- Chiral-at-Ruthenium Catalysts with Mixed Normal and Abnormal N-Heterocyclic Carbene Ligands
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We recently reported a new class of chiral ruthenium catalysts in which two achiral bidentate N-(2-pyridyl)-substituted N-heterocyclic carbene ligands in addition to two labile acetonitriles are coordinated to a central ruthenium and generate a stereogenic metal center which is responsible for the overall chirality (Zheng et al. J. Am. Chem. Soc. 2017, 139, 4322). Here we now report our discovery of related chiral-at-ruthenium catalysts in which normal and abnormal N-heterocyclic carbene (NHC) ligands are present at the same time. The synthesis of racemic complexes, their resolution into individual enantiomers by a chiral auxiliary approach, and a catalytic application are reported. The mixed normal/abnormal NHC complexes display significantly increased turnover numbers and turnover frequencies for a nitrene-mediated enantioselective C(sp3)-H amination.
- Winterling, Erik,Ivlev, Sergei,Meggers, Eric
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supporting information
p. 1148 - 1155
(2021/05/06)
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- Preparation method of chiral optical pure p-toluene sulfamide
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The invention discloses a preparation method of chiral optical pure p-toluene sulfamide. The preparation method comprises the following steps: performing acylating chlorination by using sodium p-tolylsulfinate and an acylating chlorination reagent to obta
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- Preparation method of chiral optical pure p-toluenesulfinamide
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The invention discloses a preparation method of a chiral optical pure p-toluenesulfinamide. The method includes: subjecting sodium p-tolylsulfinate and an acyl chlorination reagent to acyl chlorination to obtain p-toluene sulfinyl chloride, then reacting
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Paragraph 0014; 0041; 0055; 0057
(2018/09/13)
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- Method for synthesizing chiral optical pure para-toluene sulfenamide
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The invention discloses a method for synthesizing chiral optical pure para-toluene sulfonamide. The method comprises the following steps: ensuring that para-toluene sulfinic acid sodium salt and an acylating chlorination reagent react with each other, so
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Paragraph 0040; 0054; 0056
(2018/09/21)
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- Chiral 1,3,2-Diazaphospholenes as Catalytic Molecular Hydrides for Enantioselective Conjugate Reductions
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Secondary 1,3,2-diazaphospholenes have a polarized P?H bond and are emerging as molecular hydrides. Herein, a class of chiral, conformationally restricted methoxy-1,3,2-diazaphospholene catalysts is reported. We demonstrate their catalytic potential in asymmetric 1,4-reductions of α,β-unsaturated carbonyl derivatives, including enones, acyl pyrroles, and amides, which proceeded in enantioselectivities of up to 95.5:4.5 e.r.
- Miaskiewicz, Solène,Reed, John H.,Donets, Pavel A.,Oliveira, Caio C.,Cramer, Nicolai
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supporting information
p. 4039 - 4042
(2018/03/13)
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- Monoligated Pd(0)-catalyzed intramolecular ortho- and para-arylation of phenols for the synthesis of aporphine alkaloids. Synthesis of (-)-lirinine
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An intramolecular palladium(0)-mediated ortho-arylation of phenols applied to the synthesis of various substituted aporphines is reported. Most significantly, the efficiency of the transformation was enhanced by the use of monoligated Pd(0) complexes. This methodology was extended to para-arylation of phenols and employed in the synthesis of the aporphine alkaloid (-)-lirinine.
- Hellal, Malik,Singh, Shambhavi,Cuny, Gregory D.
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scheme or table
p. 1674 - 1681
(2012/03/10)
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- Asymmetric synthesis of sulfinamides using (-)-quinine as chiral auxiliary
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A process has been designed and demonstrated for the asymmetric synthesis of sulfinamides using quinine as auxiliary. A variety of chiral sulfinamides including N-alkyl sulfinamides with diverse structure were prepared in good yields and excellent enantioselectivity starting from easily available and inexpensive reagents. The auxiliary quinine could be recovered and recycled.
- Zhang, Yongda,Chitale, Sampada,Goyal, Navneet,Li, Guisheng,Han, Zhengxu S.,Shen, Sherry,Ma, Shengli,Grinberg, Nelu,Lee, Heewon,Lu, Bruce Z.,Senanayake, Chris H.
