- London Dispersion Interactions Rather than Steric Hindrance Determine the Enantioselectivity of the Corey–Bakshi–Shibata Reduction
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The well-known Corey–Bakshi–Shibata (CBS) reduction is a powerful method for the asymmetric synthesis of alcohols from prochiral ketones, often featuring high yields and excellent selectivities. While steric repulsion has been regarded as the key director of the observed high enantioselectivity for many years, we show that London dispersion (LD) interactions are at least as important for enantiodiscrimination. We exemplify this through a combination of detailed computational and experimental studies for a series of modified CBS catalysts equipped with dispersion energy donors (DEDs) in the catalysts and the substrates. Our results demonstrate that attractive LD interactions between the catalyst and the substrate, rather than steric repulsion, determine the selectivity. As a key outcome of our study, we were able to improve the catalyst design for some challenging CBS reductions.
- Eschmann, Christian,Song, Lijuan,Schreiner, Peter R.
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supporting information
p. 4823 - 4832
(2021/02/01)
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- Stereoselective Total Synthesis of (-)-(2 S,4 R)-3′-Methoxyl Citreochlorol: Preparation and Use of New Proline-Based Auxiliary for Asymmetric Acetate Aldol Reaction
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The first stereoselective total synthesis of (-)-(2S,4R)-3′-methoxy citreochlorol and (-)-(2S,4S)-3′-methoxy citreochlorol is demonstrated. A proline-based imidazolidinone was synthesized and used as chiral auxiliary for asymmetric acetate aldol reaction to generate initial chirality in the targeted molecule. Geminal dichloromethane functionality was introduced by the addition of in situ generated dichloromethyllithium to Weinreb's amide functional group.
- Sunnapu, Ranganayakulu,Banoth, Saikumar Naik,Reyno,Thomas, Aleena,Venugopal, Navyasree,Rajendar, Goreti
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p. 4103 - 4113
(2020/03/05)
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- Intramolecular [2+2] Photocycloaddition of Cyclic Enones: Selectivity Control by Lewis Acids and Mechanistic Implications
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The intramolecular [2+2] photocycloaddition of 3-alkenyl-2-cycloalkenones was performed in an enantioselective fashion (nine representative examples, 54–86 % yield, 76–96 % ee) upon irradiation at λ=366 nm in the presence of an AlBr3-activated oxazaborolidine as the Lewis acid. An extensive screening of proline-derived oxazaborolidines showed that the enantioface differentiation depends strongly on the nature of the aryl group at the 3-position of the heterocycle. DFT calculations of the Lewis acid–substrate complex indicate that attractive dispersion forces may be responsible for a change of the binding mode. The catalytic [2+2] photocycloaddition was shown to proceed on the triplet hypersurface with a quantum yield of 0.05. The positive effect of Lewis acids on the outcome of a given intramolecular [2+2] photocycloaddition was illustrated by optimizing the key step in a concise total synthesis of the sesquiterpene (±)-italicene.
- Poplata, Saner,Bauer, Andreas,Storch, Golo,Bach, Thorsten
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supporting information
p. 8135 - 8148
(2019/05/29)
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- Transition Metal-Free Selective Double sp3 C-H Oxidation of Cyclic Amines to 3-Alkoxyamine Lactams
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The first chemical method for selective dual sp3 C-H functionalization at the alpha-and beta positions of cyclic amines to their corresponding 3-alkoxyamine lactams is reported. Unlike traditional Cα-H oxidation of amines to amides mediated by transition metals, the present protocol, which involves the use of NaClO2/TEMPO/NaClO in either aqueous or organic solvent, not only allows the Cα-H oxidation but also the subsequent functionalization of the unreactive β-methylene group in an unprecedented tandem fashion and using environmentally friendly reactants.
