Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• to 2,2-diarylated enamines 83 isolated as a single isomer with respect to the alkene geometry. While the diarylation of anilines with cyclic diaryl-λ3-iodanes for the formation of N-arylated carbazoles has been described in 2013 [66][67], the truly intermolecular diarylation of anilines with linear

Synthesis of trifluoromethylated 2H-azirines through Togni reagent-mediated trifluoromethylation followed by PhIO-mediated azirination

• Jiyun Sun,
• Xiaohua Zhen,
• Huaibin Ge,
• Guangtao Zhang,
• Xuechan An and
• Yunfei Du

Beilstein J. Org. Chem. 2018, 14, 1452–1458, doi:10.3762/bjoc.14.123

• [52][53][54][55] have been developed for accessing this exclusive class of heterocycles. In our previous works, we have realized the application of hypervalent iodine reagents for the construction of the 2H-azirine skeleton starting from enamines 2 via intramolecular oxidative cyclization (Scheme 1

• -obtained trifluoromethylated enamines could undergo a hypervalent iodine-mediated intramolecular azirination to give the corresponding trifluoromethylated 2H-azirines [56][57]. To test this conversion, the readily available enamine 5a was used as a model substrate. The treatment of 5a with Togni reagent 1

• iodine-mediated trifluoromethylation and azirination process. In this transformation, the introduction of the CF3 group to the β-position of enamines followed by the intramolecular azirination was realized in a one-pot process, providing a general and straightforward access to biologically interesting

Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 1349–1369, doi:10.3762/bjoc.14.114

• with good yields (62–83%) and uniformly excellent enantioselectivities (92–99% ee), as shown in Scheme 6. Along with enolates employed as nucleophilic partners in Mannich reactions, related reactions involving enamines have been developed. For example in 2018, Lu, Zhang and Shi reported the first

Cross-coupling of dissimilar ketone enolates via enolonium species to afford non-symmetrical 1,4-diketones

• Keshaba N. Parida,
• Gulab K. Pathe,
• Shimon Maksymenko and
• Alex M. Szpilman

Beilstein J. Org. Chem. 2018, 14, 992–997, doi:10.3762/bjoc.14.84

• enantioselective coupling of in situ formed aldehyde enamines with excess (2 equiv) trialkylsilyl enol ethers (Scheme 1c) [27]. This reaction was proposed to proceed through a mechanism involving the attack of an enamine radical on the trialkylsilyl enol ether. The last two examples concern the even more

An air-stable bisboron complex: a practical bidentate Lewis acid catalyst

• Longcheng Hong,
• Sebastian Ahles,
• Andreas H. Heindl,
• Gastelle Tiétcha,
• Andrey Petrov,
• Zhenpin Lu,
• Christian Logemann and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2018, 14, 618–625, doi:10.3762/bjoc.14.48

• air-stable Lewis acid B for organic synthesis was then tested in several IEDDA reactions of phthalazine (3) catalyzed by B or A, respectively. As shown in Table 1, both, dihydrofuran (Table 1, entry 1) and enamines, generated in situ from aldehydes and amines (Table 1, entries 2–4), can take part in

• phthalazine: In a Schlenk tube charged with a stirring bar, the air-stable bidentate Lewis acid catalyst B (5.00 mol %) and the stated solvent were added under N2. Then, the phthalazine (1.00 equiv), dienophile (2.00 equiv; for enamines, generated in situ from aldehyde and amine) were added subsequently. The

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• formaldehyde and 2,2-disubstituted acetaldehydes 28. Formaldehyde, as a non-enolizable compound is more likely to give Mannich base product 30. In contrast, enolizable 2,2-disubstituted aldehydes easily form enamines 31 that undergo cycloaddition with electron-deficient o-QMs giving 2,2-dialkyl-3-dialkylamino

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation and chlorination. Part 2: Use of CF₃SO₂Cl

• Hélène Chachignon,
• Hélène Guyon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2800–2818, doi:10.3762/bjoc.13.273

• -trifluoromethylsulfenylation did not occur with 3-substituted substrates. Other azaarenes, such as pyrrole derivatives, as well as enamines or silyl enol ethers were also compatible with these conditions, and furnished the corresponding products in moderate to good yields. The key step of the reaction comprises the formation

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies

• Grzegorz Mlostoń and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 2235–2251, doi:10.3762/bjoc.13.221

