- Enantioselective Conjugate Addition of Catalytically Generated Zinc Homoenolate
-
We report herein an enantioselective conjugate addition reaction of a zinc homoenolate, catalytically generated via ring opening of a cyclopropanol, to an α,β-unsaturated ketone. The reaction is promoted by a zinc aminoalkoxide catalyst generated from Et2Zn and a chiral β-amino alcohol to afford 1,6-diketones, which undergo, upon heating, intramolecular aldol condensation to furnish highly substituted cyclopentene derivatives with good to high enantioselectivities. The reaction has proved applicable to various 1-substituted cyclopropanols as well as chalcones and related enones. The chiral amino alcohol has proved to enable ligand-accelerated catalysis of the homoenolate generation and its conjugate addition. Positive nonlinear effects and lower reactivity of a racemic catalyst have been observed, which can be attributed to a stable and inactive heterochiral zinc aminoalkoxide dimer.
- Sekiguchi, Yoshiya,Yoshikai, Naohiko
-
supporting information
p. 4775 - 4781
(2021/04/07)
-
- Synthesis method of chiral compound
-
The invention belongs to the technical field of chemical synthesis, and relates to a synthetic method of a chiral compound, in particular to a synthetic method of (1R, 2S)-1-phenyl-2-(pyrrolidine-1-yl) propan-1-ol. According to an ingenious synthesis strategy, asymmetric reduction can be realized during carbonyl reduction, and a target compound can be directly obtained at high yield. The problem that a target compound cannot be obtained at high yield through asymmetric reduction in the prior art is solved. Moreover, the synthesis of a high-purity compound (A) can be realized by using cheap hydrochloric acid and zinc chloride; in addition, no isomer is wasted; and according to the method, the use of norephedrine controlled product is avoided; the raw materials are cheap and easy to obtain,so that the synthesis cost is reduced; moreover, the preparation method disclosed by the invention is easy for industrial large-scale production.
- -
-
Paragraph 0169-0170
(2020/01/25)
-
- Method for preparing chiral (1R,2S)-1-phenyl-2-(1-pyrrolidyl)propane-1-alcohol
-
The invention provides a new method for simply and feasibly synthesizing (1R,2S)-1-phenyl-2-(1-pyrrolidyl)propane-1-alcohol through enzymatic catalysis. The method is easy to operate and mild in condition, an intermediate does not need to be separated, th
- -
-
Paragraph 0043-0051
(2019/01/23)
-
- ANTICANCER COMPOUND PROCESS
-
The present invention relates to a process for preparing compound 1 that useful as an anticancer agent. In particular, the invention seeks to provide new methodology for preparing compound 1 and substituted derivatives thereof.
- -
-
Page/Page column 34-36
(2019/06/23)
-
- A (S)- N - methoxy - methyl -2 - (tetrahydro-pyrrolyl) propionamide and its preparation method and application
-
The invention discloses a (S)-N-methoxy-methyl-2-(pyrrolidine) propionamide shown as a formula (5). A preparation method is as follows: subjecting a starting material L-alanine to amino protection, reaction with N,O-dimethyl hydroxylamine hydrochloride, removal of amino protecting group, and alkylation; and subjecting the prepared compound shown as (5) to addition elimination and reduction to obtain an Efavirenz chiral ligand shown as the formula (7). The synthetic method of Efavirenz chiral ligand provided by the invention has the advantages of mild reaction conditions, simple operation, high yield and low production cost, and is suitable for industrialized production.
- -
-
Paragraph 0052; 0053; 0055
(2017/08/25)
-
- Preparation method of (1R,2S)-1-phenyl-2-(1-pyrrolidyl)-1-propanol
-
The invention discloses a preparation method of (1R,2S)-1-phenyl-2-(1-pyrrolidyl)-1-propanol. According to the preparation method, DL-1-phenyl-2-(1-pyrrolidyl)-1-acetone is taken as a starting material and subjected to resolution, racemization and reduction, and (1R,2S)-1-phenyl-2-(1-pyrrolidyl)-1-propanol is prepared. The yield of one-time resolution is higher than 35%, a resolving agent is easy to recover, and the recovery rate is higher than 90%; the racemization process is performed under the slightly alkaline condition, and the racemization yield is higher; the yield of (1R,2S)-1-phenyl-2-(1-pyrrolidyl)-1-propanol obtained through reduction is higher than 85%. The preparation method has the advantages of mild reaction conditions, stable process, high product optical purity, low cost, high production safety and the like.
