- Enantioselective Construction of Sulfur-Containing Tetrasubstituted Stereocenters via Asymmetric Functionalizations of α-Sulfanyl Cyclic Ketones
-
Asymmetric functionalizations of α-sulfanyl cyclic ketones were realized via chiral phosphoric acid catalyzed enantioselective addition reactions with aldimines, azodicarboxylates and allenamides. A series of chiral organosulfur compounds possessing sulfur-containing tetrasubstituted stereocenters were accessed via these methods, with excellent regioselectivities and high stereoselectivities. (Figure presented.).
- Ye, Xueqian,Pan, Yongkai,Chen, Yunrong,Yang, Xiaoyu
-
supporting information
p. 3374 - 3379
(2020/07/16)
-
- The hydrophobically-tagged MDM2-p53 interaction inhibitor Nutlin-3a-HT is more potent against tumor cells than Nutlin-3a
-
We present the first application of hydrophobic tagging to a non-covalent inhibitor of protein-protein interactions. Nutlin-3a-HT, created by fusing the hydrophobic tag HyT13 to the MDM2-p53 interaction inhibitor Nutlin-3a, prevented cellular accumulation of MDM2 upon p53 reactivation, and had a stronger effect on cell viability and the induction of apoptosis than Nutlin-3a.
- Berg, Thorsten,Nietzold, Florian,Rubner, Stefan
-
supporting information
p. 14351 - 14354
(2019/12/02)
-
- Gold-Catalyzed Hydrophenoxylation of Propargylic Alcohols and Amines: Synthesis of Phenyl Enol Ethers
-
A practical method for the synthesis of phenyl enol ethers is reported. The combination of a gold(I) catalyst and potassium carbonate selectively mediates the addition of phenols to propargylic alcohols/amines in a chemo-, regio-, and stereoselective fash
- Laserna, Victor,Jeapes Rojas, Catherine,Sheppard, Tom D.
-
supporting information
p. 4443 - 4447
(2019/06/27)
-
- Two Distinct Ag(I)- And Au(I)-Catalyzed Olefinations between α-Diazo Esters and N-Boc-Derived Imines
-
Metal-catalyzed reactions between α-diazo esters and imines were well-known to yield aziridine derivatives exclusively. This work reports two new olefination reactions between N-Boc-derived (Boc = tert-Butyloxycarbonyl) imines and α-diazo esters with Ag(I) and Au(I) catalysts, respectively. Our mechanistic studies reveal that these new olefinations involve an initial attack of diazo esters on metal/imine complexes to form Mannich-addition intermediates, which subsequently afford α-aryl-β-aminoacrylates via a Roskamp reaction, or to form β-aryl-β-aminoacrylates via the formation of silver carbenes.
- Kardile, Rahul Dadabhau,Liu, Rai-Shung
-
supporting information
p. 6452 - 6456
(2019/09/06)
-
- Direct Catalytic Asymmetric Mannich-Type Reaction en Route to α-Hydroxy-β-amino Acid Derivatives
-
A direct catalytic Mannich-type reaction of α-oxygen-functionalized amides was achieved. The use of 7-azaindoline amide was crucial to facilitate direct enolization and subsequent stereoselective addition to imines in a cooperative catalytic system comprising a soft Lewis acid and Br?nsted base. The operationally simple room-temperature protocol furnished a syn-Mannich adduct with high stereoselectivity. Divergent functional group transformation of the amide moiety of the product allowed for expeditious access to enantioenriched syn-configured α-hydroxy-β-amino carboxylic acid derivatives, highlighting the synthetic utility of the present catalysis.
