- B(C6F5)3-catalyzed tandem protonation/deuteration and reduction of: In situ -formed enamines
-
A highly efficient B(C6F5)3-catalyzed tandem protonation/deuteration and reduction of in situ-formed enamines in the presence of water and pinacolborane was developed. Regioselective β-deuteration of tertiary amines was achieved with high chemo- and regioselectivity. D2O was used as a readily available and cheap source of deuterium. Mechanistic studies indicated that B(C6F5)3 could activate water to promote the protonation and reduction of enamines. This journal is
- Wu, Rongpei,Gao, Ke
-
supporting information
p. 4032 - 4036
(2021/05/19)
-
- Revisiting the role of acids and hydrogen bond acceptors in enamine formation
-
A systematic investigation into the effects of acids and hydrogen bond acceptors on the reaction rates and equilibria of enamine formation is reported. Acids can accelerate the reaction but do not change the reaction equilibria. In comparison, hydrogen bond acceptors facilitate the enamine formation via their strong hydrogen bonding interaction with the water generated in the reaction.
- Hammond, Gerald B.,Lu, Zhichao,Xu, Bo
-
supporting information
p. 6849 - 6852
(2020/10/02)
-
- Selective N1/N4 1,4-Cycloaddition of 1,2,4,5-Tetrazines Enabled by Solvent Hydrogen Bonding
-
An unprecedented 1,4-cycloaddition (vs 3,6-cycloaddition) of 1,2,4,5-tetrazines is described with preformed or in situ generated aryl-conjugated enamines promoted by the solvent hydrogen bonding of hexafluoroisopropanol (HFIP) that is conducted under mild reaction conditions (0.1 M HFIP, 25 °C, 12 h). The reaction constitutes a formal [4 + 2] cycloaddition across the two nitrogen atoms (N1/N4) of the 1,2,4,5-tetrazine followed by a formal retro [4 + 2] cycloaddition loss of a nitrile and aromatization to generate a 1,2,4-triazine derivative. The factors that impact the remarkable change in the reaction mode, optimization of reaction parameters, the scope and simplification of its implementation through in situ enamine generation from aldehydes and ketones, the reaction scope for 3,6-bis(thiomethyl)-1,2,4,5-tetrazine, a survey of participating 1,2,4,5-tetrazines, and key mechanistic insights into this reaction are detailed. Given its simplicity and breath, the study establishes a novel method for the simple and efficient one-step synthesis of 1,2,4-triazines under mild conditions from readily accessible starting materials. Whereas alternative protic solvents (e.g., MeOH vs HFIP) provide products of the conventional 3,6-cycoladdition, the enhanced hydrogen bonding capability of HFIP uniquely results in promotion of the unprecedented formal 1,4-cycloaddition. As such, the studies represent an example of not just an enhancement in the rate or efficiency of a heterocyclic azadiene cycloaddition by hydrogen bonding catalysis but also the first to alter the mode (N1/N4 vs C3/C6) of cycloaddition.
- Zhu, Zixi,Glinkerman, Christopher M.,Boger, Dale L.
-
supporting information
p. 20778 - 20787
(2020/12/22)
-
- METHOD FOR PRODUCING FLUORINE-CONTAINING COMPOUND
-
PROBLEM TO BE SOLVED: To provide a method for producing a fluorine-containing compound by the addition reaction of an olefin to a perfluoroalkyl radical, which can be performed industrially in a more suitable manner. SOLUTION: A method for producing a flu
- -
-
Paragraph 0101-0104; 0110-0112
(2019/10/15)
-
- Direct Catalytic Reductive N-Alkylation of Amines with Carboxylic Acids: Chemoselective Enamine Formation and further Functionalizations
-
Direct reductive N-alkylation of secondary amines with carboxylic acids using molybdenum hexacarbonyl (5 mol %) as catalyst and diethoxymethylsilane as reducing agent generate enamines in a straightforward fashion in high yields. The formed enamines are without the need for isolation or purification further reacted with trimethylsilyl cyanide in the same reaction flask to yield α-amino nitriles in good yields. In the optimized reaction conditions equimolar amounts of carboxylic acid and amine are reacted under neat conditions, and a catalytic amount of trifluoroethanol (0.1 mol %) is added along with TMSCN for the cyanation step. The reductive N-alkylation reaction is demonstrated to be highly chemoselective, tolerating a multitude of different functional groups present in the starting carboxylic acids and amines. The reaction is scalable and the generated α-amino nitriles are converted to other useful compounds, e.g., α-amino acids or amino-tetrazoles. In addition, the intermediate enamines are further transformed into triazolines, sulfonylformamidines, pyrimidinediones, and TMS-propargylamines, respectively, in high yields under mild reaction conditions. Benzoic acids react with secondary amines under similar conditions to give tertiary amines in high yields, and using this methodology, the biologically active compound Piribedil was isolated in 80% yield in a direct one-pot reaction setup.
