Tuesday, October 29, 2013

Radical Cyclizations of Cyclic Ene Sulfonamides Occur with β-Elimination of Sulfonyl Radicals to Form Polycyclic Imines

by Hanmo Zhang, E. Ben Hay, Steven J. Geib and Dennis P. Curran*


TOC Graphic

Radical cyclizations of cyclic ene sulfonamides provide stable bicyclic and tricyclic aldimines and ketimines in good yields. Depending on the structure of the precursor, the cyclizations occur to provide fused and spirocyclic imines with five-, six-, and seven-membered rings. The initial radical cyclization produces an α-sulfonamidoyl radical that undergoes elimination to form the imine and a phenylsulfonyl radical. In a related method, 3,4-dihydroquinolines can also be produced by radical translocation reactions of N-(2-iodophenylsulfonyl)tetrahydroiso-quinolines. In either case, very stable sulfonamides are cleaved to form imines (rather than amines) under mild reductive conditions.

Journal of the American Chemical Society
Publication Date (Web): October 10, 2013

Efficient Syntheses of Korupensamines A, B and Michellamine B by Asymmetric Suzuki-Miyaura Coupling Reactions

by Guangqing Xu, Wenzhen Fu, Guodu Liu, Chris H. Senanayake and Wenjun Tang*

TOC Graphic

Efficient asymmetric Suzuki-Miyaura coupling reactions are employed for the first time in total syntheses of chiral biaryl natural products korupensamine A and B in combination with an effective diastereoselective hydrogenation, allowing ultimately a concise and stereoselective synthesis of michellamine B. Chiral monophosphorus ligands L1–3 are effective for the syntheses of a series of functionalized chiral biaryls by asymmetric Suzuki-Miyaura coupling reactions in excellent yields and enantioselectivities (up to 99% ee). The presence of a polar-π interaction between the highly polarized BOP group and the extended π system of arylboronic acid coupling partner is believed to be important for the high enantioselectivity.

Journal of the American Chemical Society
Publication Date (Web): October 22, 2013

Brønsted Acid Catalyzed Enantioselective Indole Aza-Claisen Rearrangement Mediated by an Arene CH–O Interaction

by Pradip Maity, Ryan P. Pemberton, Dean J. Tantillo* and Uttam K. Tambar*


TOC Graphic

Although the aromatic aza-Claisen rearrangement is a general strategy for accessing substituted aromatic amines, there are no highly enantioselective examples of this process. We report the first Brønsted acid catalyzed enantioselective indole aza-Claisen rearrangement for the synthesis of chiral 3-amino-2-substituted indoles. We present evidence for an arene CH–O interaction as a source of activation and stereoinduction, which is an unprecedented phenomenon in enantioselective Brønsted acid catalysis. The products of this reaction can be transformed into 3-aminooxindoles, which are prevalent in many biologically active small molecules.

Journal of the American Chemical Society
Publication Date (Web): October 28, 2013

Monday, October 28, 2013

One-Pot Zinc-Promoted Asymmetric Alkynylation/Brook-Type Rearrangement/Ene–Allene Cyclization: Highly Selective Formation of Three New Bonds and Two Stereocenters in Acyclic Systems

by Polina Smirnov, Jomon Mathew, Anne Nijs, Einat Katan, Miriam Karni, Carsten Bolm, Yitzhak Apeloig, Ilan Marek*


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It’s as easy as 1, 2, 3: In a one-pot sequence, two stereocenters and three new bonds were created with high selectivity through an asymmetric alkynylation of acyl silanes, a tandem Brook-type rearrangement and Zn–ene–allene cyclization, the addition of an electrophile, and finally oxidation (see scheme). The straightforward nature of the synthetic procedure contrasts strongly with the complexity of the densely functionalized products obtained.

Angewandte Chemie Internation Edition
Article first published online: 23 OCT 2013

Organoytterbium Ate Complexes Extend the Value of Cyclobutenediones as Isoprene Equivalents

by Emma Packard, David D. Pascoe, Jacques Maddaluno, Théo P. Gonçalves, David C. Harrowven*


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Changing course: While organolithium and Grignard reagents favor addition to C1 of A (R=Me), the corresponding organoytterbium reagents add to C2 (R=tBu). Computational studies provide insights into the nature of organoytterbium species and their reactivity, and a total synthesis of (−)-mansonone B illustrates the utility of the method in terpenoid synthesis. Tf=trifluoromethanesulfonyl.

