Remote Activation of the Nucleophilicity of Isatin

The concept of the remote activation of reactivity was first applied in asymmetric organocatalysis. An isatin 3-phenylimine derivative acts as a donor in the thiourea catalyzed asymmetric addition to unsaturated 1,4-ketoesters, affording aza-Michael adducts in high enantiomeric purity and yield

Diastereoselective Multicomponent Cascade Reaction Leading to [3.2.0]-Heterobicyclic Compounds

A general three-component triple cascade reaction through an iminium–enamine–iminium sequential activation initiated by a hetero-Michael addition to α,β-unsaturated aldehydes affords [3.2.0]­heterobicycles in high diastereoselectivity. The rate and diastereoselectivity of the reaction depended on the (<i>E</i>)-4-heterocrotonate and size of the secondary amine. The enantiomers of the major diastereoisomer of oxa- and azabicyclo[3.2.0]­heptane derivatives were separated by enzymatic kinetic resolution with immobilized <i>Candida antarctica</i> Lipase B (CALB), with <i>E</i> values up to 153. The absolute configuration of the nonacylated enantiomer of oxabicyclo[3.2.0]­heptane was determined by single crystal X-ray analysis

Diastereoselective Multicomponent Cascade Reaction Leading to [3.2.0]-Heterobicyclic Compounds

A general three-component triple cascade reaction through an iminium–enamine–iminium sequential activation initiated by a hetero-Michael addition to α,β-unsaturated aldehydes affords [3.2.0]­heterobicycles in high diastereoselectivity. The rate and diastereoselectivity of the reaction depended on the (<i>E</i>)-4-heterocrotonate and size of the secondary amine. The enantiomers of the major diastereoisomer of oxa- and azabicyclo[3.2.0]­heptane derivatives were separated by enzymatic kinetic resolution with immobilized <i>Candida antarctica</i> Lipase B (CALB), with <i>E</i> values up to 153. The absolute configuration of the nonacylated enantiomer of oxabicyclo[3.2.0]­heptane was determined by single crystal X-ray analysis

Asymmetric Synthesis of Congested Spiro-cyclopentaneoxindoles via an Organocatalytic Cascade Reaction

Starting from simple alkylidene oxindoles and nitroketones, a highly stereoselective methodology was developed for the synthesis of spiro-cyclopentaneoxindoles with four consecutive stereogenic centers. Using an organocatalytic cascade of Michael and aldol reactions in the presence of a chiral thiourea catalyst products were obtained in moderate to high yields and excellent enantioselectivities. Nitro, ester, and hydroxyl groups were introduced to the spiro ring, which could be used to facilitate further functionalization of the products

CaCl₂, Bisoxazoline, and Malonate: A Protocol for an Asymmetric Michael Reaction

A mild protocol for the asymmetric Michael addition of dimethyl malonate to various α,β-unsaturated carbonyl compounds was developed. The salient feature of this methodology is that a cheap and environmentally friendly Lewis acid, CaCl₂, was used as a catalyst. An aminoindanol- and pyridine-derived ligand provided in the presence of CaCl₂ Michael adducts in moderate to high enantioselectivities. The scope of the reaction was demonstrated

Two Catalytic Methods of an Asymmetric Wittig [2,3]-Rearrangement

Two different approaches for asymmetric catalytic Wittig [2,3]-rearrangement were developed. Allyloxymalonate derivatives were converted into homoallyl alcohols via organocatalytic or Ca²⁺-catalyzed pathways in moderate to high enantioselectivities

Asymmetric Synthesis of Congested Spiro-cyclopentaneoxindoles via an Organocatalytic Cascade Reaction

Starting from simple alkylidene oxindoles and nitroketones, a highly stereoselective methodology was developed for the synthesis of spiro-cyclopentaneoxindoles with four consecutive stereogenic centers. Using an organocatalytic cascade of Michael and aldol reactions in the presence of a chiral thiourea catalyst products were obtained in moderate to high yields and excellent enantioselectivities. Nitro, ester, and hydroxyl groups were introduced to the spiro ring, which could be used to facilitate further functionalization of the products

Organocatalytic Asymmetric Synthesis of 3‑Chlorooxindoles Bearing Adjacent Quaternary–Tertiary Centers

A new methodology was developed for the synthesis of enantiomerically enriched 3,3-disubstituted 3-chlorooxindoles <b>3</b> via a Michael addition of 3-chloroxindoles to nitroolefins <b>2</b>, catalyzed by chiral squaramide <b>10</b>. Products with adjacent quaternary–tertiary centers were isolated in excellent yields (up to 99%), high diastereoselectivities (up to 11:1), and enantiomeric purities (up to 92%). This is the first example where 3-chloroxoindoles <b>1</b> have been used as nucleophiles in a highly stereoselective organocatalytic reaction

Organocatalytic Asymmetric Synthesis of 3‑Chlorooxindoles Bearing Adjacent Quaternary–Tertiary Centers

A new methodology was developed for the synthesis of enantiomerically enriched 3,3-disubstituted 3-chlorooxindoles <b>3</b> via a Michael addition of 3-chloroxindoles to nitroolefins <b>2</b>, catalyzed by chiral squaramide <b>10</b>. Products with adjacent quaternary–tertiary centers were isolated in excellent yields (up to 99%), high diastereoselectivities (up to 11:1), and enantiomeric purities (up to 92%). This is the first example where 3-chloroxoindoles <b>1</b> have been used as nucleophiles in a highly stereoselective organocatalytic reaction

Asymmetric Organocatalytic Wittig [2,3]-Rearrangement of Oxindoles

A highly enantioselective organocatalytic [2,3]-rearrangement of oxindole derivatives is presented. The reaction was catalyzed by squaramide, and this provides access to 3-hydroxy 3-substituted oxindoles in high enantiomeric purities