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A safe and efficient method for the in‐situ preparation of (diazomethyl)dimethylphosphine oxide – a hereto unexplored diazoalkane reagent – is developed. The method is based on the diazotization of the corresponding P(O)Me2‐substituted amine (readily available in multigram quantities) in non‐aqueous media. The protocol provides the target product as ca. 1.5 M CHCl3 solution which is stable at −18 °C. The utility of the synthesized diazoalkane is illustrated by its [3+2] cycloaddition with electron‐poor alkynes and alkenes providing the corresponding P(O)Me2‐substituted pyrazoles and pyrazolines with moderate to good efficiency. In this view, the title compound represents and an important extension of medicinally relevant phosphine oxide reagents. [ABSTRACT FROM AUTHOR]

A comprehensive study of physicochemical properties (pKa, LogP, and intrinsic microsomal clearance) within the series of mono‐ and difluorinated azetidine, pyrrolidine, and piperidine derivatives was performed. While the number of fluorine atoms and their distance to the protonation center were the major factors defining the compound's basicity, both pKa and LogP values were affected considerably by the conformational preferences of the corresponding derivatives. For example, features of "Janus face" (facially polarized) cyclic compounds (i. e., unusually high hydrophilicity) were identified for cis‐3,5‐difluoropiperidine, preferring a diaxial conformation. Intrinsic microsomal clearance measurements demonstrated high metabolic stability of the compounds studied (with a single exception of the 3,3‐difluoroazetidine derivative). According to pKa – LogP plots, the title compounds provide a valuable extension of the fluorine‐containing (e. g., fluoroalkyl‐substituted) saturated heterocyclic amine series as building blocks for rational optimization studies in early drug discovery. [ABSTRACT FROM AUTHOR]

Synthesis and physicochemical characterization of all possible cis‐ and trans‐1,3‐disubstituted cyclobutane‐derived amines and carboxylic acids bearing mono‐, di‐ and trifluoromethyl groups at the C‐3 position is disclosed. Tetramethylammonium fluoride (TMAF)‐ or morpholinosulfur trifluoride (Morph‐DAST)‐mediated nucleophilic fluorination of appropriate cis‐ and trans‐diastereomeric substrates was used as the key step for the preparation of CH2F‐ and CHF2‐substituted derivatives. To obtain the corresponding cis‐ and trans‐isomeric CF3‐substituted derivatives, resolution of known 3‐(trifluoromethyl)cyclobutanecarboxylic acid (obtained as a mixture of diastereomers) was applied. The proposed procedures were suitable for the preparation of corresponding fluoroalkyl‐substituted cyclobutane‐derived amines and carboxylic acids on up to 50 g scale. All 12 building blocks obtained were characterized by measuring dissociation constants (pKa) and lipophilicities (LogP, for model derivatives) to evaluate the effect of the fluoroalkyl substituents on their physicochemical properties relevant to further drug discovery applications. [ABSTRACT FROM AUTHOR]

A highly efficient multigram synthesis of spirocyclic and fused isoxazoline building blocks is described. Isoxazoline‐3‐carboxylates were synthesized via a regioselective 1,3‐dipolar cycloaddition reaction of 2‐chloro‐2‐(hydroxyimino)acetate and carbo‐ or heterocyclic alkenes bearing endo‐ or exocyclic C=C double bonds, resulting in fused or spirocyclic isoxazolines, respectively. The preparation of up to 300 g of these compounds was achieved in a single run. The ester group of isoxazolines was then subjected to common synthetic transformations for the synthesis of corresponding building blocks, including alcohols, chlorides, azides, amines, aldehydes, carboxylic acids, amino acids and their derivatives, difluoromethyl‐substituted compounds, and bicyclic γ‐lactones. Additionally, a direct cycloaddition‐based approach to the synthesis of aminoalkyl‐ and chloromethyl‐substituted isoxazolines was proposed to improve their preparation. The described isoxazoline building blocks are expected to be valuable tools for drug discovery. [ABSTRACT FROM AUTHOR]

Alternating current (AC) electrolysis is receiving increased interest as a versatile tool for mild and selective electrochemical transformations. This work demonstrates that AC can enable the concept of a stirring‐free electrochemical reactor where the periodic switch of electrode polarity, inherent to AC, provides uniform electrolysis across the whole volume of the reactor. Such design implies a straightforward approach for scaling up electrosynthesis. This was demonstrated on the range of electrochemical transformations performed in three different RVC‐packed reactors on up to a 50‐mmol scale. Redox‐neutral, oxidative, and reductive processes were successfully implemented using the suggested design and the applicable frequency ranges were further investigated for different types of reactions. The advantages of the AC‐enabled design – such as the absence of stirring and a maximized surface area of the electrodes – provide the possibility for its universal application both for small‐scale screening experimentation and large‐scale preparative electrosynthesis without significant optimization needed in between. [ABSTRACT FROM AUTHOR]

