Shu-Li You

Catalytic Asymmetric Dearomatization Reactions

This Review summarizes the development of catalytic asymmetric dearomatization (CADA) reactions. The CADA reactions discussed herein include oxidative dearomatization reactions, dearomatization by Diels-Alder and related reactions, the alkylative dearomatization of electron-rich arenes, transition-metal-catalyzed dearomatization reactions, cascade sequences involving asymmetric dearomatization as the key step, and nucleophilic dearomatization reactions of pyridinium derivatives. Asymmetric dearomatization reactions with chiral auxiliaries and catalytic asymmetric reactions of dearomatized substrates are also briefly introduced. This Review intends to provide a concept for catalytic asymmetric dearomatization.

Enantioselective Construction of Spiroindolenines by Ir-Catalyzed Allylic Alkylation Reactions

With 2-methyl-1,2,3,4-tetrahydroquinoline-derived phosphoramidite ligand (R,R(a))-L(6), Ir-catalyzed intramolecular C-3 allylic alkylation of indoles has been realized to afford highly enantioenriched spiroindolenine derivatives in 92-98% yields with up to >99/1 dr and 97% ee.

Desymmetrization of Cyclohexadienones via Brønsted Acid-Catalyzed Enantioselective Oxo-Michael Reaction

Desymmetrization of cyclohexadienones via enantioselective oxo-Michael reaction catalyzed by chiral phosphoric acid to afford highly enantioenriched 1,4-dioxane and tetrahydrofuran derivatives in excellent yields has been realized. The newly established methodology allows the facile enantioselective synthesis of cleroindicins C, D, and F.

Enantioselective N-heterocyclic carbene-catalyzed Michael addition to α,β-unsaturated aldehydes by redox oxidation.

Enantioselective N-heterocyclic carbene-catalyzed Michael addition reactions to α,β-unsaturated aldehydes by redox oxidation were realized. With 10 mol % of camphor-derived triazolium salt D, 15 mol % of DBU, 5 mol % of NaBF(4), and 100 mol % of quinone oxidant, the reactions of various dicarbonyl compounds with α,β-unsaturated aldehydes led to 3,4-dihydro-α-pyrones in good yields and excellent ees.

Recent development of direct asymmetric functionalization of inert C–H bonds

The area of direct asymmetric functionalization of inert C–H bonds has attracted considerable attention in recent years. To realize this type of challenging but promising transformations, a lot of strategies have emerged including asymmetric C–H bond insertion by metal carbenoids or analogs, cross dehydrogenative coupling, [1,5]-hydride transfer, C–H bond functionalization involving a transient metal–carbon species and other miscellaneous methods. This review is intended to summarize and discuss the most recent developments (contributions mainly after 2009) within this area.

Asymmetric Construction of Polycyclic Indoles through Olefin Cross‐Metathesis/Intramolecular Friedel–Crafts Alkylation under Sequential Catalysis

The combination of mechanistically distinct organocatalysis and transition-metal catalysis has enabled novel transformations beyond those possible with single catalytic systems. Sequential catalysis involving a binary catalytic system often reduces labor and waste and enables the use of more readily available starting materials for a given transformation. Chiral Brønsted acids have been shown to be efficient catalysts for asymmetric Friedel–Crafts reactions. 4] In particular, intramolecular Friedel–Crafts-type reactions provide a direct route to polycyclic indoles, such as tetrahydropyrano[3,4-b]indoles (THPIs) and tetrahydro-b-carbolines (THBCs), 6] which are frequently encountered in biologically active natural products and pharmaceuticals. Despite considerable efforts devoted to asymmetric intramolecular Friedel– Crafts-type Michael addition reactions, there are few successful examples. Most notably, the tedious procedure for the preparation of substrates for the intramolecular Friedel– Crafts reaction limits its synthetic applications. Xiao et al. recently demonstrated an elegant rutheniumcatalyzed tandem cross-metathesis (CM)/intramolecular hydroarylation sequence for the efficient synthesis of polycyclic indoles. The Lewis acidic ruthenium species generated in situ catalyzes the Friedel–Crafts alkylation reaction. As part of our research program towards the development of enantioselective Friedel–Crafts reactions, we envisaged that sequential olefin cross-metathesis and asymmetric intramolecular Friedel–Crafts alkylation reactions might be used to construct enantiomerically pure polycyclic indoles (Scheme 1). Chiral phosphoric acids were chosen as catalysts for the asymmetric Friedel–Crafts reaction because of their strong activation of unsaturated carbonyl compounds. We hoped that these catalysts would suppress the racemic reaction caused by Lewis acidic ruthenium species. Furthermore, the Friedel–Crafts reaction should accelerate the CM reaction by converting the metathesis product into an alkylation product. Herein, we report our preliminary results on an enantioselective intramolecular Friedel–Crafts alkylation based on sequential catalysis. When we began our study, no efficient enantioselective Friedel–Crafts alkylation of indolyl enones was known. We chose the indolyl enone 1a as the model substrate and explored the use of chiral Brønsted acid catalysts for this transformation. With chiral phosphoric acids 5 (5 mol%) in toluene at 20 8C, the desired reaction proceeded smoothly to give 2 a with 59–96% ee (Table 1). The chiral phosphoric acid 5h bearing 9-phenanthryl groups afforded 2a with greater than 95% conversion and 96% ee and thus proved to be the optimal catalyst (Table 1, entry 8). Further examination of the reaction conditions revealed that the reaction proceeded with optimal enantioselectivity (98 % ee) at 0 8C in toluene (Table 1, entry 13). Various substituted indolyl enones were subjected to the intramolecular Friedel–Crafts alkylation under these optimized reaction conditions to examine the generality of the reaction (Table 2). The phosphoric acid catalyzed intramolecular Friedel–Crafts alkylation was found to be effective with a wide range of substrates. Indolyl phenyl enones 1b–f, which contain either an electron-donating group or an electron-withdrawing group at the 5or 6-position of the indole, were good substrates; the desired products were formed in 97–99% yield with 90–97% ee (Table 2, entries 2– 6). When the protecting group on the N atom of the indole ring was changed from methyl to benzyl, the reaction proceeded relatively slowly, but the yield and enantioselectivity were satisfactory (97% yield, 95% ee ; Table 2, entry 7). In general, electron-rich indolyl enones (Table 2, entries 2 Scheme 1. Cascade reaction involving cross-metathesis and an asymmetric Friedel–Crafts alkylation. Boc= tert-butoxycarbonyl.

