Improved synthesis of 4-benzylidene-2,6-di-tert-butylcyclohexa-2,5-dienone and its derivatives

Chiral Thioureas—Preparation and Significance in Asymmetric Synthesis and Medicinal Chemistry

“…Excellent yield, diastereomeric and enantiomeric excess were reported in a domino reaction of oxa-Michael and 1,6-addition by Enders et al (Scheme 36) [278]. As privileged substrates orthohydroxyphenyl derivatives were used [279], introducing a nucleophilic group para-quinone methides that became suitable donor-Michael acceptors [280][281][282][283][284][285][286][287]. Amino acid-derived thiourea organocatalysts were used by Zhao's group in a tandem thia/oxa Michael-Michael reaction yielding optically pure chromans containing the pharmaceutically important oxindole scaffold (Scheme 35) [277].…”

Organocatalytic Domino Oxa‐Michael/1,6‐Addition Reactions: Asymmetric Synthesis of Chromans Bearing Oxindole Scaffolds

“…When the catalyst loading was decreased to 10 mol %a nd 5mol %, the yields slightly increased and the stereoselectivities remained excellent (entries 9a nd 10). No further improvements were observed when other solvents,s uch as DCM, DCE, Et 2 O, or PhCF 3 , were used (entries [11][12][13][14]. Theb est reaction conditions are those shown in entry 10, and gave 3a in 89 %y ield, 99 % ee, and 17:1 d.r.…”

“…First, thiourea catalyst A was used. No further improvements were observed when other solvents,s uch as DCM, DCE, Et 2 O, or PhCF 3 , were used (entries [11][12][13][14]. Thew idely used squaramide catalyst B delivered comparable results (entry 2).…”

“…[12] Over the past decade,o ur group has also focused on the development of asymmetric organocatalytic domino reactions. [14] To the best of our knowledge,t here are no precedents for using this donor-Michael acceptor synthon in synthesis.T of ill this gap,w e thought of an unprecedented domino oxa-Michael/1,6-con- jugate addition reaction (Scheme 1c). However,t his attempt constitutes as ignificant challenge owing to the potential dimerization of such species.After extensive investigations,w ew ere pleased to find that ortho-hydroxyphenylsubstituted p-QMs 1 are ideal substrates.…”

“…However,t his attempt constitutes as ignificant challenge owing to the potential dimerization of such species.After extensive investigations,w ew ere pleased to find that ortho-hydroxyphenylsubstituted p-QMs 1 are ideal substrates. [14] To the best of our knowledge,t here are no precedents for using this donor-Michael acceptor synthon in synthesis.T of ill this gap,w e thought of an unprecedented domino oxa-Michael/1,6-con- jugate addition reaction (Scheme 1c). [15] Moreover,anasymmetric version of such adomino reaction might be developed by employing as uitable chiral organocatalyst, leading to enantioenriched highly functionalized chromans featuring not only an oxindole scaffold but also three contiguous stereogenic centers.…”