Enantioselective synthesis of spiro[4H-pyran-3,3′-oxindole] derivatives catalyzed by cinchona alkaloid thioureas: Significant water effects on the enantioselectivity

Abstract

Compound Characterization DataEthyl (S)-2'-amino-3'-cyano-6'-methyl-2-oxospiro[indoline-3,4'-pyran]-5'-carboxylate (9a) 67

Cu(ii)-thiophene-2,5-bis(amino-alcohol) mediated asymmetric Aldol reaction and Domino Knoevenagel Michael cyclization: a new highly efficient Lewis acid catalyst

“…( R )-enantiomer eluted faster than ( S )-enantiomer in the HPLC chromatogram for Domino Knoevenagel Michael cyclized spiro-oxindole products 6a–c, 6e, 6h and 6i, while for the N -substituted spiro-oxindole 6j, 6k and 6l, reverse trends were followed, those are well reported in the literature. 97 All the spiro-oxindole products are predominantly found to be enriched with ( S )-enantiomer as their retention time and optical rotation were well in agreement with the literature data. 97 The absolute configuration for spiro-oxindole products 6d, 6f and 6g were also assigned as ( S )-enantiomer as their retention time followed the similar trends as of compound 6a–c, assuming that the reaction took place by following uniform mechanistic pathway ( Fig.…”

“… 97 All the spiro-oxindole products are predominantly found to be enriched with ( S )-enantiomer as their retention time and optical rotation were well in agreement with the literature data. 97 The absolute configuration for spiro-oxindole products 6d, 6f and 6g were also assigned as ( S )-enantiomer as their retention time followed the similar trends as of compound 6a–c, assuming that the reaction took place by following uniform mechanistic pathway ( Fig. 4 ).…”

“…Enantiomeric excess (ee) was determined by chiral HPLC [Daicel Chiralpak AD-H column], 85.0% n -hexane/i-PrOH, 1.0 mL min −1 ; t minor = 19.12 min; t major = 19.89 min; λ = 254 nm; 42% ee; [ α ] 20 D = +21.83° ( c 0.05, CH 3 OH); [ref. 97 [ α ] 24 D = +20.4° ( c 1.4, MeOH)]; 1 H-NMR (500 MHz, DMSO- d 6 ): δ (ppm) = 10.39 (s, 1H, NH), 7.18 (td, J = 7.6, 1.3 Hz, 1H, Ar–H), 7.14 (s, 2H, NH 2 ), 7.05 (dd, J = 7.4, 1.2 Hz, 1H, Ar–H), 6.93 (td, J = 7.5, 1.0 Hz, 1H, Ar–H), 6.79 (dt, J = 7.7, 0.8 Hz, 1H, Ar–H), 3.81–3.72 (m, 2H, CH 2 CH 3 ), 2.31 (s, 3H, CH 3 ), 0.78 (t, J = 7.1 Hz, 3H, CH 2 CH 3 ); 13 C-NMR (126 MHz, DMSO- d 6 ): δ (ppm) = 178.60, 164.52, 158.95, 158.52, 142.17, 134.56, 128.56, 123.41, 121.86, 117.51, 109.33, 104.67, 60.26, 56.52, 48.96, 18.57, 12.99. All the analytical data are well in agreement with the reported literature.…”

“…Enantiomeric excess (ee) was determined by chiral HPLC [Daicel Chiralpak AD-H column], 80.0% n -hexane/i-PrOH, 1.0 mL min −1 ; t major = 12.33 min; t minor = 20.59 min; λ = 254 nm; 81% ee; [ α ] 20 D = +19.55° ( c 0.06, CH 3 OH); [ref. 97 [ α ] 24 D = +20.4° ( c 1.0, MeOH)]; 1 H-NMR (500 MHz, DMSO- d 6 ): δ (ppm) = 7.48–7.45 (m, 2H, Ar–H), 7.33–7.30 (m, 2H, Ar–H), 7.28 (s, 1H, Ar–H), 7.25 (s, 2H, NH 2 ), 7.20 (td, J = 7.7, 1.3 Hz, 1H, Ar–H), 7.15 (dd, J = 7.4, 1.3 Hz, 1H, Ar–H), 7.00 (td, J = 7.5, 1.0 Hz, 1H, Ar–H), 6.86 (d, J = 7.7 Hz, 1H, Ar–H), 5.00 (d, J = 15.8 Hz, 1H, CH 2(a) Bn), 4.78 (d, J = 15.8 Hz, 1H, CH 2(b) Bn), 3.78 (q, J = 7.1 Hz, 1H, CH 2 CH 3 ), 3.52 (dd, J = 10.8, 7.1 Hz, 1H, CH 2 CH 3 ), 2.34 (s, 3H, CH 3 ), 0.58 (t, J = 7.1 Hz, 3H, CH 2 CH 3 ); 13 C-NMR (126 MHz, DMSO- d 6 ): δ (ppm) = 177.20, 164.38, 159.19, 158.86, 142.77, 136.19, 133.65, 128.40, 127.55, 123.34, 122.73, 117.57, 108.91, 104.55, 60.11, 56.12, 48.52, 43.39, 18.65, 13.08. All the analytical data are well in agreement with the reported literature.…”

“… 96 In 2019, Swapna Konda and co-workers synthesized chiral spiro[4 H -pyran-3,3′-oxindole] derivatives with good chemical yield (up to 92%) and enantioselectivity (up to 87% ee) using cinchona alkaloid thioureas as an organocatalysts. 97 However, till date very limited efforts have been made for the construction of stereoselective spiro-heterocyclic oxindole, engrafting 2-amino-4 H -pyran-3-carbonitrile ring at the C 3 position of oxindole via asymmetric Domino Michael cyclization reaction.…”