A large variety of organic substances having complicated polycyclic structures and a wide assortment of stereogenic centers are found in nature. These compounds often exhibit attractive and specific biological activities. Ideal strategies for preparing these structurally complex substances would involve sequences in which stereocontrolled formation of multiple carbon-carbon bonds occur in a single step starting with simple, readily available materials. Great attention has been given to the development of intermolecular cascade reactions and multi-component reactions owing to their high degree of atom economy and their applications in combinatorial chemistry as well as diversity-oriented syntheses. Herein we describe a new class of catalytic reaction of polycyclic structures including cyclobutane ring by utilizing cascade reaction and multi-component reaction, and its related catalytic reaction as well as their application to biologically activesubstances.
For synthesis of secondary and tertiary alcohols, practical carbon-carbon bond forming reactions between organometallic reagents and carbonyl compounds have been developed over a century since the discovery of Grignard reaction in 1900 . Traditional organometallic reagents (i.e. Li, Mg, Si, Cu, and Zn reagents) should involve some fundamental functions, such as alkylating reagents, Lewis acids, and Br.Onsted bases . Thus, in principle, the efficiency of the nucleophilic addition should significantly increase if a carbon-metal bond in organometallic reagents can be activated by Lewis base catalysts and the substrates can be activated by native Lewis acid function of organometallic reagents. We report here that the highly efficient catalytic carbon-carbon bond forming reactions via carbon-metal bond activation in organometallic reagents using simple metal salt catalysts. A variety of acid-base promoting catalytic reactions, such as Grignard reaction, organozinc addition, 1, 4-addition of organocopper reagents, trimethylsilylcyanation, and Mukaiyama aldol reaction, were achieved toward the efficient asymmetric catalyses .
This review article describes precision control of molecular weight, stereochemistry, and monomer sequence in radical polymerization. For molecular weight control, metal-catalyzed living radical polymerization, which is originated from metal-catalyzed Kharasch addition reaction, has been developed by designing the catalysts and has become applicable for a wide variety of vinyl monomers including methacrylates, acrylates, styrenes, acrylamides, vinyl acetate, etc. While the control of stereochemistry cannot be achieved by these metal catalysts, the stereochemical control based on the interaction of solvents or added Lewis acids has been combined with various living radical polymerizations for the simultaneous control of molecular weight and tacticity . A possibility of monomer sequence control has now been suggested by developing metal-catalyzed radical addition reaction to metal-catalyzed radical polyaddition of designed monomers for sequence-regulated vinyl polymers.
DNA-templated organic synthesis (DTS) has recently emerged as a general approach to translate DNA sequences into DNA-linked synthetic small molecules. DNA templates not only direct chemistries to construct small molecules but also serve as amplifiable encodings used to identify the chemical structures of the small molecules. Therefore, through DTS, synthetic small molecules can now be subjected to in vitro selection methods for the discovery of novel functional molecules. In this account, we describe the early efforts conducted in the Liu Laboratory to develop key technologies in DTS and new findings toward exploring the potential of a selection-based approach to the discovery of functional small molecules.
Facile chemoenzymatic methods for the synthesis of a variety of D- and L- iminocyclitols or L-sugars have been developed. The practicality of formerly reported methods using dihydroxyacetone phosphate (DHAP) aldolase was limited by the high cost and instability of DHAP. Here we discuss three strategies toward the facile synthesis of sugar analogues using DHA(P) aldolases from readily available non-phosphoryrated donor substrates. (1) Directed evolution of the L-rhamnulose 1-phosphate aldolase (RhaD) was employed to alter the donor substrate specificity of RhaD aldolase from DHAP to DHA. In vivo selection for the directed evolution using genetically engineered E. coli strain was constructed . (2) RhaD aldolase was found to accept non-phosphorylated dihydroxyacetone (DHA) as a donor substrate in the presence of borate. We applied this discovery to develop a practical one-step synthesis of L-fructose and two-step synthesis of L-iminocyclitols . (3) A one-pot synthesis was achieved using the recently discovered D-fructose 6-phosphate aldolse (FSA). FSA utilized DHA, hydroxyacetone, and 1-hydroxy-2-butanone as donor substrates to allow the synthesis of a variety of novel D-iminocyclitols in a concise fashion.
A total synthesis of (+)-papulacandin D which shows an antifungal activity is reported. The molecule is one of the members of C-arylglycoside isolated from Papularia spherosperma. The synthetic strategy bifurcates the molecule into two nearly equal subunits, the aryl glycoside and 18-carbon fatty acid side chain. The key strategic transformations are (1) the palladium catalyzed, organosilanolate-based cross-coupling of a protected glucal silanol and (2) a catalytic enantioselective allylation of a dienal using allyltrichlorosilane. This highly convergent synthesis was accomplished in 31 steps overall from commercial starting materials.
This mini review focuses on the recent progress in catalytic C-H amination reactions. The preparation of amine derivatives by catalytic C-H amination reactions would be extremely attractive, given the fact that the majority of the synthetic methods involve a multi step reaction sequence based on the reaction of a nitrogen-based nucleophile with an appropriate carbon electrophile. Selected examples from recent literatures will be described with a brief mechanistic insight.