Olefins are rarely used as catalysts in chemical reactions. Here, we explore the use of olefins as cocatalysts to facilitate iodonium catalysis. Our catalytic system employs a simple olefin as a cocatalyst with a simple halogen source N-iodosuccinimide (NIS) in hexafluoroisopropanol (HFIP) to form the active iodonium catalyst. Kinetic studies indicate that the olefin cocatalyst structure impacts the reaction rate significantly. In addition, NMR, kinetics, IR and computational studies were incorporated to understand the role of the olefins in these catalytic reactions, opening doors to other potentially interesting catalytic designs.

A photocatalysis process-enabled thioacylation of amines has been developed with eco-friendly feedstock potassium dithiocarboxylates as green thioacyl sources and water as the reaction solvent. The key to the success of this transformation is the light-induced generation of active dithioacyl disulfides as thioacyl donors. This green methodology has been successfully employed for the late-stage thioacylation of various amino compounds including drugs, hormones, amino acids and peptides under mild conditions.

We report herein a Cu(I)-catalyzed highly regio- and stereoselective vinylic C-H amination reaction to generate (Z)-enamines, or β-aminated heterocyclic amines and ketones. This strategy involves the CuI-CuII-CuIII catalytic cycle-mediated radical addition of in situ-generated N-centered radicals, followed by a stereocontrolled anticoplanar β-H elimination protocol. The β-C-H bond cleavage step is suggested to be involved in the rate-determining step based on the D-labeled kinetic studies.

A dichloro(2-pyridinecarboxylato)gold complex anchored on SBA-15 (SBA-15-PicAuCl2) was conveniently prepared through the addition reaction between triethoxy(3-isocyanatopropyl)silane and dichloro(3-hydroxy-2-pyridinecarboxylato)gold complex and subsequent condensation with SBA-15. The new heterogenized PicAuCl2 complex was fully characterized by using various analytic methods. In the existence of 5 mol% of SBA-15-PicAuCl2, the regioselective [3 + 2] cycloaddition reaction between ynamides and pyridine-N-aminides proceeded in toluene at 100 degrees C for 1-24 h to deliver a wide array of functionalized trisubstituted 1,3-oxazoles in 57%-95% yields. Ynamides with alkyl, benzyl, and aryl substituents as well as different sulfonyl groups at the nitrogen atom and the oxazolidinone-derived ynamides were well-tolerated. A wide range of pyridine-N-aminides bearing aroyl, naphthoyl, furoyl, vinylcarbonyl, alkylcarbonyl, and methoxycarbonyl were also allowed in the reaction. Moreover, SBA-15-PicAuCl2 is easy to recover through a simple centrifugation and recyclable at least seven cycles with only a slight drop in catalytic activity.

An efficient inverse electron-demand aza-Diels-Alder reaction of different types of olefins and 1,2-diaza-1,3-dienes, which could be readily formed in situ from α-halogeno hydrazones and a base, has been successfully developed. With the developed approach, a wide range of fused polycyclic tetrahydropyridazines were smoothly obtained in up to 95% yield and ee up to 98% with dr >20:1 under optimal reaction conditions. A gram-scale experiment and further derivatizations of the polycyclic tetrahydropyridazine products were also conducted to verify the practicability of the methodology.

Saturated N-heterocycles are important motifs in pharmaceuticals, agrochemicals, and materials. While many catalytic methods can cyclize an intramolecular N-containing substrate into one specific N-heterocycle, the regio-complementary cyclization process is often difficult to achieve. Herein, we report the development of two simple iron catalytic protocols enabling divergent cyclization of a common precursor into distinct N-heterocyclic motifs, including pyrrolidines, piperidines, and azepanes.