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p. 690 - 695
(2012/02/16)
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- Practical and highly stereoselective method for the preparation of several chiral arylsulfinamides and arylsulfinates based on the spontaneous crystallization of diastereomerically pure N-benzyl-N-(1-phenylethyl)- arylsulfinamides
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A novel and simple process for the preparation of enantiomerically pure (SS)-benzenesulfinamide (SS)-3a, (SS)-p- toluenesulfinamide (SS)-3b, (SS)-p-chloro- benzenesulfinamide (SS)-3c and (SS)-p- fluorobenzenesulfinamide (SS)-3d has been developed. The treatment of arylsulfinyl chlorides with (R)-N-benzyl-1-phenylethanamine in the presence of excess triethylamine gave diastereomeric mixtures of N-benzyl-N-(1-phenylethyl)- arylsulfinamides 1, which underwent spontaneous crystallization to furnish diastereomerically pure (R,SS)-N-benzyl-N-(1-phenylethyl)- arylsulfinamides (R,SS)-1a-1d in 28%, 29%, 27% and 31% yields, respectively. The diastereomerically pure compounds (R,SS)-1 were then converted into four enantiopure (RS)-methyl arylsulfinates (RS)-2, and finally into four enantiopure (SS)- arylsulfinamides (SS)-3 in good yields.
- Zhu, Rui-Heng,Shi, Xiao-Xin
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experimental part
p. 387 - 393
(2011/06/11)
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- Chiral sulfur derivatives in the allylation of acyl hydrazones: C 2-symmetric bis-sulfinamides as enhanced chiral organic promoters.
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Monosulfinamides and C2-symmetric bis-sulfinamides are convenient neutral chiral promoters in the allylation of acyl hydrazones, the nature of the spacer and the substituent at the sulfinyl sulfur are key elements for the enantioselectivity of the process.
- Fernandez, Inmaculada,Alcudia, Ana,Gori, Beatrice,Valdivia, Victoria,Recio, Rocio,Garcia, Maria Victoria,Khiar, Noureddine
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supporting information; experimental part
p. 4388 - 4393
(2010/10/20)
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- Synthesis of enantiopure sulfonimidamides and elucidation of their absolute configuration by comparison of measured and calculated CD spectra and X-ray crystal structure determination
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Straightforward syntheses of enantiopure N-benzoyl- and N-tert-butyloxycarbonyl-protected sulfonimidamides, which can be used as building blocks in newly designed catalysts, are presented. Key synthetic step is a dynamic resolution of a racemic sulfinic acid sodium salt. All subsequent transformations proceed stereospecifically. The absolute configurations at the sulfur atoms of both sulfonimidamides were determined by comparison of measured and calculated CD spectra. An X-ray crystal structure determination of a sulfonimidoylguanidine derivative confirmed this result.
- Worch, Christin,Atodiresei, Iuliana,Raabe, Gerhard,Bolm, Carsten
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experimental part
p. 677 - 683
(2010/06/19)
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- AMINO-PIPERIDINE DERIVATIVES AS CETP INHIBITORS
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The present invention provides a compound of formula (I), wherein the variants R1, R2, R3, R4, R5, R6, R7 are as defined herein, and wherein said compound is an inhibitor of CETP, and thus can be employed for the treatment of a disorder or disease mediated by CETP or responsive to the inhibition of CETP.
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Page/Page column 174
(2008/06/13)
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- The 3-(3-pyridine)propionyl anchor group for protease-catalyzed resolutions: p-toluenesulfinamide and sterically hindered secondary alcohols
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Compared to an acetyl acyl group, the 3-(3-pyridine)propionyl group increases substrate binding to many proteases and substrate solubility in water, thereby increasing the rates of protease-catalyzed reactions. For example, proteases reacted up to six hundred-fold faster with the 3-(3-pyridine)propionyl ester of 1-phenylethanol than with the corresponding acetate ester. In addition, the 3-(3-pyridine)propionyl group enables a simple, mild acid extraction to separate the remaining starting material and product. To demonstrate the synthetic usefulness of this strategy, we resolved multi-gram quantities of (R)- and (S)-p-toluenesulfinamide with α-chymotrypsin and gram quantities of (R)- and (S)-2,2-dimethylcyclopentanol with subtilisin Carlsberg. The 3-(3-pyridyl)propionyl group was better for these resolutions than the corresponding acetate or dihydrocinnamate because it decreased the reaction time due to increased reactivity, decreased the reaction volume due to increased substrate solubility and enabled purification without chromatography. Molecular modeling suggests the enantioselectivity of α-chymotrypsin toward (R)-p-toluenesulfinamide is high (E = 52) because of a favorable hydrophobic interaction between the p-tolyl group of the fast-reacting (R)-enantiomer and leaving group pocket. The enantioselectivity of subtilisin Carlsberg toward (S)-2,2-dimethylcyclopentanol is high (E = 43) because the large substituent (the 2,2-dimethyl quaternary carbon) of the slow-reacting (R)-enantiomer cannot fit in the S1′ leaving group pocket.