• amines, hydrazine, and carbohydrazides. In some of these reactions, the initially formed adducts, after subsequent elimination of HCN, undergo heterocyclization (see chapter Heterocyclization reactions). The reaction of E-1a with either aqueous ammonia or gaseous NH3 in acetonitrile leads to the enamines

• 51 [56] (Scheme 17). Further reaction with excess NH3 gives rise to the corresponding monoamide 52. Analogous reactions with differently substituted anilines and β-naphthylamine, respectively, afforded the corresponding enamines of type 51, when the amine was used in excess. On the other hand, the

• -1a was treated with the 4-nitroaniline anion in DMSO [57]. Diverse primary and secondary amines were reacted with dialkyl dicyanofumarates E-1 in CH2Cl2 at room temperature (molar ratio ca. 1:1), and enamines containing two ester and one cyano group were formed as exclusive products in good to high

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• nitrosoalkene generation employs their stable nitrosoacetals of type 3 (N,N-bis(silyloxy)enamines) [17][18]. The latter eliminate (Alk3Si)2O upon the action of Lewis bases generating the corresponding nitrosoalkenes at low stationary concentrations in a controllable manner. Furthermore, synthetic precursors of

• nitrosoacetals 3 are not halocarbonyl compounds as in the case of oximes 1 and 2, but aliphatic nitro derivatives, which are readily transformed into enamines 3 by double silylation involving an internal redox process [19][20][21]. This allows the preparation of nitrosoalkenes, which are difficult to access by

• their reactions with enolates. Thus, our group has demonstrated that nitrosoacetals of nitrosoalkenes (N,N-bis(silyloxy)enamines 3) smoothly react with 1,3-dicarbonyl compounds in the presence of TBAF or DBU to give the corresponding oximes 6 in moderate to good yields (Scheme 3) [24]. The process is

Regiodivergent condensation of 5-alkoxycarbonyl-1H-pyrrol-2,3-diones with cyclic ketazinones en route to spirocyclic scaffolds

• Alexey Yu. Dubovtsev,
• Maksim V. Dmitriev,
• Аndrey N. Maslivets and
• Michael Rubin

Beilstein J. Org. Chem. 2017, 13, 2179–2185, doi:10.3762/bjoc.13.218

• cyclocondensation of six-membered cyclic enamines 1 (vinylogous secondary amides) with 5-methoxycarbonyl-1H-pyrrolediones 2 [39][40][41]. This transformation involved the Michael addition of an enamine to the α,β-unsaturated carbonyl fragment of a pyrroledione and subsequent 5-exo-trig intramolecular nucleophilic

• , recyclization into the thermodynamically more favorable “normal” spirocyclic products 3a occurs. It should be further noted that in contrast to reactions of enamines, which readily provide the corresponding adducts with pyrrolediones in the absence of catalysts, the similar transformation involving enols 6

• displacement ellipsoids. ORTEP drawing of compound 22a (CCDC 1546065) showing 50% probability amplitude displacement ellipsoids. ORTEP drawing of compound 23aa (CCDC 1546064) showing 50% probability amplitude displacement ellipsoids. Spirocyclization of enamines with 5-methoxycarbonyl-1H-pyrrolediones. Non

Chiral phase-transfer catalysis in the asymmetric α-heterofunctionalization of prochiral nucleophiles

• Johannes Schörgenhumer,
• Maximilian Tiffner and
• Mario Waser

Beilstein J. Org. Chem. 2017, 13, 1753–1769, doi:10.3762/bjoc.13.170

• . Anionic PTC-catalysed α-fluorination of enamines 7 and ketones 10. PTC-catalysed α-chlorination reactions of β-ketoesters 1. Shioiri’s seminal report of the asymmetric α-hydroxylation of 15 with chiral ammonium salt PTCs. Asymmetric ammonium salt-catalysed α-hydroxylation using oxygen together with a P

Switchable highly regioselective synthesis of 3,4-dihydroquinoxalin-2(1H)ones from o-phenylenediamines and aroylpyruvates

• Juraj Dobiaš,
• Marek Ondruš,
• Gabriela Addová and
• Andrej Boháč

Beilstein J. Org. Chem. 2017, 13, 1350–1360, doi:10.3762/bjoc.13.132

• of the studied derivatives [4][5]. In this case, their tautomeric equilibrium is shifted to enamines 3 that have been stabilized by an intramolecular hydrogen bond (Scheme 1). A new pseudo-ring is formed via the hydrogen bond in 3, which further spreads the planarity of the 3,4-dihydroquinoxalin-2(1H

