- Modified guanidines as chiral superbases: Application to asymmetric Michael reaction of glycine imine with acrylate or its related compounds
-
Modified guanidines efficiently catalysed the asymmetric Michael reaction of a prochiral glycine derivative with acrylate or its related compounds either in solution or without a solvent under simple and mild conditions (> 95% ee).
- Ishikawa,Araki,Kumamoto,Seki,Fukuda,Isobe
-
-
Read Online
- Application scope and limitations of TADDOL-derived chiral ammonium salt phase-transfer catalysts
-
We have recently introduced a new class of chiral ammonium salt catalysts derived from easily available TADDOLs. To get a full picture of the scope of application and limitations of our catalysts we tested them in a variety of different important transformations. We found that, although these compounds have recently shown their good potential in the asymmetric α-alkylation of glycine Schiff bases, they clearly failed when we attempted to control more reactive nucleophiles like β-keto esters. On the other hand, when using them to catalyse the addition of glycine Schiff bases to different Michael acceptors it was found necessary to carefully optimize the reaction conditions for every single substrate class, as seemingly small structural changes sometimes required the use of totally different reaction conditions. Under carefully optimized conditions enantiomeric ratios up to 91:9 could be achieved in the addition of glycine Schiff bases to acrylates, whereas acrylamides and methyl vinyl ketone gave slightly lower selectivities (up to e.r. 77:23 in these cases). Thus, together with additional studies towards the syntheses of these catalysts we have now a very detailed understanding about the scope and limitations of the synthesis sequence to access our PTCs and about the application scope of these catalysts in asymmetric transformations.
- Gururaja, Guddeangadi N.,Herchl, Richard,Pichler, Antonia,Gratzer, Katharina,Waser, Mario
-
-
Read Online
- Enantioselective solution- and solid-phase synthesis of glutamic acid derivatives via Michael addition reactions
-
The enantioselective conjugate addition of Schiif base ester derivatives to Michael acceptors either in solution (56-89% e.e.) or on solid-phase (34-82% e.e.) gave optically active unnatural α-amino acid derivatives. The reaction was conducted in the pres
- O'Donnell, Martin J.,Delgado, Francisca,Dominguez, Esteban,De Blas, Jesus,Scott, William L.
-
-
Read Online
- Chiral calcium complexes as bronsted base catalysts for asymmetric addition of α-amino acid derivatives to α,β-unsaturated carbonyl compounds
-
A novel catalyst system based on complexes of calcium which promote the catalytic asymmetric 1,4-addition reactions and [3+2] cycloaddition reactions of α-amino acid derivatives with α,β-unsaturated carbonyl compounds have been developed. The reactions proceeded smoothly in the presence of 5-10 mol % of the chiral calcium catalyst to afford the desired adducts in high yields with high diastereo- and enantioselectivities. A wide range of α,β-unsaturated esters and amides were applicable, and other glycine and even dl-alanine derivatives reacted with several α,β-unsaturated carbonyl compounds to afford the corresponding substituted pyrrolodine derivatives in high yields with excellent diastereo- and enantioselectivities. In the reactions with dl-alanine derivatives, quaternary asymmetric carbons were constructed efficiently. Copyright
- Saito, Susumu,Tsubogo, Tetsu,Kobayashi, Shu
-
-
Read Online
- Expanding the Toolbox of Heterogeneous Asymmetric Organocatalysts: Bifunctional Cyclopropenimine Superbases for Enantioselective Catalysis in Batch and Continuous Flow
-
A strategy for the immobilization of chiral 2,3-bisaminocyclopropenium salt (pre-catalyst) onto polystyrene and silica supports is presented together with a suitable procedure for the conversion into the corresponding cyclopropenimine superbase catalysts.
- Leonardi, Costanza,Brandolese, Arianna,Preti, Lorenzo,Bortolini, Olga,Polo, Eleonora,Dambruoso, Paolo,Ragno, Daniele,Di Carmine, Graziano,Massi, Alessandro
-
-
Read Online
- Highly Enantioselective Conjugate Addition of Glycine Imines to Activated Alkenes Catalyzed by Amino-Acid-Derived Chiral Phosphonium Salts
-
Chiral quaternary phosphonium salts derived from amino acids were readily prepared and employed as phase-transfer catalysts for the highly enantioselective conjugate addition of glycine imines to various activated alkenes, including chalcones, acrylates, and vinyl ketones.