- Sun, Bo,Pluta, Roman,Kumagai, Naoya,Shibasaki, Masakatsu
-
supporting information
p. 526 - 529
(2018/02/10)
-
- Asymmetric Aminalization via Cation-Binding Catalysis
-
Asymmetric cation-binding catalysis, in principle, can generate “chiral” anionic nucleophiles, where the counter cations are coordinated within chiral environments. Nitrogen nucleophiles are intrinsically basic, therefore, its use as nucleophiles is often challenging and limiting the scope of the reaction. Particularly, a formation of configurationally labile aminal centers with alkyl substituents has been a formidable challenge due to the enamine/imine equilibrium of electrophilic substrates. Herein, we report enantioselective nucleophilic addition reactions of potassium phthalimides to Boc-protected alkyl- and aryl-substituted α-amido sulfones. In situ generated imines smoothly reacted with the nitrogen nucleophiles to corresponding aminals with good to excellent enantioselectivitiy under mild reaction conditions. In addition, transformation of aminal products gave biologically relevant pyrrolidinone-fused hexahydropyrimidine scaffold with excellent stereoselectivity and good yield.
- Park, Sang Yeon,Liu, Yidong,Oh, Joong Suk,Kweon, Yoo Kyung,Jeong, Yong Bok,Duan, Mengying,Tan, Yu,Lee, Ji-Woong,Yan, Hailong,Song, Choong Eui
-
supporting information
p. 1020 - 1025
(2017/12/15)
-
- ISOINDOLINONE INHIBITORS OF THE MDM2-P53 INTERACTION AND PROCESS FOR MAKING THEM
-
The invention relates to processes for preparing isoindolin-1-one derivatives, and in particular processes for preparing (2S,3S)-3-(4-chlorophenyl)-3-[(1R)-1-(4-chlorophenyl)-7-fluoro-5-[(1S)-1-hydroxy-1- (oxan-4-yl)propyl]-1-methoxy-3-oxo-2,3-dihydro-1H-
- -
-
Page/Page column 216
(2018/10/25)
-
- Enantioselective Additions of Stabilized Carbanions to Imines Generated from α-Amido Sulfones by Using Lipophilic Salts of Chiral Tris(1,2-diphenylethylenediamine) Cobalt(III) Trications as Hydrogen Bond Donor Catalysts
-
The enantiopure salt -[Co((S, S)-dpen) 3 ] 3+ 2Cl - BAr f - [BAr f = B(3,5-C 6 H 3 (CF 3) 2) 4 ] is an effective hydrogen bond donor catalyst (10 mol%, r.t., CH 2 Cl 2) for enantioselective additions of dialkyl malonates to Boc-derivatized aryl imines generated from sulfones [ArCH(SO 2 Ph)NHBoc] in the presence of K 2 CO 3 (ten examples, 91-97% isolated yields, 87-99% ee). The diastereomeric salt Λ-[Co((S, S)-dpen) 3 ] 3+ 2Cl - BAr f20 - [BAr f20 - = B(C 6 F 5) 4 - ] is similarly applied to additions of nitroalkanes (four examples, 89-93% isolated yields, 79-91% ee). Precautions to exclude air or moisture are unnecessary.
- Joshi, Hemant,Ghosh, Subrata K.,Gladysz, John A.
-
p. 3905 - 3915
(2017/08/29)
-
- Development of an Intermittent-Flow Enantioselective Aza-Henry Reaction Using an Arylnitromethane and Homogeneous Br?nsted Acid-Base Catalyst with Recycle
-
A stereoselective aza-Henry reaction between an arylnitromethane and Boc-protected aryl aldimine using a homogeneous Br?nsted acid-base catalyst was translated from batch format to an automated intermittent-flow process. This work demonstrates the advanta
- Tsukanov, Sergey V.,Johnson, Martin D.,May, Scott A.,Rosemeyer, Morgan,Watkins, Michael A.,Kolis, Stanley P.,Yates, Matthew H.,Johnston, Jeffrey N.
-
p. 215 - 226
(2016/03/04)
-
- Efficient synthesis of α-(N-Boc)aminoamides by addition of a carbamoylsilane to N-Boc-imines
-
N,N-Dimethylcarbamoyl(trimethyl)silane reacted with N-Boc-imines in anhydrous benzene under catalysts-free conditions to afford N-Boc-protected α-amino amides in good yields (72-89%). The electronic property and the steric hindrance of substituent on the N-Boc-imines affected the reaction.