- Savile, Christopher K.,Kazlauskas, Romas J.
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p. 1183 - 1192
(2007/10/03)
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- Subtilisin-catalyzed resolution of N-acyl arylsulfinamides
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We report the first biocatalytic route to sulfinamides (R-S(O)-NH 2), whose sulfur stereocenter makes them important chiral auxiliaries for the asymmetric synthesis of amines. Subtilisin E did not catalyze hydrolysis of N-acetyl or N-butanoyl arylsulfinamides, but did catalyze a highly enantioselective (E > 150 favoring the (R)-enantiomer) hydrolysis of N-chloroacetyl and N-dihydrocinnamoyl arylsulfinamides. Gramscale resolutions using subtilisin E overexpressed in Bacillus subtilis yielded, after recrystallization, three synthetically useful auxiliaries: (R)-p- toluenesulfinamide (42% yield, 95% ee), (R)-p-chlorobenzenesulfinamide (30% yield, 97% ee), and (R)-2,4,6-trimethylbenzenesulfinamide (30% yield, 99% ee). Molecular modeling suggests that the N-chloroacetyl and N-dihydrocinnamoyl groups mimic a phenylalanine moiety and thus bind the sulfinamide to the active site. Molecular modeling further suggests that enantioselectivity stems from a favorable hydrophobic interaction between the aryl group of the fast-reacting (R)-arylsulfinamide and the S1′ leaving group pocket in subtilisin E.
- Savile, Christopher K.,Magloire, Vladimir P.,Kazlauskas, Romas J.
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p. 2104 - 2113
(2007/10/03)
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- Practical and highly stereoselective technology for preparation of enantiopure sulfoxides and sulfinamides utilizing activated and functionally differentiated N-sulfonyl-1,2,3-oxathiazolidine-2-oxide derivatives
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A simple, general, and practical technology to prepare enantiopure 1,2,3-oxathiazolidine-2-oxide derivatives using chiral aryl N-sulfonyl aminoalcohol derivatives and thionyl chloride is reported. The versatility of these novel chiral building blocks (MIOO and TMPOO), was exemplified by the expedient production of a variety of unique chiral sulfoxides and valuable chiral sulfinamides in excellent yields and enantiopurities.
- Han, Zhengxu,Krishnamurthy, Dhileepkumar,Grover, Paul,Fang, Q. Kevin,Su, Xiping,Wilkinson, H. Scott,Lu, Zhi-Hui,Magiera, Daniel,Senanayake, Chris H.
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p. 6386 - 6408
(2007/10/03)
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- Cinchona alkaloid/sulfinyl chloride combinations: Enantioselective sulfinylating agents of alcohols
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We report a novel approach to asymmetric sulfinylation reactions based on a cinchona alkaloid/sulfinyl chloride combination that acts as the first asymmetric sulfinylating agents of achiral alcohols. Both enantiomers of arenesulfinates are obtained with u
- Shibata, Norio,Matsunaga, Mitsuharu,Nakagawa, Masaya,Fukuzumi, Takeo,Nakamura, Shuichi,Toru, Takeshi
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p. 1374 - 1375
(2007/10/03)
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- Synthesis of nonracemic α-trifluoromethyl α-amino acids from sulfinimines of trifluoropyruvate
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We describe a novel and useful method for the synthesis of nonracemic α-trifluoromethyl α-amino acids (α-Tfm-AAs). Key building blocks are the sulfinimines (S)-1a and (S)-1b, prepared by Staudinger reaction from trifluoropyruvate esters and the chiral N-sulfinyl iminophosphorane (S)-8, which were treated with benzyl, allyl, and alkylmagnesium halides. The resulting diastereomeric N-sulfinyl α-Tfm α-amino esters, 12 and 13, were produced with moderate to good stereoselectivity and yields. When alkyl Grignard reagents were used, stereocontrol became progressively higher with increasing steric bulk, while reversed, though poor, stereocontrol was achieved with benzyl/allyl Grignard reagents. An explanation for the observed stereochemical outcome is proposed, on the basis of the exclusive E geometry (N-sulfinyl and CF3 trans about the C=N bond) of the chiral sulfinimines 1. This assignment is the product of structural correlation and is supported by ab initio calculations and NOE experiments. Sulfinamides 12 and 13 were transformed into a series of nonracemic α-Tfm-AAs 16-22. The sulfinyl auxiliary can be regenerated and recycled.
