Allan D. Headley

Ionic-Liquid-Supported (ILS) Catalysts for Asymmetric Organic Synthesis

The asymmetric synthesis of compounds that contain new C-C and C-O bonds remains one of the most important types of synthesis in organic chemistry. Over the years, many different types of catalysts have been designed and used effectively to carry out such transformations. Ionic-liquid-supported (ILS) catalysts represent a new and very effective class of catalysts that are used to facilitate the asymmetric synthesis of such compounds. There are many advantages to using ILS catalysts; they are nontoxic, environmentally benign, and, most important, recyclable. An overview of the design, synthesis, mode of action, and effectiveness of this class of catalysts is reported.

Ionic liquid-supported (ILS) (S)-pyrrolidine sulfonamide, a recyclable organocatalyst for the highly enantioselective Michael addition to nitroolefins.

A new class of ionic liquid supported (ILS) (S)-pyrrolidine sulfonamide organocatalyst has been developed and shown to be a very effective catalyst for the asymmetric Michael addition reactions of ketones and aldehyde to nitroolefins with high enantio- and diastereoselectivities. This ILS organocatalyst is also easily recycled and could be reused at least five times without significant loss of its ability to affect the outcome of the asymmetric reactions.

Functionalized chiral ionic liquid as recyclable organocatalyst for asymmetric Michael addition to nitrostyrenes

A new type of pyrrolidine-based chiral ionic liquid has been developed. This chiral ionic liquid was found to catalyze the Michael addition reaction of aldehydes and nitrostyrenes to give moderate yields, good enantioselectivies, high diastereoselectivities, and recyclability.

Di(methylimidazole)prolinol silyl ether catalyzed highly Michael addition of aldehydes to nitroolefins in water.

A new pyrrolidine-based organocatalyst for asymmetric reactions has been developed and shown to be a very effective catalyst for the Michael reaction involving various nitroolefins and aldehydes in water. This design is based on the introduction of a hydrophilic group into the pyrrolidine side chain. This catalyst, di(methylimidazole)prolinol silyl ether in combination with sodium bicarbonate as additive effectively catalyzed the Michael addition of aldehydes to nitroolefins in water as solvent in high yields and excellent enantioselectivities.

Organocatalytic Direct Asymmetric Crossed-Aldol Reactions of Acetaldehyde in Aqueous Media

A new type of diarylprolinol-based catalyst, which contains a dioctylamino group in the presence of a newly developed ionic liquid supported (ILS) benzoic acid as cocatalyst, is shown to be an effective catalytic system for the asymmetric direct crossed-aldol reaction of acetaldehyde in aqueous media using brine. For the reactions studied, the catalyst loading could be reduced to 5 mol %; high yields (up to 97%) and high enantioselectivities (up to 92% ee) were also achieved for a wide variety of aromatic aldehyde.

Design and synthesis of bistereogenic chiral ionic liquids and their use as solvents for asymmetric Baylis–Hillman reactions

Three novel chiral ionic liquids (CILs) containing two chiral centers in the side chain bonded to the 2-position of the imidazolium cation and different anions have been synthesized, characterized and used as chiral solvents for asymmetric Baylis-Hillman (BH) reactions; good yields and fair enantioselectivities were obtained.

A simple and highly effective water-compatible organocatalytic system for asymmetric direct Michael reactions of linear aldehydes to maleimides

Diarylprolinol silyl ether-based organocatalyst 2, in conjunction with ionic liquid supported (ILS) sulfonic acid 6a as co-catalyst, leads to a novel organocatalyst in aqueous media. The in situ generated catalyst demonstrated high reactivity and stereoselectivity for the Michael reactions of linear aldehydes to maleimides in brine without any organic solvents. For these reactions, up to 76% yield, 9 : 1 dr and 96% ee were obtained for a broad variety of aldehydes and maleimides.

Ionic Liquid-Supported (ILS) (S)-Pyrrolidine Sulfonamide for Asymmetric Michael Addition Reactions of Aldehydes with Nitroolefins

A class of ionic liquid supported (ILS) (S)-pyrrolidine sulfonamide organocatalyst (1c), which was developed earlier in our lab, has been applied to a wider range of Michael addition reaction, involving various aryl-substituted nitroolefins and a series of aldehydes. Catalyst 1c catalyzes Michael additions in which only 2 equivalents of aldehydes to each equivalent of nitroolefin are required. With 10 mol% of ILS catalyst 1c loading, moderate to excellent yields (51- 98%) with moderate enantioselectivities (28-83% ee) and high diastereoselectivities (syn/anti ratio up to 97/3) were obtained. Moreover, the catalyst 1c could be easily recycled and reused for at least 5 times with slightly reduced activities.

Solvation effects on the tautomerization of N,N-dimethylvaline

Abstract The effects that solvents have on the tautomerization of N,N-dimethylvaline were analyzed using a linear solvation energy relationship (LSER) approach. In solution, the population of the zwitterionic tautomer is dictated mainly by the nature of the medium. Acidic solvent molecules appear to be more concentrated near the carboxylate functionality of the zwitterionic tautomer compared to the concentration of basic solvent molecules in the region of the dimethylammonium functionality.

Optimization of Microwave-Assisted Michael Addition Reaction Catalyzed by L-Proline in Ionic Liquid Medium Using Response Surface Methodology

Abstract Michael addition reactions of aldehyde to β-nitrostyrene catalyzed by L-proline were investigated by using controlled, monomode microwave-assisted technique in a closed vessel system. Ionic liquid 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([bmim]NTf2) was used as the reaction medium to replace the commonly used volatile organic solvents and as a good absorbing solvent during Michael reaction under the influence of microwave irradiation. The Michael product is clean and generates good yields in short reaction times with moderate results on enantioselectivity (ee). In this work, optimization of proline-catalyzed Michael reaction was carried out using response surface methodology (RSM) based on a three-factor-three-level central composite design (CCD). Various reaction parameters including catalyst loading (5–30 mol%), reaction time (5–40 min), and substrate (2–5 equivalent ratio) were investigated. A high Michael yield (96.5%) with 36.9 ee% was obtained at the optimum conditions of 10.0 mol% catalyst loading, 5.0 min reaction time, and 2.0 substrate equivalent ratio. [Supplementary materials are available for this article. Go to the publishers online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.] GRAPHICAL ABSTRACT