Enantioselective synthesis of biologically important spiro[indoline-3,2′-quinazolines] via catalytic asymmetric isatin-involved tandem reactions

The enantioselective synthesis of biologically important spiro[indoline-3,2′-quinazoline] scaffolds with a quaternary stereogenic center with fair to excellent enantioselectivities (up to 95% ee) has been established via an isatin-involved asymmetric catalytic tandem condensation/amide addition with 2-aminobenzamides. In addition, we also report on the enantioselective synthesis of various substituted spiro[indoline-3,2′-quinazolines], which will cast light on the preparation of chiral spiro-architectures with concomitant creation of quaternary stereogenic centers.

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(R)-1′H-Spiro[indoline-3,2′-quinazoline]-2,4′(3′H)-dioneC15H11N3O2e.e = 81%[α]D20=+34.7 (c 0.05, CH3COCH3)Source of chirality: the catalystAbsolute configuration: (R)

(R)-1-Benzyl-1′H-spiro[indoline-3,2′-quinazoline]-2,4′(3′H)-dioneC22H17N3O2e.e = 64%[α]D20=+145.9 (c 0.25, CH3COCH3)Source of chirality: the catalystAbsolute configuration: (R)

(R)-1-Methyl-1′H-spiro[indoline-3,2′-quinazoline]-2,4′(3′H)-dioneC16H13N3O2e.e = 58%[α]D20 = +209.9 (c 0.16, CH3COCH3)Source of chirality: the catalystAbsolute configuration: (R)

(R)-1-Benzyl-5-chloro-1′H-spiro[indoline-3,2′-quinazoline]-2,4′(3′H)-dioneC22H16ClN3O2e.e = 42%[α]D20=-25.8 (c 0.16, CH3COCH3)Source of chirality: the catalystAbsolute configuration: (R)

(R)-1-Benzyl-4-fluoro-1′H-spiro[indoline-3,2′-quinazoline]-2,4′(3′H)-dioneC22H16FN3O2e.e = 50%[α]D20=+41.0 (c 0.26, CH3COCH3)Source of chirality: the catalystAbsolute configuration: (R)

(R)-1-Benzyl-6-chloro-1′H-spiro[indoline-3,2′-quinazoline]-2,4′(3′H)-dioneC22H16ClN3O2e.e = 79%[α]D20=+33.6 (c 0.13, CH3COCH3)Source of chirality: the catalystAbsolute configuration: (R)

(R)-1-Benzyl-6-bromo-1′H-spiro[indoline-3,2′-quinazoline]-2,4′(3′H)-dioneC22H16BrN3O2e.e = 95%[α]D20=+149.5 (c 0.17, CH3COCH3)Source of chirality: the catalystAbsolute configuration: (R)

(R)-6-Bromo-1-methyl-1′H-spiro[indoline-3,2′-quinazoline]-2,4′(3′H)-dioneC16H12BrN3O2e.e = 87%[α]D20=+153.2 (c 0.12, CH3COCH3)Source of chirality: the catalystAbsolute configuration: (R)

(R)-1-Benzyl-6-fluoro-1′H-spiro[indoline-3,2′-quinazoline]-2,4′(3′H)-dioneC22H16FN3O2e.e = 88%[α]D20=+296.3 (c 0.14, CH3COCH3)Source of chirality: the catalystAbsolute configuration: (R)

(R)-1-Benzyl-7-(trifluoromethyl)-1′H-spiro[indoline-3,2′-quinazoline]-2,4′(3′H)-dioneC23H16F3N3O2e.e = 77%[α]D20=+37.0 (c 0.14, CH3COCH3)Source of chirality: the catalystAbsolute configuration: (R)

(R)-1-Benzyl-7-bromo-1′H-spiro[indoline-3,2′-quinazoline]-2,4′(3′H)-dioneC22H16BrN3O2e.e = 88%[α]D20=+58.0 (c 0.092, CH3COCH3)Source of chirality: the catalystAbsolute configuration: (R)

(R)-1-Benzyl-7-methyl-1′H-spiro[indoline-3,2′-quinazoline]-2,4′(3′H)-dioneC23H19N3O2e.e = 71%[α]D20=+31.7 (c 0.15, CH3COCH3)Source of chirality: the catalystAbsolute configuration: (R)

(R)-1-(Prop-2-yn-1-yl)-1′H-spiro[indoline-3,2′-quinazoline]-2,4′(3′H)-dioneC18H13N3O2e.e = 47%[α]D20=+37.0 (c 0.36, CH3COCH3)Source of chirality: the catalystAbsolute configuration: (R)

(R)-6-Bromo-1-(prop-2-yn-1-yl)-1′H-spiro[indoline-3,2′-quinazoline]-2,4′(3′H)-dioneC18H12BrN3O2e.e = 65%[α]D20=+62.8 (c 0.22, CH3COCH3)Source of chirality: the catalystAbsolute configuration: (R)

(R)-1-Benzyl-6-bromo-6′-chloro-1′H-spiro[indoline-3,2′-quinazoline]-2,4′(3′H)-dioneC22H15ClBrN3O2e.e = 52%[α]D20 = -73.4 (c 0.06, CH3COCH3)Source of chirality: the catalystAbsolute configuration: (R)

(R)-1-Benzyl-6-bromo-8′-methyl-1′H-spiro[indoline-3,2′-quinazoline]-2,4′(3′H)-dioneC23H18BrN3O2e.e = 88%[α]D20 = +344.1 (c 0.03, CH3COCH3)Source of chirality: the catalystAbsolute configuration: (R)

(R)-1-Benzyl-6-bromo-6′-chloro-8′-methyl-1′H-spiro[indoline-3,2′-quinazoline]-2,4′(3′H)-dioneC23H17ClBrN3O2e.e = 64%[α]D20=+37.5 (c 0.08, CH3COCH3)Source of chirality: the catalystAbsolute configuration: (R)

(R)-1-((1-Tosyl-1H-indol-2-yl)methyl)-1′H-spiro[indoline-3,2′-quinazoline]-2,4′(3′H)-dioneC31H24N4O4Se.e = 48%[α]D20 = +30.6 (c 0.45, CH3COCH3)Source of chirality: the substrateAbsolute configuration: (R)