- Osorio-Nieto, Urbano,Chamorro-Arenas, Delfino,Quintero, Leticia,H?pfl, Herbert,Sartillo-Piscil, Fernando
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p. 8625 - 8632
(2016/09/28)
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- Concise synthesis of chiral N -Benzyl-α,α-Diarylprolinols through shi asymmetric epoxidation
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A concise and practical synthesis of chiral N-benzyl-α,α- diaryl-2-prolinols was developed through Shi asymmetric epoxidation, followed by double nucleophilic substitution of bromo-containing olefins. A series of enantioenriched N-benzyl-α,α-diaryl-2-prolinols were obtained with excellent enantioselectivities (96% ee) in moderate to good yields (40-76% yield). For the first time, enantiopure N-benzyl-α,α-diphenyl-2- prolinol was obtained from bromo-containing olefin using this methodology. Georg Thieme Verlag Stuttgart, New York.
- Li, Jie,Zhou, Hai,Weng, Jiangsen,Wang, Mingwen,Ge, Chengsheng,Tu, Wujie
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supporting information
p. 805 - 808
(2014/04/03)
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- Synthesis of chiral 2-(anilinophenylmethyl)pyrrolidines and 2-(anilinodiphenylmethyl)pyrrolidine and their application to enantioselective borane reduction of prochiral ketones as chiral catalysts
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Chiral diamines, 2-(anilinophenylmethyl)pyrrolidines and 2-(anilinodiphenylmethyl)pyrrolidine, were prepared from N-(tert-butoxycarbonyl) pyrrolidine or (S)-proline as a starting material, respectively. These chiral diamines were efficient for the catalytic enantioselective borane reduction of acetophenone. Using (S)-2-(anilinodiphenylmethyl)pyrrolidine, chiral secondary alcohols were obtained from prochiral ketones with good to excellent enantiomeric excesses (up to 98% ee).
- Hosoda, Naoya,Kamito, Hideaki,Takano, Miki,Takebe, Yoshitaka,Yamaguchi, Yoshitaka,Asami, Masatoshi
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p. 1739 - 1746
(2013/03/13)
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- Catalytic asymmetric aldol-type reaction of zinc enolate equivalent of amides
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Treatment of phenyl isocyanate with bis(iodozincio)methane gave a zinciomethylenated product, which acts as an amide-enoate equivalent. It did not react with an aldehyde efficiently, but gave the corresponding adduct in good yield in the presence of an aminoalcohol. Use of a catalytic amount of chiral aminoalcohol led the process to the catalytic asymmetric Aldol-type reaction.
- Haraguchi, Ryosuke,Matsubara, Seijiro
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supporting information
p. 3378 - 3380
(2013/07/26)
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- Allyltin tribromide: A versatile reagent involved in the ring-opening of epoxides
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This paper presents a versatile reagent for epoxide cleavage. The allyltin tribromide could act as a novel and easily prepared allylation reagent and halide atom donor to convert epoxides to the corresponding homoallyl alcohols and halohydrins in high yields with excellent regioselectivities under mild reaction conditions, respectively. It could also act as a Lewis acid to catalyze the ring opening reactions of epoxides with alcohols.
- Chen, Guohong,Wang, Xin,Jin, Xiaoqian,Liu, Lingyan,Chang, Weixing,Li, Jing
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experimental part
p. 1294 - 1301
(2010/11/05)
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- A concise synthesis of (S)-2-(fluorodiphenylmethyl)pyrrolidine: A novel organocatalyst for the stereoselective epoxidation of α,β-unsaturated aldehydes
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A concise synthesis of (S)-2-(fluorodiphenylmethyl)pyrrolidine from cheap, commercially available starting materials is described. Pertinent features of this synthetic route include ease of synthesis, facile purification steps, and an operationally simple deoxy?fluorination step to install the C-F bond. Georg Thieme Verlag Stuttgart · New York.
