Palladium-Catalyzed Oxidative Cascade Cyclizations Via C-N/C-C Formation for Synthesis of Nitrogen Heterocycles PDF Download

Author: Wei Du
Publisher: Open Dissertation Press
ISBN: 9781361385449
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Languages : en
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This dissertation, "Palladium-catalyzed oxidative cascade cyclizations via C-N/C-C formation for synthesis of nitrogen heterocycles" by Wei, Du, 杜玮, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled PALLADIUM-CATALYZED OXIDATIVE CASCADE CYCLIZATIONS VIA C-N/C-C FORMATION FOR SYNTHESIS OF NITROGEN HETEROCYCLES submitted by Du Wei for the Degree of Doctor of Philosophy at The University of Hong Kong in May 2014 Pd(II)-catalyzed oxidative amination of alkenes is a versatile method to construct N-containing heterocycles which are found in many biologically active synthetic targets, including natural products and pharmaceuticals. Considering the efficiency of the cascade reaction, we have employed this protocol to synthesize nitrogen heterocycles (including chiral ones) via Pd(II)-catalyzed C-N/C-C bond formation. We have developed a highly efficient enantioselective method for oxidative cascade cyclization of acrylamides tethered alkene using Pd(TFA) /diPh-pyrox as catalyst under a mild aerobic condition (Scheme 1). A series of pyrrolizidine derivatives, such as 2.4a, 2.2h, and 2.2n, have been synthesized in good yields and excellent enantioselectivity. The mechanism study has indicated that the cyclization reaction proceeded through both trans-/cis-aminopalladation (AP) with a ratio of ca. 3:1 (Scheme 2). Besides, we have found that some factors, including the counterions of Pd(II) complexes, the electronic density of the isolated double bond and the steric bulkiness of ligands, affect the stereochemical selectivity in the aminopalladation step. This study has important implications for designing new catalyst systems for enantioselective Pd-catalyzed oxidative amination reactions. We have also disclosed the first enantioselective Pd(II)-catalyzed oxidative aminoarylation reaction (Scheme 3). The reactions were carried out with Pd(OAc) /β-ICD as catalyst to synthesize indoline derivatives, such as 3.2a, 3.2b and 3.2i, in moderate to good yields with moderate enantioselectivity. Base on previous successful cascade reactions of aminopalladation/C(sp )-H functionalization, we have developed a palladium (II)-catalyzed oxidative cascade aminoalkylation via aminopalladation/C(sp )-H activation for divergent synthesis of three-membered-ring (i.e. 4.2ag, 4.2an and 4.2ar) or five-membered-ring (i.e. 4.3aa, 4.3ad and 4.3bs) fused indolines (Scheme 4). The benzylic C-H and the C-H at -position of anilides can be selectively activated under different reaction conditions. 3 This is the first example of palladium catalyzed C(sp )-H activation without employment of prefunctionalized reagents (halogenated or boron-containing reagents) and directing groups, representing a green and economic protocol for construction of N-containing heterocycles. Scheme 1 Scheme 2 Scheme 3 Scheme 4 DOI: 10.5353/th_b5312312 Subjects: Heterocyclic compounds - Synthesis Organopalladium compounds