Synthesis of New Chiral Monosulfonamides Prepared from (11R,12R)11,12-Diamino-9,10-dihydro-9,10-ethanoanthracene and their Use as Ligands for Asymmetric Catalysis

Gabriela Huelgas,¹ Haydee Rojas Cabrera,¹ Domingo Madrigal,³ Ratnasamy Somanathan,³ Pilar Guzmán,^1,2 Aurelio Ortiz,² and Cecilia Anaya de Parrodi¹*

¹ Departamento de Ciencias Químico-Biológicas, Universidad de las Américas-Puebla, Sta. Catarina Mártir, 72820 Cholula, México. Telephone: +(55)222-2292005. cecilia.anaya@udlap.mx

² Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, 72570 Puebla, Puebla. México.

³ Centro de Graduados e Investigación, Instituto Tecnológico de Tijuana, Apartado Postal 1166, 22000 Tijuana, B. C., México.

Abstract

New chiral monosulfonamides 6-16 containing (11R,12R)-diamino-9,10-dihydro-9,10-ethanoanthracene as carbon skeleton were prepared. Compounds 6-12, 15 and 16 were used as optically active ligands in the enantioselective ethylation of benzaldehyde. Moreover, the monosulfonamides 6-10 were tested in the asymmetric transfer hydrogenation (ATH) of acetophenone with Rh(Cp*)L* complex.

Key words: Monosulfonamide, asymmetric catalysis, enantioselective addition.

Resumen

Nuevas monosulfonamidas quirales 6-16 teniendo a la (11R,12R)-diamino-9,10-dihidro-9,10-etanoantraceno como esqueleto carbonado fueron preparadas. Los compuestos 6-12, 15 y 16 se utilizaron como ligantes ópticamente activos en la etilación enantioselectiva de benzaldehído. Además, las monosulfonamidas 6-10 se probaron en la reducción asimétrica por transferencia de hidrógeno (ATH) de acetofenona con Rh(Cp*)L* utilizándolos como catalizadores.

Palabras clave: Monosulfonamida, catálisis asimétrica, adición enantioselectiva.

Introduction

Chiral secondary alcohols are important structures present in natural products and in many pharmaceutical compounds, and are also precursors for many other complex organic molecules [1]. Hence, there is need to develop new methods for making chiral secondary alcohol. Asymmetric catalysis has been a powerful tool to obtain enantiomerically pure or enriched alcohols, mainly by nucleophilic additions to carbonyl compounds [2]. Several and efficient chiral ligands have been used, alone or in the presence of Lewis acids. These include amino alcohols [3-6], α-hydroxy acids [7], α-amino amides [8], α-hydroxy amides [9], and hydroxysulfonamides [10-14].

Our group has recently reported the preparation of bis(sulfonamide) 1, containing (11R,12R)-11,12-diamino-9,10-dihydro-9,10-ethanoanthracene as carbon skeleton [15]. The bis(sulfonamide) 1 was used as ligand in the asymmetric alkylation of prochiral ketones with diethyl zinc in high yield and enantioselectivities up to 99% ee (Figure 1).

Subsequently, König et al. [16] described the synthesis of novel tetradentate sulfonamide ligands and used them in the catalytic asymmetric alkylation of aldehydes with diethylzinc. Quantitative yields of the corresponding secondary alcohol and good asymmetric induction (70% yield and 74% ee) were obtained with ligands 2a-b.

Somanathan et al. [17-18] reported the use of monosulfonamide ligand 3a-b, derived from trans-(1R,2R)-cyclohexane-1,2-diamine, in the asymmetric transfer hydrogenation of aromatic ketones. Enantioselectivities ranged from 70 to 99% and good yields for the synthesis of 1-phenylpropanol derivatives were achieved.

Recently Hirose [19] and co-workers described the synthesis of chiral 1,3-amino sulfonamides, 4, 5.

They were prepared from (-)-cis-2-benzamidocyclohexanecarboxylic acid and studied by tested as ligands for catalytic enantioselective addition of diethyl zinc to aldehydes. They provided secondary alcohols in quantitative yields and in good to excellent enantioselectivities (up to 98% ee).

These reports prompted us to prepare the monosulfonamides 6-12, 15 and 16 and to test their catalytic activity. First, the ethylation of benzaldehyde was performed in the presence of diethylzinc. Second, monosulfonamides 6-10 were tested in the asymmetric induce hydrogenation (ATH) of acetophenone with Rh(Cp*)L* complex.

The synthesis of monosulfonamides 6-12 were achieved from enantiopure (11R,12R)-diamino-9,10-dihydro-9,10-ethanoanthracene [20]. (11R,12R)-Diamine (1 equiv) was treated with sulfonyl chlorides (1 equiv) in DCM at 0 ^oC in the presence of triethylamine. Monosulfonamides 6-12 were obtained in good yields (62-90%) after column chromatography purification on silica gel [Hexane:EtOAc; 1:5]. (Table 1).

