Bifunctional Iminophosphorane Catalyzed Enantioselective Sulfa-Michael Addition to Unactivated α,β-Unsaturated Amides

<div>The first metal-free catalytic intermolecular enantioselective sulfa-Michael addition to unactivated <i>α</i>,<i>β</i>- unsaturated amides is described. Consistently high enantiomeric excesses, and yields were obtained over a wide range of alkyl thiol pronucleophiles and electrophiles under mild reaction conditions, enabled by a novel squaramide-based bifunctional iminophosphorane (BIMP) catalyst. Low catalyst loadings (2 mol%) were achieved on a decagram scale, demonstrating the scalability of the reaction. Computational analysis revealed the origin of the high enantiofacial selectivity, corresponding transition states, and provided substantial evidence for specific non-covalent activation of the carbonyl group of the <i>α</i>,<i>β</i>-unsaturated amide by the catalyst.</div>

Bifunctional Iminophosphorane Catalyzed Enantioselective Sulfa-Michael Addition to Unactivated α,β-Unsaturated Amides

<div>The first metal-free catalytic intermolecular enantioselective sulfa-Michael addition to unactivated <i>α</i>,<i>β</i>- unsaturated amides is described. Consistently high enantiomeric excesses, and yields were obtained over a wide range of alkyl thiol pronucleophiles and electrophiles under mild reaction conditions, enabled by a novel squaramide-based bifunctional iminophosphorane (BIMP) catalyst. Low catalyst loadings (2 mol%) were achieved on a decagram scale, demonstrating the scalability of the reaction. Computational analysis revealed the origin of the high enantiofacial selectivity, corresponding transition states, and provided substantial evidence for specific non-covalent activation of the carbonyl group of the <i>α</i>,<i>β</i>-unsaturated amide by the catalyst.</div>

NHC-catalyzed covalent activation of heteroatoms for enantioselective reactions

Covalent activation of heteroatoms enabled by N-heterocyclic carbene (NHC) organic catalysts for enantioselective reactions is evaluated and summarized in this review.

Chemo-selective cross reaction of two enals via carbene-catalyzed dual activation

An NHC-catalyzed dual activation of two different enals is disclosed with both covalent and non-covalent activation pathways involved.

Organocatalysts for enantioselective synthesis of fine chemicals: definitions, trends and developments

Organocatalysis, that is the use of small organic molecules to catalyze organic transformations, has been included among the most successful concepts in asymmetric catalysis, and it has been used for the enantioselective construction of C–C, C–N, C–O, C–S, C–P and C–halide bonds. Since the seminal works in early 2000, the scientific community has been paying an ever-growing attention to the use of organocatalysts for the synthesis, with high yields and remarkable stereoselectivities, of optically active fine chemicals of interest for the pharmaceutical industry. A brief overview is here presented about the two main classes of organocatalysis which are respectively characterized by covalent and non-covalent activation of the substrate. More detailed information about non-covalent interactions for organocatalysis are given. Finally, some successful examples of heterogenisation of organocatalysts are also discussed, in the view of a potential industrial exploitation.