Enantioselective 1,2-Difunctionalization of Dienes Enabled by Chiral Palladium Complex-Catalyzed Cascade Arylation/Allylic Alkylation Reaction

2015 ◽  
Vol 137 (42) ◽  
pp. 13476-13479 ◽  
Author(s):  
Xiang Wu ◽  
Hua-Chen Lin ◽  
Ming-Li Li ◽  
Lu-Lu Li ◽  
Zhi-Yong Han ◽  
...  
Keyword(s):  
Palladium Complex ◽  
Alkylation Reaction ◽  
Allylic Alkylation

ChemInform Abstract: Enantioselective 1,2-Difunctionalization of Dienes Enabled by Chiral Palladium Complex-Catalyzed Cascade Arylation/Allylic Alkylation Reaction.

ChemInform ◽  
2016 ◽  
Vol 47 (15) ◽  
pp. no-no
Author(s):  
Xiang Wu ◽  
Hua-Chen Lin ◽  
Ming-Li Li ◽  
Lu-Lu Li ◽  
Zhi-Yong Han ◽  
...  
Keyword(s):  
Palladium Complex ◽  
Alkylation Reaction ◽  
Allylic Alkylation

A Concise and Modular Three-Step Synthesis of (S)-Verapamil using an Enantioselective Rhodium-Catalyzed Allylic Alkylation Reaction

Synthesis ◽  
2020 ◽  
Vol 52 (15) ◽  
pp. 2185-2189 ◽  
Author(s):  
P. Andrew Evans ◽  
Mai-Jan Tom ◽  
Ben W. H. Turnbull
Keyword(s):  
Calcium Channel ◽  
Asymmetric Synthesis ◽  
Channel Blocker ◽  
Alkylation Reaction ◽  
Allylic Alkylation ◽  
Efficient Synthesis ◽  
Terminal Olefin ◽  
Bioactive Agents ◽  
Quaternary Stereocenter ◽  
Modular Nature

A concise and modular asymmetric synthesis of the calcium channel blocker (S)-verapamil is described. This approach employs an enantioselective rhodium-catalyzed allylic alkylation reaction between an α-isopropyl-substituted benzylic nitrile and allyl benzoate to construct the challenging acyclic quaternary stereocenter. The terminal olefin then serves as a convenient synthetic handle for a hydroamination to introduce the phenethylamine moiety, furnishing (S)-verapamil in three steps and 55% overall yield, thus providing the most efficient synthesis of this important pharmaceutical reported to date. Furthermore, given the modular nature of the synthesis, it can be readily modified to prepare structurally related bioactive agents.

Coordination of the Trost modular ligand to palladium allyl fragments: Oligomers, monomers and memory effects in catalysis

2004 ◽  
Vol 76 (3) ◽  
pp. 589-601 ◽  
Author(s):  
G. C. Lloyd-Jones ◽  
S. C. Stephen ◽  
I. J. S. Fairlamb ◽  
Aina Martorell ◽  
Beatriz Dominguez ◽  
...  
Keyword(s):  
Crucial Role ◽  
Dynamic Equilibrium ◽  
Catalyst System ◽  
Alkylation Reaction ◽  
Allylic Alkylation ◽  
Monomeric Form ◽  
X Ray Diffraction ◽  
Asymmetric Allylic Alkylation ◽  
X Ray ◽  
Oligomeric Form

Reaction of the C2-symmetric "Trost modular ligand" with cationic Pd(II) allyl fragments allows isolation of air- and bench-stable pro-catalysts for the asymmetric allylic alkylation of racemic cycloalkenyl esters. In solution, three distinct complexation modes are observed. When mixed in a ligand/Pd ratio of 1/2, a binuclear bis-P,O-chelate complex is generated. This species does not induce enantioselectivity in the reaction. In contrast, with a ligand/Pd ratio of 1/1, a highly enantioselective, P,P-coordinated pro-catalyst system is generated in which there are two basic coordination modes: monomeric and oligomeric. The monomeric form is mononuclear and exists as two 13-membered chelates, isomeric through loss of C2-symmetry in the ligand. The oligomeric form is polynuclear and forms chains and rings of alternating ligand and cationic Pd(allyl) units, one of which was identified by single-crystal X-ray diffraction. In solution, the monomeric and oligomeric species are in dynamic equilibrium with populations and interconversion rates controlled by concentration, temperature, and counterion. Isotopic desymmetrization analysis suggests that the monomer-oligomer equilibrium plays a crucial role in both the selectivity and efficiency of the asymmetric allylic alkylation reaction.

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