- Trillo, Paz,Adolfsson, Hans
-
p. 7588 - 7595
(2019/08/20)
-
- One-Pot Construction of 1-Phenylchromeno[3,4- b]pyrrol-4(3 H)-one: Application to Total Synthesis of Ningalin B and a Pyrrolocoumarin-Based Electrochromic Switch
-
An efficient construction of 1-phenylchromeno[3,4-b]pyrrol-4(3H)-one via coupling of 1-styrylpyrrolidine and 4-chloro-3-nitrocoumarin as a key step is reported. This reaction is further applied to the total synthesis of the natural product ningalin B in f
- Wu, Chun-Ku,Weng, Zhiqiang,Yang, Ding-Yah
-
supporting information
p. 5225 - 5228
(2019/07/08)
-
- Enamines as Surrogates of Alkene Carbanions for the Reductive Alkenylation of Secondary Amides: An Approach to Allylamines
-
A new strategy to construct allylamines through reductive alkenylation of secondary amides with enamines is reported. The method features the use of trifluoromethanesulfonic anhydride as an activation reagent of amides, and enamines as unconventional alkenylation reagents. In this manner, enamines serve as surrogates of alkene carbanions instead of the classical enolates equivalents. A possible mechanism involving a Hoffmann-like elimination of the amine-borane complex intermediate is proposed.
- Wang, Ai-E,Yu, Cun-Cun,Chen, Ting-Ting,Liu, Yong-Peng,Huang, Pei-Qiang
-
supporting information
p. 999 - 1002
(2018/02/23)
-
- Dynamic Covalent Chemistry of Aldehyde Enamines: BiIII- and ScIII-Catalysis of Amine–Enamine Exchange
-
The dynamic exchange of enamines from secondary amines and enolizable aldehydes has been demonstrated in organic solvents. The enamine exchange with amines was efficiently catalyzed by Bi(OTf)3 and Sc(OTf)3 (2 mol %) and the equilibria (60 mm) could be attained within hours at room temperature. The formed dynamic covalent systems displayed high stabilities in basic environment with 2 % by-product formation within one week after complete equilibration. This study expands the scope of dynamic C?N bonds from imine chemistry to enamines, enabling further dynamic methodologies in exploration of this important class of structures in systems chemistry.
- Zhang, Yang,Xie, Sheng,Yan, Mingdi,Ramstr?m, Olof
-
supporting information
p. 11908 - 11912
(2017/09/07)
-
- Transformation of Amides into Highly Functionalized Triazolines
-
Triazoles and triazolines are important classes of heterocyclic compounds known to exhibit biological activity. Significant focus has been given to the development of synthetic approaches for the preparation of triazoles, and they are today easily obtainable through a large variety of protocols. The number of synthetic procedures for the formation of triazolines, on the other hand, is limited and further research in this field is required. The protocol presented here gives access to a broad scope of 1,4,5-substituted 1,2,3-triazolines through a one-pot transformation of carboxamides. The two-step procedure involves a Mo(CO)6-catalyzed reduction of tertiary amides to afford the corresponding enamines, followed by in situ cycloaddition of organic azides to form triazolines. The amide reduction is chemoselective and allows for a wide variety of functional groups such as esters, ketones, aldehydes, and imines to be tolerated. Furthermore, a modification of this one-pot procedure gives access to the corresponding triazoles. The chemically stable amide functionality is demonstrated to be an efficient synthetic handle for the formation of highly substituted triazolines or triazoles.
