona alkaloid-derived thiourea catalyst provides direct and simple access to chiral trifluoromethyl tertiary thioethers in high yields and up to 76% ee.

ChemInform Abstract: Catalytic Asymmetric Conjugate Addition of Various α‐Mercaptoketones to α,β‐Unsaturated N‐Acylated Oxazolidin‐2‐ones with Bifunctional Organocatalyst.

A bifunctional squaramide catalysed enantioselective conjugate Michael addition reaction of various α-mercaptoketones to α,β-unsaturated N-acylated oxazolidinones under mild reaction conditions has been developed. This catalytic reaction afforded the corresponding adducts in good yields with high enantioselectivities (up to 92% ee). This is the first example of organocatalysed sulfa-Michael addition using various α-mercaptoketones as the Michael donors.

Highly enantioselective sulfa-Michael addition reactions using N-heterocyclic carbene as a non-covalent organocatalyst.

We report the first asymmetric sulfa-Michael addition (SMA) reactions using a chiral N-heterocyclic carbene (NHC) as a non-covalent organocatalyst. We demonstrate that a triazolium salt derived NHC functions as an excellent Brønsted base to promote enantioselective carbon-sulfur bond formation. The reaction is applicable to a wide range of thiols and electrophilic olefins. Notably, quaternary chiral centers bearing both an S atom and a CF3 group were synthesized with excellent asymmetric control. Mechanistic studies suggest that the facial discrimination is likely to be guided by non-covalent interactions: hydrogen bonding and π-π stacking.