A Practical and Stereoselective Organocatalytic Alkylation of Aldehydes with Benzodithiolylium Tetrafluoroborate

Abstract

Recently, the direct substitution of allylic, benzylic, and tertiary alcohols has been achieved via SN 1-type reactions with catalytic amounts of Brønsted or Lewis acids. When a new stereogenic center is formed most of these transformations produce the desired product as a racemate, as these reactions proceed through carbenium ions. The arsenal of activation modes available in organocatalysis can be used to set up suitable reaction conditions in which chiral nucleophiles (enamine catalysis) or chiral electrophiles (iminium catalysis, chiral counterion catalysis) can easily be generated. Recently, we have used stabilized carbenium ions, directly available or obtained from the corresponding alcohols, in new organocatalytic stereoselective SN 1-type reactions. The commercially available carbenium ion benzodithiolylium tetrafluoroborate can be used for the straightforward organocatalytic stereoselective alkylation of aldehydes. In this account we will illustrate the application of this methodology in the total synthesis of natural products and the preparation of valuable starting materials.

Photocatalysis in organic and polymer synthesis

“…The complete set of these reactions is beyond the scope of this review, but some notable examples have been mentioned for the interested reader. [99][100][101][102][103] MacMillan's group has also presented the photoredox mediated trifluoromethylation of arenes and heteroarenes including pyrroles, indoles, furans, thiophenes and notably, more complex substituted arenes such as Lipitor, the drug commonly used to treat high cholesterol. 104 The oxygenation of arenes has also been reported by Li and coworkers for a range of anisole derivatives.…”

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

“…We surprisingly found that benzodithiolylium tetrafluoborate 16 was commercially available, and its interesting chemistry was fully described 101. We have carefully optimized the alkylation of aldehydes with 16 , using a MacMillan secondary amine as the catalyst (Scheme ) 102. Notably, the reaction is performed in a mixture of water: CH 3 CN as the reaction solvent, where the carbenium ion is fully soluble.…”

“…No dried solvents or strong bases are necessary for the alkylation, and the procedure can be successfully used by undergraduate students 107. This organocatalytic alkylation was applied to the total synthesis of arundic acid,102 Lilial,108 and Bisabolans (Scheme ) 109…”