Synthesis of Arylzinc Thiolates Containing Perfluoroalkyl Chains. Model Catalyst Precursors for the Enantioselective Zinc-Mediated 1,2-Addition of Dialkylzincs to Aldehydes in Fluorous Biphase Systems

Abstract

The synthesis of perfluoroalkyl-functionalized arene trimethylsilyl ethers and their conversion to ethylzinc thiolates is described. These compounds have been successfully applied as catalysts in the enantioselective addition of diethylzinc to benzaldehyde. This is the first example of a two-phase organic/perfluorous enantioselective catalytic system.One of the major issues in applying homogeneous catalysis in fine-chemical synthesis is the design of reaction systems that enable separation of the catalyst from the product. Recent examples are the immobilization of catalytically active sites onto soluble polymers or dendrimers 1 and the use of twophase systems, usually organic solvent/water as in the RuhrChemie hydroformylation process.2 A disadvantage of the latter approach is the incompatibility of many organometallic catalyst, and also of reagents, with water.Pioneering work by Horváth et al. 3 led to a new type of two-phase catalytic system, based on the temperaturedependent phase separation of a common organic and a perfluorous solvent. These so-called fluorous biphase systems (FBS) have the advantage that most organometallic reagents are inert toward the solvents involved. A prerequisite is the use of a fluorinated catalyst that shows preferential solubility in the perfluorous solvent. Nowadays an increasing number of academic and industrial groups are working on the design of ligands containing perfluoroalkyl groups and their application in catalysis. This topic has been reviewed recently.

Asymmetric Diethyl‐ and Diphenylzinc Additions to Aldehydes by Using a Fluorine‐Containing Chiral Amino Alcohol: A Striking Temperature Effect on the Enantioselectivity, a Minimal Amino Alcohol Loading, and an Efficient Recycling of the Amino Alcohol

“…Diorganozinc addition reactions to carbonyl compounds have extensively been studied and many excellent catalysts have been developed to give the resulting secondary alcohols with very high enantioselectivities 7. The first application of a diethylzinc addition in FBS was reported by Kleijn et al5a and since then several similar approaches have been detailed by Nakamura et al5b, d, f and Tian et al,5c, e who employed fluorous chiral binaphthol derivatives and fluorous chiral amino alcohols, respectively. Herein, we wish to present an effective perfluoro catalyst for diorganozinc addition reactions based on the modification of pyrrolidinylmethanol8, 9 derivatives.…”

Asymmetric fluorous catalysis: the particular case of nitrogen-containing chiral auxiliaries

“…Nevertheless, it has been extensively studied and numerous nitrogen-containing ligands, mainly b-amino alcohols, have been developed. In 1999, van Koten et al 30 published the first example of a two-phase organic-fluorous enantioselective catalytic system using ligands 12a-12c in the enantioselective zinc-mediated 1,2-addition of diethyl zinc to aldehydes (Scheme 9).…”

Moderne Trennverfahren zur effizienten Aufarbeitung in der organischen Synthese

“…Fluorierte Zinnoxide katalysieren Umesterungen116 und die Monotosylierung von 1,2‐Diolen 117. Die enantioselektive Addition von Diethylzink an Aldehyde gelingt mit einer Reihe von fluormarkierten Katalysatoren 118–121…”