Palladium‐Catalyzed Decarbonylative Dehydration for the Synthesis of α‐Vinyl Carbonyl Compounds and Total Synthesis of (−)‐Aspewentins A, B, and C

Abstract

The direct α-vinylation of carbonyl compounds that forms a quaternary stereocenter is a challenging transformation. We discovered that δ-oxocarboxylic acids can serve as masked vinyl compounds and be unveiled by palladium-catalyzed decarbonylative dehydration. The carboxylic acids are readily available through enantioselective acrylate addition or asymmetric allylic alkylation. A variety of α-vinyl quaternary carbonyl compounds are obtained in good yields, and an application in the first enantioselective total synthesis of (−)-aspewentin A, B, and C is demonstrated.

Marine natural products

“…324 Alternariol-9-methyl ether 3-O-sulfate 545, previously obtained from Alternaria sp., an endophyte of the Egyptian medicinal plant Polygonum senegalense, 325 was obtained for the rst time from the marine environment from endophytic Alternaria alternata. 326 The norditerpenes aspewentin A-C (Aspergillus wentii 327 ) have been synthesised 328 as have the prenylated indole alkaloids, (+)-notoamide I (Aspergillus sp.) 329 and (À)-17hydroxy-citrinalin B (Penicillium citrinum) 330 via a unied strategy.…”

Transition Metal‐Mediated C−C Single Bond Cleavage: Making the Cut in Total Synthesis

“…To address this gap in synthetic methods,Stoltz and co-workers developed astrategy for accessing a-vinylcarbonyl compounds bearing an aquaternary stereocenter by Pd-catalyzed decarbonylative dehydration. [44,45] Specifically,c arboxylic acids such as 117 could be obtained as as ingle enantiomer by the enantioselective Michael addition of a,a-disubstituted enolates derived from carbonyl compounds 114 to acrylate acceptors 115;they could alternatively be accessed by the enantioselective Pdcatalyzed allylic alkylation of b-ketoesters 116 (Scheme 17 B). AP d-catalyzed decarbonylative dehydration of carboxylic acids 117 then afforded enantiopure a-vinylcarbonyl compounds 121 with an a-quaternary center;t his process presumably occurs through the in situ formation of mixed anhydrides 118,f ollowed by oxidative addition (!119), decarbonylation (!120), and b-hydride elimination.…”

Sequential Ruthenium Catalysis for Olefin Isomerization and Oxidation: Application to the Synthesis of Unusual Amino Acids

“…4 In particular, catalytic enantioselective vinylation of carbonyl enolates is still highly challenging and limited in substrate scope and, moreover, methods for the construction of quaternary stereocenters are very rare. 12,14 Even more scarce and far less established are catalytic enantioselective carboxylations (Scheme 1C). 15 …”