sulfa-Michael Addition Research Articles

Organocatalytic Asymmetric Sulfa-Michael Addition of Thiols to 4,4,4-Trifluorocrotonates

The first asymmetric sulfa-Michael addition of thiols to 4,4,4-trifluorocrotonates for the construction of a stereogenic center bearing a unique trifluoromethyl group and a sulfur atom has been achieved in high yields and excellent enantioselectivities with a 1 mol % bifunctional organocatalyst. Subsequent transformation led to the expedient preparation of enantioenriched thiochroman-4-one and the key intermediate of the potent inhibitor of MMP-3, (R)-γ-trifluoromethyl γ-sulfone hydroxamate.

Chiral Squaramide‐Catalyzed Enantioselective Conjugate Michael Addition of Various Thiols to α,β‐UnsaturatedN‐Acylated Oxazolidin‐2‐ones

AbstractA highly enantioselective sulfa‐Michael addition (SMA) of various thiols to α,β‐unsaturatedN‐acylated oxazolidinones has been achieved with a chiral squaramide catalyst under very mild reaction conditions. In addition, the conversion of the β‐thio‐substituted adduct to the corresponding methyl β‐tosylbutanoate was demonstrated in high yield through a methanolysis/oxidation sequence.

Scandium-Catalyzed Asymmetric Sulfa-Michael Addition in Water

This report describes a highly enantioselective Lewis acid catalyzed sulfa-Michael ­addition reaction of thiols to α,β-unsaturated ­ketones. The Lewis acid is scandium(III) triflate and the chiral ligand is a chiral bipyridine. Interestingly, water is found to be the best choice of solvent, which makes this process environmentally benign.

Sc(III)-Catalyzed Enantioselective Addition of Thiols to α,β-Unsaturated Ketones in Neutral Water

This report concerns Lewis acid catalyzed enantioselective sulfa-Michael addition in neutral water by using a very efficient Sc(OTf)(3)/bipyridine 1 catalytic system. It is noteworthy that the protocol presented employs water as a reaction medium and allows us to obtain very high stereoselectivity and satisfactory yields for β-keto sulphides deriving from aliphatic thiols. The recovery and reuse of both the aqueous medium and the catalytic system is also reported.

Cinchona Alkaloid Squaramide Catalyzed Sulfa-Michael Addition

Cinchona Alkaloid Squaramide Catalyzed Sulfa-Michael Addition

Asymmetric Synthesis of Thiadecalins via an Organocatalytic Triple Cascade/Sulfa-Michael Sequence

An efficient two-step asymmetric synthesis of highly substituted cis-configured thiadecalins and the corresponding hexahydrobenzothiophene core is described. Thiadecalin derivatives are known for their widespread biological activities, such as antimicrobial and neurotropic properties. The procedure is based on an organocatalytic triple cascade reaction followed by an intramolecular sulfa-Michael addition. In this manner six consecutive stereocentres are controlled and the target molecules are obtained in moderate yields, with virtually complete enantioselectivitiy (ee >99%) and after recystallisation in diastereomeric ratios of>97:3. The relative and absolute configuration was determined by NMR spectroscopy and X-ray structure analysis.

Sulfa-Michael Addition Catalyzed by a Quinine-Derived Urea Catalyst

A highly enantioselective sulfa-Michael addition between aromatic thiols and ­cyclic and acyclic enones promoted by a quinine-derived urea catalyst is reported. A remarkably low catalyst loading is used (0.1 mol). The authors suggest a transition state model.

Highly Enantioselective Organocatalytic Sulfa-Michael Addition to α,β-Unsaturated Ketones

A cinchona alkaloid-derived urea was found to be an efficient organocatalyst for catalyzing enantioselective conjugate addition between thiols and various alpha,beta-unsaturated ketones to provide optically active sulfides with high chemical yields (up to >99%) and enantiomeric excess (up to >99% ee). The reaction was performed with 0.1 mol % of catalyst in toluene at room temperature. A transition state model has been proposed to explain the stereochemical outcome of the reaction.

Conjugate Addition of Alkyl Thiols

The authors report a catalytic enantioselective conjugate addition of simple alkyl ­thiols to α,β-unsaturated N-acylated oxazolidin-2-ones using quinidine derivative QD. The thiourea moiety of this catalyst is crucial to ensure satisfactory reactivity and enantioselectivity, since 6′-OH quinidine derivative QD′ only gave the adduct in 15% yield and 74.5:25.5 er after 24 h while QD provided the product in nearly quantitative yield and 92.5:7.5 er after 2 h. Under optimized conditions (in chloroform at -20 or -50 ˚C), the sulfa-Michael addition of alkyl thiols such as benzyl ­thiols, allyl thiols to β-alkyl or aryl α,β-unsaturated N-acylated oxazolidin-2-ones furnishes the corresponding sulfides in 84-99% yields and high enantioselectivities (up to 98:2 er). Conversion of one of the 1,4-adducts into a β-mercapto ester is also demonstrated by the authors.

Methyl Mercapturate Synthesis: An Efficient, Convenient and Simple Method

A safe and simple method for methyl S-arylmercapturate synthesis is described. Thirteen such compounds, to be used afterwards in metabolism studies, have been obtained with yields ranging from 71 to 99.6%. These compounds were obtained using a sulfa-Michael addition and synthesized by adding the corresponding thiophenols to a mixture composed of methyl 2-acetamidoacrylate (MAA), potassium carbonate and a phase transfer catalyst, Aliquat 336. MAA, the initial synthon, was itself isolated in quasi quantitative yield following a fully described synthesis.

Asymmetric Sulfa‐Michael Additions

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Asymmetric Sulfa-Michael Additions

Numerous asymmetric methods have been developed over the past 30 years to effect the Michael reaction of sulfur donors and Michael acceptors. Many of these stoichiometric and catalytic methods are complementary to one another, each having a certain range of substrate tolerance. Organocatalysis has a place at the origin of this field in the discovery of cinchona alkaloid catalyzed sulfa--Michael reactions. At the same time, it is involved in the current state-of-the-art as several elegant tandem processes that employ secondary amine catalysts and involve initial sulfa-Michael additions have been developed.