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*

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

DOI: 10.1021/ja408387d

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_*

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

DOI: 10.1021/ja409669r

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*

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

DOI: 10.1021/ja4095473

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*

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

DOI: 10.1002/anie.201306749

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*

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

DOI: 10.1002/anie.201307193

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*

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

DOI: 10.1002/anie.201305766

Total Synthesis and Structural Revision of the Alkaloid Incargranine B

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

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

DOI: 10.1002/anie.201307875

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*

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

DOI: 10.1002/anie.201308112

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

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

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 Cu^III(aryl)(F) intermediate.

Journal of the American Chemical Society

Publication Date (Web): October 25, 2013

DOI: 10.1021/ja408607r

Oxidant-Free Conversion of Primary Amines to Nitriles

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

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

DOI: 10.1021/ja409223a

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*

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*(OOC^tBu)]⁺ 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

DOI: 10.1021/ja408541c

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*

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

DOI: 10.1021/ja409121s

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

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

DOI: 10.1021/ja409013m

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*

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

DOI: 10.1021/ja4087193

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

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

DOI: 10.1021/ja409661n

Dihaloiodoarenes: α,α-Dihalogenation of Phenylacetate Derivatives

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

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

DOI: 10.1021/ja408678p

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*

Bent out of shape: Silver-catalyzed insertions of silylenes into propargylic CO 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

DOI: 10.1002/anie.201306093

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

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

Triple CH functionalization: Palladium-catalyzed synthesis of benzofurans and coumarins by reacting phenols and unactivated olefins is described. The reaction comprises sequential CH 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

DOI: 10.1002/anie.201305326

Silver-Catalyzed Hydrogenation of Aldehydes in Water

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

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

DOI: 10.1002/anie.201306243

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

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

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

DOI: 10.1002/anie.201306416