A general stereoselective enamine mediated alkylation of α-substituted aldehydes

Abstract

We herein present a general enamine-mediated α-alkylation of α-substituted aldehydes with carbenium ions for the stereoselective construction of quaternary stereogenic centers.

From QCA (Quantum Cellular Automata) to Organocatalytic Reactions with Stabilized Carbenium Ions

“…In addition, these findings can be applied towards a synthesis of biologically active products, such as Baulamycin A and B 113. Benzodithiolylium can be also used for accessing alkylation of the challenging branched aldehydes, using primary amines derived from Cinchona alkaloids (Scheme ) 114. Alkylation with benzodithiolylium using a supported115 catalyst, obtained also by flow conditions,116 can enhance the applicability of the alkylation for large‐scale processes.…”

“…[113] Benzodithiolylium can be also used for accessing alkylation of the challenging branched aldehydes, using primary amines derived from Cinchona alkaloids (Scheme 17). [114] Alkylation with benzodithiolylium using a supported [115] catalyst, obtained also by flow conditions, [116] can enhance the applicability of the alkylation for large-scale processes. Benzodithiolylium can also be applied to general organometallic chemistry, [117] enolate chemistry, [118] and natural product synthesis, [119] showing that this reagent can be quite versatile.…”

A Practical and Stereoselective Organocatalytic Alkylation of Aldehydes with Benzodithiolylium Tetrafluoroborate

“…A practical and robust way to prepare alkylated alcohols, aldehydes, or acids is to use the methodology developed by Evans that relies on the use of oxazolidinone chiral auxiliaries . Recently, we turned our attention towards the organocatalytic alkylation of aldehydes, which proceeds via an S N 1‐type mechanism, during which carbenium ions are generated from a precursor such as alcohols, or can be introduced as stable carbenium ions . We used the Mayr scale of reactivity extensively as a guide in order to choose suitable precursors of these stable carbenium ions (Fig.…”

“…20 Recently, we turned our attention towards the organocatalytic alkylation of aldehydes, which proceeds via an S N 1-type mechanism, 21 during which carbenium ions are generated from a precursor such as alcohols, or can be introduced as stable carbenium ions. [22][23][24][25][26] We used the Mayr scale of reactivity extensively as a guide in order to choose suitable precursors of these stable carbenium ions ( Fig. 1).…”

The Catalytic Asymmetric α‐Benzylation of Aldehydes

“…[3] Subsequently, other groups have contributed additional aminocatalytic methods for the asymmetric a-alkylation of aldehydes, including strategies that combine enamine catalysis with radical or cationic (S N 1) reaction pathways. [4][5][6][7][8][9][10][11][12][13] Despite these unquestionable advancements though, the asymmetric intermolecular S N 2 a-alkylation of aldehydes with simple alkyl halides has remained a long-standing challenge for enamine catalysis (Scheme 1). [2] Here we report progress with the first catalytic enantioselective a-benzylation of a-branched aldehydes.…”