Hiroki Shigehisa

Cobalt-catalyzed hydrofluorination of unactivated olefins: a radical approach of fluorine transfer.

Catalytic hydrofluorination of olefins using a cobalt catalyst was developed. The exclusive Markovnikov selectivity, functional group tolerance, and scalability of this reaction make it an attractive protocol for the hydrofluorination of olefins. A preliminary mechanistic experiment showed the involvement of a radical intermediate.

Hydroalkoxylation of Unactivated Olefins with Carbon Radicals and Carbocation Species as Key Intermediates

A unique Markovnikov hydroalkoxylation of unactivated olefins with a cobalt complex, silane, and N-fluoropyridinium salt is reported. Further optimization of reaction conditions yielded high functional group tolerance and versatility of alcoholic solvent employed, including methanol, i-propanol, and t-butanol. Use of trifluorotoluene as a solvent made the use of alcohol in stoichiometric amount possible. Mechanistic insight into this novel catalytic system is also discussed. Experimental results suggest that catalysis involves both carbon radical and carbocation intermediates.

Catalytic Hydroamination of Unactivated Olefins Using a Co Catalyst for Complex Molecule Synthesis

Functional group tolerance is one of the important requirements for chemical reactions, especially for the synthesis of complex molecules. Herein, we report a mild, general, and functional group tolerant intramolecular hydroamination of unactivated olefins using a Co(salen) complex, an N-fluoropyridinium salt, and a disiloxane reagent. This method, which was carried out at room temperature (or 0 °C), afforded three-, five-, six-, and seven-membered ring nitrogen-containing heterocyclic compounds and was compatible with diverse functional groups.

Catalytic Synthesis of Saturated Oxygen Heterocycles by Hydrofunctionalization of Unactivated Olefins: Unprotected and Protected Strategies

A mild, general, and functional group tolerant intramolecular hydroalkoxylation and hydroacyloxylation of unactivated olefins using a Co(salen) complex, an N-fluoropyridinium salt, and a disiloxane reagent is described. This reaction was carried out at room temperature and afforded five- and six-membered oxygen heterocyclic compounds, such as cyclic ethers and lactones. The Co complex was optimized for previously rare medium ring formation by hydrofunctionalization of unactivated olefins. The powerful Co catalyst system also enables the deprotective hydroalkoxylation of O-protected alkenyl alcohol and hydroacyloxylation of alkenyl ester to afford cyclic ethers and lactones directly. The substrate scope and mechanistic proof of deprotection were investigated. The experimental evidence supports the concerted transition state of the bond-forming step involving a cationic Co complex.

Co-Catalyzed Hydroarylation of Unactivated Olefins

A mild, general, scalable, and functional group tolerant intramolecular hydroarylation of unactivated olefins using a Co(salen) complex, a N-fluoropyridinium salt, and a disiloxane reagent was reported. This method, which was carried out at room temperature, afforded six-membered benzocyclic compounds from mono-, 1,1- or trans-1,2-di, and trisubstituted olefins.

Markovnikov-Selective Addition of Fluorous Solvents to Unactivated Olefins Using a Co Catalyst

We developed an addition reaction of fluorous solvents to olefins using salen-cobalt (Co) complex, N-fluoro-2,4,6-trimethylpyridinium tetrafluoroborate, and 1,1,3,3-tetramethyldisiloxane. This reaction condition was found to activate olefins, which enabled them to be attacked by 2,2,2-trifluoroethanol (TFE) and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP), both of which are electronically weak nucleophiles.

Studies on Catalytic Activation of Olefins Using Cobalt Complex

In this review, I tell the story of the cobalt chemistry that has been developed in my group since 2011. First, we achieved the total synthesis of polyketide natural product trichodermatide A, which involved a late-stage Isayama-Mukaiyama hydration of an enol ether using cobalt(II) acetylacetonate (Co(acac)2) that gave the desired product chemo-, regio-, and diastereoselectively. After our report of this total synthesis in 2013, we were required to revise the originally reported structure of trichodermatide A following the accurate and important report from the Trauner group. Second, we found unique cobalt-catalyzed hydroelementation reactions of olefins involving a cobalt-salen complex, N-fluoro-2,4,6-trimethylpyridinium salt, and a silane reagent. Under these reaction conditions, a carbocationic or carbon radical species is generated from an olefin, and then C-X (X=O, N, C, F) bond formation occurs with good functional group tolerance for a broad substrate scope. This review also covers recent examples of switching chemistry and natural product synthesis involving my cobalt chemistry reported by several groups.

Corrigendum: Stereocontrolled Synthesis of Trichodermatide A

DOI: 10.1002/anie.201210099 A publication by the Trauner group[1] prompted the authors of this Communication to make structural assignments by re-examination of the NMR experiments for synthetic trichodermatide A: NOESY correlations between H10 and OH9, and between H8 and OH10, were observed. Furthermore, the coupling constant (6.8 Hz) derived from the protons at C7 and C8 indicated a cis relationship. Therefore, the configuration of the actual structure of trichodermatide A in Figure 1 should be 1’. The structure 1’ is also strongly supported by the additional experiments.[2] With the above correction, compounds 17 and 22 in Scheme 3 and compounds 23, 24, 25, and 26 in Scheme 4 should be revised in the same way with regard to the stereochemical configuration at C10.