Organocatalytic asymmetric vinylogous Michael addition of 3-alkylidene oxindoles to α-substituted β-nitroacrylates: facile construction of a chiral all-carbon quaternary center

New Developments of the Principle of Vinylogy as Applied to π-Extended Enolate-Type Donor Systems

“…The same authors published a further development of the protocol, in which the Michael addition of oxindoles to α-substituted β-nitroacrylates gave oxindole products with a quaternary stereocenter ( Table 10 , eq 2). 611 The reaction required the use of quinine-derived bifunctional squaramide C5 , which was postulated to simultaneously link via H-bonding the nitroalkene moiety and generate the oxindole dienolate by means of the tertiary amine unit.…”

Enolizable Alkylidene Heterocyclic and Carbocyclic Carbonyl Systems­: Valuable Vinylogous Donor Substrates in Synthesis

“…Asymmetric vinylogous Michael addition of 3-alkylidene-2oxindoles 8 to α-substituted β-nitroacrylates 17 19 Another example of a direct vinylogous Michael reaction of 3-alkylidene oxindoles with β-nitroalkenes was presented by Bencivenni and co-workers in 2015 (Scheme 8). 21 The starting oxindoles were non-symmetric (R 2 ≠ R 3 ) and the reaction was conducted at -20 °C to completely inhibit…”

“…The same authors 19 published a further development of this work, where the Michael addition of 3-alkylidene oxindoles 8 to α-substituted β-nitroacrylates 17 gave adducts 18 with an all-carbon quaternary stereocenter (Scheme 7). The model reaction was the addition of the isopropylidene oxindole 8 (R 1 = Boc, R 2 = H, R 3 = Me) to methyl α-phenyl-βnitroacrylate.…”

Organocatalytic Asymmetric Vinylogous Michael Reactions

“…Since then, the Wang and Chen groups successively reported organocatalytic AVM reactions between 3‐alkylidene oxindoles and nitroolefins with distinct structural features, affording to diverse chiral 3‐alkylidene oxindole derivatives including the construction of elusive but meaningful quaternary stereocenters (Scheme ) . For example, Wang and co‐workers reported β‐CF 3 ‐β‐substituted nitroolefins 86 (Scheme a) and α‐substituted β‐nitroacrylates 89 (Scheme b) as electrophiles to experience AVM reactions with 3‐alkylidene oxindoles 85 , affording two series of chiral 3‐alkylidene oxindoles 88 and 90 containing a δ‐substituted quaternary stereocenter with excellent enantioselectivities and Z / E ratios by using quinine‐based bifunctional catalysts 87 and 41 individually. Chen and co‐workers introduced quinine amine‐squaramide ( 93 )‐catalyzed 3‐(2‐oxoindolin‐3‐ylidene)butanoates 91 to react with β‐monosubstituted nitroolefins 92 to provide chiral 3‐alkylidene oxindoles 94 featuring γ and δ two stereocenters with excellent stereoselectivity (Scheme c) …”