Environmental concerns foster ever-increasing demand to improve efficiency of organic synthesis. Of strategic importance in this context is to renovate conventional synthetic methods that require multiple steps and waste much energy, instead to develop new reactions which transform readily available substances in a more straightforward manner. Dr. Masahiro Murakami has initiated innovation in synthetic chemistry by exploiting energy of light and transition metal catalysts. The followings are selected from his achievements.
1. Synthetic Transformations Exploiting Light as the Source of Energy 1-1. Reactions Incorporating CO2 into Organic Molecules
It is critically important for the sustainable society to establish technologies which exploit CO2 as a carbon resource. One of the difficulties to incorporate CO2 into simple organic molecules is ascribed to its thermodynamic stability. The stability has to be offset by energetic reagents such as Grignard reagents for a reaction capturing CO2 to proceed forward. Now, it is highly desirable to exploit renewable energy for incorporation of CO2 into organic molecules. Dr. Murakami has disclosed that simple and readily available organic compounds undergo a carboxylation reaction with CO2 when irradiated with solar or UV light. For example, o-alkylphenyl ketones incorporate CO2 into their benzylic C-H bonds under irradiation with solar light, producing the corresponding carboxylic acids. It is only solar light what is required as the driving force. Neither bases nor reductants are required. Of note is that the reaction is energetically uphill, and thus, is infeasible by a thermal method. He also developed photoinduced reactions incorporating CO2 into simple hydrocarbons such as cyclohexane and pentane. Dr. Murakami's achievements have triggered prevalent research in this emerging field of photoinduced CO2 fixation.
1-2. Reduction Reactions Exploiting Energy Derived from Light
It has been long known that benzophenone derivatives reductively dimerize to the corresponding vicinal diols when irradiated with solar light in alcohols. The reaction is energetically uphill. Thus, the dimerization reaction can be viewed as a method to harvest solar energy, to convert it into chemical energy, and to store it in a form of structural strain. Dr. Murakami has been utilizing the stored energy as the driving force of synthetic reactions. For example, Ni(0)(1,5-cyclooctadiene)2 complex, which is a versatile precursory complex for the preparation of variety of nickel(0) complexes, is prepared from nickel(II) salts using the vicinal diol as the reductant. After the reaction, the diol reverts back to the ketone, which can be readily recovered and re-used for harvesting solar energy. His method is more sustainability-oriented if compared with conventional ones which use sodium or alkylaluminum compounds as the reductant. In addition, it is far safer since the diol is stable toward air and water. The diol is applicable to a wide variety of reactions such as nickel-catalyzed coupling reactions of organic halides.
1-3. Photon-Assisted Chain-Elongation of Alkenes
Alkenes are readily available and abundant chemical feedstocks, and thus, are attractive as the starting material. Dr. Murakami recently developed a convenient method to elongate the carbon-chains of alkenes by installation of an alkoxycarbonylmethyl or cyanomethyl group using the corresponding stabilized ylide. Various alkenes, even tetra-substituted alkenes which are generally difficult to participate in C-C bond formation due to their severe steric congestion, undergo the reaction. A wide range of functional groups are tolerated. Of note is naturally occurring ascorbic acid acts as the reductant to complete the catalytic cycle.
2. Sequential Transformations Starting from Alkynes with Rapid Increase of Molecular Complexity
Preparative methods of alkynes are well-established and a number of alkynes are commercially available. Dr. Murakami has focused on alkynes as the starting substance to develop new synthetic procedures consisting of sequential transformations starting from alkynes. They increase molecular complexity with remarkable efficiency.
2-1. Construction of Nitrogen-Containing Organic Framework by Way of 1,2,3-Triazoles
A [2+3] cycloaddition reaction between terminal alkynes and azido compounds generates 1,2,3-triazoles. The reaction has been conveniently utilized to couple two organic molecules, and now is recognized as the most typical example which fits in the concept of click chemistry. Dr. Murakami has disclosed that 1,2,3-triazoles serve as the precursor of diazo imines. Upon treatment with transition metal catalysts, diazo imines generate the corresponding carbene complexes with evolution of dinitrogen. The carbene complexes are highly electrophilic to react with various nucleophiles including water and a benzene ring. Based on this finding, Dr. Murakami has developed a number of synthetic methods constructing various complex nitrogen-containing skeletons. The chemistry of 1,2,3-triazole is currently growing worldwide in a rapid pace owing to its great synthetic potential. His pioneering contribution to this field is well-recognized.
2-2. Stereoselective Construction of Carbon Skeletons Using Alkenylboranes
Allylboron compounds serve as versatile synthetic intermediates for stereoselective construction of carbon skeletons. Whereas preparative methods of simple allylboron compounds such as crotylboronates are well-established, it remains difficult to synthesize allylboron compounds of more complex structures. Dr. Murakami has developed a new method to in-situ generate allylboron compounds through metal-catalyzed transposition of the double bonds of alkenylboron compounds, which are readily available from terminal alkynes in a stereo- and regioselective fashion. The new methods allow an expedient access to a wide variety of allylboron compounds, and lead to the enantio- and diastereo-selective synthesis of various homoallylic alcohols possessing contiguous stereocenters. This method is of practical value in synthesizing complex natural products and pharmaceuticals.
As highlighted above, Dr. Murakami has developed an array of unique synthetic transformations exploiting light energy and transition metal catalysts. His pioneering achievements are continuously inspiring other chemists, playing a leading role in the field of organic synthesis. On the grounds of these achievements and international reputations, Dr. Murakami was recognized as a recipient of the Chemical Society of Japan Award.