Two Useful Directing Modes in Singlet Oxygen Reactivity: Electrostatic Effects in the Ene Reaction with Allylic Alcoholates and a Chemoselectivity Change with α‐Alkoxy Michael Esters

Abstract

The singlet oxygen reaction with trisubstituted E‐allylic alcohols resulted in the unselective formation of regioisomeric secondary and tertiary allylic hydroperoxides. Increasing the steric demand at the allylic hydroxymethyl group leads to a moderate large‐group effect that can be strongly enhanced by deprotonation of a dimethylated allylic alcohol and even more pronounced by cation complexation. The presence of alkoxide groups did additionally alter the diastereoselectivity of the singlet oxygen ene reactions with chiral allylic alcohols. The molecular combination of Michael ester and enol ether in α‐alkoxy ester substrates made possible the design of chemoselective substrates for singlet oxygen ene versus [2+2] cycloaddition, e. g. a 3,3‐dimethylated Michael ester as a selective substrate for the ene reaction and an adamantyl analogue as a selective 2+2 substrate. The Z/E‐monomethylated substrates as probes for cis regioselectivity revealed that there is no site preference for Z‐alkoxy hydrogen transfer on the way to the corresponding ene product.

New Acridone- and (Thio)Xanthone-Derived 1,1-Donor–Acceptor-Substituted Alkenes: pH-Dependent Fluorescence and Unusual Photooxygenation Properties

“…Products ( 7) and ( 10) combine the two relevant features for potential chemiluminescent oxygenation processes: the electron-rich CC double bond that is reactive in singlet oxygen [2 + 2] cycloadditions and the oxidative cleavage products, acridone and xanthone, both highly fluorescent ketones. That this substitution pattern allows efficient dioxetane formation has already been shown for non-heterocyclic tetrasubstituted alkenes [36]. This synthetic approach delivers the desired target molecules, unfortunately in low yields, which is due, on the one hand, to moderate conversions (40%-50% in most cases) and, on the other hand, to the harsh reaction conditions that lead to two reductive pathways: reductive exchange of the 1-methoxy group by hydrogen leading to Michael ester product (8) and enone hydrogenation product (11) (and similar (15) from (12), vide infra).…”

“…Summarizing all photooxygenation experiments, three significant observations were made: (a) The 1,1-donor-acceptor-substituted alkene (10) behaves as expected for an electron-rich substrate without allylic hydrogens [36]. The formation of the carbonyl cleavage products indicates an initial [2 + 2] cycloaddition with 1 O 2 and subsequent cycloreversion of the dioxetane (17).…”

“…Besides this impressive and intensive research on chemi-and bioluminescence, there is still a demand for better CL systems for analytical and/or application purposes. We have recently published the first examples of donor-acceptor-substituted alkenes and their reactivity towards singlet oxygen [36]. The investigations and synthesis of new heterocyclic donor-acceptor-substituted alkenes as potential systems for chemoselective [2 + 2] cycloadditions with singlet oxygen are described herein and add a new approach to this complex topic.…”

“…36 (5:1, n-Hex/EtOAc). 1 H-NMR (500 MHz, CDCl3, 298 K): δ [ppm] = 3.49 (s, 3H), 3.50 (s, 3H), 3.68 (s, 3H), 6.95 (td, J = 7.4 and 1.0 Hz, 1H), 7.01 (m, 1H), 7.03 (m, 1H), 7.05 (m, 1H), 7.23 (dd, J = 7.8 and 1.5 Hz, 1H), 7.30 (m, 2H), 8.13 (dd, J = 7.9 and 1.6 Hz, 1H) 13.…”