Mini-Reviews in Organic Chemistry - Volume 11, Issue 4, 2014

It is our great pleasure as Guest Editors of the journal ‘Mini-Reviews in Organic Chemistry’ to present you with a ‘mini-hot topic issue’ on nonmetal asymmetric catalysis. Asymmetric catalysis entails the catalytic, selective, and reproducible generation of a given enantiomer of a chiral product from achiral reactants. Leading the quest of asymmetric catalysis is the need of the pharmaceutical, flavors and fragrances, and agrochemical industries for enantiopure molecules because the different enantiomers or diastereomers of a molecule often have different biological activity. Nearly 85% of new drugs in the market are chiral. Organocatalysis can be used as environmentally-friendly alternatives to transition-metal catalysts as no toxic metals are required. The principle interactions of organocatalyst are non-covalent, such as hydrophobic, hydrogen bonding, van der Waals and electrostatic as in enzymes. These catalysts are often inexpensive to prepare and reaction can be performed under aerobic environments and in wet solvents. The beneficial impact of organocatalytic reactions on a large scale production of chiral intermediates has been demonstrated. Therefore, this special issue aims to review the advances in nonmetal asymmetric catalysis during the last decade, specified in organocatalysis. The first review related to the above mentioned topic is written by Drs. Leow, Shen and their colleagues, who explore organocatalytic enantioselective protonation of enol derivatives. As they mentioned, the proton is the smallest functional group in organic synthesis and it is extremely challenging to control it in terms of enantioselectivity. Traditional methods are using pre-formed enolates obtained from the direct deprotonation of carbonyl compounds by strong bases. The newer strategies involve the usage of silyl enol ethers, tautomerization of enols or in situ generation of transient enolates. They can be generated through either additions to ketenes, conjugate additions to Michael acceptors, rearrangements, or isomerization of double/triple bonds. In the following article, as an alternative of the most popular asymmetric sulfur-Michael addition, Dr. Zhiyong Jiang and his colleagues summarized the advance on asymmetric α-sulfenylation. Two asymmetric protocols were discussed respectively, including transition-metal catalysis and organocatalysis. It was noted that the unprecedented substrate scopes still exist which represents developing rooms, although asymmetric α-sulfenylation has obtained remarkable progress in recent years; and novel and easily prepared sulfenylated reagents are still highly desirable. In the last article in this issue, Dr. Hansen and his colleagues gave an overview over the major advances in asymmetric enamine catalysis since, and including, 2008 with focus on strategic transformations and catalyst development. As they noted, enamine-catalysis has become a powerful enabling technology for enantioselective chemical synthesis, which could be attributed to a rapid evolution of novel catalyst architectures and strategies, combined with the design and discovery of strategically important, asymmetric transformations. This exciting field will continue to expand, fuelled by its unique ability to generate novel and stereodefined structural complexity in the synthesis of organic molecules. We would like to sincerely thank all the reviewers for their valuable contributions that ensured the quality of articles to be published in this special issue. It was a great opportunity for us to cooperate with researchers from all over the world including United States, Norway, Taiwan and Mainland China. We hope that readers will enjoy this issue, obtain useful information, and be inspired with new ideas for future research on nonmetal asymmetric catalysis.

The proton is the smallest functional group in organic synthesis and it is extremely challenging to control it in terms of enantioselectivity. In recent years, the use of organocatalysts has witnessed rapid developments and has become the state-of-art in enantioselective protonation of transient enolate. The key prochiral enolate can be generated via various reaction types. Herein we review recent reports of organocatalytic enantioselective protonation of transient enolate, classifying them according to the type of enolate precursors.

Owing to the important utilities in many areas, the preparation of chiral sulfur-containing compounds has attracted special attention of chemists. As an alternative of the most popular asymmetric sulfur-Michael addition, asymmetric α-sulfenylation has been developed well in recent years. This short review would summarize the advance on asymmetric α-sulfenylation. Two asymmetric protocols, including transition-metal catalysis and organocatalysis, are discussed respectively.

The use of chiral amines as catalysts for enantioselective synthetic transformations has received tremendous attention from the chemistry community over the last decade. Although stoichiometric enamines have been used as enolate equivalents for about 60 years, the field of catalytic enamine reactions continues to expand. This mode of catalysis is particularly powerful, as it enables the construction of strategic C-C and C-X bonds with high levels of asymmetric induction in a variety of systems. Proline and proline-derivatives have played a central role as convenient and efficient catalyst scaffolds in this area. This mini-review will give an overview over the major advances in asymmetric enamine catalysis since, and including, 2008 with focus on strategic transformations and catalyst development.

The synthesis, chemical properties, transformations, and biological activities of mono- and multi- substituted cyclobutyl- and cyclobutenylphosphonates were broadly discussed in this article review. The synthesis of four-membered ring phosphonates was based either on phosphorylation of already constructed cyclobutyl moiety or on inter- and intramolecular cyclizations of phosphorus containing compounds. Also, emphasis was illustrated on the recent development in this field.

In green and sustainable chemistry, 2,2,2-trifluoroethanol is considered as an ideal solvent due to its high ionizing power, strong hydrogen bond donating ability and environmentally friendliness characteristics. This review highlights the use of 2,2,2-trifluoroethanol as a solvent, co-solvent and its catalytic potential in various organic transformations.

For several decades, interest in pyrrole derivatives increased due to their pharmaceutical importance, such as antimicrobial, anti-inflammatory, analgesic, anti-tumor, anti-epileptic, anti-viral, anti-hypertensive, and anti-diabetic agents. These huge therapeutic applications have motivated new efforts in searching for novel derivatives with improved biological activity and diverse applications in pharmaceutical industry. Motivated by the importance of this system, and in continuation of our research efforts, we have tried to highlight aspects reported on the chemistry and biological activity of pyrrole and its fused derivatives during the past years (till 2012).

Chiral homo-allylic amines have been recognized in biologically active natural products and synthetic medicinal compounds. The most significant aspect of chiral homo-allylic amines relies on their synthetic versatility as chiral building blocks for the construction of a broad range of multi-functional organic compounds. A measure of the value of chiral homoallylic amines in organic synthesis is the large volume of work that has been devoted to their construction. Of the known asymmetric methods for their synthesis, the most popular method involves the formation of an imine followed by asymmetric allylation of the imine with reactive allylmetal reagents. An alternative approach is the metal-free asymmetric synthesis of chiral homo-allylic amines catalyzed by small organic molecules, which will be discussed in details in this review.