A set of building blocks based on the 4,5,6,7‐tetrahydro‐pyrazolo[1,5‐a]pyrazine scaffold is synthesized in a multigram scale in a cost‐efficient manner. The possibility of the introduction of different substituents, neutral or functionalized in different positions of pyrazole and/or piperazine rings, is shown. The efficacy of using NH‐pyrazole carbonic acids as a key intermediate of the process is demonstrated. The regioselectivity for direct insertion of the substituent to the 4,5,6,7‐tetrahydro‐pyrazolo[1,5‐a]pyrazine core is discussed. The synthetic perspectives for using the functionalized 4,5,6,7‐tetrahydro‐pyrazolo[1,5‐a]pyrazine as a bifunctional scaffold is discussed. The utilizing of building blocks obtained for the different region‐ and/or stereoselective synthesis, including sole transformations or modifications of functional groups, is demonstrated. The advantages of the proposed approach are proven compared with the other known methodologies. [ABSTRACT FROM AUTHOR]

Physico‐chemical properties important to drug discovery (pKa, LogP, and aqueous solubility), as well as metabolic stability, were studied for a series of functionalized gem‐difluorinated cycloalkanes and compared to those of non‐fluorinated and acyclic counterparts to evaluate the impact of the fluorination. It was found that the influence of the CF2 moiety on the acidity/basicity of the corresponding carboxylic acids and amines was defined by inductive the effect of the fluorine atoms and was nearly the same for acyclic and cyclic aliphatic compounds. Lipophilicity and aqueous solubility followed more complex trends and were affected by the position of the fluorine atoms, ring size, and even the nature of the functional group present; also, significant differences were found for the acyclic and cyclic series. Also, gem‐difluorination either did not affect or slightly improved the metabolic stability of the corresponding model derivatives. The presented results can be used as a guide for rational drug design employing fluorine and establish the first chapter in a catalog of the key in vitro properties of fluorinated cycloalkanes. [ABSTRACT FROM AUTHOR]

Current medicinal chemistry relies heavily on the quality of building blocks, i. e. reagents used to introduce chemical diversity into the target molecules. The last decade witnessed an emergence of many novel (or well‐overlooked old) chemotypes for drug discovery, which is related to adapting new synthetic methodologies, designing new sp3‐enriched bioisosteres, paying attention to previously underrated (or even unwanted) structural motifs, or combination thereof. In this review with 532 references, a survey of selected chemotypes that emerged recently in medicinal chemistry is provided, with a focus on the synthesis of the corresponding building blocks. Thus, saturated (hetero)aliphatic boronates, sulfonyl fluorides, sulfinates, non‐classical sp3‐enriched benzene isosteres, bicyclic morpholine/piperidine/piperazine analogs, as well as gem‐difluorinated cycloalkanes (as an example of emerging fluorinated motifs) are discussed. [ABSTRACT FROM AUTHOR]

A set of 20 composites was prepared by pyrolysis of Co2+ complexes with 1,10‐phenanthroline, melamine and 1,2‐diaminobenzene. These composites were tested as the catalysts for the hydrogenation of quinolines. As shown by powder X‐ray diffraction and TEM, the composited contained Co particles of several dozen nm sizes. The composition (elements content), Raman spectra X‐ray photoelectron spectra parameters of the composites were analyzed. It was found that there was no distinct factor that controlled the yield of 1,2,3,4‐tetrahydroquinolines in the investigated process. The yields of the respective products were in the range 90–100 %. The three most active composites were selected for scale‐up and hydrogenation of a series of substituted quinolines. Up to 97 % yield of 1,2,3,4‐tetrahydroquinoline was obtained on a 50 g scale. Five representative substituted quinolines were synthesized on a 10–20 grams scale using the Co‐containing composites as the catalysts. [ABSTRACT FROM AUTHOR]

