A stereodivergent Pd/Cu catalyst system has been developed for the unprecedented dynamic kinetic asymmetric transformation (DyKAT) of racemic unsymmetrical 1,3-disubstituted allylic acetates with prochiral aldimine esters. A series of α,αdisubstituted α-amino acids bearing vicinal stereocenters were easily prepared with excellent enantioselectivities (up to >99% ee) and diastereoselectivities (up to >20:1 dr). Moreover, all four stereoisomers of the product can be readily obtained simply by switching the configurations of the two chiral metal catalysts. Furthermore, the present work highlights the power of synergistic Pd/ Cu catalysis consisting of two common bidentate chiral ligands for stereodivergent synthesis.

AC u-catalyzed diastereo-and enantioselective borylative coupling reaction of 1,3-dienes with imines was realized. Branched homoallylic amines are readily prepared in as yn-selective manner with high regio-, diastereo-and enantioselectivity.M oreover,t hese three-component coupling reactions feature good functional-group compatibility and easy access to the substrates and catalyst.Asymmetric allylation reactions [1] of imines have received increasing interests from the synthesis community [2] because enantioenriched homoallylic amine products are useful building blocks in organic synthesis and medicinal chemistry.[3] Copper catalysis is an efficient approach to promote the enantioselective addition of terminal allyl transmetalation reagents (e.g., with B, Si, and Sn) to imines, [4] however,C ucatalyzed asymmetric, nucleophilic addition to imines with functionalized (e.g., g-substituted) allyl metal reagents remain challenging.T his is probably due to inefficiencyo f the transmetalation event arising from increased steric hindrance,t he weak electrophilicity/reactivity of imines, and/or difficulties in predicting the regio-and stereochemical outcome of additions.N ew and efficient approaches to generating and utilizing functionalized allyl metal reagents in the presence of acopper catalyst hold promise for accessing complex homoallylic amines,a nd these methods will expand the application of catalytic asymmetric allylation chemistry.Since the seminal work of borylcopper catalysis reported by the Ito [5] and the Miyaura [6] groups,C u-catalyzed borylative coupling reactions have been recognized as an important method for generating boron-containing organocopper species in situ from an unsaturated hydrocarbon. [7] In this context, Hoveyda pioneered the use of boron-functional allylcopper intermediates in enantioselective allylation of aldehydes/ketones, [7f] allyllic esters, [7i] and enoates.[7k] However,Cu-catalyzed borylative coupling of unsaturated hydrocarbon substrates and imines is less developed.[8] Conjugated dienes and especially 1,3-dienes,asacommon feedstock, are ideal nucleophilic allyl metal precursors [9] and readily participate in allylic transformations of carbonyls and imines.[10] We envisioned merging the borylcupration of ac onjugated diene [11] (Scheme 1, step A) and enantioselective imine allyl ation (Scheme 1, step B) in the presence of as uitable chiral copper catalyst. This approach could afford useful homoallylic amines containing an easily derivatizable boron motif.In this method, possible complications include the undesired borylation of imines, [12] poisoning of the metal catalyst by imines or products,a nd difficulty in controlling the regio-(linear vs.b ranched products) [7k,11a] and stereoselectivity (enantio-and/or diastereoselectivity).To test the feasibility of our proposed transformation, we chose acomplex of CuCl and chiral sulfoxide-phophine (SOP, L1)[7j] as acatalyst in preliminary experiments.Inthe presence of isoprene (5 equiv), 1.5 equiv of B 2 (pin) 2 ,a nd NaO...

