title: Origin of High Regio-, Diastereo-, and Enantioselectivities in 1,6-Addition of Azlactones to Dienyl N-Acylpyrroles: A Computational Study.
abstract: Chiral P-spiro triaminoiminophosphorane (1) was developed to promote the highly regio-, diastereo-, and enantioselective 1,6- and 1,8-additions of azlactones (2·H) to dienyl and trienyl N-acylpyrroles (3 and 4). DFT calculations enabled us to gain deep insight into the whole reaction mechanism as well as the origin of the high regio- and stereoselectivities. The present reaction consists of three steps: (1) formation of the phosphonium-enolate ion-pair complex by deprotonation of 2·H with 1, (2) C-C bond formation of 2 with 3 and 4, and (3) protonation of the resulting enolate anion. The C-C bond formation is irreversible, and the rate- and stereodetermining step. The Cα-protonation preferentially proceeds rather than the thermodynamically and kinetically disfavored O- and Cγ-protonation, respectively. The high regio- and enantioselectivities are mainly attributed to the steric and electronic features of 1·H and 3/4. The hydrogen bonds (NH-O and CH-O) and the attractive CH-π interaction between 1·H and 2 and 3 play a key role in achieving high stereocontrol. The high regioselectivity is mainly controlled by the structural distortion of 1·H and the disruption of the π-conjugated system of 3 (1,4-system) and 4 (1,4- and 1,6-systems).
authors.affiliation: Department of Chemistry and Research Center for Smart Molecules, Faculty of Science, Rikkyo University , 3-34-1 Nishi-Ikebukuro, Toshima-ku, Tokyo 171-8501, Japan.
authors.forename: Masahiro
authors.identifier: 0000-0001-7978-620X
authors.initials: M
authors.lastname: Yamanaka
authors.affiliation: Faculty of Pharmaceutical Sciences, Hoshi University , Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
authors.forename: Ken
authors.identifier: 0000-0002-6920-0735
authors.initials: K
authors.lastname: Sakata
authors.affiliation: Institute of Transformative Bio-Molecules (WPI-ITbM) and Department of Applied Chemistry, Graduate School of Engineering, Nagoya University , Nagoya 464-8602, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Yoshioka
authors.affiliation: Institute of Transformative Bio-Molecules (WPI-ITbM) and Department of Applied Chemistry, Graduate School of Engineering, Nagoya University , Nagoya 464-8602, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Uraguchi
authors.affiliation: Institute of Transformative Bio-Molecules (WPI-ITbM) and Department of Applied Chemistry, Graduate School of Engineering, Nagoya University , Nagoya 464-8602, Japan.|CREST, Japan Science and Technology Agency (JST), Nagoya University , Nagoya 464-8602, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ooi