6.2-[(Neopentyl glycolato)boryl]phenyl Triflates and Halides for Fluoride Ion-Mediated Generation of Functionalized Benzynes
Takashi Ikawa, Rika Yamamoto, Akira Takagi, Toyohiro Ito, Kazunori Shimizu, Masahiko Goto, Yoshitaka Hamashima, Shuji Akai, Adv. Synth. Cat. , 357, 2287-2300 (2015), DOI:10.1002/adsc.201500315Abstract: 2-[(Neopentyl glycolato)boryl]phenyl trifluoromethanesulfonates (triflates) and halides have been developed as new benzyne precursors, which generate benzynes at 120 °C in the presence of a fluoride ion. There are two major features of these types of precursors. First, they generate benzynes bearing various reactive functional groups, such as carbonyl, cyano, bromo, and primary amino groups. Second, these precursors were directly synthesized through either the palladium-catalyzed Miyaura borylation of 2-iodophenol derivatives or ortho-selective iodination of the corresponding boronic acids as key steps without using any protecting groups. The in-situ-generated benzynes underwent [4+2], (3+2), and [2+2] cycloadditions to give the benzo-fused multicyclic compounds while maintaining such functional groups. In particular, 4-aminobenzyne was generated for the first time and underwent the Diels–Alder reaction with the free primary amino group remaining intact.
5.Transition Metal-Catalyzed Intramolecular Cyclization of Propargyl Alcohols and Their Derivatives for the Synthesis of Highly Substituted Five-Membered Oxygen Heterocycles
Masahiro Egi, Shuji Akai, Heterocycles , 91, 931–958 (2015), DOI:10.3987/REV-15-818Abstract: The transition metal-catalyzed intramolecular cyclization of propargyl alcohols and their derivatives has been widely utilized in the synthesis of five-membered oxygen heterocycles such as furans, hydrofurans, and furanones. Prerequisites for the efficient transformations into highly substituted target compounds include the regioselectivity of the cyclization step and the chemoselectivity of the transition metal-mediated activation of substrates. This review documents recent progress on the title reactions by categorizing the initial activation modes of substrates.
4.Development of a highly efficient single-mode microwave applicator with a resonant cavity and its application to continuous flow syntheses
Saori Yokozawa, Noriyuki Ohneda, Ken Muramatsu, Tadashi Okamoto, Hiromichi Odajima, Takashi Ikawa, Jun-ichi Sugiyama, Masashi Fujita, Taira Sawairi, Hiromichi Egami, Yoshitaka Hamashima, Masahiro Egi, Shuji Akai, RSC Adv. , 5, 10204-10210 (2015), DOI:10.1039/C4RA12428FAbstract: Microwave-assisted organic synthesis has many advantages and is widely applied to a variety of reactions. We have developed a new single-mode microwave applicator, specific to continuous flow synthesis, whose main feature is that it generates a uniform electromagnetic field inside its resonant cavity. Two well-known reactions, the Fischer indole synthesis and the Diels–Alder reaction, proceeded very quickly when a solution of substrates was pumped through a helical glass tube reactor inside the resonant cavity, under a pressure of 2.5 MPa. The desired products were obtained in high yields. This compact apparatus constitutes a new method for switching organic synthesis from batch to continuous flow, and enables continuous synthesis of products at a scale of 100 g h−1 or more.
3.Trifluoromethanesulfonyloxy-group-directed regioselective (3 + 2) cycloadditions of benzynes for the synthesis of functionalized benzo-fused heterocycles
Takashi Ikawa, Hideki Kaneko, Shigeaki Masuda, Erika Ishitsubo, Hiroaki Tokiwa, Shuji Akai, Org. Biomol. Chem. , 13, 520–526 (2015), DOI:10.1039/c4ob01627kAbstract: Highly regioselective (3 + 2) cycloadditions of (trifluoromethanesulfonyloxy)benzynes [(triflyloxy)benzynes] with 1,3-dipoles followed by cross-coupling reactions provided multisubstituted benzo-fused heterocycles. The triflyloxy group at the 3-position of benzynes, and even that at the remote 4-position, greatly affected the regiocontrol of the cycloaddition. These groups also served to install other substituents at their ipso-positions.
2.Central–axial–central chirality transfer: asymmetric synthesis of highly substituted indenes bearing a stereogenic quaternary carbon center from optically active propargyl alcohols
Masahiro Egi, Kaori Shimizu, Marin Kamiya, Yuya Ota, Shuji Akai, Chem. Commun. , 51, 380–383 (2015), DOI:10.1039/c4cc08034cAbstract: An asymmetric synthesis of highly substituted indenes 3, bearing a quaternary stereogenic carbon center, has been developed via the central-axial-central chirality transfer from optically active propargyl alcohols 1. This transformation involves the addition/rearrangement of 1 and ynamides 2 to give tetra-substituted allenes 4 and further cyclization of 4.
1.Total Synthesis of Clavilactone B: A Radical Cyclization–Fragmentation Strategy
Hiroshi Suizu, Daisuke Shigeoka, Hiroshi Aoyama, Takehiko Yoshimitsu, Org. Lett. , 17, 126-129 (2015), DOI:10.1021/ol503356mAbstract: A new synthetic route to clavilactone B, a naturally occurring inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, is disclosed. The route features a sequential samarium-mediated radical cyclization–fragmentation of an indanone derivative, which provides rapid access to a 10-membered carbocyclic motif fused to an aromatic ring.