Angewandte Chemie Internation Edition
Article first published online: 23 OCT 2013

Palladium(II)-Catalyzed Intramolecular Hydroamination of 1,3-Dienes to Give Homoallylic Amines

by Justin M. Pierson, Erica L. Ingalls, Richard D. Vo, Forrest E. Michael*


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A pincer for high selectivity: A mild palladium-catalyzed hydroamination of protected amino-1,3-dienes has been developed. This highly regioselective reaction employs a tridentate PNP pincer ligand and leads to cyclic and homoallylic protected amines in high yields. Substrates with a wide array of amine protecting groups and diene substitution patterns were cyclized to form five- and six-membered heterocycles. PG=protecting group.

Angewandte Chemie Internation Edition
Article first published online: 24 OCT 2013

Total Synthesis and Structural Revision of the Alkaloid Incargranine B

by Patrick D. Brown, Anthony C. Willis, Michael S. Sherburn, Andrew L. Lawrence*


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Seeing double: Consideration of the biosynthetic origins of incargranine B, which was originally assigned an unprecedented indolo[1.7]naphthyridine structure, led to the proposal of a dipyrroloquinoline framework as a more biosynthetically feasible structure (see scheme; Piv=pivaloyl). This hypothesis was validated by a short biomimetic synthesis of incargranine B.

Angewandte Chemie Internation Edition
Article first published online: 24 OCT 2013

Atropisomeric Chiral Dienes in Asymmetric Catalysis: C2-Symmetric (Z,Z)-2,3-Bis[1-(diphenylphosphinyl)ethylidene]tetralin as a Highly Active Lewis Base Organocatalyst

by Masamichi Ogasawara*, Shunsuke Kotani, Hikaru Nakajima, Haruka Furusho, Mitsuru Miyasaka, Yasushi Shimoda, Wei-Yi Wu, Masaharu Sugiura, Tamotsu Takahashi*, Makoto Nakajima*


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Diene catalysts with a twist: The title C2-symmetric tetralin-fused 1,3-butadiene derivative is atropisomeric and can be resolved into the two helical enantiomers. The optically pure compound showed excellent enantioselectivity as well as unusually high catalytic activity as a chiral Lewis basic organocatalyst in the asymmetric allylation of various aldehydes with β-substituted allyltrichlorosilanes (see scheme).

Angewandte Chemie Internation Edition
Article first published online: 25 OCT 2013


Cu(OTf)2-Mediated Fluorination of Aryltrifluoroborates with Potassium Fluoride

by Yingda Ye, Sydonie D. Schimler, Patrick S. Hanley and Melanie S. Sanford*


TOC Graphic

This Communication describes the Cu(OTf)2-mediated fluorination of aryltrifluoroborates with KF. The reaction proceeds under mild conditions (at 60 °C over 20 h) and shows a broad substrate scope and functional group tolerance. The Cu is proposed to play two separate roles in this transformation: (1) as a mediator for the aryl–F coupling and (2) as an oxidant for accessing a proposed CuIII(aryl)(F) intermediate.

Journal of the American Chemical Society
Publication Date (Web): October 25, 2013


Oxidant-Free Conversion of Primary Amines to Nitriles

by Kuei-Nin T. Tseng, Andrew M. Rizzi and Nathaniel K. Szymczak*


TOC Graphic

An amide-derived NNN-Ru(II) hydride complex catalyzes oxidant-free, acceptorless, and chemoselective dehydrogenation of primary and secondary amines to the corresponding nitriles and imines with liberation of dihydrogen. The catalyst system tolerates oxidizable functionality and is selective for the dehydrogenation of primary amines (−CH2NH2) in the presence of amines without α-CH hydrogens.

Journal of the American Chemical Society
Publication Date (Web): October 21, 2013


Rhodium(III)-Catalyzed Indole Synthesis Using N–N Bond as an Internal Oxidant

by Baoqing Liu, Chao Song, Chao Sun, Shuguang Zhou and Jin Zhu*


TOC Graphic

We report herein a Rh(III)-catalyzed cyclization of N-nitrosoanilines with alkynes for streamlined synthesis of indoles. The synthetic protocol features a distinct internal oxidant, N–N bond, as a reactive handle for catalyst turnover, as well as a hitherto tantalizingly elusive intermolecular redox-neutral manifold, predicated upon C–H activation, for the formation of a five-membered azaheterocycle. The compatibility of seemingly dichotomous acidic and basic conditions ensures reaction versatility for multifarious synthetic contexts. The tolerance of an array of auxiliary functional groups potentially permits predefined, programmable substitution patterns to be incorporated into the indole scaffold. Comprehensive mechanistic studies, under acidic condition, support [RhCp*]2+ as generally the catalyst resting state (switchable to [RhCp*(OOCtBu)]+ under certain circumstance) and C–H activation as the turnover-limiting step. Given the variety of covalent linkages available for the nitroso group, this labile functionality is likely to be harnessed as a generic handle for strikingly diverse coupling reactions.

