Dissertation/Thesis Abstract

Oxidative Palladium(II)-Catalyzed Cross-Dehydrogenative Couplings of Indolines With Arenes and Alkenes at the C-7 Position
by Jiao, Lin-Yu, Dr.Nat., Technische Universitaet Berlin (Germany), 2015, 245; 10702067
Abstract (Summary)

Previously, several different kinds of prefunctionlized coupling partners such as boronic acids or organometallic reagents had been used in combination with catalytic amounts of a transition metal to accomplish C(sp2)–C(sp2) bonds formation. Later, the concept changed to use two unactivated C‒H bonds directly under oxidative transition metal catalysis for the same type of reactions. We describe here an oxidative palladium(II)-catalyzed cross-dehydrogenative arylation of indolines. The palladium(II) catalysis requires TFA as an additive and Na2S2O8 as the terminal oxidant. An acetyl group at the indoline nitrogen atom was employed as a directing group, no such group was required at the arene coupling partner. Several mono-, di-, and trisubstituted indolines were subjected to the optimized conditions in moderate to excellent yields. For the annulated indolines, the relative configuration was determined by nOe measurements and was retained throughout the sequence. Remarkably, the amide group alone is not sufficient to allow for this transformation. In addition, NMR experiments showed that the substituent at C-2 position is a crucial factor for the regioselectivity and reactivity. This established protocol, however, requires harsh reaction conditions (100‒120 °C) under which less-substituted indolines would undergo oxidation to their corresponding indoles. Shortly afterwards, we overcame the limitations by using a urea directing group instead of an acetyl group that enabled the same transformation under milder conditions. As a result, the use of either Cu(OAc)2 in an open flask or dioxygen (balloon) at 50 °C tolerates indolines not substituted at C-2 and C-3, thereby extending the scope of the previous method that suffers from indoline-to-indole oxidation. This methodology has been successfully repeated on a gram scale with slightly diminished conversion and yield. It is worth noting that other common directing groups, even a urea with a free N‒H group at the terminus, failed to facilitate the C−H bond activation. By employing the same urea directing group attached to the indoline skeleton, a protocol for the direct alkenylation of indolines at the C-7 position is described. This catalytic system proved to be broadly applicable, mild, and efficient. Both α,β-unsaturated acceptors and styrenes participate in this direct C‒H functionalization. Even substituted α,β-unsaturated acceptors reacted, regioselectivities were good to excellent albeit yields were somewhat lower. Notably, with a free N–H group at the urea terminus, the nitrogen atom subsequently cyclizes in a 1,4-fashion to yield a six-membered heterocycle.

Indexing (document details)
Advisor: Oestreich, Martin
Commitee:
School: Technische Universitaet Berlin (Germany)
School Location: Germany
Source: DAI-C 81/1(E), Dissertation Abstracts International
Source Type: DISSERTATION
Subjects: Organic chemistry
Keywords: Palladium catalysts
Publication Number: 10702067
ISBN: 9781392341308
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