- -
-
Paragraph 0031; 0034
(2016/10/31)
-
- NOVEL PROCESS FOR PREPARATION OF OPTICALLY PURE NOREPHEDRINE AND ITS DERIVATIVES
-
The present invention relates to a novel process for preparation of norephedrine and its derivatives. The present invention also relates to a process for separation of individual isomers of norephedrine and its derivatives using suitable chiral resoluting agents.
- -
-
-
- Chiral α-alkylation/arylation in 1-phenyl-2-(1-pyrrolidinyl)-1-propanol through Grignard reactions
-
Complete asymmetric induction has been achieved during Grignard alkylations/arylations resulting in (1S,2R)- and (1R,2R)-1-phenyl-1-alkyl/aryl-2-(1-pyrrolidinyl)-1-propanols which are isolated as hydrochlorides.
- Hitesh Kumar, Borkatte N.,Murugesan, Velayudham,Prakasam, Tangirala,Srinivasan, Pathangi S.,Ramana, Devalla V.
-
body text
p. 2773 - 2779
(2010/03/30)
-
- Dimethylzinc-mediated, enantioselective synthesis of propargylic amines
-
A one-pot, enantioselective synthesis of N-aryl propargylic amines, using alkynylation reagents obtained from dimethylzinc and terminal acetylenes in combination with various aldehydes and o-methoxyaniline as starting materials, has been developed. Enanti
- Zani, Lorenzo,Eichhorn, Torsten,Bolm, Carsten
-
p. 2587 - 2600
(2008/04/01)
-
- Kinetic and computational studies of the composition and structure of activated complexes in the asymmetric deprotonation of cyclohexene oxide by a norephedrine-derived chiral lithium amide
-
Rational design of efficient chiral lithium amides for enantioselective deprotonations demands understanding of the origin of the selectivity. The mechanism of deprotonation of cyclohexene oxide 1 by lithium (1R,2S)-N-methyl-1-phenyl-2-pyrrolidinylpropanamide 3, which yields (S)-cyclohex-2-en-1-ol (S)-5 in 93% enantiomeric excess in tetrahydrofuran (THF), has been investigated. Kinetics have been used to show that the reaction is first order with respect to the reagents 1 and 3, respectively. NMR investigations of a 6Li and 15N labelled isotopologue of 3 have previously shown that 3 is mainly a dimer of the lithium amide monomer in THF in the initial state. On the basis of these results it is concluded that the rate-limiting activated complexes for the epoxide deprotonation are composed of two molecules of monomer of lithium amide 3 and one molecule of epoxide. Structures and energies of unsolvated and specific THF-solvated reagents and activated complexes have been calculated using PM3 and B3LYP/6-31+G(d). The results are currently being explored for the rational design of chiral lithium amides with improved stereoselectivities.
- Pettersen, Daniel,Amedjkouh, Mohamed,Nilsson Lill, Sten O.,Dahlen, Kristian,Ahlberg, Per
-
p. 1654 - 1661
(2007/10/03)
-
- Enantioselective rearrangement of a meso-cyclohexene oxide using norephedrine-derived chiral bases
-
Using a chiral base from a norephedrine-derived diamine, the enantioselective rearrangement of a meso-cyclohexene oxide can be performed in 94% yield and with 94% enantioselectivity. The enantioselectivity is lower (86% ee) with the diastereoisomeric chiral base. In order to prepare the diastereoisomeric chiral base, a potentially useful way of converting norephedrine into norpseudoephedrine was developed.