A novel, highly efficient heterogeneous palladium-catalyzed carbonylative cyclization of aryl iodides and benzyl acetylenes has been developed under an atmospheric pressure of CO. The reaction proceeds smoothly in a bioderived solvent 2-methyltetrahydrofuran (2-MeTHF) at 50 degrees C using an MCM-41-anchored bidentate phosphine palladium complex [Pd(OAc)2-MCM-41-P,P] as catalyst with DiPEA as base, delivering a wide variety of 3-alkylidenefuran-2-ones in good to excellent yields. The Pd(OAc)2-MCM-41-P,P complex can be easily recovered by a simple centrifugation and recycled more than ten times without any remarkable loss of catalytic activity. The present method not only avoids the use of toxic solvents such as benzene, toluene and THF, but also addresses the key problem of expensive palladium catalyst recovery and recycle, thus preventing palladium contamination in the final product. A general, efficient and practical method for the synthesis of 3-alkylidenefuran-2-ones has been developed from readily accessible aryl iodides and benzyl acetylenes via a recyclable palladium-catalyzed carbonylative coupling reaction in a green solvent 2-MeTHF. The reaction proceeds smoothly under a CO atmosphere and mild conditions, yielding a wide range of furanones in good to excellent yields.image

A method of reducing o-hydroxyphenyl enaminones with silane as the reductant to provide o-hydroxyl propiophenones has been achieved with iridium catalysis. The reduction reactions were found to proceed via the assistance of the hydroxyl group in the phenyl ring. In addition, the o-hydroxyl propiophenone products were used for the easy synthesis of 3-methyl chromones by directly incorporating N,N-dimethyl formamide dimethyl acetal (DMF-DMA) without using any catalyst.

Herein, we report a transition-metal-free C-H bond sulfoximidation protocol of sulfonyl hydrazones with hypervalent iodine(III) reagents. A library of novel N-sulfaneylidenehydrazonamides was constructed via chemoselective C-N bond formation reactions at aldehyde C-H bonds of sulfonyl hydrazones in the presence of a base. The reaction demonstrated broad substrate group diversity under exceedingly mild reaction conditions, and excellent yields were achieved at room temperature.

An oxidative cascade [4 + 2] radical cycloaddition/dehydroaromatization reaction of aryl alkenes to access α-aryl substituted naphthalenes under redox-neutral conditions was achieved. This reaction was found to require the addition of [Cu] catalyst along with stoichiometric concentrations of NFSI as a trigger of radical series of steps. Norbornene (NBE), rather than the conventional oxidant, manifested optimal performances as a H-acceptor in this procedure. The results herein might shed encouraging insight into the transition-metal-catalyzed dehydrogenative C–H activation protocols.

A Pd/norbornene-mediated three-component modular one-step reaction facilitated by dual C-H bond activation and cascade cyclization is reported. This procedure uses norbornene as a catalyst in the Catellani-type reaction and as an alkylating building block to accomplish the dual unactivated C-H bond functionalization protocol, which results in the production of polyheterocyclic eight-membered sulfoximines with an indene-fused moiety. This mild, scalable protocol's wide substrate range makes it ideal for site-selective dual C-H functionalization at the highly chemoselective aryl sites.

Hypervalent iodine catalysis has been widely utilized in olefin functionalization reactions. Intermolecularly, the regioselective addition of two distinct nucleophiles across the olefin is a challenging process in hypervalent iodine catalysis. We introduce here a unique strategy using simple lithium salts for hypervalent iodine catalyst activation. The activated hypervalent iodine catalyst allows the intermolecular coupling of soft nucleophiles such as amides onto electronically activated olefins with high regioselectivity.

This report outlines a versatile strategy for synthesizing a diverse array of N-heterocycles. By the utilization of common olefins, this simple protocol facilitates their coupling with various bifunctional reagents. Furthermore, it can be integrated with C-H amination techniques to directly produce N-heterocycles in a multicomponent cascade coupling process. The unique bond disconnection logic employed in this process underscores its efficiency in achieving rapid simplification through cascade couplings.

A new 1,10-phenanthroline-functionalized MCM-41-immobilized copper(I) complex [MCM-41-Phen-CuCl] was prepared from 1-(1,10-phenanthrolin-5-yl)-3-(3-(triethoxysilyl)propyl)urea via immobilization on MCM-41, followed by reacting with copper(I) chloride. It was found that this heterogenized copper(I) complex is a highly efficient catalyst for the oxidation of a wide variety of alcohols into aldehydes and ketones using molecular oxygen as the stoichiometric oxidant and 5 mol% of di-tert-butyl tert-butyl hydrazine-1,2-dicarboxylate (DBAD-H2) 2 ) as additive, and can be recycled more than eight cycles with almost consistent activity.