Preparation of monosulfonamides 13-16

The reaction of (11R,12R)-diamine 17 with (S)-camphorsulfonyl chloride, under the same reaction conditions, afforded ketone 13 in 70% yield. The reduction of ketone 13 with NaBH₄, gave a mixture of two diastereomeric alcohols in a 5.3:1.0 ratio exo-exo:exo-endo in 69% yield. The major diastereomer 15 was isolated in 58% yield by flash chromatography purification (Scheme 1).

On the other hand, the preparation of ketone 14 was performed using (11S,12S)-diamine-18 and (S)-camphorsulfonyl chloride. After purification by column chromatography, the desired ketone was obtained in 76% yield. Ketone 14 was reduced with NaBH₄ to provide a mixture of alcohols in a diastereomeric ratio of 8.0:1.0. The major exo-exo alcohol 16 was isolated in 67% yield, after flash chromatography purification (Scheme 2).

Enantioselective addition of diethylzinc to benzaldehyde

Chiral monosulfonamides 6-12, 15 and 16 were tested as ligands in the enantioselective addition of diethylzinc to benzaldehyde. The reaction was performed using 5 mol% of the corresponding optically active ligands in the presence of toluene as solvent and under solvent-free conditions. The chiral zinc catalyst was generated in situ upon the addition of 2.0 equivalents of diethylzinc to the corresponding chiral monosulfonamide. 1-Phenylpropan-1-ol was obtained in moderate to good yields (in toluene 55-95%, under solvent free conditions 47-92%) and low to moderate enantioselectivities (in toluene 4-52%, under solvent free conditions 8-56%). We found that the presence or absence of solvent did not lead to significant improvements. Monosulfonamide 8 (Table 2) gave the best yields and enantioselectivities (entries 5 and 6) (Table 2). Monosulfonamides 6-12 provided (R)-1-phenylpropan-1-ol as major enantiomer; however monosulfonamides 15 and 16 afforded the alcohol with the opposite configuration (Table 2). The transition state for alkylation of benzaldehyde with diethylzinc is show in (Figure 2) [23].

Asymmetric induced hydrogenation with rhodium complex as ligands 6-10

Next, we performed the catalytic enantioselective reduction reaction using ligands 6-10, in the asymmetric induced hydrogenation of acetophenone with a rhodium complex (Table 3). A mixture of the metal precursor [RhCl₂(Cp*)]₂ and the monosulfonamide was heated in water to form the Rh(Cp*)L* complex. Then sodium formate and acetophenone were added to form the 1-phenyl-1-ethanol. The reaction proceeded with low to moderate results (10-34% yield and 3-42% ee). Best enantioselectivity was achieved with ligand 10 (42% ee, entry 5) (Table 3). The transition state for ATH of aromatic ketones is show in (Figure 3).

In our previous study [21, 22] we found that the dihedral angle N-C-C-N is critical in obtaining maximum overlap, in order to get good yields and enantioselectivities. The dihedral angle calculations were carried out by B3LYP density functional level of theory, using a cc-pVDZ basis set calculations. The angles N-C-C-N of ligands 6, 7, 8, 9, and 10 were found to be in the range of 114.16 to 116.96°, compared to 59° observed for monosulfonamide of 1,2-cyclohexane diamine.

Conclusion

In conclusion, we have described an easy and simple synthesis of different chiral monosulfonamides from (11R,12R)-diamino-9,10-dihydro-9,10-ethanoanthracene in good yields (62-90%). They have been used as zinc-based catalysts in the enantioselective addition of diethylzinc to benzaldehyde with high yield (94%) and moderate ee (56%).

We also evaluated the potential of these ligands as catalysts in the asymmetric enantioselective reduction in the ATH of acetophenone with Rh(Cp*)L* complex. We observed low conversion (10-34%) and low enantioselectivities (3-42%).

These results clearly indicate that the monosulfonamides derived from (1R,2R)-cyclohexane-1,2-diamine are more stereoselective than those prepared with (11R,12R)-diamino-9,10-dihydro-9,10-ethanoanthracene. Based on these results, we are working on the design of new chiral sulfonamides based ligands that display better stereoinduction.

Experimental

All manipulations involving diethylzinc were carried out under argon atmosphere. Benzaldehyde was distilled prior to use. NMR spectra were obtained on a Varian 200 MHz. Fourier transform spectrometer. ¹H NMR spectra were referenced to tetramethylsilane; ¹³C{¹H} NMR spectra were referenced to residual solvent.