- Sparr, Christof,Tanzer, Eva-Maria,Bachmann, Julia,Gilmour, Ryan
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experimental part
p. 1394 - 1397
(2010/07/02)
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- Asymmetric addition of terminal alkynes to n-(Diphenylphosphinoyl)imines promoted by stoichiometric amounts of a proline-derlved ss-amino alcohol
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A new synthetic methodology for the preparation of optically active propargylamines is described. The alkynylation of aromatic, heteroaromatic, aliphatic and α,β-unsaturated N-(di-phenylphosphinoyl)imines was investigated by using dieth-ylzinc and a proline-derived β-amino alcohol, N-(Diphenylphosphinoyl)-protected propargylic amines can be synthesized in high yields and with good to excellent: enantio-selectivities.
- Yan, Wenjin,Mao, Bin,Zhn, Shaoqun,Jiang, Xianxing,Liu, Zhongli,Wang, Rui
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supporting information; experimental part
p. 3790 - 3794
(2009/12/07)
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- Synthesis of three novel chiral diamines derived from (S)-proline and their evaluation as precursors of diazaborolidines for the catalytic borane-mediated enantioselective reduction of prochiral ketones
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A series of chiral diazaborolidine catalysts are readily prepared in situ at 75 °C in toluene solvent and under microwave irradiation (100 W, 15 min, air cooling) using chiral diamines derived from inexpensive and commercially available (S)-proline and borane-dimethyl sulfide. Special mention deserves the synthesis of potentially versatile diamine (S)-8 [(S)-(pyrrolidin-2-yl)diphenylmethanamine], with the key step being the conversion of tertiary alcohol (S)-(1-benzylpyrrolidin-2-yl)diphenyl methanol, (S)-12, to azide (S)-13. The chiral diazaborolidine/BH3 reagent system was successfully employed in the enantioselective reduction of prochiral ketones to give the corresponding secondary alcohols in excellent yield and with up to 96% enantiomeric purities.
- Luis Olivares-Romero,Juaristi, Eusebio
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scheme or table
p. 9992 - 9998
(2009/04/11)
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- Enantioselective addition of dialkylzinc reagents to N-(diphenylphosphinoyl)imines catalyzed by β-aminoalcohols with the prolinol skeleton
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Several β-aminoalcohols with the prolinol framework are shown to be very efficient catalysts for the enantioselective addition of dialkylzinc reagents to N-(diphenylphosphinoyl)imines. The use of 0.5 equiv of the catalyst leads to the expected addition products in good yields and with ee up to 94% in a reaction time of only 4 h at room temperature. This ee is the highest value reported so far using 0.5 equiv of an aminoalcohol as a promoter. High enantioselectivities are obtained in the addition of dialkylzincs to both aromatic and aliphatic imines. The amount of the catalyst can be reduced to 0.25 equiv with a slight decrease in the ee. A very interesting effect of the addition rate and temperature on the enantioselectivity was also observed.
- Almansa, Raquel,Guijarro, David,Yus, Miguel
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p. 2828 - 2840
(2008/03/28)
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- Asymmetric Cyanosilylation of Ketones Catalyzed by Bifunctional Chiral N-Oxide Titanium Complex Catalysts
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A new bifunctional catalytic system based on chiral N-oxide titanium complexes has been used for the asymmetric cyanosilylation of ketones. Screening of a variety of chiral N-oxide metal complexes resulted in (1R,2S)-1-(2'-pyridylmethyl)-2-(diphenylhydroxymethyl)pyrrolidine N-oxide titanium complex, which gave O-TMS cyanohydrins in good yields with enantiometric excesses of up to 69 percent. A catalytic cycle based on experimental phenomena and studies was proposed to explain the origin of the asymmetric induction.