Dedicated to Professor Jingen Deng on the occasion of his 50th birthdayThe palladium-catalyzed asymmetric allylic alkylation (AAA, Tsuji-Trost reaction) is a powerful strategy for construction of carbon-carbon (C À C) and carbon-heteroatom (C À X) bonds. [1] Various ligands, such as monodentate phosphines, bidentate N,N-, P,N-, P,P-ligands, etc., have been used in this reaction, especially for symmetric 1,3-disubstituted allylic substrates. [1g, 2] To date, asymmetric alkylation (CÀC bond formation) of racemic, unsymmetric 1,3-disubstituted substrates have been rarely reported, [3] and a kinetic resolution is the only approach for providing the AAA products with a maximum of yield of 50 % [Eq. (1) and (2); see Figure 1 for catalyst structures;. [4] However, the dynamic kinetic asymmetric transformation (DYKAT), as a straightforward method to transform racemic starting materials to optically pure products with a potential 100 % yield, still remains a challenge. [5] Transition-metal-catalyzed AAA using indole as a nucleophile is an attractive strategy for the synthesis of indoles containing stereocenters, compounds which are often found in biologically important natural products and pharmaceutical agents. [6] Various chiral palladium-and iridium-complexes have been developed to catalyze enantioselective inter-or intramolecular versions of the monosubstituted or symmetrically substituted allylic electrophiles. [7] To the best of our knowledge, the catalytic asymmetric indolylation of unsymmetrical 1,3-disubstituted allylic substrates has not been realized previously.As part of our program to develop transition-metalcatalyzed asymmetric reactions, we designed several types of chiral ligands based on the stereogeometry and coordination properties of the tert-butylsulfinyl group. [8] Among these ligands, the sulfinyl moiety acts as a Lewis base which coordinates the metal. It is notable that the sulfinyl group can also readily form hydrogen bonds with some donors, like binol and indole. [9] Jacobsen and co-workers demonstrated that the hydrogen-bond interaction between the tert-butyl sulfinyl moiety of chiral urea catalysts and a protonated imine substrate effectively promoted an asymmetric [4+2] cycloaddition. [10] We envisioned that incorporation of an additional sulfinyl group into a bidentate ligand, like our previous sulfoxide phosphine ligand L1 (Figure 1), [8a-c] might generate a new type of ligand which could perform cooperatively in Figure 1. Chiral ligands used in this work. MOM = methoxymethyl.

We report a catalytic strategy that generates rhodium-carbynoids by selective diazo activation of designed carbyne sources. We found that rhodiumcarbynoid species provoke C(sp 2 )−C(sp 2 ) bond scission in alkenes by inserting a monovalent carbon unit between both sp 2 -hybridized carbons. This skeletal remodeling process accesses synthetically useful allyl cation intermediates that conduct to valuable allylic building blocks upon nucleophile attack. Our results rely on the formation of cyclopropyl-I (III) intermediates able to undergo electrocyclic ring-opening, following the Woodward−Hoffmann−DePuy rules.

An enantioselective Cu/Pd-catalyzed borylative coupling of styrenes with aryl/alkenyl iodides was realized using a chiral sulfoxide-phosphine (SOP) ligand. Enantioenriched 1,1-diarylethyl and β-aryl-homoallylic boronates are readily prepared. A streamlined procedure merging arylboration and subsequent Pd-catalyzed Suzuki–Miyaura cross-coupling enables the modular assembly of enantioenriched 1,1,2-triarylethanes, including two medicinally important chiral small-molecule targets.

Herein, we describe the first electrophilic diazomethylation of ketone silyl enol ethers with diazomethyl‐substituted hypervalent iodine reagents that gives access to unusual β‐diazocarbonyl compounds. The potential of this unexplored class of diazo compounds for the development of new reactions was demonstrated by the discovery of a rare Rh‐catalyzed intramolecular 1,3 C−H carbene insertion that led to complex cyclopropanes with excellent stereocontrol.

