- Palladium Catalyzed Enantioselective Hayashi-Miyaura Reaction for Pharmaceutically Important 4-Aryl-3,4-dihydrocoumarins
-
The first palladium-catalyzed asymmetric addition of arylboronic acids to coumarins was successfully established, providing a straightforward asymmetric approach to achieving pharmaceutically important 4-aryl-3,4-dihydrocoumarins. This methodology features easily accessible and bench-stable ligands, a wide substrate scope, mild conditions, and accommodation of electron-withdrawing arylboronic acids.
- Csuk, René,Lai, Jixing,Li, Shengkun,Song, Baoan,Yang, Chen
-
supporting information
p. 1329 - 1334
(2022/02/23)
-
- Efficient kinetic resolution in the asymmetric transfer hydrogenation of 3-aryl-indanones: Applications to a short synthesis of (+)-indatraline and a formal synthesis of (R)-tolterodine
-
Efficient kinetic resolution (KR) occurs in asymmetric transfer hydrogenation (ATH) reactions of racemic 3-aryl-1-indanones using commercial (R,R)- or (S,S)-Ts-DENEB as a catalyst, a 1?:?5 mixture of HCO2H and Et3N as a hydrogen source and MeOH as solvent
- Lee, Hyeon-Kyu,Park, Songsoon
-
p. 23161 - 23183
(2021/07/24)
-
- Asymmetric Hydroesterification of Diarylmethyl Carbinols
-
An efficient asymmetric hydroesterfication of diarylmethyl carbinols is developed for the first time with a Pd-WingPhos catalyst, resulting in a series of chiral 4-aryl-3,4-dihydrocoumarins in excellent enantioselectivities and good yields. The method features mild reaction conditions, a broad substrate scope, use of easily accessible starting materials, and low palladium loadings. A plausible stereochemical model is also proposed with the Pd-WingPhos catalyst. This method has enabled a 4-step asymmetric synthesis of (R)-tolterodine from readily available starting materials.
- Tian, Duanshuai,Xu, Ronghua,Zhu, Jinbin,Huang, Jianxun,Dong, Wei,Claverie, Jerome,Tang, Wenjun
-
p. 6305 - 6309
(2021/02/09)
-
- Chiral Fe(ii) complex catalyzed enantioselective [1,3] O-to-C rearrangement of alkyl vinyl ethers and synthesis of chromanols and beyond
-
A highly efficient enantioselective [1,3] O-to-C rearrangement of racemic vinyl ethers that operates under mild conditions was developed. This method with chiral ferrous complex catalyst provided an efficient access to a wide range of chromanols with high yields and excellent enantioselectivities. In addition, an important urological drug (R)-tolterodine and others were easily obtained after simple transformations.
- Dong, Shunxi,Feng, Xiaoming,Lin, Qianchi,Liu, Xiaohua,Wang, Lifeng,Zhou, Pengfei
-
p. 10101 - 10106
(2020/10/19)
-
- Organic Solvent-free Asymmetric 1,4-Addition in Liquid- or Solid-State using Conventional Stirring Catalyzed by a Chiral Rhodium Complex Developed as a Homogeneous Catalyst
-
Organic solvent-free asymmetric 1,4-addition of arylboronic acids to enone substrates was performed by using a chiral rhodium complex catalyst developed as a homogeneous catalyst. Reactions catalyzed by [RhOH(cod)]2 with chiral diphosphine ligands in liquid- or solid-state proceeded to give chiral 1,4-adducts in high yield with enantioselectivities up to ca. 100 % ee by conventional stirring without mechanochemistry such as ball milling. The solid-state reactions under a static condition also proceeded, but with a slight decrease in enantioselectivity of the 1,4-adduct. SEM observations of the solid-state reactions indicated that no nanoparticles catalyst was generated. The organic solvent-free reaction could be applied to gram-scale synthesis by performing a greener purification using a minimum necessary organic solvent.
- Korenaga, Toshinobu,Kori, Hiroto,Asai, Shota,Kowata, Ryo,Shirai, Masayuki
-
p. 6059 - 6066
(2020/10/28)
-
- Computationally-Led Ligand Modification using Interplay between Theory and Experiments: Highly Active Chiral Rhodium Catalyst Controlled by Electronic Effects and CH–π Interactions
-
A chiral ligand for the rhodium-catalyzed asymmetric 1,4-addition of an arylboronic acid to a coumarin substrate that could markedly reduce catalyst loading was developed using interplay between theoretical and experimental approaches. Evaluation of the transition states for insertion and for hydrolysis of intermediate complexes (which were emphasized in response to the experimental results) using DFT calculations at the B97D/6-31G(d) level with the LANL2DZ basis set for rhodium revealed that: (i) the electron-poor nature of the ligands and (ii) CH–π interactions between the ligand and coumarin substrates played significant roles in both acceleration of insertion and inhibition of ArB(OH)2 decomposition (protodeboronation). The computationally-designed ligand, incorporating the above information, enabled a decrease in the catalyst loading to 0.025 mol% (S/C=4,000), which is less than one one-hundredth relative to past catalyst loadings of typically 3 mol%, with almost complete enantioselectivity. Furthermore, the gram-scale synthesis of the urological drug, (R)-tolterodine (l)-tartrate, was demonstrated without the need of intermediate purification. (Figure presented.).