- Shen, Yongcun,Feng, Xiaoming,Li, Yan,Zhang, Guolin,Jiang, Yaozhong
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p. 129 - 137
(2007/10/03)
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- Asymmetric alternating copolymerization of cyclohexene oxide and CO2 with dimeric zinc complexes
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Dimeric zinc complex 2a [= Et2Zn2(1a)2] has been synthesized by the reaction of Et2Zn and (S)-diphenyl(pyrrolidin-2-yl)methanol (1a-H). X-ray crystallography revealed that the alkoxide ligand replaced one of the two ethyl groups of Et2Zn and formed a five-membered chelate ring through a Zn - N dative bond. Two zinc centers were bridged by oxygen atoms to form a Zn2O2 four-membered ring with a syn relationship between the two ethyl groups on the zinc centers. Dimeric zinc complex 2a was an active catalyst for asymmetric alternating copolymerization of cyclohexene oxide and CO2. An MALDI-TOF mass spectrum of the obtained copolymer showed that the copolymerization was initiated by the insertion of CO2 into Zn - alkoxide to give [(S)-diphenyl(pyrroridin-2-ly)methoxy] - [C(=O)O - (1,2-cyclohexylene) - O]n -H (copolymer I), including chiral ligand 1a as an initiating group. Complex 3a-OEt (= EtZn(1a)2ZnOEt), in which an ethoxy group replaced one of the two ethyl groups in 2a, also polymerized cyclohexene oxide and CO2 with higher catalytic activity and enantioselectivity than 2a and afforded EtO - [C(=O)O - (1,2- cyclohexylene) - O]n - H (= copolymer III), including an ethoxy group as an initiating group. Throughout the studies, dimeric zinc species are indicated to be the active species for the copolymerization. It is also depicted that the substituent on the aryl moiety in diaryl(pyrrolidin-2-yl)methanol 2b - e influenced the polymerization activity.
- Nakano, Koji,Nozaki, Kyoko,Hiyama, Tamejiro
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p. 5501 - 5510
(2007/10/03)
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- Azetidine based ligands in boron catalyzed asymmetric
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The preparation of a new class of azetidine-based auxiliaries and their selectivity in the BBr3 catalyzed Diels-Alder reaction is described. The results are compared with a similar proline-derived ligand and a known prolinol auxiliary. Results show that selectivities are highly dependent on the dienophile and the substituent of the chiral auxiliary.
- Starmans, Wim A. J.,Walgers, Richard W.A.,Thijs, Lambertus,De Gelder, Rene,Smits, Jan M.M.,Zwanenburg, Binne
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p. 4991 - 5004
(2007/10/03)
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- Enantioselective Addition of Diethylzinc to Aldehydes using Chiral Polymer Catalysts Possessing a Methylene Spacer
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N-Butylnorephedrine supported on polystyrene resin via a six-methylene spacer catalyses the enantioselective addition of diethylzinc to both aromatic and aliphatic aldehydes, providing optically active secondary alcohols in good to high enantiomeric excesses.In the enantioselective addition of diethylzinc to an aliphatic aldehyde, polymer catalyst with a six-methylene spacer is more enantioselective than other previously reported polymer catalysts.
- Watanabe, Masami,Soai, Kenso
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p. 837 - 842
(2007/10/02)
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- Synthesis and Reactions of (S)-N,N-Dialkyl-2-(hydroxydiarylmethyl)pyrrolidinium Halides as Chiral Phase-Transfer Catalysts
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Chiral quarternary spiro-ammonium salts were prepared from the reaction of (S)-α,α-diaryl-2-pyrrolidinemethanol with α,ω-dibromoalkanes and observed to exhibit activity in chiral induction in epoxidation of chalcone and the Darzens condensation of benzald
- Shi, Min,Masaki, Yukio
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p. 1460 - 1476
(2007/10/02)
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- LARGE SCALE PREPARATION OF VERSATILE CHIRAL AUXILIARIES DERIVED FROM (S)-PROLINE
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The synthesis of a variety of enantiomerically pure chiral auxiliaries based on (S)-proline and bearing sterically demanding side chains at the pyrrolidine moiety, such as the secondary amines (S)-3,5 and 7 and the hydrazines (S)-6, is described on a molar scale.As key step, the Grignard or RLi addition to the N-benzylated proline ester (S)-1 is used.
- Enders, Dieter,Kipphardt, Helmut,Gerdes, Peter,Brena-Valle, Leonardo J.,Bhushan, Vidya
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p. 691 - 704
(2007/10/02)
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