末木 俊輔

A one-shot substitution of all hydrogens at the α,β-positions of saturated cyclic amines was achieved. The key feature of this reaction is the sequential involvement of intra- and intermolecular redox processes. When N,O-acetals obtained through an internal redox process were treated with a catalytic amount of Zn(OTf)2 and an excess amount of benzylidene barbiturates, three key transformations involving intermolecular redox process occurred successively to afford α,β-unsaturated lactams in moderate to good chemical yields.

A concise and direct cyanation of secondary and tertiary benzylic and allylic alcohols catalyzed by Brønsted acid has been developed using trimethylsilyl cyanide (TMSCN) as a cyanide source and 1,1,1,3,3,3‐hexafluoro‐2‐propanol (HFIP) as a solvent. The present transition metal‐free catalytic process is operationally simple to perform under “open‐flask” conditions and it is applicable to the preparation of a number of α‐arylacetonitriles as well as late‐stage material transformations. The effectiveness of the present protocol was further demonstrated by the first enantioselective synthesis and determination of the absolute configuration of verimol F.

The first total synthesis of cadinane sesquiterpenoid alanense A, in which an intramolecular dehydrative Friedel-Crafts alkylation of 2,5-diaryl-2-pentanol is incorporated as a key step, has been achieved. The combinatorial use of p-TsOH·H2O as a catalyst and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as a solvent provides 1,1-disubstituted tetrahydronaphthalene in 97% yield. It was also found that the combination of p-TsOH and HFIP is effective for the removal of phenolic MOM ether.

Divergent synthesis of multi-substituted phenanthrenes based on an internal redox reaction/ring expansion sequence was achieved.

A Brønsted acid-catalyzed, transition metal-free intramolecular 7-endo hydroarylation reaction of 1,5-diaryl-1-pentynes has been developed. The use of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as a solvent was found to be critical for this process. Using the present methodology, we have accomplished the synthesis of KGP-18, an analogue of the anticancer natural product combretastatin A4. (Figure presented.).

We have developed a sequential hydride shift process involving a [1,8]-hydride shift. When cinnamylidene malonates having a biphenyl core were treated with 30 mol% Yb(OTf)3 and 10 mol% iPr2NEt, the desired sequential [1,8]-[1,5]-hydride shift process proceeded smoothly to afford synthetically challenging nine-membered carbocycle-fused piperidine derivatives in good chemical yields (up to 77%). Notably, the desired nine-membered carbocycles could not be obtained by a single [1,8]-hydride shift/cyclization process, suggesting that the employment of the sequential system is crucial to achieving the reaction. (Figure presented.).

In this chapter, we summarize the manganese-catalysed transformations developed over the last 20 years. Because manganese is the third most abundant transition metal according to the Clarke number, the price is cheaper than that of almost any other transition metal. Therefore, the development of synthetic organic reactions using manganese catalysts is highly important and desired. In addition, several reactions, which are specific to manganese catalysts, have also been reported. This chapter describes (1) oxidation reactions (epoxidation of alkenes, C-H oxidation, and dehydrogenation); (2) reduction (of alkenes and heterocycles, alkynes, carbonyl compounds, imine derivatives, nitriles and amides, CO2 and CO, and alcohols); (3) carbon-carbon bond formation (addition to unsaturated molecules and cross-coupling reactions); (4) C-H activation (addition to C-C multiple bonds, substitutive C-H functionalization, C-H alkylation, C-H arylation, C-N bond forming reactions, and domino C-H activation reactions); and (5) others (cyclization, annulation, addition to olefins, coupling reaction, C-C bond cleavage, and various others).

Ruthenium-catalyzed oxidative dehydrogenation of alcohols using carbodiimide as an efficient hydrogen acceptor has been developed. The protocol exhibits wide substrate scope with good to excellent yields. The results of the kinetic analysis indicated that the reaction mechanism includes the hydrogen transfer process and that the addition of carbodiimide is essential for the reaction system, and the resulting amidine also could react as a hydrogen acceptor.

