The catalytic asymmetric polyene cyclization of homofarnesol to ambrox.

Polyene cyclizations are among the most complex and challenging transformations in biology. In a single reaction step, multiple carbon-carbon bonds, ring systems and stereogenic centres are constituted from simple, acyclic precursors. Simultaneously achieving this kind of precise control over product distribution and stereochemistry poses a formidable task for chemists.

Scalable and Highly Diastereo- and Enantioselective Catalytic Diels-Alder Reaction of α,β-Unsaturated Methyl Esters.

Despite tremendous advances in enantioselective catalysis of the Diels-Alder reaction, the use of simple α,β-unsaturated esters, one of the most abundant and useful class of dienophiles, is still severely limited in scope due to their low reactivity. We report here a catalytic asymmetric Diels-Alder methodology for a large variety of α,β-unsaturated methyl esters and different dienes based on extremely reactive silylium imidodiphosphorimidate (IDPi) Lewis acids. Mechanistic insights from accurate domain-based local pair natural orbital coupled-cluster (DLPNO-CCSD(T)) calculations rationalize the catalyst control and stereochemical outcome.

Altering Copper-Catalyzed A Couplings by Mechanochemistry: One-Pot Synthesis of 1,4-Diamino-2-butynes from Aldehydes, Amines, and Calcium Carbide.

The ability of mechanochemistry to alter established chemical selectivity is demonstrated. A copper(I)-catalyzed mechanochemical aldehyde/alkyne/amine coupling using calcium carbide as the acetylene source provides selective access to 1,4-diamino-2-butynes, which contrasts classical approaches that provide propargylamine-type products. Solventless milling conditions were found to be essential to unmask A  coupling products with new compositions.

Mechanochemical Activation of Iron Cyano Complexes: A Prebiotic Impact Scenario for the Synthesis of α-Amino Acid Derivatives.

Mechanochemical activation of iron cyano complexes by ball milling results in the formation of HCN, which can be trapped and incorporated into α-aminonitriles. This prebiotic impact scenario can be extended by mechanochemically transforming the resulting α-aminonitriles into α-amino amides using a chemical route related to early Earth conditions.

Enantioselective Synthesis of N,S-Acetals by an Oxidative Pummerer-Type Transformation using Phase-Transfer Catalysis.

Reported is the first enantioselective oxidative Pummerer-type transformation using phase-transfer catalysis to deliver enantioenriched sulfur-bearing heterocycles. This reaction includes the direct oxidation of sulfides to a thionium intermediate, followed by an asymmetric intramolecular nucleophilic addition to form chiral cyclic N,S-acetals with moderate to high enantioselectivites. Deuterium-labelling experiments were performed to identify the stereodiscrimination step of this process.

Mechanochemical Lignin-Mediated Strecker Reaction.

A mechanochemical Strecker reaction involving a wide range of aldehydes (aromatic, heteroaromatic and aliphatic), amines, and KCN afforded a library of α-aminonitriles upon mechanical activation. This multicomponent process was efficiently activated by lignocellulosic biomass as additives. Particularly, commercially available Kraft lignin was found to be the best activator for the addition of cyanide to the in situ formed imines.

Mechanochemical Strecker Reaction: Access to α-Aminonitriles and Tetrahydroisoquinolines under Ball-Milling Conditions.

A mechanochemical version of the Strecker reaction for the synthesis of α-aminonitriles was developed. The milling of aldehydes, amines, and potassium cyanide in the presence of SiO2 gave the corresponding α-aminonitriles in good to high yields. The high efficiency of the mechanochemical Strecker-type multicomponent reaction allowed the one-pot synthesis of tetrahydroisoquinolines after a subsequent internal N-alkylation reaction.