A general approach to gem‐difluorocyclopropenes synthesis based on the reaction of alkynes with Ruppert‐Prakash reagent is reported. The proposed method is evaluated for the synthesis of a wide difluorocyclopropenes scope based on their bench lifespan and hydrolytic stability. The tolerance of the method for common functional groups was shown. Previously unavailable difluorocyclopropenes substituted with aliphatic were prepared using the proposed procedure. The retain of stability was proven by the multigram scale synthesis and further storage in the temperature interval −78 to −4 °C over a year. This makes them attractive building blocks and intermediates for organic synthesis. The reasons for dropping stability were defined. The relations between the structure of the substituents and the stability of the difluorocyclopropene ring were determined and discussed. [ABSTRACT FROM AUTHOR]

Scalable synthesis of saturated heterocyclic dimethyl phosphine oxides (derivatives of azetidine, pyrrolidine, piperidine, and morpholine) is disclosed. The key steps of the synthesis relied on the reactions of HP(O)Me2, i. e. the phospha‐Mannich (the Kabachnik‐Fields‐type) condensation with cyclic imines or monoprotected diamines, palladium‐catalyzed reactions of alkenyl halides or trifltates (generated from cyclic ketones), as well as base‐mediated nucleophilic substitution, Michael addition, or oxirane ring opening. It was shown that introducing the P(O)Me2 group into the saturated heterocyclic core had very strong impact on the compound's basicity: the corresponding α‐, β‐, and γ‐isomeric derivatives were by ca. 4, 2, and 1.6 pKa units less basic, respectively, as compared to the parent saturated heterocycle. Meanwhile, the P(O)Me2‐substituted compound was more basic than its SO2i‐Pr and SO2NMe2‐containing isosteres (by ca. 1.2 and 0.4 pKa units, respectively). It was also demonstrated that the P(O)Me2 group typically increased the compound's hydrophilicity and aqueous solubility. In particular, the LogP values for the corresponding derivatives were by ca. 1.4–1.7 and 0.6 units lower than for the non‐substituted counterpart and sulfonamide/sulfone isosteres, respectively. Finally, a potential of the synthesized building blocks to generate lead‐like three‐dimensional compound libraries was confirmed using the Nelson's LLAMA tool. [ABSTRACT FROM AUTHOR]

The gem‐difluorocycloalkane family was extended to all possible regioisomers of the gem‐difluorocycloheptane, monofunctionalized by carboxilic‐, amino‐ or keto‐ group, that were synthesized on a multigram scale. The preparation of the corresponding building blocks was achieved from readily accessible starting materials either via six‐membered ring homologation or deoxofluorination of the appropriate seven‐membered cyclic ketones. [ABSTRACT FROM AUTHOR]

This review discusses recent advances in the chemistry of saturated boronic acids, boronates, and trifluoroborates. Applications of the title compounds in the design of boron‐containing drugs are surveyed, with special emphasis on α‐amino boronic derivatives. A general overview of saturated boronic compounds as modern tools to construct C(sp3)−C and C(sp3)‐heteroatom bonds is given, including recent developments in the Suzuki‐Miyaura and Chan‐Lam cross‐couplings, single‐electron‐transfer processes including metallo‐ and organocatalytic photoredox reactions, and transformations of boron "ate" complexes. Finally, an attempt to summarize the current state of the art in the synthesis of saturated boronic acids, boronates, and trifluoroborates is made, with a brief mention of the "classical" methods (transmetallation of organolithium/magnesium reagents with boron species, anti‐Markovnikov hydroboration of alkenes, and the modification of alkenyl boron compounds) and a special focus on recent methodologies (boronation of alkyl (pseudo)halides, derivatives of carboxylic acids, alcohols, and primary amines, boronative C−H activation, novel approaches to alkene hydroboration, and 1,2‐metallate‐type rearrangements). [ABSTRACT FROM AUTHOR]

This article discusses the synthesis and reactions of a new diazoalkane reagent called (diazomethyl)dimethylphosphine oxide (Me₂P(O)CHN₂). Ukrainian chemists have extensively studied various diazoalkanes relevant to medicinal chemistry over the past two decades. The research article by O. O. Grygorenko and co-workers provides more information on the synthesis and [3+2] cycloaddition reactions of this novel diazoalkane reagent. The article also includes artwork by Vitalii Boklashchuk. [Extracted from the article]