- Korenaga, Toshinobu,Sasaki, Ryo,Takemoto, Toshihide,Yasuda, Toshihisa,Watanabe, Masahito
-
supporting information
p. 322 - 333
(2018/01/22)
-
- Hydrolase-mediated resolution of the hemiacetal in 2-chromanols: The impact of remote substitution
-
Hydrolase-catalysed dynamic kinetic resolutions of chroman-2-ol and 3-methyl chroman-2-ol can be effected with up to 88% conversion and 92% ee through the use of organic solvents. Extension to the resolution of the tolterodine precursor 1 proved more challenging. The presence of the remote phenyl substituent had a significant impact on the resolution and it was not possible to achieve high enantioselectivity together with efficient conversion from the focussed panel of enzymes screened.
- Gavin, Declan P.,Foley, Aoife,Moody, Thomas S.,Rao Khandavilli,Lawrence, Simon E.,O'Neill, Pat,Maguire, Anita R.
-
p. 577 - 585
(2017/05/01)
-
- Conjugate addition of aryl nucleophiles to α,β-unsaturated cinnamic acid derivatives containing Evans type chiral auxiliaries
-
Cinnamides containing oxazolidin-2-one type auxiliaries have been prepared. A novel pathway to chiral 4-aryl-6-methyl-3,4-dihydrocoumrines via the asymmetric conjugate addition of arylmagnesium bromides to these cinnamides is described.
- Leitis, Zigmārs,Lūsis, Viesturs
-
p. 843 - 851
(2016/09/02)
-
- BICMAP-rhodium(I)-catalyzed asymmetric 1,4-addition of arylboronic acids to coumarins
-
Rhodium(I)-catalyzed asymmetric 1,4-addition of arylboronic acids 2 to coumarins 1 using (S)-BICMAP as a chiral ligand gave the desired 4-arylchroman-2-one derivatives 2 in good yields and with high enantioselectivities (up to 99% ee).
- Mino, Takashi,Miura, Kazuki,Taguchi, Hiroyuki,Watanabe, Kohei,Sakamoto, Masami
-
p. 1065 - 1068
(2015/10/19)
-
- Coumarins from free ortho -hydroxy cinnamates by Heck-Matsuda arylations: A scalable total synthesis of (R)-tolterodine
-
Free ortho-hydroxy cinnamate ester derivatives are evaluated in the synthesis of structurally diverse 4-aryl-coumarins via a tandem Heck-Matsuda cyclization reaction. Free phenolic groups were considered incompatible with such a reaction, which usually provide the corresponding diazo dyes. A concise and scalable route employing a ligand-free, Pd-catalyzed Heck-Matsuda arylation under aerobic conditions for the preparation of (R)-Tolterodine in high overall yield and ee is also presented.
- Barancelli, Daniela A.,Salles, Airton G.,Taylor, Jason G.,Correia, Carlos Roque D.
-
p. 6036 - 6039
(2013/02/23)
-
- Copper-catalyzed asymmetric 1,4-hydroboration of coumarins with pinacolborane: Asymmetric synthesis of dihydrocoumarins
-
An efficient asymmetric addition of pinacolborane to 4-substituted coumarins proceeded with high enantioselectivity in the presence of a copper(I)-QuinoxP complex as a catalyst to produce the corresponding 1,4-hydroboration products. Treatment of the intermediates with electrophiles, without isolation, resulted in enantioenriched dihydrocoumarins. The utility of this protocol was demonstrated in the formal synthesis of biologically active molecules.
- Kima, Hyohyun,Yuna, Jaesook
-
supporting information; experimental part
p. 1881 - 1885
(2010/10/20)
-
- Chemoenzymatic synthesis and application of bicyclo [2.2.2] octadiene ligands: Increased efficiency in rhodium-catalyzed asymmetric conjugate additions by electronic tuning
-
(Figure Presented) On your bi(cycle)kel A series of 1,4dimethyl bicyclic [2.2.2] diene ligands with tunable substitution at the bridge positions was accessed using a lipase resolution and a high yielding six step sequence (see scheme). The bridgehead meth
- Luo, Yunfei,Cornell, Andrew J.