- Slagbrand, Tove,Volkov, Alexey,Trillo, Paz,Tinnis, Fredrik,Adolfsson, Hans
-
p. 1771 - 1775
(2017/08/09)
-
- Mild reductive functionalization of amides into N-sulfonylformamidines
-
The development of a protocol for the reductive functionalization of amides into N-sulfonylformamidines is reported. The one-pot procedure is based on a mild catalytic reduction of tertiary amides into the corresponding enamines by the use of Mo(CO)6 (molybdenum hexacarbonyl) and TMDS (1,1,3,3-tetramethyldisiloxane). The formed enamines were allowed to react with sulfonyl azides to give the target compounds in moderate to good yields.
- Trillo, Paz,Slagbrand, Tove,Tinnis, Fredrik,Adolfsson, Hans
-
p. 484 - 487
(2018/08/17)
-
- An Efficient One–pot Procedure for the Direct Preparation of 4,5-Dihydroisoxazoles from Amides
-
A Mo(CO)6 (molybdenumhexacarbonyl) catalyzed reductive functionalization of amides to afford 5-amino substituted 4,5-dihydroisoxazoles is presented. The reduction of amides generates reactive enamines, which upon the addition of hydroximinoyl chlorides and base undergoes a 1,3-dipolar cycloaddition reaction that gives access to the desired heterocyclic compounds. The transformation of amides is highly chemoselective and tolerates functional groups such as nitro, nitriles, esters, and ketones. Furthermore, a versatile scope of 4,5-dihydroisoxazoles derived from a variety of hydroximinoyl chlorides and amides is demonstrated. (Figure presented.).
- Slagbrand, Tove,Kervefors, Gabriella,Tinnis, Fredrik,Adolfsson, Hans
-
p. 1990 - 1995
(2017/06/09)
-
- Facile preparation of pyrimidinediones and thioacrylamides: Via reductive functionalization of amides
-
The development of an efficient protocol for the reductive functionalization of amides into pyrimidinediones and amino-substituted thioacrylamides is presented. Enamines are generated in a highly chemoselective amide hydrosilylation reaction catalyzed by
- Trillo, Paz,Slagbrand, Tove,Tinnis, Fredrik,Adolfsson, Hans
-
p. 9159 - 9162
(2017/08/17)
-
- The pyrrole ring η2-hapticity bridged binuclear tricarbonyl Mo(0) and W(0) complexes: catalysis of regioselective hydroamination reactions and DFT calculations
-
Following the report of the ferrocene structure, metal complexes containing the heteroatom-substituted cyclopentadienyl (Cp) analogue, that is the η5 pyrrolyl ligand, have been reported. While the Cp ligand continues to be a favorite ligand in
- Jha, Vikesh Kumar,Mani, Ganesan,Davuluri, Yogeswara Rao,Anoop, Anakuthil
-
supporting information
p. 1840 - 1847
(2017/02/23)
-
- Anti-Selective Organocatalytic Michael Addition between Phenylacetaldehyde and Nitrostyrene
-
Using the reaction between phenylacetaldehyde and nitrostyrene catalyzed by pyrrolidine as a simple model, we have studied the diastereochemical outcome of the organocatalytic Michael reactions between benzylic aldehydes and nitrostyrenes. We found that t
- Donadío, Lucía Gandolfi,Galetti, Mariana A.,Giorgi, Gianluca,Rasparini, Marcello,Comin, Maria J.
-
p. 7952 - 7957
(2016/09/09)
-
- A facile one-pot metal-free synthesis of 1,4-disubstituted 1,2,3-triazoles
-
Abstract A 1,3-dipolar cycloaddition reaction of commercially available aldehydes with azides and secondary amines through a one-pot strategy has been developed. This method furnishes 1,4-disubstituted 1,2,3-triazoles in good to excellent yields and high
- Jia, Qianfa,Yang, Gongming,Chen, Lei,Du, Zhiyun,Wei, Jia,Zhong, Yanqiong,Wang, Jian
-
supporting information
p. 3435 - 3440
(2015/06/08)
-
- 1,3-Dipolar cycloaddition reactivities of perfluorinated aryl azides with enamines and strained dipolarophiles
-
The reactivities of enamines and predistorted (strained) dipolarophiles toward perfluoroaryl azides (PFAAs) were explored experimentally and computationally. Kinetic analyses indicate that PFAAs undergo (3 + 2) cycloadditions with enamines up to 4 orders of magnitude faster than phenyl azide reacts with these dipolarophiles. DFT calculations were used to identify the origin of this rate acceleration. Orbital interactions between the cycloaddends are larger due to the relatively low-lying LUMO of PFAAs. The triazolines resulting from PFAA-enamine cycloadditions rearrange to amidines at room temperature, while (3 + 2) cycloadditions of enamines and phenyl azide yield stable, isolable triazolines. The 1,3-dipolar cycloadditions of norbornene and DIBAC also show increased reactivity toward PFAAs over phenyl azide but are slower than enamine-azide cycloadditions.