Synthesis of previously unavailable 1,2‐disubstituted cyclobutane building blocks bearing mono‐, di‐ and trifluoromethyl groups are disclosed. The key steps included deoxofluorination or TMAF‐mediated nucleophilic substitution in the appropriate bifunctional cyclobutanes; for the CF3‐substituted derivatives, alternative methods based on cyano‐ or azidotrifluoromethylation of cyclobutene using the Togni reagent II were also proposed. All methods provided trans diastereomers of the target primary amines and carboxylic acids (6 representatives) and were suitable for their multigram preparation. Furthermore, dissociation constants (pKa) and lipophilicity (logP) values were measured to evaluate the effect of the fluoroalkyl substituents on acidity/basicity and lipophilicity of the building blocks obtained. [ABSTRACT FROM AUTHOR]

A dimeric complex of trivalent europium [Eu2Cl4(bc)2(ptpy)2] (1), containing the separate ligands 4'‐phenyl‐2,2':6',2''‐terpyridine (ptpy) and benzoate (bc–) and a one‐dimensional double strand coordination polymer of the composition 1∞[EuCl2(cptpy)] (2) with 4‐[2,2':6',2''‐terpyridin]‐4'‐yl‐benzoate (cptpy–) were obtained. The products exhibit structural similarities despite the character of joint and separate functionality of the ligands. The dimer 1 shows photoluminescence with high quantum yield [61(2) %]. Eu3+ emission lifetime is 1.493(1) ms at room temperature and rises to 1.649(1) ms upon cooling to 77 K. [ABSTRACT FROM AUTHOR]

The electrochemical Shono oxidation of Boc‐protected cyclic amines was revised. The conditions for scalable electrochemical synthesis of cyclic enecarbamates were found. The developed protocol included recycling of the full range of used reagents, favoring to E‐factor reduction according to Green Chemistry requirements. The method opened the way for the convenient preparation of previously uncommon materials, which could become useful synthetic intermediates. Their synthetic potential was evaluated in [2+1] and [2+2] cycloadditions as well as electrophilic functionalization. Moreover, functionalized enecarbamates with carbonyl groups in β‐position were used as latent 1,3‐bielectrophiles in classical heterocyclizations. In a case of the hydrazine, the corresponding unusually decorated pyrazoles were prepared. The proposed methodology is a straightforward tool for the design and synthesis of Medicinal Chemistry relevant building blocks. As examples, 5‐fluoro pipecolic and 3‐fluoro isonipecotic acids were synthesized starting from Boc‐protected esters of the pipecolic and the isonipecotic acids respectively; the 5‐step approach to pyrazole containing α‐aminoacids with different linkers between the aminoacidic and pyrazole moieties was elaborated based on the cheapest commercially available racemic and chiral cyclic α‐aminoacids; the convenient approach to the functionalized tetrahydropyrido[3,4‐d]pyridazines was proposed starting from Boc‐protected ester of the isonipecotic acids. [ABSTRACT FROM AUTHOR]

All pharmaceutical products contain organic molecules; the source may be a natural product or a fully synthetic molecule, or a combination of both. Thus, it follows that organic chemistry underpins both existing and upcoming pharmaceutical products. The reverse relationship has also affected organic synthesis, changing its landscape towards increasingly complex targets. This Review article sets out to give a concise appraisal of this symbiotic relationship between organic chemistry and drug discovery, along with a discussion of the design concepts and highlighting key milestones along the journey. In particular, criteria for a high‐quality compound library design enabling efficient virtual navigation of chemical space, as well as rise and fall of concepts for its synthetic exploration (such as combinatorial chemistry; diversity‐, biology‐, lead‐, or fragment‐oriented syntheses; and DNA‐encoded libraries) are critically surveyed. [ABSTRACT FROM AUTHOR]

Base‐promoted cyclization of N‐Boc‐ω‐(4‐(chloromethyl)oxazol‐5‐yl)alkylamines led to the corresponding "dimerization" products containing fused 10‐, 12‐, and 14‐membered rings. Experimental data showed that the formation of these ring systems is favored over the corresponding 5‐/6‐/7‐membered ones, which was partially confirmed by DFT calculations; this effect was especially significant in the case of the 5‐/10‐membered pair. [ABSTRACT FROM AUTHOR]

Difluorocyclopropanation of N‐vinylazoles with the CF3SiMe3–NaI system was studied. It was found that N‐vinylpyrazoles could be transformed into the corresponding N‐difluorocyclopropyl‐substituted derivatives. The method was efficient on a 100 g scale and could be applied for the preparation of various functionalized regioisomeric pyrazole derivatives bearing a gem‐difluorocyclopropane moiety, such as amines, carboxylic acids, aldehydes, bromides, and boronic esters. It was found that N‐difluorocyclopropylpyrazole moiety tolerated many common reagents including nitrating mixture, bromine, aqueous acids and alkali, KMnO4, LiBH4, and Pd0 complexes; it was unstable towards AlCl3, catalytic hydrogenation and lithiation conditions. The products obtained are advanced building blocks which of potential importance to medicinal and agrochemistry. [ABSTRACT FROM AUTHOR]

