Pd^II-Catalyzed Oxidative Aldehyde-sp²C–H Functionalization and Cyclization Using NHC with Mild Oxidant DMSO for the Selective Synthesis of Esters, Sugar-Based Analogues, and β-Hydroxy Chromanones: An ¹⁸O-Labeling Study

Abstract

We assume formation of acyl-PdII–N-heterocyclic-carbene (NHC) organometalics for diverse C–O/O–C and C–C/C–O coupling catalysis of direct functionalization and cyclization reactions. We report the first use of dimethyl sulfoxide (DMSO) as an oxidant under an inert atmosphere to O2-sensitive NHC for oxidative transformations. In situ generated imidazolium halides are utilized as a precursor of NHC and as a source of alkyl group for the sp2C–H functionalization of aldehydes to esters under mild conditions. In contrast to the reported NHC-catalyzed esterification strategies, the outstanding substrate scope of this mild catalysis approach is established through synthesis of thermally labile sugar-based chiral esters. Our competition experiments using various unsymmetrical imidazolium halides revealed an ascending rate of migratory aptitude among methyl ≪ allyl < crotyl < cinnamyl < benzyl moiety. DMSO is used as an oxidant for both esterification and cyclization reactions, and the transfer of the DMSO-oxygen to ester is confirmed using an 18O-labeling experiment. The diverse activity using DMSO-oxygen to acyl-PdII–NHC is verified by developing a unique C–C-coupled cyclization with side-chain hydroxylation of olefin to achieve valuable β-hydroxy chromanones.

Copper Catalyzed‐TBHP/DTBP Promoted C(sp2)−H Bond Scission of Aldehydes: An Approach to Transform Aldehyde to Esters

“…In this respect, the most successful approaches are the direct esterification of aldehydes via C(sp 3 )−H functionalisation utilizing methyl arenes, [6] cycloalkanes, [7] and cyclic ethers [8] as coupling partners. An interesting alternative strategy to achieve direct esterification of aldehydes is through the in‐situ activation of the aldehyde with N‐heterocyclic carbene (NHC) with [9] or without metal, [10] followed by an interception with appropriate alkyl halides to afford the desired ester. Alternatively, there are numerous nonclassical strategies to access esters starting from aldehyde and desired alcohol by utilizing carboxylic acid surrogates, [11] noble‐metal catalysed cross dehydrogenative coupling, [12] NHC‐catalyzed direct oxidative esterification of aldehydes [13] and direct conversion of aldehydes to esters via the oxidation of in situ formed hemiacetal intermediate [14] .…”

“…Alternatively, there are numerous nonclassical strategies to access esters starting from aldehyde and desired alcohol by utilizing carboxylic acid surrogates, [11] noble‐metal catalysed cross dehydrogenative coupling, [12] NHC‐catalyzed direct oxidative esterification of aldehydes [13] and direct conversion of aldehydes to esters via the oxidation of in situ formed hemiacetal intermediate [14] . Despite significant progress, these aforementioned methodologies require the pre‐activation of acyl surrogate [11,7a] use of sophisticated ligand system [12,13a–c,14m] expensive catalyst [9,12] and use of one of the coupling partners in large excess (usually as solvent) [6,7,8,14a–b,d−e,g−l] . Additionally, although this transformation has been widely studied, their synthetic utility is curtailed by narrow substrate scope mostly covering esters of primary aliphatic alcohols ,[12,13b,14] (mostly methanol) and simple aromatic aldehydes due to instability of the hemiacetal intermediate, the major challenge being oxidative esterification of aliphatic aldehydes ,[6,7,11c,13b,14a,14e–f,14i,14k] In this context, to overcome these limitations, we envisioned that there is still an urge to develop a new versatile methodology for the synthesis of esters starting from readily available aldehydes that can be successfully utilized to synthesize both alkyl and benzyl esters.…”