- Wen, Shan,Li, Xing,Yao, Weijun,Waheed, Abdul,Ullah, Nisar,Lu, Yixin
-
supporting information
p. 4298 - 4301
(2016/09/13)
-
- Structure-activity relationship studies of cyclopropenimines as enantioselective Bronsted base catalysts
-
We recently demonstrated that chiral cyclopropenimines are viable Bronsted base catalysts in enantioselective Michael and Mannich reactions. Herein, we describe a series of structure-activity relationship studies that provide an enhanced understanding of the effectiveness of certain cyclopropenimines as enantioselective Bronsted base catalysts. These studies underscore the crucial importance of dicyclohexylamino substituents in mediating both reaction rate and enantioselectivity. In addition, an unusual catalyst CH...O interaction, which provides both ground state and transition state organization, is discussed. Cyclopropenimine stability studies have led to the identification of new catalysts with greatly improved stability. Finally, additional demonstrations of substrate scope and current limitations are provided herein.
- Bandar, Jeffrey S.,Barthelme, Alexandre,Mazori, Alon Y.,Lambert, Tristan H.
-
p. 1537 - 1547
(2015/02/05)
-
- Design of chiral urea-quaternary ammonium salt hybrid catalysts for asymmetric reactions of glycine Schiff bases
-
Bifunctional chiral urea-containing quaternary ammonium salts can be straightforwardly synthesised in good yield and with high structural diversity via a scalable and operationally simple highly telescoped sequence starting from trans-1,2-cyclohexanediamine. These novel hybrid catalysts were systematically investigated for their potential to control glycine Schiff bases in asymmetric addition reactions. It was found that Michael addition reactions and the herein presented aldol-initiated cascade reaction can be carried out to provide enantiomeric ratios up to 95:5 and good yields under mild conditions at room temperature.
- Tiffner, Maximilian,Novacek, Johanna,Busillo, Alfonso,Gratzer, Katharina,Massa, Antonio,Waser, Mario
-
p. 78941 - 78949
(2015/10/05)
-
- Chiral octahedral complexes of cobalt(III) as "organic catalysts in disguise" for the asymmetric addition of a glycine schiff base ester to activated olefins
-
Stereochemically inert and positively charged chiral complexes of cobalt(III) prepared from Schiff bases derived from chiral diamines and salicylaldehydes were shown to be efficient catalysts of the benchmark asymmetric phase-transfer Michael addition of nine activated olefins to O'Donnell's substrate. The reaction products had enantiomeric purities of up to 96%. DFT calculations were invoked to rationalize the stereochemistry of the addition.
- Maleev, Victor I.,North, Michael,Larionov, Vladimir A.,Fedyanin, Ivan V.,Savel'Yeva, Tatyana F.,Moscalenko, Margarita A.,Smolyakov, Alexander F.,Belokon, Yuri N.
-
supporting information
p. 1803 - 1810
(2014/06/09)
-
- Transition state analysis of enantioselective br?nsted base catalysis by chiral cyclopropenimines
-
Experimental 13C kinetic isotope effects have been used to interrogate the rate-limiting step of the Michael addition of glycinate imines to benzyl acrylate catalyzed by a chiral 2,3-bis(dicyclohexylamino) cyclopropenimine catalyst. The reaction is found to proceed via rate-limiting carbon-carbon bond formation. The origins of enantioselectivity and a key noncovalent CH?O interaction responsible for transition state organization are identified on the basis of density functional theory calculations and probed using experimental labeling studies. The resulting high-resolution experimental picture of the enantioselectivity-determining transition state is expected to guide new catalyst design and reaction development.
- Bandar, Jeffrey S.,Sauer, Gregory S.,Wulff, William D.,Lambert, Tristan H.,Vetticatt, Mathew J.
-
supporting information
p. 10700 - 10707
(2014/08/18)
-
- CYCLOPROPENIMINE CATALYST COMPOSITIONS AND PROCESSES
-
The present invention provides, inter alia, a cyclopropenimine Br?nsted base catalyst and a cyclopropenimine scaffold for use as a Br?nsted base catalyst. This cyclopropenimine has the structure (100). Methods for making such a cyclopropenimine are also provided. Further provided are processes for carrying out an organic synthetic reaction and processes for catalyzing a proton transfer reaction enantioselectively using such a cyclopropenimine Br?nsted base catalyst.