ADVERTISEMENT RETURN TO ISSUEPREVGreen Chemistry High...Green Chemistry HighlightsNEXTGreen Chemistry Articles of Interest to the Pharmaceutical IndustryMarian C. Bryan*Marian C. BryanJanssen R&D, 1400 McKean Road, Spring House, Pennsylvania 19002, United States*Email: [email protected]More by Marian C. Bryan, Charlotte DaltonCharlotte DaltonCatSci Ltd, CBTC2, Capital Business Park, Cardiff, South Glamorgan CF3 2PX, U.K.More by Charlotte Dalton, Jaika DoerflerJaika DoerflerDrug Substance Technologies, Amgen Inc., One Amgen Center Drive, Thousand Oaks, California 91320, United StatesMore by Jaika Doerfler, Oliver D. EnglOliver D. EnglTakeda, 35 Landsdowne Street, Cambridge, Massachusetts 02139, United StatesMore by Oliver D. Engl, Paul FergusonPaul FergusonNew Modalities Product Development, Pharmaceutical Technology & Development, Operations, AstraZeneca, Macclesfield SK10 2NA, U.K.More by Paul Ferguson, Alejandro Gimenez MolinaAlejandro Gimenez MolinaJanssen Pharmaceutica NV, Turnhoutseweg 30, B-2340 Beerse, Antwerpen, BelgiumMore by Alejandro Gimenez Molina, Vanessa HarawaVanessa HarawaSynthetic Biochemistry, GSK, Gunnels Wood Road, Stevenage SG1 2NY, U.K.More by Vanessa Harawa, Joseph HosfordJoseph HosfordSynthetic Biochemistry, GSK, Gunnels Wood Road, Stevenage SG1 2NY, U.K.More by Joseph Hosford, Gareth P. HowellGareth P. HowellChemical Development, Pharmaceutical Technology & Development, Operations, AstraZeneca, Macclesfield SK10 2NA, U.K.More by Gareth P. Howellhttps://orcid.org/0000-0003-2845-6459, Christopher B. KellyChristopher B. KellyJanssen R&D, 1400 McKean Road, Spring House, Pennsylvania 19002, United StatesMore by Christopher B. Kellyhttps://orcid.org/0000-0002-5530-8606, Wei LiWei LiNovartis, Suzhou Novartis Technical Development Co., Ltd., 18-1 Tonglian Road, Bixi Subdistrict, Changshu, Jiangsu 215537, ChinaMore by Wei Li, Rachel H. MundayRachel H. MundayChemical Development, Pharmaceutical Technology & Development, Operations, AstraZeneca, Macclesfield SK10 2NA, U.K.More by Rachel H. Munday, Antonio NavarroAntonio NavarroEli Lilly and Company, Lilly Technology Center, 1400 West Raymond Street, Indianapolis, Indiana 46221, United StatesMore by Antonio Navarrohttps://orcid.org/0000-0002-3623-0946, Michael ParmentierMichael ParmentierChemical and Analytical Development, Novartis AG, CH-4056 Basel, SwitzerlandMore by Michael Parmentierhttps://orcid.org/0000-0002-1732-9641, Jan PawlasJan PawlasPolyPeptide Group, Limhamnsvägen 108, P.O. Box 30089, SE-200 61 Limhamn, SwedenMore by Jan Pawlas, Paul F. RichardsonPaul F. RichardsonPfizer, Chemistry, 10578 Science Center Drive (CB6), San Diego, California 09121, United StatesMore by Paul F. Richardsonhttps://orcid.org/0000-0002-3700-8749, Alan Steven*Alan StevenCatSci Ltd, CBTC2, Capital Business Park, Cardiff, South Glamorgan CF3 2PX, U.K.*Email: [email protected]More by Alan Stevenhttps://orcid.org/0000-0002-0134-0918, Balaram S. TakaleBalaram S. TakaleChemical Development, Neurocrine Biosciences, San Diego, California 92130, United StatesMore by Balaram S. Takale, Jack A. TerrettJack A. TerrettGenentech Inc., 1 DNA Way, South San Francisco, California 94080, United StatesMore by Jack A. Terretthttps://orcid.org/0000-0001-8777-046X, Daniel S. TreitlerDaniel S. TreitlerBristol Myers Squibb, 1 Squibb Drive, New Brunswick, New Jersey 08903, United StatesMore by Daniel S. Treitlerhttps://orcid.org/0000-0001-5375-4920, and Mingshuo ZengMingshuo ZengGenentech Inc., 1 DNA Way, South San Francisco, California 94080, United StatesMore by Mingshuo ZengCite this: Org. Process Res. Dev. 2022, 26, 9, 2550–2559Publication Date (Web):September 6, 2022Publication History Received29 August 2022Published online6 September 2022Published inissue 16 September 2022https://pubs.acs.org/doi/10.1021/acs.oprd.2c00274https://doi.org/10.1021/acs.oprd.2c00274research-articleACS PublicationsCopyright © 2022 American Chemical SocietyRequest reuse permissionsArticle Views2853Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. 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N-heterocycles are privileged pharmaceutical scaffolds in drug discovery and development. We disclose here divergent intermolecular coupling strategies that can access diverse N-heterocycles directly from olefins. The radical-to-polar mechanistic switching is key for the divergent cyclization processes. These distinctive annulations result in the coupling of alkenes with simple bifunctional reagents for divergent N-heterocycle syntheses.

