Restricted Rotation in Aryl Olefins. I. Preparation and Resolution of β-Chloro-β-(2,4,6-trimethyl-3-bromophenyl)-α-methylacrylic Acid

Construction of Axially Chiral Styrenes Linking an Indole Moiety by Chiral Phosphoric Acid

“…Tetramethylsilane (TMS) served as the internal standard for 1 H NMR spectroscopy, and either CDCl 3 or DMSO-d 6 served as the internal standard for 13 C{ 1 H} NMR spectroscopy. 1 H NMR data were reported as follows: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet, td = triplet of doublet, dt = doublet of triplet, dd = doublet of doublet), coupling constants (Hz), and integration. Infrared spectroscopy was conducted on Thermo Fisher Nicolet iS 10 spectrometer.…”

“…Prepared according to the general procedure above and purified by a flash chromatography column with V PE /V EA (50:1) as the eluent, yellow oil (188.5 mg, 62% yield). 1 H NMR (500 MHz, CDCl 3 ) δ 7.93 (d, J = 8.5 Hz, 1H), 7.80 (s, 1H), 7.61 (d, J = 9.0 Hz, 1H), 7.47 (dd, J = 8.5, 1.5 Hz, 1H), 7.16 (d, J = 9.0 Hz, 1H), 6.07 (s, 1H), 1.45 (s, 9H), 1.35 (s, 9H) ppm; 13 C{ 1 H} NMR (126 MHz, CDCl 3 ) δ 155. 8, 132.8, 131.5, 130.2, 129.5, 128.2, 124.8, 119.5, 116.7, 111.5, 103.6, 98.54, 8.34, 71.3, 31.4, 3.26, 28.9, 28.2 General Procedure for the Synthesis of 3 or 5. To a reaction tube were added the corresponding alkynes 1 (0.1 mmol), indoles 2 or 4 (0.2 mmol), C-1 (3.3 mg, 5 mol %), and DCM (1.0 mL) under a N 2 atmosphere.…”

“…(aR)-(Z)-1-(1-(5-Bromo-1H-indol-3-yl)-3,3-dimethylbut-1-en-1yl)naphthalen-2-yl Trifluoromethanesulfonate (7). Prepared according to the procedure above and purified by a flash chromatography column with V PE /V EA (30:1) as the eluent, white foam (44.1 mg, 80% yield, 97% ee, Z/E > 20), melting point 104−105 °C, [α] D 20 = −75.6 (c = 0.13, CHCl 3 ); the crystal was cultivated from hexane/DCM (50:1) with the volatilization method; 1 H NMR (500 MHz, CDCl 3 ) δ 8.13 (s, 1H), 7.98 (d,J = 8.5 Hz,1H),3H),3H),7.31 (dd,J = 8.5,1.0 Hz, 1H), 7.17 (d,J = 8.5 Hz,1H),6.59 (s,1H),6.44 (d,J = 2.5 Hz,1H), 0.94 (s, 9H) ppm; 13 C{ 1 H} NMR (126 MHz, CDCl 3 ) δ 144. 2, 141.8, 135.4, 133.6, 132.2, 131.6, 129.8, 128.0, 127.6, 127.3, 126.9, 125.3, 125.2, 123.0, 121.8, 119.0, 118.8, 113.7, 112.8, 34.8, 30.0 ppm; IR (acetone, cm −1 ) 3415, 3046,2928,1712,1582,1491,1412,1263,1051,833,812,638; HRMS (ESI) m/z [M + Na] + Calcd for C 25 H 21 BrF 3 NNaO 3 S + 574.0270, found 574.0272.…”

Construction of Axially Chiral Styrenes Linking an Indole Moiety by Chiral Phosphoric Acid

“…Tetramethylsilane (TMS) served as the internal standard for 1 H NMR spectroscopy, and either CDCl 3 or DMSO-d 6 served as the internal standard for 13 C{ 1 H} NMR spectroscopy. 1 H NMR data were reported as follows: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet, td = triplet of doublet, dt = doublet of triplet, dd = doublet of doublet), coupling constants (Hz), and integration. Infrared spectroscopy was conducted on Thermo Fisher Nicolet iS 10 spectrometer.…”

