- Method for asymmetric catalytic synthesis of gamma-cyanoamide compound and chiral drug using gamma-cyanoamide compound
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The invention relates to a method for asymmetric catalytic synthesis of a gamma-cyanoamide compound and a chiral drug using the gamma-cyanoamide compound. The method specifically comprises the following step: with silicon group-protected allene ketimine and alpha,beta-unsaturated pyrazolecarboxamide as raw materials, a complex formed by chiral amine oxide and cobalt trifluoromethanesulfonate as a catalyst, water as an additive, and trichloromethane as a solvent, conducting reacting for 2 to 48 hours at 0 to -60 DEG C so as to obtain the chiral gamma-cyanopyrazolecarboxamide compound which is high in property and good in substrate universality. A plurality of chiral natural products or drug molecules such as verapamil, Sporochnol A and key intermediates for synthesizing Epilarene, Aphanorphine and Ammoglutethimide can be obtained by performing some simple conversion on the catalytic product, namely the gamma-cyanopyrazolecarboxamide compound.
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- Enantioselective synthesis of nitriles containing a quaternary carbon center by michael reactions of silyl ketene imines with 1-acrylpyrazoles
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The enantioselective construction of quaternary carbon centers is a marked challenge in asymmetric catalysis research. It is extremely difficult when a chiral catalyst can not distinguish the facial selectivity of the substrate through bond interactions. Here we realized an enantioselective Michael reaction of silyl ketene imines to 1-acrylpyrazoles using a chiral N,N′-dioxide-Co(II) complex. The protocol is highly efficient for the construction of nitrile-, aryl-, and dialkyl-bearing carbon centers and has been successful applied in the divergent synthesis of pharmaceuticals and natural products. The through-space dispersion interactions between unbound silyl ketene imines and the 1-acrylpyrazole-bonded catalyst play a key role in facilitating the reactivity and the enantioselectivity of this process.
- Chen, Long,Pu, Maoping,Li, Shiyang,Sang, Xinpeng,Liu, Xiaohua,Wu, Yun-Dong,Feng, Xiaoming
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p. 19091 - 19098
(2021/11/22)
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- ProPhenol Derived Ligands to Simultaneously Coordinate a Main-Group Metal and a Transition Metal: Application to a Zn?Cu Catalyzed Reaction
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A new bifunctional ligand bearing chiral N-heterocyclic carbene (NHC) and prolinol moieties is presented. Utilizing the designed ligand, an in situ formed Cu/Zn hetero-bimetallic complex unlocks the asymmetric allylic alkylation reactions of allyl phosphates with zinc keto-homoenolates, leading to the formation of various γ-vinyl ketones with good regio- and enantio-selectivity. DF sT calculation supports that the chelation of allyl phosphates with catalyst promotes the SN2’ addition and the ligand-substrate steric interactions account for the stereoselective outcome.
- Qi, Xiaotian,Trost, Barry M.,Xu, Minghao,Zhang, Guoting
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supporting information
(2022/01/06)
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- Enantioselective construction of quaternary stereogenic centers from tertiary boronic esters: Methodology and applications
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Pin it down: A range of substrates that bear versatile functional groups with quaternary stereogenic centers have been prepared with very high enantioselectivity from tertiary boronic esters (see scheme; Cb=N,N-diisopropylcarbamoyl, pin=pinacolato). The preparation of allylboronic esters bearing contiguous quaternary and tertiary stereogenic centers, and applications to natural product synthesis are also reported.
- Sonawane, Ravindra P.,Jheengut, Vishal,Rabalakos, Constantinos,Larouche-Gauthier, Robin,Scott, Helen K.,Aggarwal, Varinder K.
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supporting information; experimental part
p. 3760 - 3763
(2011/06/22)
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- Total synthesis of sporochnols, fish deterrents from a marine alga
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Sporochnols, fish deterrents from a marine alga, were synthesized, using intramolecular C-H insertion of alkylidenecarbene as a key step to construct the chiral quaternary center.
- Ohira, Susumu,Kuboki, Atsuhito,Hasegawa, Taisuke,Kikuchi, Takato,Kutsukake, Tatsuhiko,Nomura, Maki
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p. 4641 - 4644
(2007/10/03)
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- Modular pyridinyl peptide ligands in asymmetric catalysis: Enantioselective synthesis of quaternary carbon atoms through copper-catalyzed allylic substitutions
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Highest enantioselectivities so far with dialkylzinc reagents! Quaternary carbon centers are formed enantioselectively through a Cu-catalyzed allylic substitution reaction that is promoted by pyridinyl peptide-based ligands in the presence of dialkylzinc reagents (see scheme). The modularity of this new class of chiral ligands is exploited for reactivity and selectivity optimization.
- Luchaco-Cullis, Courtney A.,Mizutani, Hirotake,Murphy, Kerry E.,Hoveyda, Amir H.
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p. 1456 - 1460
(2007/10/03)
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- Remarkable effect of aluminum reagents on rearrangements of epoxy acylates via stable cation intermediates and its application to the synthesis of (S)-(+)-sporochnol A
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A remarkable effect of (C6F5O)3Al for promoting the rearrangement of epoxy acylates via stable cation intermediates was found, and new methods for constructing chiral benzylic, vinylic, and acetylenic quaternary carbon centers were developed. During the study, the importance of the ionic nature of the O - metal bond in the intermediates of such epoxides was addressed. This method was applied to the asymmetric total synthesis of (S)-(+)-sporochnol A.
- Kita,Furukawa,Futamura,Ueda,Sawama,Hamamoto,Fujioka
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p. 8779 - 8786
(2007/10/03)
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