Sequential One-Pot Combination of Multireactions through Multicatalysis: A General Approach to Rapid Assembly of Functionalized Push−Pull Olefins, Phenols, and 2-Methyl-2H-chromenes

Abstract

A general, sustainable and practical process for the sequential cascade one-pot synthesis of library of highly substituted push-pull olefins, phenols and 2-methyl-2H-chromenes was reported through multicatalysis cascade (MCC) reactions. Direct sequential one-pot combination of amine- or amino acid-catalyzed cascade Knoevenagel/Michael/aldol condensation/decarboxylation with other reactions like amine- or amino acid-catalyzed cascade Claisen-Schmidt/iso-aromatization, Claisen-Schmidt/isomerization, Claisen-Schmidt/iso-aromatization/isomerization, Michael addition, Claisen-Schmidt/Michael, ruthenium-base-silica-catalyzed ring closing metathesis/base-induced ring-opening/benzylic oxidation/[1,7]-sigmatropic hydrogen shift, or ruthenium-base-heat-catalyzed ring closing metathesis/base-induced ring-opening/[1,7]-sigmatropic hydrogen shift reactions of alkyl acetoacetates, a variety of aldehydes and alkyl halides furnished the highly functionalized push-pull olefins, phenols and 2-methyl-2H-chromenes with high yields. The yields and regioselectivities were good to excellent. Evidence for a new reaction pathway involving in situ formation of novel push-pull dienamines under amine- or amino acid-catalysis is presented along with examples demonstrating the amenability of the process to MCC chemistry.

Recent advances in the discovery and design of multicomponent reactions for the generation of small-molecule libraries

“…Overall, the protocol was used to produce a total of 26 of functionalized phenols in 50%-80% yields for the second step of the sequential process. 33 Another example of the powers of the MCR/elaboration strategy was reported by Yu et al, 34 who was seeking synthetic approaches to highly diversified H-pyrazolo(5,1-a) isoquinolines. For the initial MCR, Yu et al 34 devised a tandem one-pot process involving inter-and intramolecular condensations and electrophilic cyclization between 2-alkynyl benzaldehyde, sulfonylhydrazide, bromine, or iodine as electrophiles, and ketones or aldehydes to afford H-pyrazolo(5,1-a)isoquinolines.…”

“…Organocatalysis is a synthetic field rapidly growing in popularity. Ramachary et al 33 reported an interesting application of amine-catalyzed classical condensation reactions for the preparation of diverse libraries of "push-pulls" olefins, phenols, and 2-methyl-2H-chromenes. A three-component coupling reaction of two equivalents of ethyl acetoacetate with an aldehyde catalyzed by piperidine afforded Hagemann's esters via a tandem cascade of Knoevenagel/Michal/aldol/condensation/decarboxylation events (reaction A; Figure 3).…”

“…Notes: (A) Sequential MCR/elaboration strategy. 33 (B) Tandem MCR/cyclization/elaboration strategy. 34 Modified with permission from Ramachary DB, Ramakumar K, Bharanishashank A, Narayana vv.…”

Organo‐Cascade Catalysis: Application of Merged Iminium‐Enamine Activation Technique and Related Cascade Reactivities

“…The suitably substituted phenolic (À OH) moiety then attacks the newly generated iminium centre by an oxa-Michael fashion in order to generate the tricyclic compound, hemiaminal (102). The α-tocopherol (103) which is the target molecule can be achieved by only four successive steps. The (EN-IM) activated aldol/oxa-Michael cascade reaction was achieved with 97 % diastereoselective excess and 58 % yield (Scheme 33).…”

“…[102] Ramachary's research group reported the synthesis of highly functionalized (E)-1,3-dienes (152) on reaction between the aldehydes (149) and Hagemann's ester (150) in presence of the generated dienamine catalyst (151) (Scheme 48). [103] This dienamine chemistry has been further extended to trienamine activation techniques for further application. Synthetic organic chemists draw significant attention to this new reaction strategy for further developments.…”