Deyun Qian

Diastereo‐ and Enantioselective Gold(I)‐Catalyzed Intermolecular Tandem Cyclization/[3+3]Cycloadditions of 2‐(1‐Alkynyl)‐2‐alken‐1‐ones with Nitrones

Asymmetric cationic gold(I)-catalyzed intermolecular and intramolecular reactions have emerged as powerful tools for the enantioselective synthesis of versatile carbocycles and heterocycles over the past five years. Aside from a few examples using a chiral counteranion strategy and monodentate phosphoramidite ligands, most of these transformations have largely relied on the use of bis(phosphines) as ligands. In order to gain high enantioselectivity, these ligands are often further modified by introducing bulky substituents onto the phosphorous aryl moieties. 2f–j] We have recently reported the gold(I)-catalyzed intermolecular regioand diastereoselctive tandem cyclization/[3+3]-cycloaddition reactions of 2-(1-alkynyl)-2-alken-1-ones with nitrones, thus leading to fused heterobicyclic furo[3,4-d][1,2]oxazines. 8] The preliminary result showed that (R)MeO-biphep can induce a moderate enantioselectivity. We envisaged that better enantioselectivity might be obtained by modification of this chiral MeO-biphep ligand. Herein, we report the gold(I)-catalyzed diastereoand enantioselective intermolecular tandem cyclization/[3+3]-cycloaddition reactions of 2-(1-alkynyl)-2-alken-1-ones with nitrones using (R)C1-tunephos (which acts through modification the bite angle) and (R)-MeO-dtbm-biphep (which acts through introduction of bulky substituents on the phosphorous aryl moieties) as chiral ligands. To the best of our knowledge, this is the first report using Cn-tunephos/(AuCl)2 as a chiral catalyst in asymmetric gold-catalyzed reactions. Ketone 1 a and nitrone 2a were selected as the model substrates for screening the chiral ligand (Table 1). The (R)-

Gold(I)‐Catalyzed Highly Diastereo‐ and Enantioselective Alkyne Oxidation/Cyclopropanation of 1,6‐Enynes

A highly enantioselective oxidative cyclopropanation of 1,6-enynes catalyzed by cationic Au(I)/chiral phophoramidite complexes is presented. The new method provides convenient access to densely functionalized bicyclo[3.1.0]hexanes bearing three contiguous quaternary and tertiary stereogenic centers with high enantioselectivity (up to e.r. 98:2). 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.

Gold‐Catalyzed Cascade Reactions for Synthesis of Carbo‐ and Heterocycles: Selectivity and Diversity

This account describes our recent efforts devoted to gold chemistry since 2009. Based on furyl-Au 1,3-dipole analogues and related gold carbene intermediates, a rich variety of gold-catalyzed cascade reactions have been developed, which provide facile access to a diverse range of novel carbo- and heterocycles. In these reactions, the selectivity can be well controlled by the catalyst (ligand and metal), substrate or reagent. In addition, we have also developed the corresponding enantioselective variants, which are guided by bis(phosphinegold) complexes derived from axially chiral scaffolds and asymmetric gold/chiral Brønsted acid relay catalysis.

Highly Regio‐, Diastereo‐, and Enantioselective Gold(I)‐Catalyzed Intermolecular Annulations with N‐Allenamides at the Proximal CC Bond

A highly enantioselective gold(I)-catalyzed intermolecular annulation of 2-(1-alkynyl)-2-alken-1-ones with N-allenamides is presented. The present work represents the first example of a gold-catalyzed annulation with the proximal C=C bond of an N-allenamide, and is distinctly different from the previously observed annulations at the distal C=C bond. Interestingly, both enantiomers of the products could be obtained in good yields with high regio-, diastereo-, and enantioselectivity by using either diastereomer of a binol-derived phosphoramidite as a chiral ligand.