• group in imines 2 shifts their tautomeric equilibrium to enamines 3. Selective synthesis of both 3,4-dihydroquinoxalin-2(1H)-one regioisomers 16e (SYN) and 17e (ANTI). The proposed mechanism for the synthesis of 3-methylquinoxalin-2(1H)-one regioisomers 22 and 23. In the case of starting 11g (Y: -H

New syntheses of (±)-tashiromine and (±)-epitashiromine via enaminone intermediates

• Darren L. Riley,
• Joseph P. Michael and
• Charles B. de Koning

Beilstein J. Org. Chem. 2016, 12, 2609–2613, doi:10.3762/bjoc.12.256

• -bromoacetonitrile. The preparation of 3 in three steps from commercially available 3-amino-1-propanol and γ-butyrolactone (4) and its subsequent transformation into the substituted enamines is shown in Scheme 1. As described previously [28], 3-amino-1-propanol was condensed with γ-butyrolactone (4) in a sealed

• attempt to circumvent the issues associated with the purification of the cyclic enamines, we investigated the conversion of alcohols 8c and 8d into the corresponding tosylates followed by treatment with sodium iodide as an alternative for the cyclisation step. The tosylations afforded 10c and 10d in 19

Combined experimental and theoretical studies of regio- and stereoselectivity in reactions of β-isoxazolyl- and β-imidazolyl enamines with nitrile oxides

• Ilya V. Efimov,
• Marsel Z. Shafikov,
• Nikolai A. Beliaev,
• Natalia N. Volkova,
• Tetyana V. Beryozkina,
• Wim Dehaen,
• Zhijin Fan,
• Viktoria V. Grishko,
• Gert Lubec,
• Pavel A. Slepukhin and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2016, 12, 2390–2401, doi:10.3762/bjoc.12.233

• Lazarettgasse, 1090 Vienna, Austria I. Ya. Postovsky Institute of Organic Synthesis, Ural Branch of Russian Academy of Sciences, 20 S. Kovalevskaya str., 620990 Yekaterinburg, Russia 10.3762/bjoc.12.233 Abstract Reactions of β-azolyl enamines and nitrile oxides were studied by both experimental and theoretical

• methods. (E)-β-(4-Nitroimidazol-5-yl), (5-nitroimidazol-4-yl) and isoxazol-5-yl enamines smoothly react regioselectively at room temperature in dioxane solution with aryl, pyridyl, and cyclohexylhydroxamoyl chlorides without a catalyst or a base to form 4-azolylisoxazoles as the only products in good

• yields. The intermediate 4,5-dihydroisoxazolines were isolated as trans isomers during the reaction of (E)-β-imidazol-4-yl enamines with aryl and cyclohexylhydroxamoyl chlorides. Stepwise and concerted pathways for the reaction of β-azolyl enamines with hydroxamoyl chlorides were considered and studied

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

• -vinyl-2-cyclopentenones 277 in high yield (Table 15). In the case of acyclic enamine 278, the initial dioxetane product from the photochemical oxidation of 279 rearranged to amide 280. The reactions using cyclic enamines 281 involve the Kornblum–DeLaMare rearrangement of dioxetanes 282 into 1,2

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• the reaction, the iminium ions rapidly interconvert via single-bond rotation. After irreversible C–C bond formation the E-s-cis- and E-s-trans-iminiums give rise to the Z- and E-enamines, respectively, which undergo a directed enantiospecific protonation to give either the R- or S-product. Thus, the

Studies on the synthesis of peptides containing dehydrovaline and dehydroisoleucine based on copper-mediated enamide formation

• Franziska Gille and
• Andreas Kirschning

Beilstein J. Org. Chem. 2016, 12, 564–570, doi:10.3762/bjoc.12.55

• , they can also be regarded as enamines. Due to the lack of reactivity of the amino group as well as the carboxylate, dehydroamino acids have hardly employed as building blocks in peptide synthesis. Therefore, the olefinic double bond is commonly introduced after the peptide backbone is assembled and

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• of intermediates have been proposed to be the reactive intermediates in many reactions such as aldol, Michael, Mannich, and α-functionalization (α-chlorination, α-amination, α-fluorination) reactions. Proline-type organocatalysts are considered priviliged, because their corresponding enamines exist

• mainly in the s-trans conformation, that factor is crucial since complete prediction of the stereochemical outcome of the reaction is possible. Generally, the enamines formed can interact with the substrates in two ways, via electronic or steric interactions (Scheme 2). The electronic interaction