General procedure for synthesis of monosulfonamides 6-14

To a solution of enantiopure 11,12-diamino-9,10-dihydro-9,10-ethanoanthracene (300 mg, 1.3 mmol) in CH₂Cl₂ (10 mL) and triethylamine (0.5 mL, 1.3 mmol) at 0 °C a sulfonyl chloride solution was added dropwise (300 mg, 1.3 mmol) in CH₂Cl₂ (10 mL) over 60 min. After the addition was completed, the mixture was allowed to warm to room temperature. After being stirred for 5 h, the mixture was washed with water (3 x 50 mL). The organic phase was separated and dried over NaSO₄. The solution was filtered and the solvent was removed under vacuum, the crude product was purified by flash chromatography on silica gel, (Hexane/EtOAc 1:5 as eluent).

Affording a white solid (85% yield): mp 188-190 °C; [α]_D²⁰ = −6.6 (c 1.0, CHCl₃). ¹H NMR (CDCl₃, 200 MHz) δ 1.36 (s, 9H), 1.42 (s, 3H), 2.81-2.84 (m, 1H), 3.07-3.10 (m, 1H), 3.95 (d, 1H, J = 2.6 Hz), 4.04 (d, 1H, J = 3.0 Hz), 7.07-7.27 (m, 8H), 7.54 (d, 2H, J = 8.8 Hz), 7.80 (d, 2H, J = 8.4 Hz). ¹³C NMR (50 MHz, CDCl₃) δ 31.8, 50.0, 52.2, 61.1, 63.6, 124.1, 124.2, 125.6, 125.9, 126.2, 126.3, 126.7, 126.8, 137.2, 137.5, 138.6, 139.6, 141.5, 156.2. IR-FT (KBr) ν_max/cm⁻¹: 3344, 3277, 3072, 2958, 2874, 2799, 2754, 1595, 1575, 1464, 1398, 1368, 1335, 1268, 1228, 1199, 1162, 1109, 1088, 1021, 930, 902, 836, 792, 757, 641, 582, 555, 525, 406. HRMS-FAB⁺: m/z [M+H]⁺ calcd. for C₂₆H₂₉O₂N₂S: 433.1950; found: 433.1942.

(Phenylmethanesulfonamido)-(11R,12R)-diamino-9,10-dihydro-9,10-ethanoanthracene (7)

Affording a white solid (75% yield): mp 185-186 °C; [α]_D²⁰ = −26.0 (c 1.0, CHCl₃). ¹H NMR (CDCl₃, 200 MHz) δ 1.25 (broad, 2H), 2.74-2.76 (m, 1H), 2.91 (broad, 1H), 4.00-4.01 (m, 1H), 4.04-4.10 (m, 2H), 4.28 (s, 2H), 7.06-7.42 (m, 13H). ¹³C NMR (CDCl₃, 50 MHz) δ 51.0, 52.8, 60.2, 61.4, 64.0, 124.1, 124.2, 125.7, 125.9, 126.2, 126.4, 126.7, 128.5, 129.1, 130.5, 137.2, 138.3, 139.6, 141.4. IR-FT (KBr) ν_max/cm⁻¹: 3341, 3278, 3066, 3041, 2951, 2924, 2880, 2753, 1947, 1800, 1603, 1578, 1487, 1459, 1410, 1378, 1322, 1257, 1228, 1200, 1149, 1123, 1099, 1069, 1030, 960, 935, 909, 872, 847, 824, 782, 758, 696, 635, 603, 564, 543, 509, 462, 347. HRMS-FAB⁺: m/z [M+H]⁺ calcd. for C₂₃H₂₃O₂N₂S: 391.1480; found: 391.1478.

(2,4,6-Triisopropylbenzenesulfonamido)-(11R,12R)-diamino-9,10-dihydro-9,10-ethanoanthracene (8)

Affording a white solid (90% yield): mp 183-184 °C; [α]_D²⁰ = −8.6 (c 1.0, CHCl₃). ¹H NMR (CDCl₃, 200 MHz) δ 1.19-1.27 (m, 18H), 2.80-2.93 (m, 3H), 3.17-3.24 (m, 1H), 4.01-4.27 (m, 6H), 7.08-7.31 (m, 10H). ¹³C NMR (CDCl₃, 50 MHz) δ 24.3, 25.5, 30.2, 34.7, 50.3, 52.1, 61.0, 63.7, 123.5, 124.2, 125.6, 125.9, 126.2, 126.3, 126.7, 132.9, 137.4, 138.6, 139.7, 141.6, 149.5, 152.4. IR-FT (KBr) ν_max/cm⁻¹: 3343, 3275, 3074, 2958, 2873, 1599, 1572, 1462, 1420, 1361, 1324, 1256, 1227, 1195, 1158, 1104, 1066, 1037, 932, 903, 881, 788, 757, 660, 546. HRMS-FAB⁺: m/z [M+H]⁺ calcd. for C₃₁H₃₉O₂N₂S: 503.2732; found: 503.2737.