Gold/Brønsted Acid Relay Catalysis for Enantioselective Construction of Spirocyclic Diketones

Enantiopure spirocycles represent a structural motif present in natural products and biologically active compounds such as fusarisetin A, a potent cancer migration inhibitor, and acutumine, an alkaloid with antiamnesic and selective T-cell cytotoxicity. Furthermore, their rigid structures make them a privileged platform for the development of chiral ligands. The ability to enantioselectively construct such important spirocyclic molecules in a rapid and efficient manner still represents a major challenge in modern organic synthesis. Moreover, catalytic enantioselective synthesis of adjacent quaternary and tertiary chiral centers still remains scarce by existing methodologies. Gold catalysis has witnessed tremendous activity in recent years, which allows readily available substrates to be converted into diverse carbocyclic or heterocyclic scaffolds with a significant increase in molecular complexity. Although inherently apt for asymmetric synthesis, current methods are mostly based on the principle of a chiral phosphine or carbene ligand on the metal center. In this context, the successful variant of asymmetric gold catalysis applied to the cascade or domino reaction has been largely unexplored, which may result from the fact that enantioselectivity control in three or more mechanistically distinct reactions in a consecutive process by one simple gold complex is an extremely difficult task. Very recently, gold/Brønsted acid relay catalysis is emerging as an alternative approach for the creation of new enantioselective transformations (Scheme 1a). Despite being straightforward, the reported reactions have encountered several restrictions: 1) the reaction type disclosed so far is relatively onefold, in which the gold catalyst is commonly responsible for the alkyne hydrofunctionalization (hydroamination, hydroxylation, and hydrosiloxylation), 2) in most cases, stoichiometric Hantzsch esters for the asymmetric transfer hydrogenation are required, and 3) the intramolecular cascade version has not been achieved. Thus the attempted application of this gold/Brønsted acid relay catalysis strategy to other more various transformations, especially to those cascade reactions, is highly encouraged. Based on the importance of the spirocyclic scaffold, we focused our attention on the efficient redox-pinacol-Mannich cascade reaction developed by Shin and co-workers (Scheme 1b). Undoubtedly, ability to control the reaction enantioselectivity is extremely attractive. If successful, this would permit facile access to spirocyclic diketones with contiguous chiral centers, which is still an urgent need for enantioselective construction of quaternary stereocenters by using gold catalysts. Specifically, it would provide a redox-, atom-, and step-economic approach to enantiopure spirocycles by starting from readily available nitrone compounds. Our exploratory studies began with the first strategy, that is, using chiral-ligand-derived gold complexes to attempt the enenatioselective synthesis (Figure 1). Unfortunately, extremely poor levels of enantioinduction (up to 4 % ee ; ee= enantiomeric excess) and low to moderate diastereoselectivity were obtained when using those privileged chiral ligands in asymmetric gold catalysis, such as 1,1’-binaphthalene-2,2’[a] D. Qian, Prof. J. Zhang Shanghai Key Laboratory of Green Chemistry and Chemical Processes, Department of Chemistry East China Normal University, Shanghai 200062 (P. R. China) E-mail : jlzhang@chem.ecnu.edu.cn Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201301208. Scheme 1. Gold/chiral Brønsted acid catalyzed consecutive transformations.

Au(I)/Au(III)-catalyzed Sonogashira-type reactions of functionalized terminal alkynes with arylboronic acids under mild conditions

Summary A straightforward, efficient, and reliable redox catalyst system for the Au(I)/Au(III)-catalyzed Sonogashira cross-coupling reaction of functionalized terminal alkynes with arylboronic acids under mild conditions has been developed.

Enantioselective gold-catalyzed intermolecular [2 + 2]-cycloadditions of 3-styrylindoles with N-allenyl oxazolidinone

The enantioselective intermolecular [2 + 2] cycloaddition of 3-styrylindoles with N-allenyl oxazolidinone has been achieved for the first time by the employment of a Xiang-Phos derived chiral gold-catalyst. The corresponding cycloadducts could be obtained in good yields (up to 95%) with up to 95% ee.