- Xie, Sheng,Lopez, Steven A.,Ramstr?m, Olof,Yan, Mingdi,Houk
-
supporting information
p. 2958 - 2966
(2015/03/18)
-
- Phosphoric acid catalyzed desymmetrization of bicyclic bislactones bearing an all-carbon stereogenic center: Total syntheses of (-)-rhazinilam and (-)-leucomidine B
-
In the presence of a catalytic amount of an imidodiphosphoric acid, enantioselective desymmetrization of bicyclic bislactones by reaction with alcohols took place smoothly to afford enantiomerically enriched monoacids having an all-carbon stereogenic center. Concise catalytic enantioselective syntheses of both (-)-rhazinilam and (-)-leucomidine B were subsequently developed using (S)-methyl 4-ethyl-4-formylpimelate monoacid as a common starting material. Breaking symmetry: Achiral bislactones (1) undergo desymmetrization by reaction with alcohol in the presence of chiral imidodiphosphoric acids. The monoacids 2, having an all-carbon stereogenic center, were obtained in good to excellent yields and enantioselectivities. Concise total syntheses of (-)-rhazinilam and (-)-leucomidine B were subsequently developed using 2 as a common starting material.
- Gualtierotti, Jean-Baptiste,Pasche, Delphine,Wang, Qian,Zhu, Jieping
-
supporting information
p. 9926 - 9930,5
(2014/12/09)
-
- Efficient and selective synthesis of e-vinylamines via tungsten(0)-catalyzed hydroamination of terminal alkynes
-
The hydroamination of terminal alkynes (RC≡CH=phenylacetylene, 4-methylphenylacetylene, 4-fluorophenylacetylene, 1-hexyne, methyl 2-propynyl ether, prop-2-yn-1-ol) with secondary amines (piperidine, pyrrolidine, morpholine, piperazine, methylpiperazine, 4
- Kocicka, Paulina,Czelusniak, Izabela,Szymaska-Buzar, Teresa
-
supporting information
p. 3319 - 3324
(2015/01/09)
-
- Mechanistic Studies on the Catalytic Oxidative Amination of Alkenes by Rhodium(I) Complexes with Hemilabile Phosphines
-
Cationic rhodium(I) complexes with P,O-functionalised arylphosphine ligands are efficient catalysts for the regioselective anti-Markovnikov oxidative amination of styrene with piperidine. The mechanism of the catalytic reaction has been investigated by spectroscopic means under stoichiometric and catalytic conditions. In the presence of piperidine, the catalyst precursor [Rh{κ2-P,O-Ph2P(CH2)3OEt}2]+ (5) gave the piperidine complex [Rh{κ1-P-Ph2P(CH2)3OEt}2(HNC5H10)2]+ (8) that was transformed into the neutral amido-piperidine species [Rh{κ1-P-Ph2P(CH2)3OEt}2(NC5H10)(HNC5H10)] (9) under thermal conditions. NMR studies performed in the presence of styrene under catalytic conditions showed that 9 is a key species in the catalytic oxidative amination of styrene. Related cyclooctadiene-containing catalyst precursors [Rh(cod){κ1-P-Ph2P(CH2)3OEt}n]+ (n=1, 2) also gave 9 under the same conditions. The proposed catalytic cycle has been established by a series of DFT calculations including the transition states of the key steps that have been identified and characterised. These studies have shown that, after elimination of the enamine, regeneration of catalytic active species takes place by direct transfer of the proton of a piperidine ligand to the alkyl group resulting from the insertion of styrene into the Rh-H bond and formation of ethylbenzene. Against the expectations, the formation of a dihydride intermediate by NH oxidative addition is a highly energy-demanding process. Catalyst 5 has also been applied for the oxidative amination of substituted vinylarenes with several secondary cyclic and acyclic amines.
