Koichi Mitsudo

Pyridylsilyl group-driven cross-coupling reactions

Abstract Summarized herein are the demonstrations that the use of 2-PyMe 2 Si group as a removable directing group is a powerful strategy for enhancing the efficiency of otherwise sluggish processes and for steering the course of the reaction by taking advantage of attractive substrate–catalyst interaction in the palladium-catalyzed cross-coupling chemistry. The 2-PyMe 2 Si group-driven Heck-type coupling, Hiyama-type coupling, Stille-type coupling, and allylic alkylation are described.

Directed Intermolecular Carbomagnesation across Vinylsilanes: 2‐PyMe2Si Group as a Removable Directing Group

Facile addition of primary alkyl Grignard reagents to vinylsilanes has been realized for the first time by exploiting the directing effect of a 2-pyridyl group on silicon [Eq. (1)]. Three-component coupling reactions of a Grignard reagent, the vinylsilane, and an electrophile, followed by oxidative removal of the 2-pyridyldimethylsilyl group with H2 O2 furnishes various secondary alcohols in excellent overall yields.

Facile generation of α-silyl carbanion of trimethylsilyl group assisted by intramolecular pyridyl group coordination

Abstract Novel methodology for the generation of α-silyl carbanion by the deprotonation of trimethylsilyl group with tert -butyllithium or LDA has been developed. This newly developed α-lithiation protocol is based on the intramolecular pyridyl group coordination to stabilize the α-silyl carbanion, together with the inherent silicon α effect. The importance of the use of the 2-pyridyl group in ‘pyridyl’- and ‘silyl’-directed α-lithiation has been confirmed by the control experiments utilizing phenyltrimethylsilane and (3-pyridyl)trimethylsilane.

Kinetic Resolution of Secondary Alcohols by the Combination of a Chiral Brønsted Acid, DABCO, and Acetyl Chloride

An efficient and simple protocol for the kinetic resolution of secondary alcohols is presented. The new system is based on a combination of chiral Brønsted acid, DABCO, and acetyl chloride and gives various enantioenriched alcohols with selectivity factors up to 105.

Electrochemical generation of silver acetylides from terminal alkynes with a Ag anode and integration into sequential Pd-catalysed coupling with arylboronic acids

An electro-oxidative method for generating silver acetylides from acetylenes with a Ag anode was developed. The reaction could be integrated into a Pd-catalysed electrochemical Sonogashira-type reaction. In the presence of the catalytic amount of Pd(OAc)(2) and 4-BzO-TEMPO, electro-generated silver acetylides reacted immediately with arylboronic acids to afford the corresponding coupling adducts in high yields.

Enantioselective acyl transfer catalysis by a combination of common catalytic motifs and electrostatic interactions

Catalysts that can promote acyl transfer processes are important to enantioselective synthesis and their development has received significant attention in recent years. Despite noteworthy advances, discovery of small-molecule catalysts that are robust, efficient, recyclable and promote reactions with high enantioselectivity can be easily and cost-effectively prepared in significant quantities (that is, >10 g) has remained elusive. Here, we demonstrate that by attaching a binaphthyl moiety, appropriately modified to establish H-bonding interactions within the key intermediates in the catalytic cycle, and a 4-aminopyridyl unit, exceptionally efficient organic molecules can be prepared that facilitate enantioselective acyl transfer reactions. As little as 0.5 mol% of a member of the new catalyst class is sufficient to generate acyl-substituted all-carbon quaternary stereogenic centres in quantitative yield and in up to 98:2 enantiomeric ratio (er) in 5 h. Kinetic resolution or desymmetrization of 1,2-diol can be performed with high efficiency and enantioselectivity as well.

(2-Pyridyldimethylsilyl)methyl lithium as a novel hydroxymethylating reagent

Abstract (2-Pyridyldimethylsilyl)methyl lithium was found to react with organic bromides, aldehydes, ketones, and hydrosilanes in good to excellent yields. The resultant adducts were further oxidized with H 2 O 2 /KF to give the corresponding alcohols in excellent yields. Thus, this two-step transformation provides an efficient method for hydroxymethylation.

Site-selective sequential coupling reactions controlled by "electrochemical Reaction Site Switching": A straightforward approach to 1,4-bis(diaryl)buta-1,3-diynes

Site-selective sequential coupling reactions directed toward bis(diaryl)butadiynes are described. The reaction site could be controlled completely by the on/off application of electricity. The electro-oxidative homo-coupling of terminal alkynes (electricity ON) and the subsequent Suzuki-Miyaura coupling (electricity OFF) afforded bis(diaryl)butadiynes in high yields. The obtained 1,4-bis(diaryl)butadiynes could be converted to a 2,5-bis(diaryl)thiophene derivative, which exhibited blue fluorescence.

Studies on the Synthesis of DMAP Derivatives by Diastereoselective Ugi Reactions

Diastereoselective Ugi reactions of DMAP-based aldehydes with α-amino acids and tert-butyl isocyanide were examined. The reactions of 4-(dimethylamino)-2-pyridine-carboxaldehyde with various α-amino acids afforded 2-substituted DMAP derivatives with low diastereoselectivity. On the contrary, reactions with 4-(dimethylamino)-3-pyridine-carboxaldehyde delivered 3-substituted DMAP derivatives with moderate to high diastereoselectivity. The combination of α-amino acid and DMAP-based aldehyde is thus important to achieve high diastereoselectivity. Kinetic resolution of a secondary alcohol using a chiral DMAP derivative obtained through these reactions was also examined.

Synthesis of hexa(furan-2-yl)benzenes and their π-extended derivatives.

The first synthesis of hexa(furan-2-yl)benzene derivatives is described. The RhCl3/i-Pr2NEt-catalyzed cyclotrimerization of di(furan-2-yl)acetylenes was an effective method for constructing hexa(furan-2-yl)benzene derivatives in good yields. Their π-extended derivatives were also synthesized by Suzuki-Miyaura coupling between hexakis(5-Bpinfuran-2-yl)benzene (Bpin = (pinacolato)boryl) and several aryl iodides.