“…Prepared according to the general procedure above and purified by a flash chromatography column with V PE /V EA (50:1) as the eluent, yellow oil (188.5 mg, 62% yield). 1 H NMR (500 MHz, CDCl 3 ) δ 7.93 (d, J = 8.5 Hz, 1H), 7.80 (s, 1H), 7.61 (d, J = 9.0 Hz, 1H), 7.47 (dd, J = 8.5, 1.5 Hz, 1H), 7.16 (d, J = 9.0 Hz, 1H), 6.07 (s, 1H), 1.45 (s, 9H), 1.35 (s, 9H) ppm; 13 C{ 1 H} NMR (126 MHz, CDCl 3 ) δ 155. 8, 132.8, 131.5, 130.2, 129.5, 128.2, 124.8, 119.5, 116.7, 111.5, 103.6, 98.54, 8.34, 71.3, 31.4, 3.26, 28.9, 28.2 General Procedure for the Synthesis of 3 or 5. To a reaction tube were added the corresponding alkynes 1 (0.1 mmol), indoles 2 or 4 (0.2 mmol), C-1 (3.3 mg, 5 mol %), and DCM (1.0 mL) under a N 2 atmosphere.…”

“…(aR)-(Z)-1-(1-(5-Bromo-1H-indol-3-yl)-3,3-dimethylbut-1-en-1yl)naphthalen-2-yl Trifluoromethanesulfonate (7). Prepared according to the procedure above and purified by a flash chromatography column with V PE /V EA (30:1) as the eluent, white foam (44.1 mg, 80% yield, 97% ee, Z/E > 20), melting point 104−105 °C, [α] D 20 = −75.6 (c = 0.13, CHCl 3 ); the crystal was cultivated from hexane/DCM (50:1) with the volatilization method; 1 H NMR (500 MHz, CDCl 3 ) δ 8.13 (s, 1H), 7.98 (d,J = 8.5 Hz,1H),3H),3H),7.31 (dd,J = 8.5,1.0 Hz, 1H), 7.17 (d,J = 8.5 Hz,1H),6.59 (s,1H),6.44 (d,J = 2.5 Hz,1H), 0.94 (s, 9H) ppm; 13 C{ 1 H} NMR (126 MHz, CDCl 3 ) δ 144. 2, 141.8, 135.4, 133.6, 132.2, 131.6, 129.8, 128.0, 127.6, 127.3, 126.9, 125.3, 125.2, 123.0, 121.8, 119.0, 118.8, 113.7, 112.8, 34.8, 30.0 ppm; IR (acetone, cm −1 ) 3415, 3046,2928,1712,1582,1491,1412,1263,1051,833,812,638; HRMS (ESI) m/z [M + Na] + Calcd for C 25 H 21 BrF 3 NNaO 3 S + 574.0270, found 574.0272.…”

Nucleophilic Dechlorocarbomethoxylation of (E)-Methyl β-Chloro-α-methyl-β-(3-bromo- 2,4,6-trimethylphenyl)acrylate

“…( E )-Methyl α-methyl-β-chloro-β-(3-bromo-2,4,6-trimethylphenyl)acrylate ( 1 ) was prepared by a configuration-retaining esterification either with diazomethane or with thionyl chloride and then methanol of the ( E )-acid, which was prepared in turn according to Adams and Miller …”

Recent Advances in Catalytic Asymmetric Construction of Atropisomers

“…Another dominant class of nonbiaryl C–C atropisomers display rotationally constrained σ bond that connects an alkene and an arene. This stereochemical phenomenon in aryl olefins has been disclosed and investigated by Adams in the 1940s but efforts to advance catalytic preparation of these entities stereoselectively could have been thwarted by the innately low flipping energy between the two stereochemically distinct conformers . They can be broadly grouped into two subclasses: one features an enclosed double bond in 6-membered carbo- or heterocycles to emulate a stable biaryl core (cyclic alkene) while the other scaffold presents an open-chain alkene.…”

Construction of Axially Chiral Styrenes Linking an Indole Moiety by Chiral Phosphoric Acid

“…Tetramethylsilane (TMS) served as the internal standard for 1 H NMR spectroscopy, and either CDCl 3 or DMSO-d 6 served as the internal standard for 13 C{ 1 H} NMR spectroscopy. 1 H NMR data were reported as follows: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet, td = triplet of doublet, dt = doublet of triplet, dd = doublet of doublet), coupling constants (Hz), and integration. Infrared spectroscopy was conducted on Thermo Fisher Nicolet iS 10 spectrometer.…”