- Jimenez, M. Victoria,Bartolome, M. Isabel,Perez-Torrente, Jesus J.,Gomez, Daniel,Modrego, F. Javier,Oro, Luis A.
-
p. 263 - 276
(2013/03/14)
-
- Inverse electron demand hetero-Diels-Alder reaction in preparing 1,4-benzodioxin from o-quinone and enamine
-
A process for synthesizing 1,4-benzodioxin, through oxidation of a phenol to an o-quinone followed by treatment with an enamine, has been developed. Adduct stereochemistry is found to be retained via this one-pot reaction. The method uses hypervalent iodine reagent under mild conditions and is compatible with a wide scope of phenols and enamines.
- Zhang, Jinsong,Taylor, Chris,Bowman, Erich,Savage-Low, Leo,Lodewyk, Michael W.,Hanne, Larry,Wu, Guang
-
supporting information
p. 6298 - 6302
(2013/11/06)
-
- Imidazolidinone-derived enamines: Nucleophiles with low reactivity
-
Extraordinarily weak nucleophiles: Enamines derived from imidazolidinones are 103-105 times less reactive than those derived from the Hayashi-Jorgensen catalyst. This finding explains the lower activity of MacMillan catalysts for enamine-activated reactions. Copyright
- Lakhdar, Sami,Maji, Biplab,Mayr, Herbert
-
supporting information; experimental part
p. 5739 - 5742
(2012/08/14)
-
- Synthesis of 6 H-dibenzo[ b, d ]pyran-6-ones using the inverse electron demand Diels-Alder reaction
-
A set of coumarin-fused electron-deficient 1,3-dienes was synthesized, which differ in the nature of the electron-withdrawing group (EWG) at the terminus of the diene unit and (when EWG = CO2Me) the nature and position of substituents. These dienes reacted with the enamine derived from cyclopentanone and pyrrolidine to afford the corresponding cyclopenteno-fused 6H-dibenzo[b,d]pyran-6-ones, most likely via a domino inverse electron demand Diels-Alder (IEDDA)/elimination/transfer hydrogenation sequence. The parent diene (EWG = CO2Me, no substituents) was reacted with a range of electron-rich dienophiles (mostly enamines) to afford the corresponding 6H-dibenzo[b,d]pyran-6-ones or their nondehydrogenated precursors, which were aromatized upon treatment with a suitable oxidant. The enamines could either be synthesized prior to the reaction or generated in situ. The syntheses of 30 dibenzopyranones are reported.
- Pottie, Ian R.,Nandaluru, Penchal Reddy,Benoit, Wendy L.,Miller, David O.,Dawe, Louise N.,Bodwell, Graham J.
-
experimental part
p. 9015 - 9030
(2011/12/03)
-
- Hydro(trispyrazolyl)borato-ruthenium(II) diphosphinoamino complex-catalyzed addition of β-diketones to 1-alkynes and anti-markovnikov addition of secondary amines to aromatic 1-alkynes
-
The hydro(trispyrazolyl)borato-ruthenium(II) diphosphinoamino complex TpRu[4-CF3C6H4N(PPh2) 2](OTf) (I) [Tp=hydro(trispyrazolyl)borate] catalyzes the Markovnikov addition of β-diketones to unactivated 1-alkynes in good to excellent yields. The reaction proceeds under solvent-free and additive-free conditions and the catalyst loading can be reduced down to 0.4amol%. Complex I (1amol%) also catalyzes the addition of secondary amines to aromatic terminal alkynes, unusual anti-Markovnikov products are exclusively formed.
- Cheung, Hung Wai,So, Chau Ming,Pun, Kwok Hung,Zhou, Zhongyuan,Lau, Chak Po
-
experimental part
p. 411 - 425
(2011/04/17)
-
- Highly chemoselective formation of aldehyde enamines under very mild reaction conditions
-
Although ketone enamines are widely used in organic synthesis, aldehyde enamines are rarely employed due to the limitations of their preparation using known methods (need for acid or base, excess of amine, and/or elevated temperature). We have successfull
- Belanger, Guillaume,Dore, Michael,Menard, Frederic,Darsigny, Veronique
-
p. 7481 - 7484
(2007/10/03)
-
- Amination of aryl- and vinylacetylenic compounds catalyzed by rhodium(I) complexes
-
New rhodium-catalyzed amination reactions of arylacetylenes and cyclohexen-1-ylacetylene in the presence of strong bases with the use of carbon dioxide as an auxiliary are described. Secondary amines attack the terminal carbon atom of the triple bond followed by protonation of the adjacent carbon atom. Alternatively, the reaction can proceed further with the addition of the second alkyne molecule. The conditions for the selective synthesis of enamines (up to 87% yield) or α-substituted propynylamines (up to 86% yield) are reported.