Journal of the American Chemical Society
Publication Date (Web): October 7, 2013

Bifunctional Iminophosphorane Organocatalysts for Enantioselective Synthesis: Application to the Ketimine Nitro-Mannich Reaction

by Marta G. Núñez, Alistair J. M. Farley and Darren J. Dixon*


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The design, synthesis, and development of a new class of modular, strongly basic, and tunable bifunctional Brønsted base/H-bond-donor organocatalysts are reported. These catalysts incorporate a triaryliminophosphorane as the Brønsted basic moiety and are readily synthesized via a last step Staudinger reaction of a chiral organoazide and a triarylphosphine. Their application to the first general enantioselective organocatalytic nitro-Mannich reaction of nitromethane to unactivated ketone-derived imines allows the enantioselective construction of β-nitroamines possessing a fully substituted carbon atom. The reaction is amenable to multigram scale-up, and the products are useful for the synthesis of enantiopure 1,2-diamine and α-amino acid derivatives.

Journal of the American Chemical Society
Publication Date (Web): October 9, 2013

Rapid Access to Spirocyclic Oxindole Alkaloids: Application of the Asymmetric Palladium-Catalyzed [3 + 2] Trimethylenemethane Cycloaddition

by Barry M. Trost*, Dustin A. Bringley, Ting Zhang and Nicolai Cramer


TOC Graphic

The marcfortines are complex secondary metabolites that show potent anthelmintic activity and are characterized by the presence of a bicyclo[2.2.2]diazaoctane fused to a spirooxindole. Herein, we report the synthesis of two members of this family. The synthesis of marcfortine B utilizes a carboxylative TMM cycloaddition to establish the spirocyclic core, followed by an intramolecular Michael addition and oxidative radical cyclization to access the strained bicyclic ring system. In addition, the first asymmetric synthesis of (−)-marcfortine C is described. The key step involves a cyano-substituted TMM cycloaddition, which proceeds in nearly quantitative yield with high diastereo- and enantioselectivity. The resulting chiral center was used to establish all remaining stereocenters in the natural product.

Journal of the American Chemical Society
Publication Date (Web): October 1, 2013

Ruthenium Catalyzed Hydrohydroxyalkylation of Isoprene with Heteroaromatic Secondary Alcohols: Isolation and Reversible Formation of the Putative Metallacycle Intermediate

by Boyoung Y. Park, T. Patrick Montgomery, Victoria J. Garza and Michael J. Krische*



TOC Graphic


Heteroaromatic secondary alcohols react with isoprene to form products of hydrohydroxyalkylation in the presence of ruthenium(0) catalysts generated from Ru3(CO)12and tricyclohexylphosphine, enabling direct conversion of secondary to tertiary alcohols in the absence of premetalated reagents or stoichiometric byproducts. The putative oxaruthenacycle intermediate has been isolated and characterized, and reversible metallacycle formation has been demonstrated.

Journal of the American Chemical Society
Publication Date (Web): October 24, 2013

An Efficient Generation of a Functionalized Tertiary-Alkyl Radical for Copper-catalyzed Tertiary-Alkylative Mizoroki-Heck type Reaction

by Takashi Nishikata*, Yushi Noda, Ryo Fujimoto and Tomomi Sakashita


TOC Graphic

α-Halocarbonyl compounds undergo β-hydrogen elimination to give conjugated olefins in the presence of a transition-metal catalyst. However, a copper/triamine catalyst system can induce the alkylative Mizoroki–Heck reaction of styrenes with tertiary-alkyl halides possessing a withdrawing group under very mild conditions. This reaction provides an efficient synthetic methodology for tertiary-alkylated styrenes.

Journal of the American Chemical Society
Publication Date (Web): October 21, 2013

Dihaloiodoarenes: α,α-Dihalogenation of Phenylacetate Derivatives

by Jason Tao, Richard Tran and Graham K. Murphy*



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A hypervalent iodine reagent-based α-carbonyl dihalogenation reaction is reported. Treating diazoacetate derivatives with either iodobenzene dichloride or iodotoluene difluoride results in gem-dichlorination or gem-difluorination products, respectively. The reaction is catalyzed by either Lewis acid or Lewis base activation of the aryl-λ3-iodane (ArIX2) species and proceeds rapidly and chemoselectively to the desired gem-difunctionalized products in good to excellent yield.

