Multistereogenic Phosphine Ligand‐promoted Palladium‐Catalyzed Allylic Alkylation of Cyanoesters

Abstract

A palladium-catalyzed allylic alkylation of unsubstituted 2-cyanoacetates using a 1,1'-bi-2-naphthol-derived multifunctional N,O,P ligand is reported. A number of chiral monosubstituted 2-cyanoacetates with two adjacent stereogenic carbon centers are obtained in this Pd-catalyzed asymmetric allylic alkylation reaction, in which the multistereogenic and multifunctional 1,1'-bi-2-naphthol-derived N,O,P ligand-promoted Pd-catalyzed asymmetric allylic alkylation reaction proceeds smoothly in high diastereo-and enantioselectivity (up to > 99:1 dr and up to 96 % ee).The allylic alkylation of carbon-based nucleophiles to allylic reagents, including allylic acetates, is one of the most important methods for carbon-carbon bond construction.[1] Accordingly, the development of catalytic asymmetric versions of this type of transformation and the design and application of various ligands for enantioselectivity enhancement have been the subject of intensive research in the field of asymmetric catalysis and organic chemistry over the past decades. [2][3][4] In this respect, the asymmetric allylic alkylation (AAA) of activated methylene compounds, such as 1,3-dicarbonyl compounds, is very important and one of the most attractive approaches to the synthesis of chiral carbonyl derivatives. [3,4] To attain high stereoselectivity, numerous chiral ligands, especially P ligands, have been developed. [4] In addition, similarly to catalytic asymmetric hydrogenation, the catalytic AAA of 1,3-dicarbonyl compounds has been applied extensively as a model reaction in the evaluation of chiral ligands in asymmetric catalysis, which would be beneficial to the exploration of novel backbones or strategies for chiral ligand chemistry. Despite the development of various well-defined palladium catalysts derived from chiral ligands for this AAA reaction, effective chiral ligands were still lacking for the allylic alkylation of unsubstituted 2-cyanoacetates, [5, 6] for example, only ethyl 2-cyanoacetate (1 a) or methyl 2-cyanoacetate has attracted limited attention in the past decades. To the best of our knowledge, there are only a few examples of the asymmetric palladium-catalyzed allylic alkylation of unsubstituted 2-cyanoaetates with allylic acetates.[6] Unfortunately, the enantioselectivities in these reported reactions were not good enough, possibly as a result of the difficulty in forming two adjacent stereogenic centers simultaneously from two substrates.As shown in Scheme 1, these reported methods involving chiral ligands bearing a phosphine, sulfur, or oxazoline moiety did not achieve a high level of enantioselectivity. Notably, in combination with the application of ionic liquids in catalysis, Scheme 1. Previous results and this work on the catalytic AAA reaction of 2-cyanoacetates. dba = Dibenzylideneacetone, bmim = 1-butyl-3-methylimidazolium.[a] W

Lewis‐Base‐Mediated Diastereoselective Silylations of Alcohols: Synthesis of Silicon‐Stereogenic Dialkoxysilanes Controlled by Chiral Aryl BINMOLs

“…( 4 b – 4 h ). These experimental results also indirectly supported the privileged role of the phosphine center on the Ar‐BINMOLs in this diastereoselective silylation because of dichlorosilane activation by phosphine . Notably, an advantage of this procedure is that the silylation reaction reached completion with perfect chirality transfer from chiral Ar‐BINMOL to silicon‐stereogenic center.…”

“…The effect of functional groups on the diastereoselective silylation of Ar‐BINMOL‐derived diols with dichlorosilane is important for the construction of silicon‐stereogenic dialkoxysilanes. Furthermore, having established the desymmetrization of dichlorosilanes with Ar‐BINMOL‐derived phosphines, we also examined the diastereoselective silylation of Ar‐BINMOL‐derived aldehyde 5 under the optimized reaction conditions. However, we did not get any the desired products 6 in this reaction even with various dichlorosilanes (Scheme ).…”

“…These experimental results also indirectly supported the privileged role of the phosphine centero nt he Ar-BINMOLsi nt his diastereoselective silylation because of dichlorosilane activation by phosphine. [20,21] Notably,a na dvantage of this procedure is that the silylation reaction reached completion with perfect chirality transfer from chiral Ar-BINMOL to silicon-stereogenic center. More importantly,t his simple and highly diastereoselective silylation provided access to the synthesis of af amily of chiral phosphine ligands bearing atropisomeric and silicon-based central chirality ((R A ,S C, S Si )-dioxasilane 4).…”

Development of Ar‐BINMOL‐Derived Atropisomeric Ligands with Matched Axial and sp3 Central Chirality for Catalytic Asymmetric Transformations

“…Furthermore, these catalytic asymmetric allylic alkylations of ethyl 2‐cyanoacetate only afforded low yields and up to 80% ee . Our work is an exciting example that the unsubstituted 2‐cyanoacetates can be successfully utilized to construct two adjacent stereogenic centers in the Pd‐AAA reaction using the powerful BINOL‐derived ligand 64 (Scheme ) . We believe that this multifunctional and multistereogenic ligand bearing matched axial and sp 3 central chirality could exhibit unexpected activity for the highly enantioselective synthesis of functionalized molecules.…”

The Synthesis of Diamidediallylcalix[4]arene Derivatives as Ligand for Bromide Anion

“…[1][2][3][4] One of the main aspects of this multi-disciplinary field of chemistry is the design and creation of unusual compounds based on these receptors and sensors for biological and inorganic cation and anion. [5][6][7][8] It is known that compounds containing allyl group are good starting materials for polymerization reaction [9][10][11][12] and chiral molecules receiving, [13][14][15] but there are only few examples of such reactions in supramolecular chemistry. [16,17] So, calixarene bearing allyl group is a promising molecule for design of various host compounds.…”