“…Prepared according to the general procedure above and purified by a flash chromatography column with V PE /V EA (50:1) as the eluent, yellow oil (188.5 mg, 62% yield). 1 H NMR (500 MHz, CDCl 3 ) δ 7.93 (d, J = 8.5 Hz, 1H), 7.80 (s, 1H), 7.61 (d, J = 9.0 Hz, 1H), 7.47 (dd, J = 8.5, 1.5 Hz, 1H), 7.16 (d, J = 9.0 Hz, 1H), 6.07 (s, 1H), 1.45 (s, 9H), 1.35 (s, 9H) ppm; 13 C{ 1 H} NMR (126 MHz, CDCl 3 ) δ 155. 8, 132.8, 131.5, 130.2, 129.5, 128.2, 124.8, 119.5, 116.7, 111.5, 103.6, 98.54, 8.34, 71.3, 31.4, 3.26, 28.9, 28.2 General Procedure for the Synthesis of 3 or 5. To a reaction tube were added the corresponding alkynes 1 (0.1 mmol), indoles 2 or 4 (0.2 mmol), C-1 (3.3 mg, 5 mol %), and DCM (1.0 mL) under a N 2 atmosphere.…”

“…(aR)-(Z)-1-(1-(5-Bromo-1H-indol-3-yl)-3,3-dimethylbut-1-en-1yl)naphthalen-2-yl Trifluoromethanesulfonate (7). Prepared according to the procedure above and purified by a flash chromatography column with V PE /V EA (30:1) as the eluent, white foam (44.1 mg, 80% yield, 97% ee, Z/E > 20), melting point 104−105 °C, [α] D 20 = −75.6 (c = 0.13, CHCl 3 ); the crystal was cultivated from hexane/DCM (50:1) with the volatilization method; 1 H NMR (500 MHz, CDCl 3 ) δ 8.13 (s, 1H), 7.98 (d,J = 8.5 Hz,1H),3H),3H),7.31 (dd,J = 8.5,1.0 Hz, 1H), 7.17 (d,J = 8.5 Hz,1H),6.59 (s,1H),6.44 (d,J = 2.5 Hz,1H), 0.94 (s, 9H) ppm; 13 C{ 1 H} NMR (126 MHz, CDCl 3 ) δ 144. 2, 141.8, 135.4, 133.6, 132.2, 131.6, 129.8, 128.0, 127.6, 127.3, 126.9, 125.3, 125.2, 123.0, 121.8, 119.0, 118.8, 113.7, 112.8, 34.8, 30.0 ppm; IR (acetone, cm −1 ) 3415, 3046,2928,1712,1582,1491,1412,1263,1051,833,812,638; HRMS (ESI) m/z [M + Na] + Calcd for C 25 H 21 BrF 3 NNaO 3 S + 574.0270, found 574.0272.…”

Nucleophilic Dechlorocarbomethoxylation of (E)-Methyl β-Chloro-α-methyl-β-(3-bromo- 2,4,6-trimethylphenyl)acrylate

“…( E )-Methyl α-methyl-β-chloro-β-(3-bromo-2,4,6-trimethylphenyl)acrylate ( 1 ) was prepared by a configuration-retaining esterification either with diazomethane or with thionyl chloride and then methanol of the ( E )-acid, which was prepared in turn according to Adams and Miller …”

Recent Advances in Catalytic Asymmetric Construction of Atropisomers

“…Another dominant class of nonbiaryl C–C atropisomers display rotationally constrained σ bond that connects an alkene and an arene. This stereochemical phenomenon in aryl olefins has been disclosed and investigated by Adams in the 1940s but efforts to advance catalytic preparation of these entities stereoselectively could have been thwarted by the innately low flipping energy between the two stereochemically distinct conformers . They can be broadly grouped into two subclasses: one features an enclosed double bond in 6-membered carbo- or heterocycles to emulate a stable biaryl core (cyclic alkene) while the other scaffold presents an open-chain alkene.…”

Construction of Axially Chiral Styrenes Linking an Indole Moiety by Chiral Phosphoric Acid