- Costa,Chiusoli,Gaetti,Gabriele,Salerno
-
p. 936 - 940
(2007/10/03)
-
- Novel Two-Step Stereoselective Synthesis of (E)-Enamines and 1-Amino-1,3-dienes from Terminal Alkynes
-
(E)-Enamines and 1-amino-1,3-dienes have been prepared by reaction of secondary amines with alk-1-en-1-yl acetates resulting from the ruthenium-catalyzed anti-Markovnikov addition of acetic acid to terminal alkynes and enynes.
- Doucet, Henri,Bruneau, Christian,Dixneuf, Pierre H.
-
p. 807 - 808
(2007/10/03)
-
- Indium-mediated reactions of enamines in the presence of acid
-
The reaction of enamines with allyl bromide and metallic indium in THF to afford homoallylamines was greatly accelerated by the addition of one equivalent of a suitable carboxylic acid, such as acetic acid. It was established that the likely mechanism con
- Tussa, Laurent,Lebreton, Chrystele,Mosset, Paul
-
p. 1064 - 1070
(2007/10/03)
-
- Regioselective Synthesis of 6-Alkylated Lumazine Derivatives
-
The regiospecific synthesis of alkylated lumazines is achieved by hetero Diels-Alder addition between an oxadiazinone 2 and enamine.The reactions proceed stepwise by cycloaddition, decarboxylation and deamination to produce the 6-alkylated lumazines.
- Igarashi, Mamoru,Tada, Masaru
-
p. 807 - 810
(2007/10/02)
-
- A facile new synthesis of aldehyde enamines in high yield and high purity
-
Aldehyde enamines were synthesized in excellent yield and purity by reacting an aldehyde with 2 equivalents of a secondary amine in cyclohexane in the presence of 1.5 equivalents of CaH2. Distilled yields ranged from 65%-92%.
- Fisher,Lee,Klettke
-
p. 1541 - 1546
(2007/10/02)
-
- Reaction of Thioaldehydes with Amines
-
The reaction of phosphonium ylides with elemental sulfur gave thioaldehydes, which changed to the corresponding thioamides in good yields when treated with amines.When thioaldehydes containing α-hydrogens were treated with secondary amines, the corresponding enamines or reduction products were obtained.
- Okuma, Kentaro,Komiya, Yasuo,Ohta, Hiroshi
-
p. 2402 - 2406
(2007/10/02)
-
- Phenanthroindolizidine and Related Alkaloids: Synthesis of Tylophorine, Septicine, and Deoxytylophorinine
-
Tylophorine (1) is synthesized in two ways.The first method begins with the synthesis of the amide-ester (7), which on reaction, successively, with triethyloxonium fluoroborate and sodium borohydride, gives the aminoester (8) selectively; hydrolysis and polyphosphoric acid-catalysed ring-closure of compound (9) gives the ketone (10) which yields tylophorine (1) on Clemmensen reduction.An alternative approach is by a biogenetically patterned sequence which involves condensation of (3,4-dimethoxybenzoyl)acetic acid (26) with 1-pyrroline (24) generated either in situ from putrescine by pea-seedling diamine oxidase or from ornithine by oxidation with N-bromosuccinimide; the product (16) condenses with 3,4-dimethoxyphenylacetaldehyde in benzene to give an enamine .This undergoes cyclisation and dehydration in methanol; sodium borohydride reduction then gives the alkaloid septicine (19) which, on oxidation with thallium(III) trifluoroacetate, yields tylophorine (1).Deoxytylophorinine (34) is made in an exactly analogous manner to the latter method for tylophorine.
- Cragg, John E.,Herbert, Richard B.,Jackson, Frederick B.,Moody, Christopher J.,Nicolson, Ian T.
-
p. 2477 - 2486
(2007/10/02)
-