C2-Symmetric Chiral Bis(Oxazoline) Ligands in Asymmetric Catalysis

This treatise is an update to a preceding highlight (CH/π hydrogen bonds in crystals) published in this journal 5 years ago (M. Nishio, CrystEngComm, 2004, 6, 130–156). After the introductory part (sections 1 and 2), we survey recent results (mostly since 2004) relevant to the CH/π hydrogen bond: crystal conformation, packing and host/guest chemistry (section 3). Section 4 summarizes the results obtained by crystallographic database (CSD and PDB) analyses. In section 5, several topics in related fields (selectivity in organic reactions, surface chemistry, structural biology, drug design and high-level ab initio calculations of protein/substrate complexes and natural organic compounds) are introduced, and in the final part we comment on the prospects of this emerging field of chemistry.

CH/π hydrogen bonds in organic and organometallic chemistry

A novel C−C bond formation method was developed via the cross-dehydrogenative-coupling (CDC) reaction catalyzed by using copper bromide in the presence of an oxidizing reagent, tert-BuOOH. The CDC reaction provides a simple and efficient catalytic method to construct β-nitroamine via the reaction between sp3 C−H and sp3 C−H bonds.

Highly Efficient Copper-Catalyzed Nitro-Mannich Type Reaction: Cross-Dehydrogenative-Coupling between sp3 C−H Bond and sp3 C−H Bond

Recent Advances in the Catalytic Asymmetric Nitroaldol (Henry) Reaction

Control of stereochemistry during aldol addition reactions has attracted considerable interest over the years as the aldol reaction is one of the most fundamental tools for the construction of new carbon–carbon bonds. Several strategies have been implemented whereby eventually any single possible stereoisomeric aldol product can be accessed by choosing the appropriate procedure. With earlier methods, stoichiometric quantities of chiral reagents were required for efficient asymmetric induction, with the auxiliary most often attached covalently to the substrate carbonyl. Lewis acid catalyzed addition reactions of silyl enolates to aldehydes (Mukaiyama reaction) later opened the way for catalytic asymmetric induction. In the last few years, both chiral metal complexes and small chiral organic molecules have been found to catalyse the direct aldol addition of unmodified ketones to aldehydes with relatively high chemical and stereochemical efficiency. These techniques along with the more recent developments in the area are discussed in this tutorial review.

Current progress in the asymmetric aldol addition reaction

A highly enantioselective, nitroaldol reaction catalyzed by a chiral Cu(II) bis(oxazoline) complex has been developed. The reaction scope includes both aromatic and aliphatic aldehydes (15 examples) affording products in good yields and enantioselectivities (87−94% ee). An X-ray structure of the catalyst has been provided along with a rationalization of the sense of asymmetric induction.

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A new copper acetate-bis(oxazoline)-catalyzed, enantioselective Henry reaction

A chiral auxilliary-based direct aldol reaction is reported. The reactions are catalytic in magnesium salts and are facilitated by silylation with chlorotrimethylsilane. The adducts isolated are in high diastereoselectivity (up to 32:1 dr) and favor the anti-aldol diastereomer B. Reactions are operationally simple and can be run under ambient atmosphere without rigorous exclusion of water. Many of the adducts are highly crystalline and a single diastereomer can be isolated without chromatography.

C. Wade Downey

Papers

A new copper acetate-bis(oxazoline)-catalyzed, enantioselective Henry reaction

Diastereoselective Magnesium Halide-Catalyzed anti-Aldol Reactions of Chiral N-Acyloxazolidinones

Magnesium halide-catalyzed anti-aldol reactions of chiral N-acylthiazolidinethiones.

Synthesis of (-)-epibatidine.

Diastereoselective Magnesium Halide‐Catalyzed anti‐Aldol Reactions of Chiral N‐Acyloxazolidinones.