(4-Fluorobenzenesulfonamido)-(11R,12R)-diamino-9,10-dihydro-9,10-ethanoanthracene (9)

Affording a white solid (81% yield): mp 178-179 °C; [α]_D²⁰ = −13.5 (c 1.0, CHCl₃). ¹H NMR (CDCl₃, 200 MHz) δ 2.72-2.74 (m, 1H), 2.98-3.0 (m, 1H), 3.87 (d, 1H, J = 3.0 Hz), 3.94 (d, 1H, J = 2.6 Hz), 5.18 (s, 3H), 6.97-7.21 (m, 10H), 7.82 (dd, 2H, J = 5.2, 5.2 Hz).. ¹³C NMR (50 MHz, CDCl₃) δ 50.1, 52.4, 60.9, 63.5, 116.0, 116.5, 124.2, 125.6, 126.0 126.2, 126.4, 126.7, 129.5, 129.7, 136.7, 136.7, 137.1, 138.4, 139.4, 141.5, 161.9, 166.9. IR-FT (KBr) ν_max/cm⁻¹ 3359, 3298, 3070, 3029, 2948, 2867, 2746, 1591, 1491, 1463, 1407, 1330, 1291, 1233, 1158, 1091, 1020, 980, 925, 892, 840, 788, 758, 669, 635, 579, 551. HRMS-FAB⁺: m/z [M+H]⁺ calcd. for C₂₂H₂₀O₂N₂F₁S: 395.1230; found: 395.1234.

(Methansulfonamido)-(11R,12R)-diamino-9,10-dihydro-9,10-ethanoanthracene (10)

Affording a white solid (62% yield): mp 112-113 °C; [α]_D²⁰ = −8.7 (c 1.0, CHCl₃). ¹H NMR (CDCl₃, 200 MHz) δ 2.02 (s, 3H), 2.94 (broad, 1H), 3.10 (s, 3H), 3.26 (broad, 1H), 4.10 (broad, 1H), 4.28 (d, 1H, J = 2.6 Hz), 7.14-7.40 (m, 8H). ¹³C NMR (CDCl₃, 50 MHz) δ 42.1, 50.8, 53.0, 61.0, 62.8, 124.0, 124.3, 125.8, 126.0, 126.3, 126.4, 126.5, 126.6, 137.3, 138.1, 139.8, 141.3. IR-FT (KBr) ν_max/cm⁻¹: 3349, 3281, 3070, 3042, 3023, 2954, 2930, 2872, 1629, 1588, 1463, 1411, 1323, 1227, 1149, 1116, 1068, 1023, 982, 868, 845, 823, 762, 718, 671, 636, 603, 563, 519, 459. HRMS-FAB⁺: m/z [M+H]⁺ calcd. for C₁₇H₁₉O₂N₂S: 315.1167; found: 315.1171.

Affording a white solid (66% yield): mp 190-191 °C; [α]_D²⁰ = −10 (c 1.0, CHCl₃). ¹H NMR (CDCl₃, 200 MHz) δ 2.33 (broad, 3H), 2.71-2.74 (m, 1H), 3.04 (s, 1H), 3.94-3.95 (m, 2H), 6.96-7.21 (m, 8 H), 7.71 (d, 2H, J = 8.4 Hz), 7.94 (d, 2H, J = 8.0 Hz). ¹³C NMR (CDCl₃, 50 MHz) δ 50.2, 52.5, 60.8, 63.5, 98.2, 124.0, 124.1, 125.6, 126.0, 126.2, 126.5, 126.7 127.3, 137.2, 138.1, 138.3, 139.4, 141.4, 144.3. IR-FT (KBr) ν_max/cm⁻¹: 3349, 3281, 3065, 3033, 2950, 2929, 2872, 2750, 1583, 1491, 1460, 1415, 1323, 1226, 1203, 1152, 1124, 1068, 1026, 951, 901, 849, 785, 758, 728, 698, 636, 604, 543, 508, 450. HRMS-FAB⁺: m/z [M+H]⁺ calcd. for C₂₃H₂₀O₂N₂F₃S: 445.1198; found: 445.1202.

(4-Methylbenzenesulfonamido)-(11R,12R)-diamino-9,10-dihydro-9,10-ethanoanthracene (12)