Enantioselective synthesis of planar chiral ferrocenes via palladium-catalyzed direct coupling with arylboronic acids.

Enantioselective Pd(II)-catalyzed direct coupling of aminomethylferrocene derivatives with boronic acids was realized. With commercially available Boc-L-Val-OH as a ligand, planar-chiral ferrocenes could be synthesized in yields of 14-81% with up to 99% ee under mild conditions.

Iridium-Catalyzed Allylic Vinylation and Asymmetric Allylic Amination Reactions with o-Aminostyrenes

An Ir-catalyzed allylic vinylation reaction of allyl carbonates with o-aminostyrene derivatives has been realized, providing skipped (Z,E)-diene derivatives. With (E)-but-2-ene-1,4-diyl dimethyl dicarbonate as the substrate, an efficient enantioselective synthesis of 1-benzazepine derivatives via an Ir-catalyzed domino allylic vinylation/intramolecular allylic amination reaction has been developed. Mechanistic studies of the allylic vinylation reaction have been carried out, and the results suggest that the leaving group of the allylic precursor plays a key role in directing the reaction pathway. Screening of various allylic precursors showed that Ir-catalyzed reactions of allyl diethyl phosphates with o-aminostyrene derivatives proceed via an allylic amination pathway. A subsequent ring-closing metathesis (RCM) reaction of the amination products led to a series of enantiomerically enriched 1,2-dihydroquinoline derivatives. Their utility is indicated by an asymmetric total synthesis of (-)-angustureine.

Asymmetric Dearomatization of Naphthols via a Rh-Catalyzed C(sp2)–H Functionalization/Annulation Reaction

A Rh-catalyzed enantioselective dearomatization of 1-aryl-2-naphthols with internal alkynes via C-H functionalization reaction was achieved. In the presence of a chiral Cp/Rh catalyst and combined oxidants of Cu(OAc)2 and air (oxygen), various highly enantioenriched spirocyclic enones bearing an all-carbon quaternary stereogenic center could be synthesized in 33-98% yields with up to 97:3 er.

Enantioselective Michael/Mannich Polycyclization Cascade of Indolyl Enones Catalyzed by Quinine-Derived Primary Amines†

Cascade reactions have become a subject of intense research in recent years, as they often reduce labor and waste, and enables the use of more readily available starting materials to construct complex targets. Particularly with indole substrates, a cascade involving nucleophilic addition of C3 of an indole and subsequent intramolecular nucleophilic addition to the in situ formed indolenine proved to be a very useful strategy in complex natural product synthesis. In this regard, developing an enantioselective catalytic version of this synthetic strategy is in great demand. To our knowledge, however, there are only limited successful examples documented in the literature. Both the tricyclic and tetracyclic core of 1 has drawn considerable attention because of its complexity and frequent appearance in natural products and pharmaceuticals (Figure 1). An enantioselective cascade synthesis towards these scaffolds is highly desirable but poses a challenge given