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

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

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

by Soumik Biswas and Daniel J. Weix*

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

DOI: 10.1021/ja407589e

Article first published online: 18 AUG 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

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

DOI: 10.1021/ja407501h

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*

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

DOI: 10.1021/ja408149n

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*

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

DOI: 10.1021/ja409100y

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

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

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

DOI:10.1021/ja4092648 

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*

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

DOI: 10.1021/ja409012q