Diastereomer | EPFL Graph Search

In stereochemistry, diastereomers (sometimes called diastereoisomers) are a type of stereoisomer. Diastereomers are defined as non-mirror image, non-identical stereoisomers. Hence, they occur when two or more stereoisomers of a compound have different configurations at one or more (but not all) of the equivalent (related) stereocenters and are not mirror images of each other. When two diastereoisomers differ from each other at only one stereocenter, they are epimers. Each stereocenter gives rise to two different configurations and thus typically increases the number of stereoisomers by a factor of two. Diastereomers differ from enantiomers in that the latter are pairs of stereoisomers that differ in all stereocenters and are therefore mirror images of one another. Enantiomers of a compound with more than one stereocenter are also diastereomers of the other stereoisomers of that compound that are not their mirror image (that is, excluding the opposing enantiomer). Diastereomers have

Access to Chiral Cyclopentane Scaffolds by Enantioselective Nickel-Catalyzed Annulations

Joachim Sven Ernst Ahlin

The cyclopentane scaffold has attracted much attention due to its ubiquity in numerous bioactive natural products such as prostaglandins and polyquinanes. However, despite a plethora of available procedures to access this motif, a lack of methods that rival the generality of the Diels-Alder reaction for the synthesis of six-membered rings represents an important gap. Thus, the development of protocols providing efficient access to functionalized chiral cyclopentanes from simple and readily accessible starting materials is highly desirable. In this respect, the tremendous advances in the development of nickel-catalyzed carbon-carbon bond-forming reactions, combined with the unique properties of N-heterocyclic carbenes have led to the development of new approaches to five-membered carbocyclic rings. These include nickel-catalyzed reductive couplings and reductive [3+2] cycloadditions. These strategies are attractive, as functionalized five-membered carbocyclic rings can be accessed from two simple pi-components without any changes in atom connectivity. Despite the recent development of numerous chiral N-heterocyclic carbenes and their successful application in various transition metal-catalyzed reactions, applications in asymmetric nickel catalysis remain scarce. This thesis describes the development of efficient enantioselective nickel-catalyzed methodologies for the formation of five-membered carbocycles from readily accessible and inexpensive starting materials, enabled by two novel chiral N-heterocyclic carbene ligands. First, the development of an intermolecular enantioselective nickel-catalyzed reductive [3+2] cycloaddition of unsaturated aromatic esters and internal alkynes for the synthesis of cyclopentenones is described. For this scalable methodology, a bulky chiral C1-symmetric N-heterocyclic carbene ligand was shown to facilitate the efficient asymmetric synthesis of cyclopentenones from a wide range of mesityl enoates and internal alkynes under mild conditions. Unsymmetrically substituted alkynes were incorporated in a regioselective fashion and the cyclopentenones were synthesized in high yields and enantioselectivity. As a second methodology for the construction of chiral cyclopentane scaffolds, an intermolecular diastereoselective and enantioselective nickel-catalyzed reductive three-component coupling of various aryl aldehydes, norbornene derivatives and silanes is described, which gives access to synthetically valuable silyl-protected indan-1-ols via an aromatic C(sp2)-H functionalization. A bulky chiral C2-symmetric N-heterocyclic carbene ligand possessing a 1,2-(dinaphthalen-1-yl)ethylene diamine scaffold provided the silylated indan-1-ols under mild and scalable conditions, as a single diastereoisomer, in high enantioselectivity and good regioselectivity in the case of meta-substituted aryl aldehydes.

EPFL2016

Chiral N-Heterocyclic Carbene Ligand Enabled Nickel(0)-Catalyzed Enantioselective Three-Component Couplings as Direct Access to Silylated Indanols

Joachim Sven Ernst Ahlin, Nicolai Cramer

An enantioselective nickel(0)-catalyzed reductive three-component coupling between aromatic aldehydes, norbornenes, and silanes affords directly silyl-protected indanol derivatives. A new bulky chiral C-2-symmetric NHC (NHC = N-heterocyclic carbene) ligand basing on the 1,2-di(napthalen-1-yl)ethylene diamine backbone allows accessing the annulated products as single diastereoisomers in high enantioselectivity.

American Chemical Society2016

Catalytic Enantioselective Aminopalladation–Heck Cascade

Jian Cao, Yuping He, Qian Wang, Hua Wu, Jieping Zhu

Domino processes initiated by intramolecular nucleopalladation of alkynes have been developed into powerful synthetic tools for the synthesis of functionalized heterocycles. However, a catalytic enantioselective version of this class of reactions remains scarce. We report herein that reaction of 2-alkynylanilines with prochiral cyclopentenes in the presence of a catalytic amount of Pd(OAc)2, a chiral bidentate pyrox ligand and O2 as terminal oxidant affords the structurally diverse indole-cyclopentene conjugates bearing two stereocenters in a highly diastereo- and enantio-selective manner. One of the products is converted to a heavily functionalized tetracyclic indolinone derivative.

2021

Access to Chiral Cyclopentane Scaffolds by Enantioselective Nickel-Catalyzed Annulations

Joachim Sven Ernst Ahlin

EPFL2016