Affording a white solid (68% yield): mp 166-168 °C; [α]_D²⁰ = −23.5 (c 1.0, CHCl₃). ¹H NMR (CDCl₃, 200 MHz) δ 1.3 (broad, 3H), 2.44 (s, 3H), 2.79 (t, 1H, J = 2.6 Hz), 4.03 (d, 1H, J = 2.6 Hz), 3.92 (d, 1H, J= 2.6 Hz), 4.03 (d, 1H, J = 2.6 Hz), 7.06-7.35 (m, 10 H), 7.76 (d, 2H, J = 8.4 Hz). ¹³C NMR (CDCl₃, 50 MHz) δ 22.3, 50.0, 52.1, 61.0, 63.6, 124.1, 124.1, 125.6, 125.9, 126.2, 126.3, 126.7, 126.9, 129.5, 137.2, 137.6, 138.5, 139.6, 141.5, 143.2. IR-FT (KBr) ν_max/cm⁻¹: 3339, 3262, 3069, 3023, 2959, 2878, 1739, 1593, 1492, 1460, 1327, 1295, 1224, 1154, 1091, 1022, 975, 923, 889, 842, 818, 791, 760, 710, 666, 636, 601, 578, 552, 532. HRMS-FAB⁺: m/z [M+H]⁺ calcd. for C₂₃H₂₃O₂N₂S: 391.1480; found 391.1485.

[7,7-Dimethyl-2-oxobicyclo[2.2.1]heptan-1-methylsulfonamido](11R,12R)-diamino-9,10-dihydro-9,10-ethanoanthracene (13)

Affording a white solid (70% yield): mp 218-219 °C; [α]_D²⁰ = +13.2 (c 1.0, CHCl₃). ¹H NMR (CDCl₃, 200 MHz) δ 0.91 (s, 3H), 1.02 (s, 3H), 1.36-1.48 (m, 2H), 1.74-2.47 (m, 7H), (d, 1H, J = 15 Hz) 2.99-3.01 (m, 1H), 3.25-3.29 (m, 1H), (d, 1H, J = 15 Hz), 4.11 (d, 1H, J = 2.6 Hz), 4.30 (d, 1H, J = 2.6 Hz), 4.80 (d, 1H, J = 8 Hz), 7.08-7.36 (m, 8H). ¹³C NMR (CDCl₃, 50 MHz) δ 20.3, 20.6, 26.5, 27.6, 43.2, 43.3, 48.9, 50.4, 51.0, 52.5, 59.3, 61.4, 63.9, 124.2, 125.5, 125.9, 126.2, 126.3, 126.7, 137.3, 138.7, 139.8, 141.6, 215.0. IR-FT (KBr) ν_max/cm⁻¹: 3354, 3297, 3073, 3029, 2950, 2929, 2911, 2884, 2807, 2764, 1742, 1593, 1456, 1414, 1389, 1330, 1279, 1235, 1202, 1149, 1098, 1067, 1051, 1026, 975, 937, 913, 888, 850, 785, 765, 748, 637, 602, 571, 527, 500. HRMS-FAB⁺: m/z [M+H]⁺ calcd. for C₂₆H₃₁O₃N₂S: 451.2055; found: 451.2059.

[7,7-Dimethyl-2-oxobicyclo[2.2.1]heptan-1-methylsulfonamido](11S,12S)-diamino-9,10-dihydro-9,10-ethanoanthracene (14)

Affording a white solid (76% yield): mp 225-226 °C; [α]_D²⁰ = +32.1 (c 9.2, CHCl₃). ¹H NMR (CDCl₃, 200 MHz) δ 0.92 (s, 3H), 0.98 (s, 3H), 1.31-1.44 (m, 2H), 1.80-2.39 (m, 7H), 2.91-2.94 (m, 1H), 3.04 (d, 1H, J = 15.0 Hz), 3.26-3.30 (m, 1H), (d, 1H, J = 15.4 Hz), 4.02 (d, 1H, J = 2.6 Hz), 4.32 (d, 1H, J = 2.6 Hz), 4.90 (d, 1H, J = 8.6 Hz), 7.10-7.38 (m, 8H). ¹³C NMR (CDCl₃, 50 MHz) δ 20.2, 20.6, 27.3, 27.7, 43.1, 43.4, 49.2, 51.5, 51.8, 53.9, 59.7, 61.0, 63.5, 123.9, 124.4, 126.0, 126.3, 126.5, 126.6, 137.4, 138.3, 140.4, 141.5, 215.6. IR-FT (KBr) ν_max/cm⁻¹: 3363, 3264, 3070, 3021, 2952, 2899, 1732, 1585, 1442, 1390, 1326, 1276, 1209, 1135, 1060, 1032, 1020, 989, 941, 900, 864, 821, 781, 752, 710, 663, 606, 555, 519, 503, 423, 387, 353, 329, 297. HRMS-FAB⁺: m/z [M+H]⁺ calcd. for C₂₆H₃₁O₃N₂S: 451.2055; found: 451.2051

General procedure for synthesis of ligands 15 and 16

In a 100 mL flask ketone (300 mg, 0.67 mmol) was dissolved in a mixture solvent (40 mL, MeOH/ THF = 4:1). Next NaBH₄ (180 mg, 4.6 mmol, 7 equiv) was added slowly. The mixture was stirred for another 4 h. The reaction mixture was quenched with saturated aqueous ammonium chloride, and the solid was filtered. The filtrate was extracted with CH₂Cl₂ (3 × 50 mL). The organic phase was washed with water and was dried over NaSO₄. The solvent was removed under vacuum; the crude product was purified by flash chromatography on silica gel (Hexane/EtOAc 7:3 as eluent).