Journal of the American Chemical Society
Publication Date (Web): October 23, 2013


Wednesday, October 23, 2013

Diastereoselective Synthesis of Eight-Membered-Ring Allenes from Propargylic Epoxides and Aldehydes by Silylene Insertion into Carbon–Oxygen Bonds

by Christina Z. Rotsides, Chunhua Hu, K. A. Woerpel*


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Bent out of shape: Silver-catalyzed insertions of silylenes into propargylic C[BOND]O bonds of epoxides regioselectively form 1,2-silaoxetanes, which add to aldehydes to give the title allenes as single diastereomers (see scheme; Ts=4-toluenesulfonyl). An X-ray crystal structure confirmed the stereochemistry of the allene, which is bent significantly from linearity (164°).

Angewandte Chemie International Edition
Article first published online: 9 OCT 2013

Palladium-Catalyzed Synthesis of Benzofurans and Coumarins from Phenols and Olefins


by Upendra Sharma, Togati Naveen, Arun Maji, Srimanta Manna, Debabrata Maiti*


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Triple C[BOND]H functionalization: Palladium-catalyzed synthesis of benzofurans and coumarins by reacting phenols and unactivated olefins is described. The reaction comprises sequential C[BOND]H functionalization and shows diverse functional group compatibility. Preliminary mechanistic studies shed light into the possible mechanisms.

Angewandte Chemie International Edition
Article first published online: 11 OCT 2013

Silver-Catalyzed Hydrogenation of Aldehydes in Water

by Zhenhua Jia, Feng Zhou, Mingxin Liu, Xingshu Li,  Albert S. C. Chan, Chao-Jun Li*

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Silver bullet: The first silver-catalyzed hydrogenation in water was developed. A silver complex containing a bulky monodentate phosphine ligand was used to generate alcohols from a broad range of aldehydes, including aliphatic, aromatic, and heterocyclic aldehydes. This method provides a direct and efficient route to alcohols from aldehydes and opens a new avenue in silver catalysis.

Angewandte Chemie International Edition
Article first published online: 14 OCT 2013

Copper-Mediated Synthesis of 1,2,3-Triazoles from N-Tosylhydrazones and Anilines

by Zhengkai Chen, Qiangqiang Yan, Zhanxiang Liu, Yiming Xu, Yuhong Zhang*



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NNNifty targets: In a straightforward copper-mediated synthesis of 1,4-disubstituted and 1,4,5-trisubstituted 1,2,3-triazoles, readily available aniline and N-tosylhydrazone substrates underwent cyclization through C-N and N-N bond formation (see scheme; Piv=pivaloyl, Ts=p-toluenesulfonyl). This method enables the preparation of 1,2,3-triazoles with high efficiency under mild conditions without the use of azides.

Angewandte Chemie International Edition
Article first published online: 15 OCT 2013



Mechanism and Selectivity in Nickel-Catalyzed Cross-Electrophile Coupling of Aryl Halides with Alkyl Halides

by Soumik Biswas and Daniel J. Weix*


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The direct cross-coupling of two different electrophiles, such as an aryl halide with an alkyl halide, offers many advantages over conventional cross-coupling methods that require a carbon nucleophile. Despite its promise as a versatile synthetic strategy, a limited understanding of the mechanism and origin of cross selectivity has hindered progress in reaction development and design. Herein, we shed light on the mechanism for the nickel-catalyzed cross-electrophile coupling of aryl halides with alkyl halides and demonstrate that the selectivity arises from an unusual catalytic cycle that combines both polar and radical steps to form the new C–C bond.

Journal of the American Chemical Society

Article first published online: 18 AUG 2013

Transfer of Chirality in the Rhodium-Catalyzed Intramolecular [5+2] Cycloaddition of 3-Acyloxy-1,4-enynes (ACEs) and Alkynes: Synthesis of Enantioenriched Bicyclo[5.3.0]decatrienes

by Xing-zhong Shu, Casi M. Schienebeck, Wangze Song, Ilia A. Guzei, Weiping Tang*



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Chiral bicycles: Enantioenriched bicyclo[5.3.0]decatrienes were prepared from readily available chiral 3-acyloxy-1,4-enynes (ACEs) for the first time. In most cases, the chirality of the ACEs could be transferred to the bicyclic products with high efficiency. Inversion of the configuration was observed, thus confirming the predictions of previous computational studies.

Angewandte Chemie International Edition
Article first published online: 21 OCT 2013



Axially Chiral Dicarboxylic Acid Catalyzed Activation of Quinone Imine Ketals: Enantioselective Arylation of Enecarbamates

by Takuya Hashimoto, Hiroki Nakatsu, Yuka Takiguchi and Keiji Maruoka


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The synthetic utility of quinone imine ketals in the context of asymmetric catalysis was disclosed for the first time. By expanding the utility of chiral Brønsted acid catalysis to the electrophilic activation of quinone imine ketals, we succeeded in the development of highly enantioselective arylation of encarbamates to give α-amino-β-aryl ethers wherein quinone imine ketals act as functionalized aromatic ring surrogate. Further transformations of the products were also examined to establish procedures to provide chiral β-aryl amines and α-aryl esters.