- Colman, Bob,De Sousa, Simon E.,O'Brien, Peter,Towers, Timothy D.,Watson, Will
-
p. 4175 - 4182
(2007/10/03)
-
- A new norephedrine-derived chiral base for epoxide rearrangement reactions
-
The conversion of (1R,2S)-norephedrine into a novel chiral diamine (83% yield, simple two step synthesis) and its use as a chiral base in two epoxide rearrangement reactions is reported. Rearrangement of a 4,5-disubstituted cyclohexene oxide and of a 4-aminosubstituted cyclopentene oxide generated allylic alcohols of >90% ee. These results represent the highest levels of enantioselectivity reported to date for such substrates.
- De Sousa, Simon E.,O'Brien, Peter,Steffens, H. Christian
-
p. 8423 - 8425
(2007/10/03)
-
- Efficient synthesis of a chiral mediator
-
An efficient method for the quantitative preparation and isolation of a compound of formula I STR1 or its enantiomer, a chiral mediator used in enantioselective synthesis.
- -
-
-
- Practical asymmetric synthesis of Efavirenz (DMP 266), an HIV-1 reverse transcriptase inhibitor
-
A highly enantioselective and practical synthesis of the HIV-1 reverse transcriptase inhibitor efavirenz (1) is described. The synthesis proceeds in 62% overall yield in seven steps from 4-chloroaniline (6) to give efavirenz (1) in excellent chemical and optical purity. A novel, enantioselective addition of Li-cyclopropyl acetylide (4a) to p-methoxybenzyl-protected ketoaniline 3a mediated by (1R,2S)-N-pyrrolidinylnorephedrine lithium alkoxide (5a) establishes the stereogenic center in the target with a remarkable level of stereocontrol.
- Pierce, Michael E.,Parsons Jr., Rodney L.,Radesca, Lilian A.,Lo, Young S.,Silverman, Stuart,Moore, James R.,Islam, Qamrul,Choudhury, Anusuya,Fortunak, Joseph M. D.,Nguyen, Dieu,Luo, Chi,Morgan, Susan J.,Davis, Wayne P.,Confalone, Pat N.,Chen, Cheng-Yi,Tillyer, Richard D.,Frey, Lisa,Tan, Lushi,Xu, Feng,Zhao, Dalian,Thompson, Andrew S.,Corley, Edward G.,Grabowski, Edward J. J.,Reamer, Robert,Reider, Paul J.
-
p. 8536 - 8543
(2007/10/03)
-
- Enantioselective Addition of Diethylzinc to α-Branched Aldehydes
-
Reaction of diethylzinc with α-branched aldehydes in the presence of a catalytic amount of (1R,2S)-(-)-1-phenyl-2-piperidinopropane-1-thiol 1 provided the corresponding secondary alcohols in almost 100percent enantiomeric excess.
- Kang, Jahyo,Lee, Jun Won,Kim, Joo In
-
p. 2009 - 2010
(2007/10/02)
-
- Chiral Co(II) and Mn(II) catalysts for the 1,3-dipolar cycloaddition reactions of azomethine ylides derived from arylidene imines of glycine
-
Anhydrous MnBr2 and CoCl2 in conjunction with chiral ephedrine ligands effect substantial asymmetric induction in cycloadducts derived from methyl acrylate and imines of glycine methyl ester. CoCl2 is most effective and gi
- Allway,Grigg
-
p. 5817 - 5820
(2007/10/02)
-
- Chiral N,N-Dialkylnorephedrines as Catalysts of the Highly Enantioselective Addition of Dialkylzincs to Aliphatic and Aromatic Aldehydes. The Asymmetric Synthesis of Secondary Aliphatic and Aromatic Alcohols of High Optical Purity
-
The chiral N,N-dialkylnorephedrine-catalyzed addition of dialkylzincs to aliphatic and aromatic aldehydes afforded secondary alcohols of high optical purity (to > 95percent ee).Among the N,N-di(primary alkyl)norephedrines, N,N-di-n-butylnorephedrine (DBNE, 3d) was found to be the most effective catalyst. 1-Phenyl-2-(1-pyrrolidinyl)propan-1-ol (3i) and N,N-diallylnorephedrine (3j) were also highly effective catalysts.The method described provides optically active secondary aliphatic alcohols of high optical purity which cannot be prepared by conventional methods.
- Soai, Kenso,Yokoyama, Shuji,Hayasaka, Tomoiki
-
p. 4264 - 4268
(2007/10/02)
-