Affording a white solid (58% yield): mp 128-129 °C; [α]_D²⁰ = +6.1 (c 1.0, CHCl₃). ¹H NMR (CDCl₃, 200 MHz) δ 0.81 (s, 3H), 0.96 (s, 3H), 1.61-1.89 (m, 5H), 2.21-2.27 (m, 5H), 2.79-2.82 (m, 1H), 2.93 (d, 2H, J = 14.4 Hz), 3.13-3.20 (m, 1H), (d, 1H, J = 14.6 Hz), 3.92-4.00 (m, 2H), 4.50 (d, 1H, J = 2.6 Hz), 7.11-7.42 (m, 8H). ¹³C NMR (CDCl₃, 50 MHz) δ 20.6, 21.3, 28.0, 29.9, 41.3, 44.6, 49.4, 50.3, 51.3, 51.7, 54.0, 60.9, 62.6, 74.6, 123.9, 124.7, 126.0, 126.3, 126.5, 126.6, 126.8, 136.9, 137.5, 140.1, 141.1. IR-FT (KBr) ν_max/cm⁻¹: 3459, 3377, 3304, 3146, 3072, 3043, 3021, 2954, 2931, 2892, 1585, 1460, 1415, 1392, 1320, 1280, 1207, 1139, 1062, 1027, 988, 955, 887, 848, 817, 789, 753, 713, 638, 582, 560, 506, 450, 347. HRMS-FAB⁺: m/z [M+H]⁺ calcd. for C₂₆H₃₃O₃N₂S: 453.2212; found: 453.2218.

[2-(S)-Hydroxy-7,7-dimethylbicyclo[2.2.1]heptan-1-methylsulfonamido](11S,12S)-diamino-9,10-dihydro-9,10-ethanoanthracene (16)

Affording a white solid (68% yield): mp 217-219 °C; [α]_D²⁰ = +19.7 (c 9.0, CHCl₃). ¹H NMR (CDCl₃, 200 MHz) δ 0.81 (s, 3H), 0.96 (s, 3H), 1.15-1.28 (m, 2H), 1.68-1.87 (m, 6H), 2.78-2.81 (m, 1H), 2.93 (d, 2H, J = 14.4 Hz), 3.16-3.19 (m, 1H), 3.71 (d, 1H, J = 14.4 Hz), 3.90-4.00 (m, 4H), 4.50 (d, 1H, J = 2.6 Hz), 7.12-7.42 (m, 8H). ¹³C NMR (CDCl₃, 50 MHz) δ 20.9, 21.5, 28.2, 30.2, 41.5, 44.8, 49.6, 50.6, 51.5, 52.0, 54.2, 61.0, 62.9, 74.8, 124.1, 124.9, 126.3, 126.6, 126.7, 126.8, 127.0, 127.1, 137.2, 137.7, 140.3, 141.4. IR-FT (KBr) ν_max/cm⁻¹: 3457, 3377, 3136, 2954, 2927, 2890, 1459, 1414, 1398, 1356, 1317, 1272, 1137, 1061, 1024, 986, 954, 885, 848, 814, 790, 748, 710, 638, 602, 581, 557, 529, 502, 447, 421, 394, 344, 317. HRMS-FAB⁺: m/z [M+H]⁺ calcd. for C₂₆H₃₃O₃N₂S: 453.2212; found: 453.2220.

General procedure for the asymmetric diethylzinc addition to benzaldehyde

The ligands 6-12, 15 and 16 (5 mol %) were weighed into the reaction vessel that was then purged with nitrogen, and dissolved in toluene (3 mL). Diethylzinc (1.0 M in hexane, 2.0 equiv, 0.94 mL) was then added at rt. After 10 min, benzaldehyde (1.0 equiv, 0.47 mmol) was added. The homogeneous reaction mixture was stirred at rt, after 20 h the reaction was quenched with water (5 mL), extracted with EtOAc (2 × 40 mL) and the combined organic layers were washed with brine, dried over NaSO₄ and concentrated in vacuo. The residue was purified by flash chromatography on deactivated silica gel (Et₃N/SiO₂ = 2.5% v/w, Hexane/EtOAc 95:5) to afford 1-phenyl-1-propanol. The enantiomeric excess of the product was determined by HPLC analysis using a Chiracel OD column, 254 nm UV detector, 95:5 Hexane/i-propanol, flow rate 0.5 mL min, retention time (R): 14 min, retention time (S): 15 min. Specific rotations of the secondary alcohols were measured and compared with those reported on the literature to assign configuration [23].