Journal of the American Chemical Society
Article first published online: 22 OCT 2013

Hydrogenation of Carboxylic Acids Catalyzed by Half-Sandwich Complexes of Iridium and Rhodium


by Timothy P. Brewster, Alexander J. M. Miller *, D. Michael Heinekey , Karen I. Goldberg*


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A series of half-sandwich Ir and Rh compounds are demonstrated to be competent catalysts for the hydrogenation of carboxylic acids under relatively mild conditions. Of the structurally diverse group of catalysts tested for activity, a Cp*Ir complex supported by an electron-releasing 2,2′-bipyridine ligand was the most active. Higher activity was achieved with employment of Brønsted or Lewis acid promoters. Mechanistic studies suggest a possible reaction pathway involving activated carboxylic acid substrates. The hydrogenation reaction was shown to be general to a variety of aliphatic acids.

Journal of the American Chemical Society
Article first published online: 21 OCT 2013


Asymmetric Palladium(II)-Catalyzed Cascade Reaction Giving Quaternary Amino Succinimides by 1,4-Addition and a Nef-Type Reaction

by Manuel Weber, Wolfgang Frey, René Peters*



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Simple starting materials, high-value products: A dinuclear ferrocene-based PdII complex transforms mixtures of racemic N-benzoyl α-amino acids, nitroolefins, acetic anhydride, and manganese acetate into biologically interesting quaternary aminosuccinimides. The products are obtained as single diastereomers in enantioenriched form. Key steps of the cascade mechanism are a 1,4-addition of in situ generated azlactones to nitroolefins and a Nef-type reaction.

Angewandte Chemie International Edition
Article first published online: 21 OCT 2013



Catalytic Enantioselective Synthesis of Functionalized Tropanes Reveals Novel Inhibitors of Hedgehog Signaling

by Rishikesh Narayan, Jonathan O. Bauer, Carsten Strohmann, Andrey P. Antonchick*, Herbert Waldmann*



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Dipolar cycloaddition: A highly efficient copper(I)-catalyzed enantioselective [3+2] cycloaddition reaction of 1,3-fused cyclic azomethine ylides and nitroalkenes has been developed. This method provides access to functionalized tropane scaffolds with several quaternary and tertiary stereocenters in a single step under mild reaction conditions.

Angewandte Chemie International Edition
Article first published online: 21 OCT 2013

A Streamlined Strategy for Aglycone Assembly and Glycosylation

by Katherine M. Partridge, Scott J. Bader, Zachary A. Buchan, Christopher E. Taylor, John Montgomery*



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Multipurpose sugars: Carbohydrate-derived silane reagents are utilized as the reductant for nickel-catalyzed aldehyde–alkyne reductive coupling reactions and as the glycosyl donor for subsequent intramolecular glycosylation. The approach enables the assembly of the carbon–carbon framework and stereochemical features of an aglycone while simultaneously establishing the site of glycosylation.

Angewandte Chemie International Edition
Article first published online: 21 OCT 2013

Profound Methyl Effects in Drug Discovery and a Call for New CH Methylation Reactions


by Heike Schönherr, Tim Cernak*



The methyl group is one of the most commonly occurring carbon fragments in small-molecule drugs. This simplest alkyl fragment appears in more than 67 % of the top-selling drugs of 2011 and can modulate both the biological and physical properties of a molecule. This Review focuses on so-called magic methyl effects on binding potency, where the seemingly mundane change of C-H to C-Me improves the IC50 value of a drug candidate more than 100-fold. This discussion is followed by a survey of recent advances in synthetic chemistry that allow the direct methylation of C(sp2)-H and C(sp3)-H bonds. It is our hope that the relevance of the meager methyl group to drug discovery as presented herein will inspire reports on new C-H methylation reactions.


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It′s a kind of magic: The methyl group is one of the most prominent functional groups in bioactive small molecules and appears in more than 67 % of the top-selling drugs. This Review highlights examples of the magic methyl effect, whereby the installation of a single methyl group boosts potency by more than two orders of magnitude. New C-H activation reactions are required to facilitate the direct introduction of methyl groups.

