Buchler Glossary

Asymmetric Alkylation

Alkylation is the introduction of an alkyl group into an organic compound by substitution or addition. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene (or their equivalents). Alkylating agents are reagents for effecting alkylation. In order to be able to carry out the reaction in a highly enantioselective manner, chiral Cinchona alkaloid catalysts are predominantly used.

Asymmetric Alkylation

The enantioselective alkylation of enolates is a particularly versatile method for the construction of α-stereogenic carbonyl derivatives, which are ubiquitous in synthetic chemistry. Also substituted α-amino acids are valuable building blocks that are needed in a variety of syntheses. Through asymmetric α-alkylation of glycine Schiff base with substituted benzyl bromides under the catalysis of Cinchona alkaloid PTCs such as O-allyl-N-(9-anthracenmethyl) cinchoninium bromide and O-allyl-N-(9-anthracenylmethyl)cinchonidium bromide, respectively, a series of both (R)- and (S)-enantiomers of unnatural α-amino acid derivatives can be obtained in excellent yields and enantioselectivity. The synthetic method is simple and scalable. In addition the stereochemistry of the products is fully predictable and controlled: the Cinchonine-type phase transfer catalyst resulted in (R)-α-amino acid derivatives, and the Cinchonidine-type phase transfer catalyst afforded (S)-α-amino acid derivatives. Asymmetric phase transfer catalysis has been recognized as an approach that is greener and more sustainable than synthetic alternatives.

The asymmetric allylic alkylation is a challenging reaction. It can be performed in highly enantioselective manner using Cinchona alkaloid derivatives. A highly efficient method to access axially chiral anilides through enantioselective allylic alkylation reaction with achiral Morita–Baylis–Hillman carbonates by using a bis-Cinchona alkaloid catalyst is feasible. Through the atroposelective approach, a broad range of axially chiral anilide products with different acyl groups, such as substituted phenyl, naphthyl, alkyl, enyl, styryl, and benzyl, can be generated with very good yields, excellent cis:trans ratios, and good to excellent enantioselectivities.

Please find some examples of Alkylations promoted by Cinchona Alkaloids in our Buchler Chiral Catalyst Search.

Exanple from literature

Synthesis of Both Enantiomers of Chiral Phenylalanine Derivatives Catalyzed by Cinchona Alkaloid Quaternary Ammonium Salts as Asymmetric Phase Transfer Catalysts. (Jin et al.; Molecules 2018, 23, 1421.)

Enantioselective Alkylation

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