General procedure for the asymmetric diethylzinc addition to benzaldehyde under solvent-free conditions

The ligands 6-12, 15 and 16 (5 mol %) were weighed into the reaction vessel and diethylzinc (1.0 M in hexane, 2.0 equiv, 0.94 mL) was then added at rt. After 10 min, benzaldehyde (1.0 equiv, 0.47mmol) was added. The homogeneous reaction mixture was stirred at rt. After 20 h the reaction was quenched with water (5 mL), extracted with EtOAc (2 × 40 mL) and the combined organic layers were washed with brine, dried over NaSO₄ and concentrated in vacuo. The residue was purified by flash chromatography on deactivated silica gel (Et₃N/SiO₂ = 2.5% v/w, Hexane/EtOAc 95:5) to afford 1-phenyl-1-propanol.

The enantiomeric excess of the product was determined by HPLC analysis using a Chiracel OD column, 254 nm UV detector, 95:5 Hexane/i-propanol, flow rate 0.5 mL min, retention time (R): 14 min, retention time (S): 15 min. Specific rotations of the secondary alcohols were measured and compared with those reported on the literature to assign configuration [24].

General procedure for the asymmetric transfer hydrogenation of acetophenone in water

Specific rotations of the secondary alcohols were measured and compared with those reported on the literature to assign configuration [23].

Acknowledgments

This work was supported by CONACYT, Consejo Nacional de Ciencia y Tecnología (Project No. 153594. and P. Guzmán Grants No. 207757). We thank F. J. Perez. L. Velasco, E. Garcia Ríos, E. Huerta, R. Patiño, and M. A. Peña (Instituto de Química, UNAM) for their technical assistance.

References

1. (a) Wang, G.; Liu, X.; Zhao, G. Tetrahedron: Asymmetry 2005, 16, 1873-1879;         [ Links ] (b) Zhu, D.; Mukherjee, C.; Hua, L. Tetrahedron: Asymmetry 2005, 16, 3275-3278;         [ Links ] (c) Reilly, M.; Anthony, D. R.; Gallagher, C. Tetrahedron Lett. 2003, 44, 2927-2930;         [ Links ] (d) Okano, K.; Murata, K.; Ikariya, T. Tetrahedron Lett. 2000, 41, 9277-9280;         [ Links ] (e) Soai, K.; Niwa, S. Chem. Rev. 1992, 92, 833-856.         [ Links ]

2. (a) Ojima Iwao, Catalytic Asymmetric Synthesis (2nd ed.) Wiley Interscience, New York 2000;         [ Links ] (b) Pu. L.; Yu, H. B. Chem. Rev. 2001, 101, 757-824.         [ Links ]

3. (a) Wu, X. Y.; Liu, X. Y.; Zhao, G. Tetrahedron: Asymmetry 2005, 16, 2299-2305;         [ Links ] (b) Park, J. K.; Lee, H. G.; Bolm, C.; Kim, B. M. Chem. Eur. J. 2005, 11, 945-950;         [ Links ] (c) Cobb, A. J. A.; Marson, C. M. Tetrahedron 2005, 61, 1269-1279;         [ Links ] (d) Tseng, S. L.; Yang, T. K. Tetrahedron: Asymmetry 2004, 15, 3375-3380;         [ Links ] (e) Sibi, M. P.; Stanley, L. M. Tetrahedron: Asymmetry 2004, 15, 3353-3356;         [ Links ] (f) Mao, J. C.; Wan, B. S.; Wang, R. L.; Wu, F.; Lu, S. W. J. Org. Chem. 2004, 69, 9123-9127;         [ Links ] (g) Da, C. S.; Han, Z. J.; Ni, M.; Ynag, F.; Liu, D. X.; Zhou, Y. F.; Wang, R. Tetrahedron: Asymmetry 2003, 14, 659-665;         [ Links ] (h) Wu, Y. J.; Yun, H. Y.; Wu, Y. S.; Ding, K. L.; Zhou, Y. Tetrahedron: Asymmetry 2000, 11, 3543-3552;         [ Links ] (i) Dosa, P. I.; Fu, G. C. J. Am. Chem. Soc. 1998, 120, 445-446.         [ Links ]

4. (a) Ji, J. X.; Wu, J.; Au-Yeung, T. L.; Yip, C. W.; Haynes, R. K.; Chan, A. S. C. J. Org. Chem. 2005, 70, 1093-1095;         [ Links ] (b) Panda, M.; Phuan, P. W.; Kozlowski, M. C. J. Org. Chem. 2003, 68, 564-571;         [ Links ] (c) Cimarelli, C.; Palmieri, G.; Volpini, E. Tetrahedron: Asymmetry 2002, 13, 2417-2426;         [ Links ] (d) Lu, J.; Xu, X.; Wang, S. Z.; Wang, C. D.; Hu, Y. F.; Hu, H. W. J. Chem. Soc., Perkin Trans. 2002, 1, 2900-2903.         [ Links ]