Angewandte Chemie International Edition
Article first published online: 22 OCT 2013

Synergistic Effect of Ketone and Hydroperoxide in Brønsted Acid Catalyzed Oxidative Coupling Reactions

by Bertrand Schweitzer-Chaput, Abhishek Sud, Áron Pintér, Stefanie Dehn, Philipp Schulze, Martin Klussmann*




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Waste not wasted: A mechanistic study of the autoxidative coupling of xanthene with cyclopentanone uncovered an autoinductive effect of the waste product hydrogen peroxide. It generates radicals in the presence of acid and ketones, which accelerate the reaction by providing an additional pathway to the reactive hydroperoxide intermediate. This discovery could be applied to achieve other Brønsted acid-catalyzed oxidative coupling reactions.

Angewandte Chemie International Edition
Article first published online: 22 OCT 2013

Tuesday, October 22, 2013

One-pot three-component sulfone synthesis exploiting palladium-catalysed aryl halide aminosulfonylation

by Charlotte S. Richards-Taylor, David C. Blakemore, Michael C. Willis*



A palladium-catalysed aminosulfonylation process is used as the key-step in a one-pot, three-component sulfone synthesis. The process combines aryl-, heteroaryl- and alkenyl iodides with a sulfonyl unit and an electrophilic coupling fragment. The sulfonyl unit is delivered in the form of an aminosulfonamide, which then serves as a masked sulfinate. The sulfinate is combined,in situ, with an electrophilic coupling partner, such as a benzylic, allylic or alkyl halide, an electron-poor arene, or a cyclic epoxide, to provide the corresponding sulfone products in good to excellent yields. The mild reaction conditions and use of commercially available reaction components allows the easy preparation of a broad range of sulfones featuring a variety of functional groups. The process obviates the need to employ thiol starting materials, and oxidative operations.

Chemical Science
DOI: 10.1039/C3SC52332B

How much do van der Waals dispersion forces contribute to molecular recognition in solution?

by Lixu Yang, Catherine Adam, Gary S. Nichol & Scott L. Cockroft*


Attractive van der Waals dispersion forces have been implicated in mechanisms as diverse as gecko adhesion and anaesthesia. Now, it has been found using synthetic molecular balances that dispersion forces between alkyl chains are an order of magnitude weaker in solution than they are in the gas phase.

Nature Chemistry
DOI: 10.1038/nchem.1779

Highly Enantioselective Synthesis of Chiral 7-Ring O- and N-Heterocycles by a One-pot Nitro-Michael/Cyclization Tandem Reaction

by Renate Rohlmann, Constantin Gabriel Daniliuc, Olga Garcia Mancheno*

A concise enantioselective approach to medium-sized 7-ring O- and N-heterocycles has been developed. The synthetic strategy relies on an organocatalytic nitro-Michael/nitrile oxide cycloaddition tandem reaction, leading to the corresponding chiral benzoxe- and benzazepine derivatives containing an additional fused dihydroisoxazoline ring in good yields and excellent enantioselectivities (up to 97% ee).

Chemical Communications


Synthesis of a,b-Unsaturated Carbonyl Compounds via a Visible-Light -Promoted Organocatalytic Aerobic Oxidation

by Zhen Yang, Junling Zhang, Leming Wang, Qi Liu, Yong Huang*



a,b-Unsaturated ketones and aldehydes have been synthesized from the corresponding silyl enol ethers in a straightforward protocol involving a visible-light promoted organocatalytic, aerobic oxidation reaction. A cheap organic dye was used in catalytically in the reaction as the photosensitizer.

Chemical Communications
DOI: 10.1039/C3CC46778C

Synthesis of 3-((trifluoromethyl)thio)indoles via a reaction of 2-alkynylaniline with trifluoromethanesulfanylamide

by Jie Sheng, Shaoyu Li, Jie Wu



3-((Trifluoromethyl)thio)indoles can be accessed through a palladium(II)-catalyzed reaction of 2-alkynylaniline with trifluoromethanesulfanylamide in the presence of bismuth(III) chloride. The presence of bismuth(III) chloride is crucial for the success of this transformation, which would activate the trifluoromethanesulfanylamide during the process.

Chemical Communications
DOI: 10.1039/C3CC45958F

Enantioselective synthesis of 1,2,4-triazolines catalyzed by a cinchona alkaloid-derived organocatalyst

by Qian Shao, Jiean Chen, Meihua Tu, David W. Piotrowski, Yong Huang



An enantioselective organocatalytic process for the one-step synthesis of poly-substituted 1,2,4-triazolines is reported. The heterocycle formation is believed to go through a step-wise mechanism of nucleophilic addition of an azlactone to an azodicarboxylate in the presence of an organic base catalyst, followed by a TMSCHN2 mediated heterocyclization. Both theoretical calculations and experimental evidence suggest the pre-organization of the transition state for the chirality determining step via a unique 7-membered intramolecular hydrogen bonding.

