Takahiko Akiyama

Abstract The hydrosilylation of alkenes is one of the most important methods for the synthesis of organosilicon compounds. In addition to the platinum‐catalyzed hydrosilylation, silyl radical addition reactions are notable as economic reactions. An efficient and widely applicable silyl radical addition reaction was developed by using 2‐silylated dihydroquinazolinone derivatives under photocatalytic conditions. Electron‐deficient alkenes and styrene derivatives underwent hydrosilylation to give addition products in good to high yields. Mechanistic studies indicated that the photocatalyst functioned not as a photoredox catalyst but as an energy transfer catalyst. DFT calculations clarified that the triplet excited state of 2‐silylated dihydroquinazolinone derivatives released a silyl radical through the homolytic cleavage of a carbon‐silicon bond, and this was followed by the hydrogen atom transfer pathway, not the redox pathway.

Abstract A chiral calcium phosphate-catalyzed enantioselective Friedel–Crafts alkylation reaction of pyrroles and α-trifluoromethyl-β-nitrostyrenes has been developed. Pyrroles bearing an all-carbon quaternary center at 2-position were obtained with high to excellent enantioselectivity. Use of 4,7-dihydroindole as a nucleophile and subsequent oxidation resulted in the formation a 2-substituted indole derivative with excellent enantioselectivity. A 3,4-dihydropyrrolo[1,2-c]pyrimidine derivative was successfully synthesized by reduction followed by benzoylation of the product without loss of enantioselectivity. Application to a 1 mmol scale reaction was successfully achieved.

An enantioselective Friedel-Crafts alkylation reaction of pyrroles and indoles with N-unprotected trifluoromethyl ketimines by use of chiral phosphoric acid provided α-trifluoromethylated primary amines bearing chiral tetrasubstituted carbon centers in high yields and with high to excellent enantioselectivities. The present reaction is unique to N-unprotected trifluoromethyl ketimines. No reaction took place with N-p-methoxyphenyl (PMP)-substituted ketimine. Corresponding α-trifluoromethylated amines were transformed without loss of enantioselectivity.

L-Quebrachitol (1L-(-)-2-O-methyl-chiro-inositol) is a naturally abundant chiral cyclitol obtained from the serum of the rubber tree. Although total syntheses of natural products starting from L-quebrachitol have been studied extensively, asymmetric reaction employing L-quebrachitol as chiral source had not been reported. Thus diastereoselective asymmetric reaction employing chiral cyclitol (2 and 3) as chiral auxiliaries were investigated. Reduction of α-keto ester (4) derived from 1L-3-O-t-butyldimethylsilyl-1,2:5,6-di-O-cyclohexylidene-chiro-inositol, which is readily available from L-quebrachitol, with K-Selectride in Et_2O underwent highly diastereoselectively and α-hydroxy ester with 2'S isomer was obtained in 96% de. On the other hand, addition of 18-Crown-6 completely reversed the diastereoselectivity and 2'R-isomer was obtained in 92%de. While addition of Grignard reagents to the α-keto ester (4) proceeded via re-face attack of the ketone to afford α-hydroxy ester with 2'S isomer in 96% de, those of alkyl lithium took place via si-face attack to afford 2'R isomer preferentially. SnCl4 promoted addition of allyl silane or sillyl enol ether to 4 also took place to afford single diastereomer exclusively. 1,3-Dipolar cycloaddition of an acryloyl ester (5) bearing 1L-3-O-t-butyldiphenylsilyl-1,2:5,6-di-O-cyclohexylidene-chiro-inositol with nitrile oxide furnished Δ^2-isoxazolines of high diastereomeric excess. It was found chiral cyclitols derived from L-quebrachitol are efficient chiral auxiliaries.