5. (a) Scarpi, D.; Lo Galbo, F.; Occhiato, E. G.; Guarna, A. Tetrahedron: Asymmetry 2004, 15, 1319-1324;         [ Links ] (b) García Martínez, A.; Teso Vilar, E.; García Fraile, A.; de la Moya Cerero, S.; Lora Maroto, B. Tetrahedron: Asymmetry 2003, 14, 1959-1963;         [ Links ] (c) Hanyu, N.; Aoki, T.; Mino, T.; Sakamoto, M.; Fujita, T. Tetrahedron: Asymmetry 2000, 11, 2971-2979.         [ Links ]

6. (a) Kitamura, M.; Suga, S.; Kawai, K.; Noyori, R. J. Am. Chem. Soc. 1986, 108, 6071;         [ Links ] (b) Noyori, R.; Kitamura, M. Angew. Chem.; Int. Ed. 1991, 30, 49-69.         [ Links ]

7. (a) Bauer, T.; Gajewiak, J. Tetrahedron 2004, 60, 9163;         [ Links ] (b) Bauer, T.; Tarasiuk, J. Tetrahedron Lett. 2002, 43, 687-689.         [ Links ]

8. Burguete, M. I.; Collado, M.; Escorihuela, J.; Galindo, F.; García-Verdugo, E.; Luis, S. V.; Vicent, M. J. Tetrahedron Lett. 2003, 44, 6891-6894.         [ Links ]

9. Blay, G.; Fernández, I.; Hernández-Olmos, V.; Marco-Aleixandre, A.; Pedro, J. R. Tetrahedron: Asymmetry 2005, 16, 1953-1958.         [ Links ]

10. (a) Mino, T.; Oishi, K.; Yamashita, M. Synlett 1998, 965;         [ Links ] (b) Fleischer, R.; Braun, M. Synlett 1998, 1441-1443.         [ Links ]

11. Bauer, T.; Gajewiak, J. Tetrahedron 2003, 59, 10009-10012.         [ Links ]

12. (a) Guo, C.; Qui, J.; Zhang, X. M.; Verdugo, D.; Larter, M. L.; Christie, R.; Kenney, P.; Walsh, P. J. Tetrahedron 1997, 53, 4145-4148;         [ Links ] (b) Qiu, J.; Guo, C.; Zhang, X. M. J. Org. Chem. 1997, 62, 2665-2668.         [ Links ]

13. Zhang, X. M.; Guo, C. Tetrahedron Lett. 1995, 36, 4947-4474.         [ Links ]

14. Ito, K.; Kimura, Y.; Okamura, H.; Katsuki, T. Synlett 1992, 573-574.         [ Links ]

15. Huelgas, G.; LaRochelle, L.; Rivas, L.; Loutchinina, Y.; Toscano, R. B.; Carroll, P. J.; Walsh, P. J.; de Parrodi C^. A. Tetrahedron 2011, 67, 4467-4474.         [ Links ]

16. Hechavarría, M. F.; Eibler, E.; Zabel, M.; Hönig, B. Tetrahedron: Asymmetry 2003, 14, 1989-1994.         [ Links ]

17. Cortez, N. A.; Aguirre, G.; Parra-Hake, M.; Somanathan, R.; Arita, A, J.; Coksy, A L.; de parrodi, C. A.; Huelgas, G. Synth. Commun. 2011, 41, 73-84.         [ Links ]

18. Cortez, N. A.; Aguirre, G.; Parra-Hake, M.; Somanathan, R. Tetrahedron Lett. 2007, 48, 4335-4338.         [ Links ]

19. Hirose, T.; Sugawara, K.; Kodoma, K. J. Org. Chem. 2011, 76, 5413-5428.         [ Links ]

20. Fox, M. E.; Gerlach, A.; Lennon, I. C.; Meek, G.; Praquin, C. Synthesis 2005, 3196-3198.         [ Links ]

21. Cortez, N. A.; Aguirre, G.; Parra-Hake, M.; Somanathan, R. Tetrahedron: Asymmetry 2008, 19, 1304-1309.         [ Links ]

22. Barrón-Jaime, A.; Aguirre, G.; Parra-Hake, M.; Chávez, D.; Madrigal, D.; Sanders, B.; Cooksy, A. L.; Somanathan, R. J. Mex. Chem. Soc. 2011, 55, 16-20.         [ Links ]

23. Vidal-Ferran, A.; Moyano, A.; Pericàs, M. A.; Riera, A. Tet. Lett. 1997, 38, 8773-8776.         [ Links ]

24. Sosa-Rivadeneyra, M.; Muños-Muñis, O.; de Parrodi, C. A.; Quintero, L.; Juaristi, E. J. Org. Chem. 2003, 68, 2369-2375.         [ Links ]