Direct Catalytic Asymmetric Vinylogous Mannich‐Type Reaction of γ‐Butenolides with Ketimines

Abstract

Ein kooperativer Katalysator aus einer weichen Lewis‐Säure und einer „harten“ Brønsted‐Base katalysierte die Titelreaktion. Die N‐Thiophosphinoyl‐Gruppe der Ketimine war entscheidend zur Überwindung der hohen Aktivierungsbarriere durch die „Weich‐weich“‐Wechselwirkung von Schwefel und Kupfer. Mannich‐Addukte mit einem tetrasubstituierten Stereozentrum wurden mit ausgezeichneten Diastereo‐ und Enantioselektivitäten hergestellt. TANIAPHOS=Ferrocenyl‐Ligand.

Diastereodivergent and Enantioselective [4+2] Annulations of γ-Butenolides with Cyclic 1-Azadienes

“…The solution was stirred at room temperature for 4 h. Purification by column chromatography on silica gel (eluting with DCM/EA = 150:1) to give 9 as a white solid. [4,5]isothiazolo [2,3-a]furo [2,3- [4,5]isothiazolo [2,3-a]furo [2,3- [4,5]isothiazolo [2,3-a]furo [2,3-e]pyridin-2(11aH)-one 10,10-dioxide (4c) was obtained in 43% yield; the enantiomeric excess was determined to be 94% by HPLC analysis on Daicel Chiralcel IA column (10% 2-propanol/ n-hexane, 1 mL/min, temperature 35 °C), UV 285 nm, tminor = 33.00 min, tmajor = 41.11 min.…”

“…[α] [4,5]isothiazolo [2,3- [4,5]isothiazolo [2,3-a]furo [2,3- [4,5]isothiazolo [2,3-a]furo [2,3- [4,5]isothiazolo [2,3-a]furo [2,3-e] pyridin-2(11aH)-one 10,10-dioxide (4g) was obtained in 57% yield; the enantiomeric excess was determined to be 87% by HPLC analysis on Daicel Chiralcel IA column (20% 2-propanol/n-hexane, 1 mL/min, temperature 35 °C), UV 285 nm, tmajor = 22. (3aS,4R,11aS)-4-(4-Bromophenyl)-3a-methyl-3a,4-dihydro-1H-benzo [4,5]isothiazolo [2,3-a]furo [2,3- [4,5]isothiazolo [2,3-a]furo [2,3-e] pyridin-2(11aH)-one 10,10-dioxide (4i) was obtained in 29% yield; the enantiomeric excess was determined to be 92% by HPLC analysis on Daicel Chiralcel IA column (20% 2-propanol/n-hexane, 1 mL/min, temperature 35 °C), UV 285 nm, tmajor = 42.11 min, tminor = 58.68 min.…”

“…62 (s, 3H) [4,5]isothiazolo [2,3-a]furo [2,3- [4,5]isothiazolo [2,3-a]furo [2,3- [4,5]isothiazolo [2,3-a]furo [2,3-e] pyridine -2(11aH)-one 10,10-dioxide (5a) was obtained in 60% yield; the enantiomeric excess was determined to be 55% by HPLC analysis on Daicel Chiralcel IE column (40% 2-propanol/n-hexane, 1 mL/min, temperature 35 °C), UV 285 nm, tmajor = 20.97 min, tminor = 28.28 min. (3aS,4S,11aS)-3a-Methyl-4-(p-tolyl)-3a,4-dihydro-1H-benzo [4,5]isothiazolo [2,3-a]furo [2,3- [4,5]isothiazolo [2,3-a]furo [2,3- [4,5]isothiazolo [2,3-a]furo [2,3-e] pyridin-2(11aH)-one 10,10-dioxide (5d) was obtained in 34% yield; the enantiomeric excess was determined to be 63% by HPLC analysis on Daicel Chiralcel IA column (10% 2-propanol/n-hexane, 1 mL/min, temperature 35 °C), UV 285 nm, tminor = 57.94 min, tmajor = 73.67 min. [4,5]isothiazolo [2,3-a]furo [2,3- (3aS,12R,12aS)-8-Bromo-12a-methyl-12-phenyl-3,3a,12,12a-tetrahydro-2H-benzo[e]furo [2ʹ,3ʹ:5,6] pyrido [1,2-c] [1,2,3]oxathiazin-2-one 5,5-dioxide (8b) was obtained in 45% yield; the enantiomeric excess was determined to be >99% by HPLC analysis on Daicel Chiralcel IA column (40% 2-propanol/n-hexane, 1 mL/min, temperature 35 °C), UV 285 nm, tmajor = 6.28 min, tminor = 8.00 min.…”

“…[a] [4,5]isothiazolo [2,3-a] furo [2,3-e]pyridin-2-one 10,10-dioxide (9) was obtained in 86% yield; the diastereomer ratio was determined to be 4:1 by …”

“…In addition, the γ-butenolides act as competent direct vinylogous nucleophiles in addition reactions for the construction of an array of structurally diverse architectures [3][4][5][6], even for preparing more challenging molecules with quaternary carbon centers by using γ-substituted butenolides [7][8][9][10][11][12][13]. In contrast to abundant γ-regioselective OPEN ACCESS vinylogous addition reactions, to the best of our knowledge, no examples have been reported to utilize the γ-butenolides as the reactants towards tandem reactions in consideration of the potential reactivity of both γ-and β-positions [14].…”