A novel direct C4 benzylation of indoles utilizing 2-benzyloxyindoles has been developed to access 4-benzyl-2-oxindoles. This strategy involves the in situ formation of isotoluene intermediates via benzyl Claisen rearrangements, which undergoes Cope rearrangement and aromatization. The method provides the desired products in moderate to high yields and shows good functional group tolerance.

Precise, efficient one-pot synthesis of star shaped (tri-, tetra-arm) π-conjugated systems has been achieved by olefin metathesis of 5-substituted-2-propenyl-thiophene or N-vinyl carbazole (arm segment) using a molybdenum-alkylidene reagent and subsequent Wittig-type cleavage with core segments containing aldehydes [tri(4-formylphenyl)amine, 2,4,6-tri(4-formyl-biphenyl)benzene, 1,4-dimethoxy-2,3,5,6-tetra(4-formylphenyl)-benzene, etc.]; effects of the core and the arm have been clearly demonstrated.

<p>ホウ素アニオン含有N-ヘテロ環状カルベン（WCA-NHC）配位子を有するイミド配位バナジウム錯体，V（N-2,6-Me₂C₆H₃）Cl₂（WCA-NHC）（1），触媒によるエチレン重合およびノルボルネンとの共重合における触媒活性は，使用するAl助触媒の影響を強く受け，特にAlⁱBu₃助触媒存在下でメチルアルミノキサン（MAO）より高活性を示した。触媒溶液の⁵¹V NMRスペクトル測定およびESR測定，V K-Edge XANES測定より，MAOの存在下での触媒溶液では価数変化が見られないのに対し，AlⁱBu₃の存在下の触媒溶液ではNMRおよびESRスペクトルが観察されず，XANESスペクトルよりAlによる還元反応が進行している可能性が示唆された。したがって，この触媒反応で見られるAl助触媒の効果は，価数の異なる触媒活性種の生成に起因することが示唆された。</p>

A series of end-functionalized poly(9,9′-di-n-octylfluorene vinylene)s (EF-PFVs) with different end groups were obtained by 1) synthesizing EF-PFV with vinyl end groups by acyclic diene metathesis (ADMET) polymerization with a molybdenum catalyst and termination with an aldehyde and 2) subsequent olefin metathesis of the vinyl group with the molybdenum catalyst followed by Wittig-type coupling with another aldehyde. The exclusive formation of EF-PFVs containing a vinyl end group by the ADMET polymerization was confirmed by grafting PEG, and by the synthesis of amphiphilic triblock copolymers by combining atom transfer radical polymerization from the PFV chain end with PEG grafting through a click reaction. Various EF-PFVs with different end groups, such as C6F5, pyridyl, ferrocenyl, and terthiophene, have thus been prepared. Their fluorescence spectra (e.g., intensities, emission wavelengths) were influenced by the end groups and the length of the conjugation.

アゼチジンは窒素原子を含む飽和四員環複素環式化合物であり，医薬品や天然物などの部分骨格中に認められる．しかし，一般にアゼチジンはその大きなひずみのために合成が困難であり，これまでに効率的な合成法が少なかった．今回Chenらは，Pd触媒による分子内C–Hアミノ化反応を利用したベンズアゼチジン類合成法の開発に成功したので，紹介したい．<br>なお，本稿は下記の文献に基づいて，その研究成果を紹介するものである.<br>1) He G. et al.，Nature Chem., 8, 1131-1136(2016).<br>2) He G. et al., J. Am. Chem. Soc., 134, 3–6 (2012).<br>3) Gary J. B., Sanford M. S. Organometallics， 30， 6143–6149(2011).<br>4) Nielsen M. C. et al., J. Am. Chem. Soc., 135, 1978–1985(2013).

The rhenium-catalyzed synthesis of 1,3-diiminoisoindolines and their related compounds from aromatic or heteroaromatic imidates and carbodiimides are reported via C-H bond activation. This reaction is the first example of a transition-metal-catalyzed insertion of carbodiimides into an aromatic or heteroaromatic C-H bond and a novel method for synthesizing 1,3-diiminoisoindolines and their related compounds. Unsymmetrical 1,3-diiminoisoindolines were easily obtained using this method. The reaction proceeded in good to excellent yield using a variety of substrates.