• organocatalysts. Review Primary amine-thioureas as organocatalysts promoting asymmetric transformations that lead to a six-membered ring As discussed earlier, except from the activation of the substrates with the formation of the corresponding enamines or iminium ions, the synthesis of enantiopure products can be

Photoinduced 1,2,3,4-tetrahydropyridine ring conversions

• Baiba Turovska,
• Henning Lund,
• Viesturs Lūsis,
• Anna Lielpētere,
• Edvards Liepiņš,
• Sergejs Beljakovs,
• Inguna Goba and
• Jānis Stradiņš

Beilstein J. Org. Chem. 2015, 11, 2166–2170, doi:10.3762/bjoc.11.234

• –carbon double bond in enamines to give the corresponding epoxides, however, in most cases they have not been isolated [36]. The hydroperoxide 2 reacts in the same way. Fission of the epoxide ring may be induced by the base itself producing 3. Attack of a second molecule of hydroperoxide 2 on the imine

An intramolecular C–N cross-coupling of β-enaminones: a simple and efficient way to precursors of some alkaloids of Galipea officinalis

• Hana Doušová,
• Radim Horák,
• Zdeňka Růžičková and
• Petr Šimůnek

Beilstein J. Org. Chem. 2015, 11, 884–892, doi:10.3762/bjoc.11.99

• ) indicates the presence of an intramolecular hydrogen bond N–H···O. The enaminones 3 therefore possess Z configuration on the C=C bond. The intramolecular C–N cross-coupling β-Enaminones and related polarized ethylenes (generally enamines substituted by EWG on β-carbon atom) belong among the rather neglected

• be considered vinylogous amides. Hence, their nucleophilicity is lowered and enaminones can be more challenging substrates for C–N cross-coupling compared to ordinary enamines. We used 3a as the model substrate for the optimization study. The reaction conditions were surveyed from the following

Hydrogenation of unactivated enamines to tertiary amines: rhodium complexes of fluorinated phosphines give marked improvements in catalytic activity

• Sergey Tin,
• Tamara Fanjul and
• Matthew L. Clarke

Beilstein J. Org. Chem. 2015, 11, 622–627, doi:10.3762/bjoc.11.70

• tetrasubstituted enamines. The use of the sustainable and environmentally benign solvent (R)-limonene for the reaction is also reported with the amine isolated by acid extraction. Keywords: alkenes; homogeneous catalysis; hydrogenation; renewable solvents; tertiary amines; Introduction A potentially very direct

• method to produce tertiary amines is by the hydrogenation of enamines. While the hydrogenations of enamides, bearing coordinating acyl substituents is probably the most developed and studied of all hydrogenation processes, studies on the hydrogenation of unactivated enamines are scarce and several

• appeared for enamines that are activated by a chelating group, or can potentially isomerise to an NH imine during catalysis [4][5]. A few papers have appeared with good enantioselectivity for some quite specific enamines, but despite the importance of these contributions, catalyst loadings around 1 mol

Cross-dehydrogenative coupling for the intermolecular C–O bond formation

• Igor B. Krylov,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2015, 11, 92–146, doi:10.3762/bjoc.11.13

(CF₃CO)₂O/CF₃SO₃H-mediated synthesis of 1,3-diketones from carboxylic acids and aromatic ketones

• JungKeun Kim,
• Elvira Shokova,
• Victor Tafeenko and
• Vladimir Kovalev

Beilstein J. Org. Chem. 2014, 10, 2270–2278, doi:10.3762/bjoc.10.236

• condensation, which comprises the C-acylation of the α-position of ketones in the form of their metal enolates, enamines or silyl ethers, with or without a catalyst. To appear as an acylating agent one of the following compounds could be required: acyl halides and acid esters, including formates and oxalates

A new charge-tagged proline-based organocatalyst for mechanistic studies using electrospray mass spectrometry

• J. Alexander Willms,
• Rita Beel,
• Martin L. Schmidt,
• Christian Mundt and
• Marianne Engeser

Beilstein J. Org. Chem. 2014, 10, 2027–2037, doi:10.3762/bjoc.10.211

• 415.20 (R = Ph) and 367.20 (R = Et), respectively, is not a proof for the presence of reactive enamines [IIa]+/[IIb]+ since the isomeric zwitterionic iminiums [II’a]+/[II’b]+ and oxazolidinones [II’’a]+/[II’’b]+ (Scheme 4) have the same elemental composition. Using one of the most important mass