An efficient approach towards introducing (cyclo)alkyl substituents at C‐2, C‐3 or C‐4 positions of the piperidine ring was described. The method relied on the straightforward two‐step reaction sequence based on the formal sp3–sp3 retrosynthetic disconnection. The procedure commenced with selective directed ortho metalation of 2‐ and 3‐bromopyridine, followed by reaction with aldehydes or ketones. The optimized methods were developed for all three isomers of hydroxyalkyl‐substituted pyridines, which were synthesized in 28–84 % overall yield (20 examples). Catalytic hydrogenation of these adducts could be performed selectively with or without retention of the hydroxyl group in their molecules, so that either (cyclo)alkylpiperidines (14 examples) or the corresponding saturated amino alcohols (16 examples) were obtained (28–96 % and 82–96 % yield, respectively). After minor modifications, the developed method was also implemented in a flow reactor and a 5 L autoclave, which allowed for the preparation of up to 0.5 kg of the representative (cyclo)alkylpiperidines. [ABSTRACT FROM AUTHOR]

Reaction of various electron‐deficient alkenes, as well as functionalized styrene derivatives with CF3SiMe3−NaI system is studied. Relative reactivity of the substrates is established. It is shown that many α,β‐unsaturated esters can be difluorocyclopropanated efficiently under "slow addition protocol" conditions, which provides access to mono‐ and spirocyclic gem‐difluorocyclopropyl‐substituted carboxylic acids with good yields (36–79% for two steps) on up to 100 g scale. [ABSTRACT FROM AUTHOR]

An approach to 4‐hetarylisoxazole‐derived amines and other related 3,4‐disubstituted isoxazoles which relies on [3+2] cycloaddition of amino acid‐derived halogenoximes and push‐pull enamines is described. The target products are obtained at gram scale in up to 81 % overall yield. The efficiency of the method is affected by the electronic properties of the enamine component at the key step. Reaction of chloroximes with protected amino group and enamines bearing electron‐withdrawing groups at the β position (i.e. push‐pull enamines) under basic conditions led to 3,4‐disubstituted isoxazole derivatives bearing hetaryl, nitro, or difluoroacetyl group at the 4th position. [ABSTRACT FROM AUTHOR]

The synthesis of monocyclic, spirocyclic and fused bicyclic secondary amines bearing a gem-difluorocyclopropane moiety via difluorocyclopropanation of unsaturated N-Boc derivatives using the trifluoromethyl(trimethyl)silane/sodium iodide [CF3SiMe3-NaI] system is described. The relative order of the substrate reactivity is established. It is shown that for the reactive alkenes the standard reaction conditions can be used, whereas for the substrates with low reactivity, slow addition of the Ruppert-Prakash reagent is necessary. [ABSTRACT FROM AUTHOR]

Five CF3-substituted 3-azabicyclo[ n.1.0]alkanes were synthesized by CuCl-mediated trifluoromethylcyclopropanation reaction of the corresponding cyclic enamides with CF3CHN2. [ABSTRACT FROM AUTHOR]

Front Cover: Effect of gem-Difluorination on the Key Physicochemical Properties Relevant to Medicinal Chemistry: The Case of Functionalized Cycloalkanes (Chem. Eur. J. 19/2022) Fluorine, cycloalkanes, lipophilicity, acidity and basicity, metabolic stability Keywords: fluorine; cycloalkanes; lipophilicity; acidity and basicity; metabolic stability EN fluorine cycloalkanes lipophilicity acidity and basicity metabolic stability 1 1 1 04/05/22 20220401 NES 220401 B The CF SB 2 sb dragon reborn b !. [Extracted from the article]

A new strategy for the synthesis of polycyclic imidazole-containing N-heterocycles, based on the two general synthetic ways, namely the Pd(II)-catalyzed intramolecular arylation via CH/CHal and CH/CH coupling reactions, was developed. The method proposed here enables the synthesis of many fused N-heterocycles containing purine, 1-deazapurines and benzimidazole structural units. [ABSTRACT FROM AUTHOR]