A highly efficient heterogeneous gold(I)-catalyzed heterocyclization of ynamides with benzyl or indolyl azides has been achieved in 1,2-dichloroethane under mild conditions via a heterogenized α-imino gold carbene intermediate using 5 mol% of SBA-15-anchored strongly hindered NHC-gold(I) complex [IPr-SBA-15-AuNTf2] as the catalyst, delivering a wide range of valuable 2-aminoindoles or 3-amino-β-carbolines in mostly good to excellent yields with high regioselectivity. Furthermore, the new heterogenized NHC-gold(I) complex displays the same catalytic activity as IPrAuNTf2 and is facile to recover by centrifugation of the reaction mixture and can be reused at least seven times without any appreciable drop in its catalytic activity.

A highly efficient heterogeneous copper(I)-catalyzed cross-coupling of trialkylsilylethynes with N-tosylhydrazones has been achieved in dioxane at 90-110 °C via the Cu carbene migratory insertion with an SBA-15-immobilized l-proline-Cu(I) complex [SBA-15-l-Proline-CuI] as the catalyst and LiOtBu as the base, leading to the formation of C(sp)-C(sp3) bonds. The reaction generates a wide variety of alkyltrialkylsilylalkynes in moderate to high yields. This new heterogenized copper(I) complex exhibits a comparable catalytic efficiency to homogeneous CuI and can be easily recovered through a simple centrifugation process and is recyclable up to 12 times without a remarkable loss of activity.

An efficient heterogeneous copper(I)-catalyzed cross-coupling of aryl iodides and pinacolborane has been developed. The reaction proceeds smoothly in THF at room temperature by using 10 mol% of MCM-41-anchored NHC-copper(I) complex [MCM-41-NHC-CuI] as catalyst and sodium hydride as base and provides a general and practical route for the synthesis of a wide variety of arylboronates in good to high yields. This heterogenized copper(I) catalyst can be facilely prepared via a simple two-step procedure starting from easily accessible and inexpensive reagents, and exhibits a higher catalytic activity than CuI and can be recycled more than ten times without any significant loss of its catalytic activity.

N-heterocycles are valuable motifs in pharmaceuticals and materials, but divergent synthetic strategies are lacking. Now, bifunctional sulfilimines have been shown to form nitrogen-centred radicals under photocatalytic conditions, and subsequent coupling with olefins enables the synthesis of diverse N-heterocycles.