ORGN 196 |
| Reaction conditions for the first time have been developed for palladium-catalyzed terminal (beta) arylation of acyclic vinyl ethers with high regioselectivity using inexpensive aryl chlorides as starting materials and the P(t-Bu)3 releasing pre-ligand [(t-Bu)3PH]BF4 as the key additive. This swift and straightforward protocol exploits non-inert conditions and controlled microwave heating to reduce handling and processing times, and aqueous DMF or environmentally friendly PEG-200 as the reaction medium. DFT calculations at the B3LYP level of theory were performed for the regioselectivity determining insertion step in the Heck reaction, following a neutral pathway. The calculations support a ligand-driven selectivity rationale, where the electronic and steric influence of bulky P(t-Bu)3 ligand provides improved beta-selectivity in the essential insertion step. The methodology was finally used to provide efficient access to linear para-[2-(cyclopropylmethoxy)ethyl] phenol from para-nitrophenyl chloride, a key intermediate in the synthesis of the beta-adrenergic blocking agent Betaxolol.
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Asymmetric Reactions and Syntheses, Metal-Mediated Reactions, Combinatorial, Parallel, and Solid-Phase Chemistry
8:00 PM-10:00 PM, Sunday, 10 September 2006 Moscone Center -- Hall D, Poster
Division of Organic Chemistry |