- Guo, Qilin,Wen, Xueping,Chen, Jianxin
-
p. 8117 - 8122
(2016/11/19)
-
- Chiral ureas and thioureas supported on polystyrene for enantioselective aza-Henry reactions under solvent-free conditions
-
Novel bifunctional ureas and thioureas immobilized on sulfonylpolystyrene have been prepared as recoverable and reusable organocatalysts and have been used in the stereoselective aza-Henry reaction under solvent-free conditions. The activity and stereoselection of the catalysts are dependent on the length of the tether bridging the active site and the polymer, the catalyst derived from 1,6-hexane diamine being the best one. It has also been demonstrated that the supported catalysts are more effective than the homologous soluble catalysts.
- Pedrosa, Rafael,Andrés, José M.,ávila, Deisy P.,Ceballos, Miriam,Pindado, Rodrigo
-
supporting information
p. 2217 - 2225
(2015/04/22)
-
- Copper(I)-Catalyzed Asymmetric Pinacolboryl Addition of N-Boc-imines Using a Chiral Sulfoxide - Phosphine Ligand
-
Highly efficient and enantioselective copper(I)-catalyzed pinacolboryl addition of N-Boc-imines is reported. By using a single chiral sulfoxide-(dialkyl)phosphine (SOP) ligand, both enantiomeric isomers of α-amino boronic esters were obtained through an achiral counteranion switch.
- Wang, Ding,Cao, Peng,Wang, Bing,Jia, Tao,Lou, Yazhou,Wang, Min,Liao, Jian
-
supporting information
p. 2420 - 2423
(2015/05/27)
-
- Construction of chiral quaternary carbon center via catalytic asymmetric aza-Henry reaction with α-substituted nitroacetates
-
The catalytic enantioselective aza-Henry reaction of N-Boc aldimines 2 and 2-nitropropionic acid ethyl ester 3 in the mixed solvents of toluene-saturated brine (10:1) was catalyzed by cinchona quaternary ammonium salts to form a new quaternary carbon center. High yields (up to 90%), and excellent enantioselectivities (up to 99% ee) and diastereoselectivity ratio (up to 22:1) were successfully obtained with mild conditions. This journal is the Partner Organisations 2014.
- Li, Minghua,Ji, Nan,Lan, Ting,He, Wei,Liu, Rui
-
p. 20346 - 20350
(2014/06/09)
-
- Asymmetric synthesis of anti -β-amino-α-hydroxy esters via dynamic kinetic resolution of β-amino-α-keto esters
-
A method for the asymmetric synthesis of enantioenriched anti-α-hydroxy-β-amino acid derivatives by enantioconvergent reduction of the corresponding racemic α-keto esters is presented. The requisite α-keto esters are prepared via Mannich addition of ethyl
- Goodman, C. Guy,Do, Dung T.,Johnson, Jeffrey S.
-
supporting information
p. 2446 - 2449
(2013/06/27)
-
- Preparation of (-)-nutlin-3 using enantioselective organocatalysis at decagram scale
-
Chiral nonracemic cis-4,5-bis(aryl)imidazolines have emerged as a powerful platform for the development of cancer chemotherapeutics, stimulated by the Hoffmann-La Roche discovery that Nutlin-3 can restore apoptosis in cells with wild-type p53. The lack of efficient methods for the enantioselective synthesis of cis-imidazolines, however, has limited their more general use. Our disclosure of the first enantioselective synthesis of (-)-Nutlin-3 provided a basis to prepare larger amounts of this tool used widely in cancer biology. Key to the decagram-scale synthesis described here was the discovery of a novel bis(amidine) organocatalyst that provides high enantioselectivity at warmer reaction temperature (-20 C) and low catalyst loadings. Further refinements to the procedure led to the synthesis of (-)-Nutlin-3 in a 17 g batch and elimination of all but three chromatographic purifications.
- Davis, Tyler A.,Vilgelm, Anna E.,Richmond, Ann,Johnston, Jeffrey N.