- Asensio, Amparo,Bravo, Pierfrancesco,Crucianelli, Marcello,Farina, Alessandra,Fustero, Santos,Soler, Juan García,Meille, Stefano V.,Panzeri, Walter,Viani, Fiorenza,Volonterio, Alessandro,Zanda, Matteo
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p. 1449 - 1458
(2007/10/03)
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- Synthesis of enantiomerically pure ethylenediamines from chiral sulfinimines: A new twist to the Strecker reaction
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Addition of various cyanide nucleophiles on chiral t-butylsulfinimine and p-tolylsulfinimine derivatives are described and demonstrated that aliphatic t-butylsulfinimines are excellent substrates for a new variant of the Strecker reaction where cyanide ions are delivered through ethylisopropoxyaluminum cyanide or trimethylsilylcyanide combined with a Lewis acid catalyst. The reaction proceeds with high yield and high diastereoselectivity, which can be further improved by additional crystallizations.
- Mabic, Stéphane,Cordi, Alex A.
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p. 8861 - 8866
(2007/10/03)
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- First method for the preparation of strongly electrophilic chiral sulfinimines, and applications in asymmetric synthesis
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A new and preparatively useful method for the synthesis of non racemic α-trifluoromethyl α-amino acids is presented, using chiral sulfinimines of trifluoropyruvate as key-building blocks.
- Bravo, Pierfrancesco,Crucianelli, Marcello,Zanda, Matteo
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p. 345 - 346
(2007/10/03)
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- Sulfinimines of trifluoropyruvate: Novel intermediates for chiral non racemic α-trifluoromethyl α-amino acids
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A new and preparatively useful method for the synthesis of non racemic α-trifluoromethyl (Tfm)α-amino acids (AAs) is presented. Key-building blocks are the sulfinimines (S)-1a,b, prepared via Staudinger reaction from trifluoropyruvic esters and the chiral N-sulfinyl iminophosphorane (S)-5, which were reacted with benzyl and alkylmagnesium halides. The resulting N- sulfinyl α-Tfm α-amino esters 6a,b and 6c-g, respectively, were produced with opposite stereoselectivity. The stereocontrol with alkyl Grignard reagents was progressively higher with increasing steric bulk. Some of the adducts 6 were transformed into a-Tfm-phenylalanine (R)-8 (with regeneration and recycling the chiral auxiliary), αTfm-leucine (S)-11c, α-Tfm-butyrine (S)-11f and α-Tfm-alanine (8),11g in two steps in one-pot.
- Bravo, Pierfrancesco,Crucianelli, Marcello,Vergani, Barbara,Zanda, Matteo
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p. 7771 - 7774
(2007/10/03)
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- Asymmetric Synthesis Properties of Sulfinimines (Thiooxime S-Oxides)
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Enantiomerically pure sulfinimines (thiooxime S-oxides 10), important building blocks in the asymmetric synthesis of amine derivatives, are prepared in good to excellent yields in one step from aromatic, heteroaromatic, and aliphatic aldehydes. This protocol involves treating commercially available (R)- or (S)-menthyl p-toluenesufinate (Andersen reagent 4) with LiHMDS, followed by the aldehyde, affording (E)-10 exclusively. The sulfinimines 10 are formed via a Peterson-type olefination reaction of silylsulfinamide anion 13 with the aldehyde. Anion 13 is generated by reaction of lithium menthoxide (12a) with bis(trimethylsilyl)sulfinamide 11, which is formed in the reaction of 4 with LiHMDS. The other product formed is O-(trimethylsilyl)menthol (12c), which is isolated in >80% yield for recycling. Two other less efficient methods for the asymmetric synthesis of 10 are discussed: (i) the asymmetric oxidation of sulfenimines 6 with chiral nonracemic oxaziridines and (ii) the reaction of metal aldimines, prepared from nitriles, with 4. All of these protocols fail with ketones.
- Davis, Franklin A.,Reddy, Rajarathnam E.,Szewczyk, Joanna M.,Reddy, G. Venkat,Portonovo, Padma S.,Zhang, Huiming,Fanelli, Dean,Reddy, R. Thimma,Zhou, Ping,Carroll, Patrick J.
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p. 2555 - 2563
(2007/10/03)
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