Pyruvate Enolate Arylation and Alkylation: OBO Ester Protected Pyruvates as Useful Reagents in Organic Synthesis

Abstract

A protected pyruvate equivalent is described that allows arylation and arylation/alkylation reactions to be performed at the methyl group. Utilization of the OBO derivative of the pyruvate ester allowed the application of palladium catalyzed arylation reactions together with subsequent alkylation, under basic conditions. Moreover, the OBO protecting group could be easily removed in one step to provide access to a wide range of substituted pyruvate derivatives.

Synthesis of lamellarin alkaloids using orthoester-masked α-keto acids

“…6 ) under acidic conditions. Synthesis of the required 1,4-dicarbonyl 7 would be achieved using a strategic enolate arylation of OBO-ketone 1 , and subsequent enolate alkylation using α-bromoacetophenone 8 11. A possible one-pot procedure from 1 to 7 , by the sequential addition of 10 and 8 under basic conditions, was envisaged.…”

“…Through a short screening process, optimal conditions for the coupling of 1 and 10 were found, using NaO t Bu and Pd(dtbpf)Cl 2 (5 mol%) in THF to give 9 in 75% yield (Scheme 3). 11,13 The α-bromoacetophenone 8 required for alkylation of 9 was prepared by O-alkylation of acetovanillone with 2-bromopropane followed by α-bromination using (±)-10-camphorsulfonic acid/NBS. Treatment of 9 with NaO t Bu followed by addition of 8 gave the desired 1,4-dicarbonyl 7 in quantitative yield after purification.…”

“…Previously, we have demonstrated the synthetic utility of OBO-ester (oxabicyclo[2.2.2]octyl orthoester) masked α-keto acid 1 in the construction of 1,4- and 1,5-dicarbonyls, via a Pd-catalysed enolate arylation/alkylation sequence, and subsequent condensation to form aromatic heterocycles, e.g. 2-carboxy-pyrroles 11. Inspired by the key role of α-keto acids in Nature, we envisioned that appropriately substituted OBO-ester α-keto acids 2 could serve as powerful building blocks with which to prepare the lamellarin alkaloids.…”

Applications of alkyl orthoesters as valuable substrates in organic transformations, focusing on reaction media

“…429 Manojveer and Balamurugan presented a facile and efficient process to get substituted benzo[a]uorenes (524), with regioselectivity via a domino three-component reaction of o-alkynylbenzaldehydes, alkynes, and TMOF by TfOH (20 mol%) in CH 3 CN or CH 2 Cl 2 at room temperature. This reaction proceeded through the reaction of aldehydes (515) with TMOF (4) by TfOH to obtain the in situ formed acetal (521). Subsequent [2 + 2] cycloaddition between acetal (521) and alkynes (522) generated the cis-isomer (523) which on intramolecular annulation reaction achieved substituted benzo TfOH catalyzed the one-pot three-component reaction of ketones, such as acetophenones and ethyl phenyl ketones (525), chalcones (526), and TMOF (4) in carbon tetrachloride (CCl 4 ) at room temperature to obtain a series of symmetrical and unsymmetrical 1,5-diketones (527) within 6-8 h. This reaction progressed through the in situ formation of acetals (528) from the reaction of ketones with TMOF which set up an equilibrium with the enol ether (529), as an Michael acceptor, which was followed by Michael addition with the activated chalcones by an acidic catalyst (530) to afford 1,5-diketones (527).…”

Orthoesters: Multiple Role Players in Organic Synthesis

“…The utility of orthoesters as protective groups for carboxylic acids, hydroxyl groups, esters, and α‐keto acids has been well documented . This protective ability has made orthoesters indispensable in a range of reactions, including the synthesis of RNA oligonucleotides, plant alkaloids, and preparation of a tetracationic macrocycle that can be used as a constituent of a hydrogel .…”