-
p. 10605 - 10616
(2013/11/19)
-
- One-pot synthesis of α-amino acids from CO2 using a bismetal reagent with Si-B bond
-
In the presence of 1.1 equiv of PhMe2Si-Bpin, 5 equiv of CsF, and 20 mol % of TsOH·H2O, precursors of N-Boc-imines can be converted into the corresponding α-aryl or α-alkenyl glycine derivatives under gaseous CO2 in moderate-to-high yields with a single operation. α-Isobutenyl glycine thus obtained can be further derivatized into various types of α-amino acids including N-Boc-leucine, serine, and glycine derivatives in short steps.
- Mita, Tsuyoshi,Chen, Jianyang,Sugawara, Masumi,Sato, Yoshihiro
-
supporting information
p. 6202 - 6205
(2013/02/23)
-
- Catalytic asymmetric synthesis of trisubstituted aziridines
-
A method is described which provides for the direct asymmetric catalytic synthesis of trisubstituted aziridines from imines and diazo compounds. While unactivated imines were not reactive to α-diazo carbonyl compounds in which the diazo carbon was disubstituted, N-Boc imines react with both α-diazo esters and α-diazo-N-acyloxazolidinones to give trisubstituted aziridines with excellent diastereo- and enantioselectivities.
- Huang, Li,Wulff, William D.
-
supporting information; experimental part
p. 8892 - 8895
(2011/08/04)
-
- One-pot synthesis of α-amino acids from imines through CO2 incorporation: An alternative method for strecker synthesis
-
Itas a gas: A novel one-pot process for the synthesis of α-amino acids from imine equivalents using CO2 gas as a carbon source has been developed. This reaction was made possible by the reagent combination of TMSSnBu3 and CsF (see scheme). Three successive reactions (imine formation, stannylation, and carboxylation) proceeded in the same flask under these conditions to give products in up to 79 % yield. Boc=tert-butoxycarbonyl, TMS=trimethylsilyl.
- Mita, Tsuyoshi,Chen, Jianyang,Sugawara, Masumi,Sato, Yoshihiro
-
supporting information; experimental part
p. 1393 - 1396
(2011/04/22)
-
- Highly enantio- And diastereoselective mannich reactions of glycine schiff bases with in situ generated N-boc-imines catalyzed by a cinchona alkaloid thiourea
-
(Figure Presented) Highly ena(Figure Presented)ntlo- and dlastereoselectlve organocatalytlc Mannlch reactions of glycine Schiff bases with N-Boc-protected lmlnes are described. Imlnes were generated In situ from bench-stable a-amldo sulfones. Catalysis mediated by a cinchona alkaloid thiourea provided optically active α,βdlamlno acid derivatives with up to 99% ee and near-perfect dlastereoselection.
- Zhang, Halle,Syed, Salahuddin,Barbas, Carlos F.
-
supporting information; scheme or table
p. 708 - 711
(2010/04/02)
-
- A novel bis-thiourea organocatalyst for the asymmetric aza-Henry reaction
-
A novel bis-thiourea/2,2′-diaminobinaphthalene (BINAM)-based catalyst for the asymmetric aza-Henry reaction has been developed. This catalyst promotes the reaction of N-Boc imines with nitroalkanes to afford β-nitroamines with good yields and high enantioselectivities. This catalyst has the advantage that it can be prepared in a single step from commercially available materials. A model is proposed for the catalyst action where both components of the reaction are activated simultaneously by hydrogen bonding. Regardless of the mechanism, the success of the present catalyst demonstrates the potential of bis-thioureas as an interesting class of relatively unexplored catalysts.
- Rampalakos, Constantinos,Wulff, William D.
-
supporting information; experimental part
p. 1785 - 1790
(2009/08/07)
-
- Enantioselective aza-Henry reactions assisted by ZnII and N-methylephedrine
-
(Chemical Equation Presented) Hooray aza-Henry! A combination of zinc triflate, an amine base, and (-)-N-methylephedrine (NME), which can be easily recovered and reused, leads to high enantioselectivities in the aza-Henry reaction of N-Boc-protected aldimines and nitromethane (see scheme; Boc = tert-butyloxycarbonyl).
- Palomo, Claudio,Oiarbide, Mikel,Halder, Rajkumar,Laso, Antonio,Lopez, Rosa
-
p. 117 - 120
(2007/10/03)
-