A manganese- and borane-mediated synthesis of isobenzofuranones from esters and oxiranes is developed. The reaction proceeded at aromatic, heteroaromatic, and olefinic C-H bonds with high functional group tolerance. This is the first example of a manganese-catalyzed C-H transformation using an oxygen-directing group. Triphenylborane played an important role in this reaction to cooperatively promote the annulation reaction. Kinetic isotope effect experiments revealed that C-H bond activation of the aromatic rings was the rate-determining step.

Dihydropyridines (DHPs) are one of the most important nitrogencontaining heterocycles which are widely recorginized in the scaffold of various biologically active compounds and natural products. DHPs are also utilized as medicines and useful building blocks for the complex molecules. On the other hand, some DHPs exhibit blue fluorescence in organic solvents and have potential to apply as functional materials. Based on the novel utility of DHPs in both medicinal chemistry and material sciences, development of efficient and robust synthetic methods for DHPs has been paid much attention and a large number of synthesis of DHPs have been reported. In this review chapter, we would like to summarize the recent progress in synthetic methodologies for construction of DHP scaffolds both in catalytic and in stoichiometric manners (particularly from 2000 to present), which are classified by the reaction patterns as 1) Multi-Component Coupling Reactions, 2) Pericyclic Reactions, 3) Regioselective Transformations of Pyridines, and 4) Miscellaneous.

© Georg Thieme Verlag Stuttgart New York Synthesis 2015. In this review, transition-metal-catalyzed or -mediated C-H transformations leading to the synthesis of organic functional materials, such as oligomers, polymers, and π-conjugated molecules, are summarized. 1 Introduction 2 Oligomers and Polymers 2.1 Synthesis of Oligomers and Polymers 2.2 Chemical Modification of Polymers 3 π-Conjugated Molecules 3.1 Indenes and Fluorenes 3.2 Acenes 3.3 Triphenylenes 3.4 Chemical Modification of Perylene Diimides 3.5 Nanographenes 3.6 Condensed Polycyclic π-Conjugated Molecules with Five-Membered Heteroaromatic Rings 3.7 π-Conjugated Molecules with Nitrogen-Containing Six-Membered Heteroaromatics 3.8 Porphyrins 3.9 Miscellaneous (π-Conjugated Molecules) 4 Miscellaneous (Excluding Polymers and π-Conjugated Molecules) 5 Outlook and Conclusions.

<p>We successfully developed rhodium-catalysed synthesis of multi-substituted silylindenes from 2 equivalents of aryl alkynes and 1 equivalent of hydrosilanes in moderate to good yields <italic>via</italic> C–H bond activation for the first time.</p>

We have successfully synthesized 3,4,5-substituted 1,4-dihydropyridines (1,4-DHPs) from amine hydrochloride salts, aldehydes, and acetals in good yields without the addition of a catalyst. The synthesized 1,4-DHPs exhibit various wavelengths of fluorescence, which could be tuned by changing the substituents at the 3- and 5-positions of the 1,4-DHPs. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Polyimide solution: Synthesis of the title compounds from aromatic imidates and isocyanates in good to excellent yields by a rhenium-catalyzed C-H bond transformation is described. The reaction also proceeded in high yield on gram scale and could be applied to the synthesis of polyimide derivatives (see figure), which are highly soluble in organic solvents. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

By the reaction of amines with alkylborane reagents in the presence of a catalytic amount of copper(II) acetate Cu(OAc)(2) and di-tert-butyl peroxide, a cross-coupling reaction proceeded and alkylated amines were obtained in good to excellent yields. Phenols are also applicable for this reaction, and the corresponding alkyl aryl ethers were produced.

The reaction of anilines, benzaldehydes, and ethyl 3,3-diethoxypropionate in the presence of Yb(OTf)3 proceeded under mild reaction conditions to give dihydropyridines (DHPs). We have found that the reaction depended on the solvent and the DHPs were obtained selectively in 1,4-dioxane as a solvent. Various 2,6-unsubstituted DHPs were synthesized in one pot in satisfactory yields. © 2011 Elsevier Ltd. All rights reserved.