Why do you think your paper is highly cited?

This paper describes bismuth nitrate-catalyzed versatile Michael reaction.  For example, several substituted amines, imidazoles, thio compounds, indoles, and carbamates were prepared at room temperature by following this method.  The main aim of the paper is to reduce the complications that characterize the current standard Michael reaction.  In contrast to the existing methods using many acidic catalysts, this method is very general, simple, high-yielding, environmentally friendly, and oxygen- and moisture-tolerant.

  Does it describe a new discovery or a new methodology that’s useful to others?

Our method of bismuth nitrate-catalyzed Michael reaction for the preparation of β-amino ketones is very simple and efficient.  These are versatile intermediates for a large number of organic compounds, as exemplified in the preparation of antibiotics, natural products, γ-amino alcohols, and chiral auxilliaries.  As a result of vast range of applications, synthesis of β-amino ketones has remained an important objective for a number of years.  Acid- or base-induced conjugate addition reaction of unsaturated carbonyl groups to amines has been the method used for this purpose for many years.  However,  because of the many side reactions that result from the presence of strong acids (polymerization of vinyl ketones) or bases in the medium, this method has not been applied in industry or resulted in any practical applications.  To avoid many of the disadvantages of stoichiometric addition of a Lewis acid-mediated (AlCl3, SnCl4, or TiCl4) conjugate addition reaction, two new methods have appeared in the literature.  The first is Michael reaction of amines to enones in the presence of the CeCl3.7H20-NaI system supported in silica gel under refluxing conditions.  The second method is addition reaction of zinc ester enolates to sulfones.  Since our method has better versatility, this will be used by many other researchers.

  Could you summarize the significance of your paper in layman’s terms?

Development of organic reactions under catalytic conditions using minimum reagents and solvents or without solvents is the area of current investigation.  This can cut down the cost of waste disposal.  Bismuth and its salts are not toxic.  Many of the bismuth salts have been used for the treatment of different types of medical disorders.  This paper describes the development of a new bismuth nitrate-catalyzed Michael reaction for the first time.  If one of the reactants is a liquid, the experiment can be conducted without using solvent.  No other reports in the literature demonstrated methods that are as versatile and general.  The intermediates may have potential values for the preparation of several biologically active compounds.

  How did you become involved in this research?

We have been studying reactions mediated by metals or their salts with the aim of developing several biologically active compounds, including anticancer agents and β-lactams.  We have also reported the use of bismuth-derived reagents in several organic transformations.  For example, nitration of aromatic hydrocarbons, phenolic compounds, and β-lactams by bismuth nitrate was performed in excellent yields.  Facile deprotection of hydrazones and oximes also worked well using bismuth nitrate.  These reactions, in principle, require the presence of acids.  We hypothesized that the drawbacks of the catalysts employed in Michael reaction may be avoided if we used bismuth nitrate as a mild reagent, as long as the acidity is controlled by using it in catalytic proportions.  Our hypothesis was further strengthened by the recent discovery by Ram Mohan and his group who demonstrated that bismuth triflate is an efficient catalyst for the deprotection of acyclic O,O-acetals derived from ketones and conjugated aldehydes.  However, reactions of cyclic acetals and TBDMS ethers are not affected by this reagent.  Since Michael reactions are among the most important acid-mediated reactions, development of a reaction that uses catalytic quantities of lowly toxic, readily available, economic reagent should greatly contribute to the creation of environmentally benign processes.  Our results and the facts describe above prompted us to investigate a bismuth nitrate-mediated Michael reaction (conjugate reaction) with a wide variety of substrates in a general reaction.

Bimal K. Banik, Ph.D.
University of Texas M. D. Anderson Cancer Center
Houston, Texas, USA