Chemical Communications
DOI:10.1039/C3CC46757K

Copper nanoparticle-catalyzed cross-coupling of alkyl halides with Grignard reagents

by Ju Hyun Kim and Young Keun Chung*

Graphical abstract: Copper nanoparticle-catalyzed cross-coupling of alkyl halides with Grignard reagents


A cross-coupling reaction between alkyl bromides and chlorides and various Grignard reagents was carried out in the presence of commercially available copper or copper oxide nanoparticles as a catalyst and an alkyne additive. The catalytic system shows high activity, a broad scope, and good functional group tolerance.

Chemical Communications
DOI: 10.1039/C3CC46419A

Monday, October 21, 2013

Synthesis of Enantioenriched Tertiary Boronic Esters by the Lithiation/Borylation of Secondary Alkyl Benzoates

by Alexander P. Pulis, Daniel J. Blair, Eva Torres and Varinder K. Aggarwal*

TOC Graphic


Simple, secondary 2,4,6-triisopropyl benzoates (TIB esters) and secondary dialkyl N,N-diisopropyl carbamates have been reported to be resistant to deprotonation by strong bases. We have found that the combination of sBuLi (1.6 equiv) and TMEDA (6 equiv) in CPME at −60 °C enables deprotonation of unactivated secondary dialkyl TIB esters, but not the carbamates. These carbanions were reacted with a range of neopentyl boronic esters which, after 1,2-metalate rearrangement and oxidation, gave a range of tertiary alcohols in high yield and universally high er. Further functional group transformations of the tertiary boronic esters were demonstrated (conversion to quaternary centers, C-tertiary amines) together with application of the methodology to the synthesis of the simplest unbranched hydrocarbon bearing a quaternary center, (R)-4-ethyl-4-methyloctane, validating the synthetic utility of the methodology.


Journal of the American Chemical Society

Thiophosphoramide-Based Cooperative Catalysts for Brønsted Acid Promoted Ionic Diels–Alder Reactions

by Alina Borovika, Pui-In Tang, Seth Klapman, Pavel Nagorny*

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Three's a crowd: The combination of a Brønsted acid and a hydrogen-bond donor cocatalyst was found to promote various ionic [2+4] cycloadditions under mild reaction conditions (see scheme; Ts=4-toluenesulfonyl). Thiophosphoramides are the most effective cocatalysts because of the stronger counterion activation effect resulting from three, rather than two, hydrogen bonds involved in anion binding.


Angewandte Chemie International Edition

Halogen and Chalcogen Cation Pools Stabilized by DMSO. Versatile Reagents for Alkene Difunctionalization

by Yosuke Ashikari, Akihiro Shimizu, Toshiki Nokami and Jun-ichi Yoshida*

TOC Graphic


Halogen and chalcogen cations (X+ = Br+, I+, ArS+, and ArSe+) were generated by low-temperature electrochemical oxidation in the presence of dimethyl sulfoxide (DMSO) and were accumulated in the solution. DFT calculations indicated that DMSO stabilizes these cations by coordination. The complexes of I+ with one and two DMSO molecules were observed by cold-spray-ionization MS analyses. The stability of the resulting cation pools of X+ increased in the order of Br+ < I+ < ArS+ < ArSe+, which could be explained in terms of the electronegativity of X. The cation pools served as versatile reagents for organic synthesis; the reactions with alkenes gave β-X-substituted alkoxysulfonium ions, which were converted to the corresponding carbonyl compounds by the treatment with triethylamine, whereas the treatment with methanol gave the corresponding alcohols. The reactions with aminoalkenes and 1,6-dienes gave the cyclized products.


Journal of the American Chemical Society

Squaramide-Catalyzed Enantioselective Michael Addition of Masked Acyl Cyanides to Substituted Enones

by Kin S. Yang, Antoinette E. Nibbs, Yunus E. Türkmen and Viresh H. Rawal*

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Masked acyl cyanide (MAC) reagents are shown to be effective umpolung synthons for enantioselective Michael addition to substituted enones. The reactions are catalyzed by chiral squaramides and afford adducts in high yields (90–99%) and with excellent enantioselectivities (85–98%). The addition products are unmasked to produce dicyanohydrins that, upon treatment with a variety of nucleophiles, provide γ-keto acids, esters, and amides. The use of this umpolung synthon has enabled, in enantiomerically enriched form, the first total synthesis of the prenylated phenol (+)-fornicin C.