Bicyclic compounds, Building blocks, Organoboron compounds, Organofluorine compounds, Organosulfur compounds Cover Feature: Emerging Building Blocks for Medicinal Chemistry: Recent Synthetic Advances (Eur. J. Org. Keywords: Bicyclic compounds; Building blocks; Organoboron compounds; Organofluorine compounds; Organosulfur compounds EN Bicyclic compounds Building blocks Organoboron compounds Organofluorine compounds Organosulfur compounds 6473 6473 1 12/24/21 20211221 NES 211221 B The Cover Feature b shows a "building block triangle" that represents recent trends in the chemical space of building blocks. [Extracted from the article]

Boronation, cross-coupling, metalocatalysis, organoboron compounds, organocatalysis, photochemical reactions Keywords: boronation; cross-coupling; metalocatalysis; organoboron compounds; organocatalysis; photochemical reactions EN boronation cross-coupling metalocatalysis organoboron compounds organocatalysis photochemical reactions 1 1 1 11/09/21 20211105 NES 211105 B Even a gifted musician b needs a good instrument to present his/her talent in the best possible light. Organoboron compounds have provided such an opportunity for many decades; nevertheless, they are currently receiving increasing attention. [Extracted from the article]

Keywords: boronation; cross-coupling; metalocatalysis; organoboron compounds; organocatalysis; photochemical reactions EN boronation cross-coupling metalocatalysis organoboron compounds organocatalysis photochemical reactions 15272 15272 1 11/09/21 20211105 NES 211105 B In a musical allegory for chemical synthesis b a guitar player in a flask creates notes that become an organic compound. Boronation, cross-coupling, metalocatalysis, organoboron compounds, organocatalysis, photochemical reactions. [Extracted from the article]

Front Cover: Fluoroalkyl-Containing 1,2-Disubstituted Cyclobutanes: Advanced Building Blocks for Medicinal Chemistry (Eur. J. Org. B The Front Cover b shows fluoroalkyl-containing I trans i -1,2-disubstituted cyclobutanes, depicted as a planet rover exploring and expanding new horizons of chemical space. The picture symbolizes combined efforts of Enamine chemists and Ukrainian academic institutions towards synthesis of previously unavailable building blocks for modern drug discovery. [Extracted from the article]

Keywords: chemoinformatics; combinatorial chemistry; drug discovery; natural products; organic synthesis B Drug discovery uses both b natural product sources and synthetic organic chemistry to provide suitable starting points for further optimization. Chemoinformatics, combinatorial chemistry, drug discovery, natural products, organic synthesis. [Extracted from the article]

Highlights from the article: B The Front Cover b shows the "difluoro-cyclopropanating dragon" (which has been already used to depict the CF SB 3 sb SiMe SB 3 sb - the NaI system through the series of authors' previous works), who has aimed at new class of substrates, i.e. I N i -vinylazoles, and thus reached a novel area of chemical space occupied by fluorinated cyclopropane derivatives. This method has been used for multigram preparation of all isomeric functionalized I N i -difluorocyclopropylpyrazoles - advanced building blocks for drug discovery. B The Front Cover b shows the "difluoro-cyclopropanating dragon" (which has been already used to depict the CF SB 3 sb SiMe SB 3 sb - the NaI system through the series of authors' previous works), who has aimed at new class of substrates, i.e. I N i -vinylazoles, and thus reached a novel area of chemical space occupied by fluorinated cyclopropane derivatives.

The front cover image, provided by Pavel Nosik, Andriy Gerasov, Sergey Ryabukhin, Oleksandr Grygorenko, and Dmitriy Volochnyuk illustrates the synthesis of secondary amines bearing a gem ‐ difluorocyclopropane moiety via reaction of unsaturated N ‐ Boc derivatives with the CF3SiMe3−NaI system. For the reactive alkenes, the standard reaction conditions can be used, whereas for those substrates with low reactivity, slow addition of the Ruppert ‐ Prakash reagent is necessary. (Background artwork by Web Design Studio “ZORELiT”). Details can be found in the full paper on pages 3126 – 3136 (P. S. Nosik, A. O. Gerasov, R. O. Boiko, E. Rusanov, S. V. Ryabukhin, O. O. Grygorenko, D. M. Volochnyuk, Adv. Synth. Catal. 2017, 359, 3126 – 3136; DOI: 10.1002/adsc.201700857). [ABSTRACT FROM AUTHOR]

The synthesis of all four possible title compounds can be achieved from pyridines of type (I). [ABSTRACT FROM AUTHOR]