- -
-
Paragraph 0167
(2013/05/09)
-
- Synthesis of glutamic acid and highly functionalized pyrrolidine derivatives by utilizing tunable calcium catalysts for chemoselective asymmetric 1,4-addition and [3+2] cycloaddition reactions
-
A current trend in organic chemistry is the development of highly efficient, environmentally friendly and inexpensive catalysts for asymmetric transformations. Alkaline earth metals, due to their specific chemical properties and abundance in nature, provide promising and challenging catalysts in organic synthesis. This article describes the utilization of alkaline earth metals in the development of an effective catalytic system based on calcium salts in combination with Box-type ligands. We disclose asymmetric 1,4-addition and [3+2] cycloaddition reactions using simple catalytic systems consisting of calcium chloride dihydrate, chiral ligands and tetramethylguanidine. Various Box ligands were synthesized and the most effective proved to be that bearing an indane chiral backbone and a cyano group. Depending on the structure of both glycine Schiff bases and α,β-unsaturated compounds, the corresponding Michael adducts or pyrrolidine derivatives were obtained in moderate to high yields with high enantioselectivities. Modification of the catalytic system by using more Lewis acidic calcium salts such as calcium triflate and neutral Pybox-type ligands allows a tuning of the chemoselectivity and leads to suppression of the [3+2] cycloadition reactions. Various β-substituted acrylates provided 1,4-addition adducts exclusively in high yields with moderate to high diastereo- and enantioselectivities. This methodology has broadened a synthetic route to β-branched glutamic acid derivatives and established calcium salts as useful and attractive catalysts for asymmetric catalysis. Copyright
- Hut'Ka, Martin,Tsubogo, Tetsu,Kobayashi, Shu
-
supporting information
p. 1561 - 1569
(2013/06/27)
-
- Chiral octahedral complexes of CoIII as a family of asymmetric catalysts operating under phase transfer conditions
-
Stereochemically inert and positively charged chiral complexes of Co III prepared from Schiff bases derived from chiral diamines and salicylaldehydes were shown to be efficient catalysts of the asymmetric phase transfer benchmark reaction of alkylation of O'Donnell's substrate with alkyl halides. The enantiomeric purities of the reaction products were up to 92%.
- Belokon, Yuri N.,Maleev, Victor I.,North, Michael,Larionov, Vladimir A.,Savel'Yeva, Tat'Yana F.,Nijland, Aike,Nelyubina, Yuliya V.
-
p. 1951 - 1955
(2013/09/24)
-
- Enantioselective Bronsted base catalysis with chiral cyclopropenimines
-
Cyclopropenimines are shown to be a highly effective new class of enantioselective Bronsted base catalysts. A chiral 2,3-bis(dialkylamino) cyclopropenimine catalyzes the rapid Michael reaction of a glycine imine substrate with high levels of enantioselectivity. A preparative scale reaction to deliver 25 g of product is demonstrated, and a trivial large scale synthesis of the optimal catalyst is shown. In addition, the basicity of a 2,3-bis(dialkylamino)cyclopropenimine is measured for the first time and shown to be approximately equivalent to the P1-tBu phosphazene base. An X-ray crystal structure of the protonated catalyst is shown along with a proposed mechanistic and stereochemical rationale.
- Bandar, Jeffrey S.,Lambert, Tristan H.
-
supporting information; experimental part
p. 5552 - 5555
(2012/05/20)
-
- Rate enhancement of phase transfer catalyzed conjugate additions by CsCI
-
A rate enhancement of phase transfer catalyzed conjugate additions was accomplished using a catalytic amount of CsCl. The utility of this method was demonstrated in the asymmetric synthesis of glutamic acid derivatives by using a chiral phase transfer cat
- Kano, Taichi,Kumano, Takeshi,Maruoka, Keiji
-
scheme or table
p. 2023 - 2025
(2009/09/08)
-
- Co-catalyst enhancement of enantioselective PTC Michael additions involving glycine imines
-
In this Letter we demonstrate that the use of 2,4,6-trimethylphenol (mesitol) as a co-catalyst facilitates highly enantioselective addition of benzophenone glycine imine tert-butyl ester to a range of Michael acceptors.
- Lygo, Barry,Beynon, Christopher,Lumley, Christopher,McLeod, Michael C.,Wade, Charles E.
-
experimental part
p. 3363 - 3365
(2009/08/17)
-
- Development of catalytic asymmetric 1,4-addition and [3 + 2] cycloaddition reactions using chiral calcium complexes
-
Catalytic asymmetric 1,4-addition and [3 + 2] cycloaddition reactions using chiral calcium species prepared from calcium isopropoxide and chiral bisoxazoline ligands have been developed. Glycine Schiff bases reacted with acrylic esters to afford 1,4-addition products, glutamic acid derivatives, in high yields with high enantioselectivities. During the investigation of the 1,4-addition reactions, we unexpectedly found that a [3 + 2] cycloaddition occurred in the reactions with crotonate derivatives, affording substituted pyrrolidine derivatives in high yields with high enantioselectivities. On the basis of this finding, we investigated asymmetric [3 + 2] cycloadditions, and it was revealed that several kinds of optically active substituted pyrrolidine derivatives containing contiguous stereogenic tertiary and quaternary carbon centers were obtained with high diastereo- and enantioselectivities. In addition, optically active pyrrolidine cores of hepatitis C virus RNA-dependent polymerase inhibitors and potential effective antiviral agents have been synthesized using this [3 + 2] cycloaddition reaction. NMR spectroscopic analysis and observation of nonamplification of enantioselectivity in nonlinear effect experiments suggested that a monomeric calcium species with an anionic ligand was formed as an active catalyst. A stepwise mechanism of the [3 + 2] cycloaddition, consisting of 1,4-addition and successive intramolecular Mannich-type reaction was suggested. Furthermore, modification of the Schiff base structure resulted in a modification of the reaction course from a [3 + 2] cycloaddition to a 1,4-addition, affording 3-substituted glutamic acid derivatives with high diasterero- and enantioselectivities.