-
supporting information; scheme or table
p. 2750 - 2754
(2010/07/03)
-
- Highly active rhodium catalyst with electron-poor diphosphine enables efficient synthesis of chiral 4-aryl-δ-lactones
-
Chiral 4-aryl-δ-lactones could be synthesized efficiently with high enantioselectivity through asymmetric 1,4-addition of arylboronic acid to α,β-unsaturated lactones using Rh catalyst including electron-poor diphosphine (MeO-F12-BIPHEP) at room temperature for 1 h. In particular, our catalytic system proved to be applicable to relatively large coumarin analogues, giving optically pure 4-phenylchroman-2-one analogues in a short time.
- Korenaga, Toshinobu,Maenishi, Ryota,Osaki, Kazutaka,Sakai, Takashi
-
experimental part
p. 157 - 162
(2010/04/29)
-
- Asymmetrie Conjugate reductions of coumarins. A new route to tolterodine and related coumarin derivatives
-
"Chemical Equation Presented" The combination of catalytic amounts of [(R)-DTBM-SEGPHOS]CUH In the presence of stoichiometric DEMS (dlethoxymethylsllane) In toluene at room temperature leads to asymmetric reductions of 4-substituted coumarins. Several targets or their known precursors can be prepared In high yields and ee's, Including the muscarine receptor antagonist (R)-tolterodine.
- Gallagher, Brian D.,Taft, Benjamin R.,Lipshutz, Bruce H.
-
supporting information; experimental part
p. 5374 - 5377
(2010/02/28)
-
- Enantioselective synthesis of (S)- and (R)-tolterodine by asymmetric hydrogenation of a coumarin derivative obtained by a Heck reaction
-
(Chemical Equation Presented) An efficient and short enantioselective synthesis of (S)- and (R)-tolterodine was performed by asymmetric hydrogenation of a coumarin intermediate, easily obtained by a Heck reaction from inexpensive and commercially available starting materials.
- Ulgheri, Fausta,Marchetti, Mauro,Piccolo, Oreste
-
p. 6056 - 6059
(2008/02/10)
-
- ENANTIOSELECTIVE SYNTHESIS OF ENANTIOMERICALLY ENRICHED COMPOUNDS
-
Method of preparing an enantiomerically enriched compound of formula (II) comprising enantioselective hydrogenation of a compound of general formula (I): where W, X and Z have the meanings indicated in the description, to give a compound of general formula (II): where W, Y, T and C* have the meanings indicated in the description, in the presence of a catalyst or its suitable precursor based on Rh, Ru or Ir, having an oxidation state of 0, +1 or +2, and containing at least one enantiomerically enriched chiral ligand.
- -
-
Page/Page column 9; 10
(2010/02/10)
-
- Rhodium-catalyzed asymmetric 1,4-addition of arylboronic acids to coumarins: Asymmetric synthesis of (R)-tolterodine
-
(Chemical Equation Presented) Rhodium-catalyzed asymmetric 1,4-addition of arylboronic acids to coumarins proceeded with high enantioselectivity in the presence of a rhodium catalyst (3 mol %) generated from Rh(acac)(C 2H4)2 and (R)-Segphos to give the corresponding (R)-4-arylchroman-2-ones in over 99% ee. This asymmetric reaction was applied to the synthesis of (R)-tolterodine.
- Chen, Gang,Tokunaga, Norihito,Hayashi, Tamio
-
p. 2285 - 2288
(2007/10/03)
-
- Process for the preparation of tolterodine and intermediates thereof
-
A process for the preparation of 6-methyl-4-(R)-phenyl-chroman-2-one and 6-methyl-4-(S)-phenyl-chroman-2-one, intermediates for the synthesis of tolterodine and its (S) enantiomer, by reaction of 6-methyl-coumarin with phenylboronic acids, esters and derivatives thereof, in the presence of chiral catalysts.
- -
-
Page/Page column 4
(2010/02/14)
-
- A process for the preparation of tolterodine and intermediates thereof
-
A process for the preparation of 6-methyl-4-(R)-phenyl-chroman-2-one and 6-methyl-4-(S)-phenyl-chroman-2-one, intermediates for the synthesis of tolterodine and its (S) enantiomer, by reaction of 6-methyl-coumarin with phenylboronic acids, esters and derivatives thereof, in the presence of chiral catalysts.
- -
-
Page/Page column 8
(2010/02/14)
-
- Catalytic asymmetric total synthesis of the muscarinic receptor antagonist (R)-tolterodine
-
A convenient and high yielding method for the preparation of (R)-tolterodine, utilizing a catalytic asymmetric Me-CBS reduction was developed. Highly enantioenriched (A)-6-methyl-4-phenyl-3,4-dihydrochromen-2-one (94% ee) was recrystallized to yield practically enantiopure material (ee >99%) and converted to (R)-tolterodine in a four-step procedure. The configuration of the crucial stereocenter was preserved during the synthesis and the obtained product was identified by chiral HPLC to be the (R)-tolterodine enantiomer.
- Hedberg, Christian,Andersson, Pher G.
-
p. 662 - 666
(2007/10/03)
-