Journal of the American Chemical Society

Simple Catalytic Mechanism for the Direct Coupling of α-Carbonyls with Functionalized Amines: A One-Step Synthesis of Plavix

by Ryan W. Evans, Jason R. Zbieg, Shaolin Zhu, Wei Li and David W. C. MacMillan*

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The direct α-amination of ketones, esters, and aldehydes has been accomplished via copper catalysis. In the presence of catalytic copper(II) bromide, a diverse range of carbonyl and amine substrates undergo fragment coupling to produce synthetically useful α-amino-substituted motifs. The transformation is proposed to proceed via a catalytically generated α-bromo carbonyl species; nucleophilic displacement of the bromide by the amine then delivers the α-amino carbonyl adduct while the catalyst is reconstituted. The practical value of this transformation is highlighted through one-step syntheses of two high-profile pharmaceutical agents, Plavix and amfepramone.

Journal of the American Chemical Society

Enantioselective Functionalization of Radical Intermediates in Redox Catalysis: Copper-Catalyzed Asymmetric Oxytrifluoromethylation of Alkenes

by Rong Zhu, Stephen L. Buchwald*

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Something radical: An efficient enantioselective oxytrifluoromethylation of alkenes has been developed using a copper catalyst system. Mechanistic studies are consistent with a metal-catalyzed redox radical addition mechanism in which a C[BOND]O bond is formed by the copper-mediated enantioselective trapping of a prochiral alkyl radical intermediate derived from the initial trifluoromethyl radical addition.

Angewandte Chemie International Edition

Hexameric Resorcinarene Capsule is a Brønsted Acid: Investigation and Application to Synthesis and Catalysis

by Qi Zhang and Konrad Tiefenbacher*

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Molecular capsules have attracted interest as simple enzyme mimetics and several examples of catalytic transformations in water-soluble metal–ligand based systems have been reported. This is not the case for hydrogen-bond based molecular capsules, which in contrast can be employed in organic solvents. We describe herein our investigations of such a system: The resorcin[4]arene hexamer is one of the largest hydrogen bond-based self-assembled capsules and has been studied intensively due to its ready availability. We present evidence that the capsule acts as a reasonably strong Brønsted acid (pKa approximately 5.5–6). This finding explains the capsule’s high affinity toward tertiary amines that are protonated and therefore encounter cation-π interactions inside the cavity. We were able to translate this finding into a first synthetic application: A highly substrate-selective Wittig reaction. We also report that this property renders the capsule an efficient enzyme-like catalyst for substrate selective diethyl acetal hydrolysis.

Journal of the American Chemical Society


Copper(I)/ABNO-Catalyzed Aerobic Alcohol Oxidation: Alleviating Steric and Electronic Constraints of Cu/TEMPO Catalyst Systems

by Janelle E. Steves and Shannon S. Stahl*

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Cu/TEMPO catalyst systems promote efficient aerobic oxidation of sterically unhindered primary alcohols and electronically activated substrates, but they show reduced reactivity with aliphatic and secondary alcohols. Here, we report a catalyst system, consisting of (MeObpy)CuI(OTf) and ABNO (MeObpy =4,4′-dimethoxy-2,2′-bipyridine; ABNO = 9-azabicyclo[3.3.1]nonane N-oxyl), that mediates aerobic oxidation of all classes of alcohols, including primary and secondary allylic, benzylic, and aliphatic alcohols with nearly equal efficiency. The catalyst exhibits broad functional group compatibility, and most reactions are complete within 1 h at room temperature using ambient air as the source of oxidant.

Journal of the American Chemical Society

Dynamic Kinetic Cross-Coupling Strategy for the Asymmetric Synthesis of Axially Chiral Heterobiaryls

by Abel Ros, Beatriz Estepa, Pedro Ramírez-López, Eleuterio Álvarez, Rosario Fernández and José M. Lassaletta

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A dynamic kinetic asymmetric transformation (DYKAT) technique has been designed for the synthesis of 2′-substituted 2-aryl pyridines/isoquinolines and related heterobiaryls. In this way, the Pd(0)-catalyzed coupling of racemic 2-triflates with aryl boroxines using a TADDOL-derived phosphoramidite as the ligand provides the corresponding coupling products with good to excellent enantioselectivities. Structural studies support that the formation of configurationally labile oxidative addition palladacycles is the key for the success of the methodology.

Journal of the American Chemical Society

Platinum-Catalyzed C–H Arylation of Simple Arenes

by Anna M. Wagner, Amanda J. Hickman and Melanie S. Sanford*

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This report describes the Na2PtCl4 catalyzed C–H arylation of arene substrates with diaryliodonium salts. The site selectivity of these reactions is predominantly controlled by steric factors. Remarkably, Na2PtCl4-catalyzed naphthalene arylation proceeds with opposite site selectivity compared to that obtained with Na2PdCl4 as the catalyst. Preliminary mechanistic studies provide evidence for a PtII/PtIV catalytic cycle involving rate-limiting C–C bond-forming reductive elimination.

Journal of the American Chemical Society