- Tsubogo, Tetsu,Saito, Susumu,Seki, Kazutaka,Yamashita, Yasuhiro,Kobayashi, Shu
-
supporting information; scheme or table
p. 13321 - 13332
(2009/02/06)
-
- Catalytic asymmetric Michael reaction under phase-transfer catalysis: Construction of chiral tetrasubstituted carbon and its application to the synthesis of a chiral pyrrolidone
-
A catalytic asymmetric Michael reaction using Schiff bases promoted by D2-symmetrical ammonium salts as phase-transfer catalysts is described. The reaction of glycine Schiff base (1a) gave the Michael adduct with up to 91% ee and tetrasubstituted carbons was also constructed using alanine Schiff base (3a) with up to 63% ee.
- Arai, Shigeru,Takahashi, Fumie,Tsuji, Riichiro,Nishida, Atsushi
-
p. 495 - 501
(2007/10/03)
-
- Catalytic asymmetric phase-transfer reactions using tartrate-derived asymmetric two-center organocatalysts
-
A new highly versatile asymmetric two-center catalyst, tartrate-derived diammonium salt (TaDiAS), was designed and a catalyst library containing more than 70 new two-center catalysts was constructed. A variety of (S,S)- and (R,R)-TaDiAS were easily synthesized from diethyl L- and D-tartrate, respectively, using common and inexpensive reagents under operationally simple reaction conditions. TaDiAS was used in phase-transfer alkylations and Michael additions to afford various optically active α-amino acid equivalents in up to 93% yield. Moreover, dramatic counter anion effects were observed in phase-transfer catalysis (PTC) for the first time, making it possible to further improve reactivity and selectivity. These findings validate the usefulness of three-dimensional fine-tuning of the catalyst (acetal, Ar, and counter anion) for optimization. Recovery and reuse of the catalyst was also possible using simple procedures. The present asymmetric PTC was successfully applied to enantioselective syntheses of serine protease inhibitor aeruginosin 298-A and its analogues.
- Ohshima, Takashi,Shibuguchi, Tomoyuki,Fukuta, Yuhei,Shibasaki, Masakatsu
-
p. 7743 - 7754
(2007/10/03)
-
- Synthesis of (ε-13C-,ε-15N)-enriched L-lysine - Establishing schemes for the preparation of all possible 13C and 15N isotopomers of L-lysine, L-ornithine, and L-proline
-
In this paper we describe a simple synthetic strategy that, with the right rational adaptation, gives direct access to any 13C/15N isotopomer of L-glutamate, L-ornithine, L-proline, L-lysine, and L-α, amino adipic acid. This strategy also allows access to nonproteinogenic amino acids like L-citrulline in high yields and optical purity. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.
- Siebum, Arjan H. G.,Tsang, Robert K. F.,Van Der Steen, Rob,Raap, Jan,Lugtenburg, Johan
-
p. 4391 - 4396
(2007/10/03)
-
- Development of new asymmetric two-center catalysts in phase-transfer reactions
-
A new asymmetric two-center phase-transfer catalyst was designed and a catalyst library containing more than 40 new two-center catalysts was constructed. The catalysts were applied in phase-transfer alkylations and Michael additions to afford the correspo
- Shibuguchi, Tomoyuki,Fukuta, Yuhei,Akachi, Yoko,Sekine, Akihiro,Ohshima, Takashi,Shibasaki, Masakatsu
-
p. 9539 - 9543
(2007/10/03)
-
- Highly enantioselective synthesis of cyclic and functionalized α-amino acids by means of a chiral phase transfer catalyst
-
The chiral quaternary ammonium salt 1 serves as phase transfer catalyst for the enantioselective conversion of the glycine derivative 2 to a variety of cyclic and acyclic chiral α amino acids with enantioselectivities as high as 200:1 in alkylation and Michael addition reactions.
- Corey,Noe, Mark C,Xu, Feng
-
p. 5347 - 5350
(2007/10/03)
-