Development and application of transition metal-catalyzed cross-coupling reactions

Abstract

Chapter 1. PALLADIUM-CATALYZED REGIOSELECTIVE HYDRODEBROMINATION OF DIBROMOINDOLES A novel approach to the selective preparation of 4-bromoindoles has been developed via a Pd-catalyzed reaction. A variety of 4,6-dibromoindoles, which are prepared via Cu-catalyzed chemoselective C-N bond-forming reaction and subsequent Fischer indole cyclization, are transformed to 4-bromoindoles with high regioselectivity using a catalytic Pd(OAc)2/rac-BINAP system. This new method allowes for the preparation of a variety of 2,3,4,5-polysubstituted indoles from aryl halides. Chapter 2. ENANTIOSELECTIVE SYNTHESIS OF INDOLODIOXANE (S)- U86192A The enantioselective synthesis of the antihypertensive agent indolodioxane (S)-U86192A is described. The 4-bromo-5-alkoxy indole, a key intermediate of the synthesis, is prepared according to the new approach developed in chapter 1. The other noteworthy metal-catalyzed transformations, which play a crucial role in the synthesis, include a palladium-catalyzed intramolecular C-O bond-forming reaction to construct the 1,4-benzodioxane structure. The optical purity of U86192A arises from the use of cobalt-catalyzed enantioselective epoxide ring-opening reaction.

(cont.) Chapter 3. ONE-POT SEQUENTIAL COPPER-CATALYZED CONJUGATE REDUCTION AND PALLADIUM-CATALYZED SILYL ENOL ETHER ARYLATION Enantiomerically enriched 3-substituted diphenylsilyl enol ethers of cyclopentanones, which can be prepared from Cu-catalyzed asymmetric conjugate reduction, are utilized in the Pd-catalyzed arylation of various aryl bromides in the presence of CsF. This new method provides a simple means to access [alpha] aryl-[beta]-alkylcycloalkanones with two new tertiary stereogenic centers in excellent levels of enantiomeric and diastereomeric excess, which are difficult to prepare via other methods. The isolation of the intermediate diphenylsilyl enol ethers is not necessary. The procedure can be carried out in one-pot by choosing the proper solvents and catalyst loadings. This new protocol obviates the need to block the [alpha]'-carbon necessary in our previous method.