In nature, many complex structures are assembled from simple molecules by a series of tailored enzyme-catalyzed reactions. One representative example is the deoxypropionate motif, an alternately methylated alkyl chain containing multiple stereogenic centers, which is biosynthesized by a series of enzymatic reactions from simple building blocks. In organic synthesis, however, the majority of the reported routes require the syntheses of complex building blocks. Furthermore, multistep reactions with individual purifications are required at each elongation. Here we show the construction of the deoxypropionate structure from propylene in a single step to achieve facile (formal) total syntheses of natural products containing syn or anti-deoxypropionate motif. To realize this strategy, we focused on the coordinative chain transfer polymerization and optimized the reaction condition to afford a stereo-controlled oligomer, which is contrastive to the other synthetic strategies developed to date that require 3-6 steps per unit, with unavoidable byproduct generation. Furthermore, multiple oligomers with different number of deoxypropionate units were isolated from one batch, showing application to the construction of library. Our strategy opens the door for facile synthetic routes toward other natural products that share the deoxypropionate motif.

Polyacetate-type and acetate-propionate hybrid-type polyketide skeletons have been constructed by the remote asymmetric induction of the vinylogous Mukaiyama aldol reactions using chiral oxazolidinone-attached vinylketene silyl N,O-acetals. In the acetate-propionate hybrid-type reaction, anti- and syn-adducts were selectively afforded using aldehydes and acetals, respectively. Therefore, in conjunction with the previously reported polypropionate-type reaction, all types of polyketide skeletons have been able to be synthesized. In addition to the transition states of the acetate-propionate hybrid-type reactions, difference of the stereo-control systems between the polyacetate-type reaction and the polypropionate-type reaction is discussed. Interestingly, in polyacetate-type and acetate-propionate hybrid-type reactions, the chiral auxiliary controlled the stereoselectivity indirectly. Additionally, (S)-massoialactone (α,β-unsaturated δ-lactone) and tabtoxinine-β-lactam, an inhibitor of glutamate synthetase, were synthesized by the remote asymmetric induction reactions.

Oxidative addition of carbon-halogen bonds to transition metal catalysts is one of the most important elementary reactions in synthetic organic chemistry that catalyzes the conversion of organohalides to organotransition metal intermediates. In particular, palladium catalysts have enabled a variety of carbon-carbon bond formation reactions on numerous carbon skeletons triggered by oxidative addition of organohalides. On the other hand, in recent years, much attention has been paid to investigating new catalytic behaviors of ubiquitous metal catalysts and the development of new catalytic transformations using ubiquitous metal catalysts as an alternative to rare transition metal catalysts. The ubiquitous metal catalysts belonging to the first row of transition metals exhibit a unique redox behavior in which organohalides are oxidatively added to produce high-valent adducts that are converted to low-valent organo-cobalt and -nickel species under reducing conditions. Utilizing the unique redox behavior of the cobalt and nickel catalysts, we have successfully developed stereoselective reductive bifunctionalizations of alkynes consisting of oxidative addition of organohalides, carbometallation, re-oxidative addition, and reductive elimination. Furthermore, we have discovered the excellent nucleophilicity and transmetalation ability of the low-valent organo-cobalt and -nickel species, and have developed reductive functionalization of organohalides, such as stannylation and borylation. On the other hand, monovalent planar cobalt complexes, whose structures are immobilized by planar tetradentate ligands, serve as excellent metallonucleophiles. We have exploited the nucleophilic properties of them to achieve a variety of reductive cross-coupling reactions with alkyl tosylates as ubiquitous carbon sources.

Natural products, well known for unique chemical diversity and bioactivity, are the compounds that organisms have acquired in evolutionary history. They have attracted attentions from not only organic chemists but also scientists in related fields and have provided breakthroughs for science. Against this background, we have investigated the secondary metabolites of marine organisms, especially cyanobacteria, and have discovered various novel bioactive compounds. In this account, our recent research activities regarding the isolation, structure determination, total syntheses and biological activities of our novel natural products are described.

For more than a century, quinine(1)has remained a persistent fascination to human beings for its use in medicine and chemistry. More recently, 1 has garnered increased attention due to its widespread application in the field of asymmetric catalysis. Although there is no doubt that the importance of 1, quinine and its derivatives are currently only available in economically viable quantities from the natural sources. From a synthetic standpoint, since Stork’s stereoselective total synthesis of quinine(1)has been reported in 2001- and due to rapid progress in contemporary synthetic chemistry-several asymmetric total syntheses of quinine have been reported to date. New synthetic routes to 1 remain desirable and important, highlighted in the fact that four asymmetric approaches to quinine have been reported since 2018. This review article details strategies for the asymmetric total synthesis of quinine from the last two decades.

Gold-catalyzed reaction initiated by π-activation of unsaturated bonds is well-established, where the oxidation state of the gold complex is unchanged throughout the catalytic cycle. Recently, the coupling reactions involving Au(I)/Au(III) catalytic cycle have been developed. The key to success is the kinetic or thermodynamic stabilization of Au(III) species. This mini-review focuses on the generation of Au(III) species by direct oxidative addition of carbon-halogen bond to Au(I) and their application to coupling reactions.