Organocatalytic enantioselective construction of multi-functionalized spiro oxindole dienes

Abstract

A diastereo- and enantio-selective domino Michael-cyclization-tautomerization reaction of isatylidene malononitriles with α,α-dicyanoalkenes catalyzed by a cinchona alkaloid-derived bifunctional thiourea catalyst has been developed. A series of multi-functionalized spiro oxindole diene derivatives have been obtained in good to excellent yields (up to 97%) with good to excellent enantioselectivities (up to 96%) as well as good diastereoselectivities (up to 7.9 : 1). In addition, an anomalous temperature effect on the enantioselectivity has also been studied for this transformation.

Synthesis of Bicyclic ortho-Aminocarbonitrile Derivatives Catalyzed by 1,4-Diazabicyclo[2.2.2]octane

“…According to the literature [4][5][6][7][8][9][10][11][12] and our experiment, the possible mechanism was proposed in Scheme 3. A was formed from the Knoevenagel condensation reaction of cyclohexanone and malononitrile.…”

“…[4] Organic bases, such as pyrrolidine, [5a] morpholine, [5b] imidazole, [5c] ethanediamine [5d] and NEt 3 , [5e,5f] as efficient catalysts for the synthesis of ortho-aminocarbonitriles de-rivatives have also been reported. In addition, zinc titanate nanopowder, [6] glucose-containing imidazolium salt, [7] saccharine, [8] triethylamine acetate (TEAA), [8] benzyltriethylammonium chloride (TEBAC), [9] Borax, [10] deep eutectic solvent [11] and cinchona alkaloid-derived bifunctional thiourea [12] have been used to promote the formation of ortho-aminocarbonitriles derivatives. Despite these developments, many of these methods still have limitations such as the use of commercially unavailable reactants or catalysts, involve relatively harsh conditions, go through multistep procedures, require specific solvents or workup precausions.…”

Organocatalytic Asymmetric Vinylogous Michael Reactions

“…Since then, such nucleophiles were extensively employed in asymmetric vinylogous reactions to access many significant chiral frameworks ,. For example, Wang and co‐workers reported that hydroquinine‐derived thiourea 67 could catalyze the reaction of 2‐cyclohexylidene malononitrile 64 and 2‐cyclopentylidene malononitrile 65 with isatylidene malononitriles 66 (Scheme ) . After the reaction experienced a domino vinylogous Michael‐cyclization‐tautomerization process, spiro oxindole dienes 68 and 69 were obtained in moderate to excellent enantioselectivites and poor to moderate diastereoselectivities.…”

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

“…The process yielded highly functionalized spiro-oxindole dienes 106 . The products were obtained in good to excellent yields (up to 97%) and enantioselectivities (up to 96%), but the diastereoselectivities were moderate (up to 7.9:1) ( Scheme 34 ) [ 53 ].…”