“…Tetramethylsilane (TMS) served as the internal standard for 1 H NMR spectroscopy, and either CDCl 3 or DMSO-d 6 served as the internal standard for 13 C{ 1 H} NMR spectroscopy. 1 H NMR data were reported as follows: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet, td = triplet of doublet, dt = doublet of triplet, dd = doublet of doublet), coupling constants (Hz), and integration. Infrared spectroscopy was conducted on Thermo Fisher Nicolet iS 10 spectrometer.…”

“…Prepared according to the general procedure above and purified by a flash chromatography column with V PE /V EA (50:1) as the eluent, yellow oil (188.5 mg, 62% yield). 1 H NMR (500 MHz, CDCl 3 ) δ 7.93 (d, J = 8.5 Hz, 1H), 7.80 (s, 1H), 7.61 (d, J = 9.0 Hz, 1H), 7.47 (dd, J = 8.5, 1.5 Hz, 1H), 7.16 (d, J = 9.0 Hz, 1H), 6.07 (s, 1H), 1.45 (s, 9H), 1.35 (s, 9H) ppm; 13 C{ 1 H} NMR (126 MHz, CDCl 3 ) δ 155. 8, 132.8, 131.5, 130.2, 129.5, 128.2, 124.8, 119.5, 116.7, 111.5, 103.6, 98.54, 8.34, 71.3, 31.4, 3.26, 28.9, 28.2 General Procedure for the Synthesis of 3 or 5. To a reaction tube were added the corresponding alkynes 1 (0.1 mmol), indoles 2 or 4 (0.2 mmol), C-1 (3.3 mg, 5 mol %), and DCM (1.0 mL) under a N 2 atmosphere.…”

“…(aR)-(Z)-1-(1-(5-Bromo-1H-indol-3-yl)-3,3-dimethylbut-1-en-1yl)naphthalen-2-yl Trifluoromethanesulfonate (7). Prepared according to the procedure above and purified by a flash chromatography column with V PE /V EA (30:1) as the eluent, white foam (44.1 mg, 80% yield, 97% ee, Z/E > 20), melting point 104−105 °C, [α] D 20 = −75.6 (c = 0.13, CHCl 3 ); the crystal was cultivated from hexane/DCM (50:1) with the volatilization method; 1 H NMR (500 MHz, CDCl 3 ) δ 8.13 (s, 1H), 7.98 (d,J = 8.5 Hz,1H),3H),3H),7.31 (dd,J = 8.5,1.0 Hz, 1H), 7.17 (d,J = 8.5 Hz,1H),6.59 (s,1H),6.44 (d,J = 2.5 Hz,1H), 0.94 (s, 9H) ppm; 13 C{ 1 H} NMR (126 MHz, CDCl 3 ) δ 144. 2, 141.8, 135.4, 133.6, 132.2, 131.6, 129.8, 128.0, 127.6, 127.3, 126.9, 125.3, 125.2, 123.0, 121.8, 119.0, 118.8, 113.7, 112.8, 34.8, 30.0 ppm; IR (acetone, cm −1 ) 3415, 3046,2928,1712,1582,1491,1412,1263,1051,833,812,638; HRMS (ESI) m/z [M + Na] + Calcd for C 25 H 21 BrF 3 NNaO 3 S + 574.0270, found 574.0272.…”

Nucleophilic Dechlorocarbomethoxylation of (E)-Methyl β-Chloro-α-methyl-β-(3-bromo- 2,4,6-trimethylphenyl)acrylate

“…( E )-Methyl α-methyl-β-chloro-β-(3-bromo-2,4,6-trimethylphenyl)acrylate ( 1 ) was prepared by a configuration-retaining esterification either with diazomethane or with thionyl chloride and then methanol of the ( E )-acid, which was prepared in turn according to Adams and Miller …”

Recent Advances in Catalytic Asymmetric Construction of Atropisomers

“…Another dominant class of nonbiaryl C–C atropisomers display rotationally constrained σ bond that connects an alkene and an arene. This stereochemical phenomenon in aryl olefins has been disclosed and investigated by Adams in the 1940s but efforts to advance catalytic preparation of these entities stereoselectively could have been thwarted by the innately low flipping energy between the two stereochemically distinct conformers . They can be broadly grouped into two subclasses: one features an enclosed double bond in 6-membered carbo- or heterocycles to emulate a stable biaryl core (cyclic alkene) while the other scaffold presents an open-chain alkene.…”