Palladium-catalyzed asymmetric intermolecular hydroalkoxylation of allenes has been developed by using phenol as a pronucleophile. Acyclic O,O-acetals were obtained in high yields (up to 98%) with good to excellent enantiomeric excesses (up to 94% ee). (Figure 1) represent a class of important scaffolds in many natural products and bioactive compounds, 1 such as carbohydrates, spiroketal polyketides, and chromene acetals derivatives. E nantiopure cyclic and acyclic O,O-acetals2 These compounds are also useful intermediates for asymmetric transformations.3 Therefore, development of efficient methods to generate stereodefined O,O-acetals are highly desired. Over the past decades, methods have been mainly focused on substrate-or auxiliary-directed stereoinduction. 4 Until recently, List and co-workers have disclosed a new and efficient organocatalytic strategy (CPAs catalysis) for the synthesis of cyclic O,O-acetals.5 However, this method is unsuitable for the synthesis of acyclic O,O-acetals, due to the product's inherent instability in acidic conditions. 4a Enzymatic resolutions and metal-catalyzed desymmetrizations (ring closing metathesis) are options, but a special substrate's skeleton is required. Transition-metal-catalyzed enantioselective hydrofunctionalization of allenes 7 represents an atom economic strategy for generating stereogenic C−O bonds. Particularly, chiral Aubiphophine or Au-phosphate, 8 Ag-phosphate, 9 and Rhbiphosphine 10 complexes are effective catalysts for the transformations of allenes into allylic ethers or esters in excellent regio-and enantioselectivities. Our recent research interest is focused on asymmetric metal catalysis, and we assumed that an asymmetric metal-catalyzed intermolecular O− H addition to alkoxyallenes (hydroalkoxylation) under mild condition might allow the access to acyclic O,O-acetals. Lately, Rhee reported a Pd-catalyzed intermolecular enantioseletive hydroalkoxylation 11 of alkoxyallenes with alcohols. 12 In this letter, we present an enantioselective hydroalkoxylation of alkoxyallenes using phenols as pronucleophiles 13 to furnish acyclic O,O-acetals in high yields and with good to excellent enantioselectivities.In recent years, we developed a class of chiral sulfinylphophine ligands 14 and employed them in palladium-catalyzed reactions.15 These ligands would be expected to work well in this title reaction. 16 The initial test was performed in the presence of 2 mol % of {Pd 2 (dba) 3 ·CHCl 3 }, 5 mol % of ligand, 2.0 equiv of Et 3 N, and dicholoroethane (DCE) as solvent. Unfortunatetly, the desired product 3a was obtained with good yields but poor enantioselectivities (<15%) when using sulfinylphosphine L2 and L3 as ligands (Table 1, entries 1− 3). So we turn our attention to commercially available ligands, such as BINAP and Trost ligands (L5, L6, and L7) ( Table 1, entries 4−7). To our delight, (S,S)-DACH-naphthyl Trost ligand L7 proved to be the right ligand to examine; the product 3a was afforded with a 98% yield and 90% ee. 1,4-Dioxane was test...

Dedicated to Professor Jingen Deng on the occasion of his 50th birthdayThe palladium-catalyzed asymmetric allylic alkylation (AAA, Tsuji-Trost reaction) is a powerful strategy for construction of carbon-carbon (C À C) and carbon-heteroatom (C À X) bonds.[1] Various ligands, such as monodentate phosphines, bidentate N,N-, P,N-, P,P-ligands, etc., have been used in this reaction, especially for symmetric 1,3-disubstituted allylic substrates. [1g, 2] To date, asymmetric alkylation (CÀC bond formation) of racemic, unsymmetric 1,3-disubstituted substrates have been rarely reported, [3] and a kinetic resolution is the only approach for providing the AAA products with a maximum of yield of 50 % [Eq. (1) and (2); see Figure 1 for catalyst structures;[4] However, the dynamic kinetic asymmetric transformation (DYKAT), as a straightforward method to transform racemic starting materials to optically pure products with a potential 100 % yield, still remains a challenge. [5] Transition-metal-catalyzed AAA using indole as a nucleophile is an attractive strategy for the synthesis of indoles containing stereocenters, compounds which are often found in biologically important natural products and pharmaceutical agents.[6] Various chiral palladium-and iridium-complexes have been developed to catalyze enantioselective inter-or intramolecular versions of the monosubstituted or symmetrically substituted allylic electrophiles. [7] To the best of our knowledge, the catalytic asymmetric indolylation of unsymmetrical 1,3-disubstituted allylic substrates has not been realized previously.As part of our program to develop transition-metalcatalyzed asymmetric reactions, we designed several types of chiral ligands based on the stereogeometry and coordination properties of the tert-butylsulfinyl group.[8] Among these ligands, the sulfinyl moiety acts as a Lewis base which coordinates the metal. It is notable that the sulfinyl group can also readily form hydrogen bonds with some donors, like binol and indole.[9] Jacobsen and co-workers demonstrated that the hydrogen-bond interaction between the tert-butyl sulfinyl moiety of chiral urea catalysts and a protonated imine substrate effectively promoted an asymmetric [4+2] cycloaddition.[10] We envisioned that incorporation of an additional sulfinyl group into a bidentate ligand, like our previous sulfoxide phosphine ligand L1 (Figure 1), [8a-c] might generate a new type of ligand which could perform cooperatively in Figure 1. Chiral ligands used in this work. MOM = methoxymethyl.