Gold-Catalyzed Oxidative Alkyne Functionalization & Asymmetric Cyclization

Homogeneous gold catalysis has emerged as a powerful tool in organic synthesis due to its rich chemistry and fascinating reactivity. Recently, the gold-catalyzed alkyne oxidation for the generation of a-oxo gold carbenoid intermediates is widely applied in organic synthesis, since it provides efficient access to functionalized carbo- and heterocycles. Despite significant achievements in the functionalization of alkynes by this novel strategy, the catalytic enantioselective version is extremely formidable and chanllenging. Moreover, the mechanistic aspects that determine the outcome of gold-catalyzed alkyne oxidation are still under debate (gold carbene versus β-gold vinyloxyquinolinium intermediate). Therefore, breakthroughs in several fronts are desirable:1) expanding the current toolbox of alkyne oxidation reactions, and in particular the number of enantioselective variants promoted by chiral gold complexes, to prepare new and challenging molecular targets; 2) better understanding of the reactivity modes of gold carbenes via extensive mechanistic investigations and DFT calculations; 3) the coupling of the new reactivity of gold complexes with their capability to catalyze alkyne oxidations should offer ample opportunities for the design of new reactions.In this paper, we show that electron-deficient internal alkynes can indeed effectively serve as precursors to versatile a-oxo gold carbenoids. In this manner, two synthetically challenging yet highly valuable transformations, i.e., cyclopropanation reaction and C-H functionalization, have been developed. We demonstrate that we can efficiently trap exclusively formed acceptor-acceptor carbene centers by internal nucleophiles en route to the formation of cyclic products, including, carbo-and hetero[n.1.0]bicyclics as well as functionalized 3-acyloxindole derivatives.Secondly, a highly diastereo- and enantioselective oxidative cyclopropanation of 1,6-enynes catalyzed by cationic Au(I)/chiral phophoramidite complexes has been developed. The new method provides convenient access to densely functionalized bicyclo[3.1.0]hexane architectures bearing three contiguous quaternary and tertiary stereogenic centers with high enantioselectivity (up to 96% ee). Control experiments suggest that the quinoline moiety of the β-gold vinyloxyquinolinium intermediate in the reaction plays an important role in promoting good enantioselectivity through a transitional auxiliary effect in the transition state. Furthermore, the new method features a practical one-pot protocol without slow addition of substrates, i.e., ynones can be visualized as a safe and reliable surrogates of acceptor/acceptor diazo compounds.Thirdly, we demonstrate that the powerful combination and compatibility of the unique reactivity of gold species with chiral phosphoric acid (CPA) enables the first highly efficient asymmetric redox-pinacol-Mannich cascade, affording optically functionalized β-amino spirocyclic and quaternary diketones. This methodology showed good to excellent overall yields and enantioselectivities (up to> 99% ee), redox-, atom-and step-economic synthesis, and high efficiency in establishing densely multiplechiral centers including quaternary carbons of spirocyclic ring systems.Finally, we have developed an efficient Au(I)/Au(III)-catalyzed Sonogashira-type cross-coupling reaction of terminal alkynes and arylboronic acids under mild conditions. The good tolerance toward many functional groups of substrates considerably extends the scope of a number of organic transformations and performs modular C(sp)-C(sp2) bond constructions at appropriate stages in the whole synthetic sequence.